bluuebunny/crossref_metadata_2025 huggingface dataset:
Reduction of inter-observer variability using MRI and CT fusion in delineating of primary tumor for radiotherapy in lung cancer with atelectasis
Authors: Zhang Hongjiao , Fu Chengrui , Fan Min , Lu Liyong , Chen Yiru , Liu Chengxin , Sun Hongfu , Zhao Qian , Han Dan , Li Baosheng , Huang Wei
Published: August 2022

Purpose

To compare the difference between magnetic resonance imaging (MRI) and computed tomography (CT) in delineating the target area of lung cancer with atelectasis.

Method

A retrospective analysis was performed on 15 patients with lung cancer accompanied by atelectasis. All positioning images were transferred to Eclipse treatment planning systems (TPSs). Six MRI sequences (T1WI, T1WI+C, T1WI+C Delay, T1WI+C 10 minutes, T2WI, DWI) were registered with positioning CT. Five radiation oncologists delineated the tumor boundary to obtain the gross tumor volume (GTV). Conformity index (CI) and dice coefficient (DC) were used to measure differences among observers.

Results

The differences in delineation mean volumes, CI, and DC among CT and MRIs were significant. Multiple comparisons were made between MRI sequences and CT. Among them, DWI, T2WI, and T1WI+C 10 minutes sequences were statistically significant with CT in mean volumes, DC, and CI. The mean volume of DWI, T2WI, and T1WI+C 10 minutes sequence in the target area is significantly smaller than that on the CT sequence, but the consistency is higher than that of CT sequences.

Conclusions

The recognition of atelectasis by MRI was better than that by CT, which could reduce interobserver variability of primary tumor delineation in lung cancer with atelectasis. Among them, DWI, T2WI, T1WI+C 10 minutes may be a better choice to improve the GTV delineation of lung cancer patients with atelectasis.
Growth-promoting function of the cGAS-STING pathway in triple-negative breast cancer cells
Authors: Liu Liang-Chih , Shen Yi-Chun , Wang Yuan-Liang , Wu Wan-Rong , Chang Ling-Chu , Chen Ya-Huey , Lee Chuan-Chun , Wang Shao-Chun
Published: August 2022

The cGAS-STING axis is one of the key mechanisms guarding cells from pathogen invasion in the cytoplasmic compartment. Sensing of foreign DNA in the cytosol by the cGAS-STING axis triggers a stress cascade, culminating at stimulation of the protein kinase TBK1 and subsequently activation of inflammatory response. In cancer cells, aberrant metabolism of the genomic DNA induced by the hostile milieu of tumor microenvironment or stresses brought about by cancer therapeutics are the major causes of the presence of nuclear DNA in the cytosol, which subsequently triggers a stress response. However, how the advanced tumors perceive and tolerate the potentially detrimental effects of cytosolic DNA remains unclear. Here we show that growth limitation by serum starvation activated the cGAS-STING pathway in breast cancer cells, and inhibition of cGAS-STING resulted in cell death through an autophagy-dependent mechanism. These results suggest that, instead of being subject to growth inhibition, tumors exploit the cGAS-STING axis and turn it to a survival advantage in the stressful microenvironment, providing a new therapeutic opportunity against advanced cancer. Concomitant inhibition of the cGAS-STING axis and growth factor signaling mediated by the epidermal growth factor receptor (EGFR) synergistically suppressed the development of tumor organoids derived from primary tumor tissues of triple-negative breast cancer (TNBC). The current study unveils an unexpected function of the cGAS-STING axis in promoting cancer cell survival and the potential of developing the stress-responding pathway as a therapeutic target, meanwhile highlights the substantial concerns of enhancing the pathway’s activity as a means of anti-cancer treatment.
Combined treatment with epigenetic agents enhances anti-tumor activity of MAGE-D4 peptide-specific T cells by upregulating the MAGE-D4 expression in glioma
Authors: Bi Shui-Qing , Zhang Qing-Mei , Zeng Xia , Liu Chang , Nong Wei-Xia , Xie Huan , Li Feng , Lin Li-Na , Luo Bin , Ge Ying-Ying , Xie Xiao-Xun
Published: August 2022

Objective

The study evaluated the efficacy of combined epigenetic drugs of decitabine (DAC), valproic acid (VPA), and trichostatin A (TSA) on immunotherapy against glioma.

Methods

The expression and prognosis of MAGE-D4 in glioma were analyzed online, and the expression of MAGE-D4 and HLA-A2 in glioma induced by epigenetic drugs was detected by qRT-PCR, Western blot, and flow cytometry. The methylation status of the MAGE-D4 promoter was determined by pyrosequencing. An HLA-A2 restricted MAGE-D4 peptide was predicted and synthesized. An affinity assay and a peptide/HLA complex stability assay were performed to determine the affinity between peptide and HLA. CCK8 assay, CFSE assay, ELISA and ELISPOT were performed to detect the function of MAGE-D4 peptide-specific T cells. Flow cytometry, ELISA, and cytotoxicity assays were used to detect the cytotoxicity effect of MAGE-D4 peptide-specific T cells combined with epigenetic drugs against glioma in vitro. Finally, the glioma-loaded mouse model was applied to test the inhibitory effect of specific T cells on gliomas in vivo.

Results

MAGE-D4 was highly expressed in glioma and correlated with poor prognosis. Glioma cells could be induced to express MAGE-D4 and HLA-A2 by epigenetic drugs. MAGE-D4-associated peptides were found that induce DCs to stimulate the highest T-cell activities of proliferation, IL-2 excretion, and IFN-γ secretion. MAGE-D4 peptide-specific T cells treated with TSA only or combining TSA and DAC had the most cytotoxicity effect, and its cytotoxicity effect on glioma cells decreased significantly after HLA blocking. In vivo experiments also confirmed that MAGE-D4-specific T cells inhibit TSA-treated glioma.

Conclusion

MAGE-D4 is highly expressed in glioma and correlated with the prognosis of glioma. The novel MAGE-D4 peptide identified was capable of inducing MAGE-D4-specific T cells that can effectively inhibit glioma growth, and the epigenetic drug application can enhance this inhibition.
Case report: immunotherapy successfully treated brain metastasis in intrahepatic cholangiocarcinoma and literature review
Authors: Xie Peiyi , Guo Lei , Zhang Bo , Xu Yongfeng , Song Qi , Shi Hongcheng , Ye Qinghai , Li Hui , Xiao Yongsheng
Published: August 2022

Brain metastasis from intrahepatic cholangiocarcinoma (iCCA) is extremely rare, and no standard therapeutic strategy has been established. Camrelizumab is a programmed cell death protein 1 (PD-1) inhibitor that has been widely studied in treating liver cancer. Combined immunotherapy and targeted therapy are a promising approach for treating advanced iCCA. Despite that immune checkpoint inhibitor (ICI)-based neoadjuvant therapy on iCCA has shown a significant response rate and resection rate, few reports have shown the therapeutic efficacy of immunotherapy in treating brain metastasis from iCCA. Although PD-1 inhibitors such as pembrolizumab, nivolumab, or camrelizumab are increasingly applied in clinic practice to treat multiple malignancies, to the best of our knowledge, we report the first case of an iCCA patient with brain metastasis successfully treated with a combined immunotherapy and targeted therapy. The patient is a 54-year-old man with metastatic iCCA in brain treated though camrelizumab plus lenvatinib therapy with a complete response (CR). By the time of writing, he has had a progression-free survival of 17.5 months and did not experience any severe side effects related to this therapy. Camrelizumab plus lenvatinib therapy showed favorable efficacy and manageable toxicity for this patient with advanced iCCA and could be of interest for more prospective randomized trials to further verify the potential clinical benefits.
Preferred place of death and end-of-life care for adult cancer patients in Iran: A cross-sectional study
Authors: Fereidouni Armin , Salesi Mahmood , Rassouli Maryam , Hosseinzadegan Fariba , Javid Mohammad , Karami Maryam , Elahikhah Maryam , Barasteh Salman
Published: August 2022

Background

More than 50,000 deaths in terms of cancer occur annually in Iranian hospitals. Determining the preferred place of end-of-life care and death for cancer patients in Iran is a quality marker for good end-of-life care and good death. The purpose of this study was to determine the preferred place of end-of-life care and death in cancer patients.

Method

In 2021, the current descriptive cross-sectional investigation was carried out. Using the convenience sample approach, patients were chosen from three Tehran referral hospitals (the capital of Iran). A researcher-made questionnaire with three parts for demographic data, clinical features, and two questions on the choice of the desired location for end-of-life care and the death of cancer patients served as the data collecting instrument. Data were analyzed using SPSS software version 18. The relationship between the two variables preferred place for end-of-life care and death and other variables was investigated using chi-square, Fisher exact test, and multiple logistic regression.

Result

The mean age of patients participating in the study was 50.21 ± 13.91. Three hundred ninety (69.6%) of the patients chose home, and 170 (30.4%) patients chose the hospital as the preferred place of end-of-life care. Choosing the home as a preferred place for end-of-life care had a significant relationship with type of care (OR = .613 [95% CI: 0.383–0.982], P = .042), level of education (OR = 2.61 [95% CI: 1.29–5.24], P = 0.007), type of cancer (OR = 1.70 [1.01–2.89], P = .049), and income level (Mediate: (OR: 3.27 (1.49, 7.14), P = .003) andLow: (OR: 3.38 (1.52–7.52), P = .003). Also, 415 (75.2%) patients chose home and 137 (24.8%) patients chose hospital as their preferred place of death. Choosing the home as a preferred place of death had a significant relationship with marriage (OR = 1.62 [95% CI: 1.02–2.57], P = .039) and time to diagnostic disease less than 6 months (OR = 1.62 [95% CI: 0.265–0.765], P = .002).

Conclusion

The findings of the current research indicate that the majority of cancer patients selected their homes as the preferred location for end-of-life care and final disposition. Researchers advise paying more attention to patients’ wishes near the end of life in light of the findings of the current study. This will be achieved by strengthening the home care system using creating appropriate infrastructure, insurance coverage, designing executive instructions, and integration of palliative care in home care services.
High salt intake combined with hypertension elevated the risk of primary liver cancer: a prospective cohort study
Authors: Liu Tong , Zhang Qingsong , Xiao Xiaoli , Wang Yiming , Ma Xiangming , Song Mengmeng , Zhang Qi , Cao Liying , Shi Hanping
Published: August 2022

Background

Hypertension and high-salt intake may act synergistically to increase the risk of primary liver cancer (PLC). We prospectively examined the joint effect of hypertension and salt intake on the risk of PLC incidence.

Methods

A total of 92,978 participants were included in the final analyses. The study population was divided into 4 groups according to the presence or absence of hypertension and salt intake. Cox proportional hazards regression models were used to evaluate the association of hypertension and/or high-salt intake with the risk of incident cancers. The CAUSALMED procedure was used to perform the mediation analyses.

Results

During a median follow-up of 12.69 years, a total of 418 incident cancer cases were identified. Hypertension was a risk factor for PLC in women but not in men. High salt intake was associated with an elevated risk of PLC in men. A significant interaction between salt intake and hypertension was found for the risk of PLC (P for interaction=0.045). Compared with Group 1 (hypertension-, high salt intake-), participants in Group 2 (hypertension-, high salt intake+) and Group 4 (hypertension+, high salt intake+) were associated with an elevated risk of PLC with the corresponding multivariate HRs (95%CIs) of 1.73(0.96,3.10) and 1.96(1.09,3.53) respectively. No significant mediation effect was found for the association between hypertension, salt intake and PLC risk.

Conclusions

The combination of high salt intake and hypertension could significantly increase the risk of PLC. It may be reasonable to recommend a low-salt intake to prevent and control the prevalence of PLC and hypertension.

Trial registration

Kailuan study, ChiCTR–TNRC–11001489. Registered 24 August, 2011-Retrospectively registered, https://www.chictr.org.cn/showprojen.aspx?proj=8050
Elevated expression of LIF predicts a poor prognosis and promotes cell migration and invasion of clear cell renal cell carcinoma
Authors: Zhong Wenting , Liu Hongxia , Li Feng , lin Youyu , Ye Yan , Xu Luyun , Li ShengZhao , Chen Hui , Li Chengcheng , Lin Yuxuan , Zhuang Wei , Lin Yao , Wang Qingshui
Published: August 2022

Background

Renal cell carcinoma (RCC) is the seventh most common cancer in humans, of which clear cell renal cell carcinoma (ccRCC) accounts for the majority. Recently, although there have been significant breakthroughs in the treatment of ccRCC, the prognosis of targeted therapy is still poor. Leukemia inhibitory factor (LIF) is a pleiotropic protein, which is overexpressed in many cancers and plays a carcinogenic role. In this study, we explored the expression and potential role of LIF in ccRCC.

Methods

The expression levels and prognostic effects of the LIF gene in ccRCC were detected using TCGA, GEO, ICGC, and ArrayExpress databases. The function of LIF in ccRCC was investigated using a series of cell function approaches. LIF-related genes were identified by weighted gene correlation network analysis (WGCNA). GO and KEGG analyses were performed subsequently. Cox univariate and LASSO analyses were used to develop risk signatures based on LIF-related genes, and the prognostic model was validated in the ICGC and E-MTAB-1980 databases. Then, a nomogram model was constructed for survival prediction and validation of ccRCC patients. To further explore the drug sensitivity between LIF-related genes, we also conducted a drug sensitivity analysis based on the GDSC database.

Results

The mRNA and protein expression levels of LIF were significantly increased in ccRCC patients. In addition, a high expression of LIF has a poor prognostic effect in ccRCC patients. LIF knockdown can inhibit the migration and invasion of ccRCC cells. By using WGCNA, 97 LIF-related genes in ccRCC were identified. Next, a prognostic risk prediction model including eight LIF-related genes (TOB2, MEPCE, LIF, RGS2, RND3, KLF6, RRP12, and SOCS3) was developed and validated. Survival analysis and ROC curve analysis indicated that the eight LIF-related-gene predictive model had good performance in evaluating patients’ prognosis in different subgroups of ccRCC.

Conclusion

Our study revealed that LIF plays a carcinogenic role in ccRCC. In addition, we firstly integrated multiple LIF-related genes to set up a risk-predictive model. The model could accurately predict the prognosis of ccRCC, which offers clinical implications for risk stratification, drug screening, and therapeutic decision.
Investigation of the inhibition effect of 1,2,3,4,6-pentagalloyl-β-D-glucose on gastric cancer cells based on a network pharmacology approach and experimental validation
Authors: Bi Jing-hui , Jiang Yu-han , Ye Shi-jie , Wu Min-rui , Yi Yang , Wang Hong-xun , Wang Li-mei
Published: August 2022

Background

Gastric cancer (GC) is ranked as the third leading cause of cancer-related mortality worldwide. 1,2,3,4,6-Pentagalloyl-β-D-glucose (β-PGG) has various pharmacological activities and has been shown to suppress cancer development. However, the mechanism by which β-PGG inhibits gastric cancer has not been elucidated.

Objective

This study explored the potential targets and mechanism of β-PGG in GC using the network pharmacology approach combined with in-vitro experiments.

Methods

The PharmMapper software was used to predict the potential targets of β-PGG, and GC-related genes were identified on the GeneCards database. PPI analysis of common genes was performed using the STRING database. The potential regulatory mechanism of β-PGG in GC was explored through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses. The binding ability of key genes and target proteins was verified by molecular docking. The effects of β-PGG on genes and proteins were evaluated using the CCK-8 assay, cell cycle analysis, apoptosis assay, real-time fluorescence quantification polymerase chain reaction (qRT-PCR), and Western blotting.

Results

Eight hub genes involved in cell cycle progression and apoptosis were identified. Cancer-related signaling pathways were identified using the Cytoscape tool. Some of those genes were significantly enriched in the p53 signaling pathway. The CCK-8 assay showed that β-PGG inhibited the proliferation of GC cells. Cell cycle and apoptosis experiments revealed that β-PGG induced cell cycle arrest and apoptosis of gastric cancer cells. qRT-PCR and Western blot analysis showed that β-PGG inhibited β-PGG cells by modulating the p53 signaling pathway.

Conclusion

In the present study, the targets and mechanism of β-PGG in gastric cancer were explored. The results indicate that β-PGG can be used to develop treatments for GC.
Discussion of tumor mutation burden as an indicator to predict efficacy of immune checkpoint inhibitors: A case report
Authors: Wu Mingrui , Liang Lan , Dai Xiaotian
Published: August 2022

There are many treatment options for advanced lung cancer, among which immunotherapy has developed rapidly and benefited a lot of patients. However, immunotherapy can only benefit a subgroup of patients, and how to select patients suitable for this therapy is critical. Tumor mutation burden (TMB) is one of the important reference indicators for immune checkpoint inhibitors (ICIs). However, there are many factors influencing the usage of this indicator, which will lead to considerable consequences if not treated well. In this study, we performed a case study on a male advanced lung squamous cell carcinoma patient of age 83. The patient suffered from “cough and sputum”, and did chest CT scans on 24 October 2018, which showed “a mass-like mass in the anterior segment of the right lung upper lobe, about 38mm×28mm”. He was treated with systemic chemotherapy; however, the tumor was still under progression. Although PD-L1 was not tested in gene testing, he had a TMB value of 10.26 mutations/Mb with a quantile value 88.63%. Thus, “toripalimab injection” was added as immunotherapy and the size of the lesion decreased. In summary, we adopted a clinical case as the basis to explore the value and significance of TMB in immunotherapy in this study. We hope that more predictive molecular markers will be discovered, which will bring more treatment methods for advanced lung cancer.
Sex-specific differences in immunogenomic features of response to immune checkpoint blockade
Authors: Scott Susan C. , Shao Xiaoshan M. , Niknafs Noushin , Balan Archana , Pereira Gavin , Marrone Kristen A. , Lam Vincent K. , Murray Joseph C. , Feliciano Josephine L. , Levy Benjamin P. , Ettinger David S. , Hann Christine L. , Brahmer Julie R. , Forde Patrick M. , Karchin Rachel , Naidoo Jarushka , Anagnostou Valsamo
Published: August 2022

Introduction

The magnitude of response to immune checkpoint inhibitor (ICI) therapy may be sex-dependent, as females have lower response rates and decreased survival after ICI monotherapy. The mechanisms underlying this sex dimorphism in ICI response are unknown, and may be related to sex-driven differences in the immunogenomic landscape of tumors that shape anti-tumor immune responses in the context of therapy.

Methods

To investigate the association of immunogenic mutations with HLA haplotypes, we leveraged whole exome sequence data and HLA genotypes from 482 non-small cell lung cancer (NSCLC) tumors from The Cancer Genome Atlas (TCGA). To explore sex-specific genomic features linked with ICI response, we analyzed whole exome sequence data from patients with NSCLC treated with ICI. Tumor mutational burden (TMB), HLA class I and II restricted immunogenic missense mutation (IMM) load, and mutational smoking signature were defined for each tumor. IMM load was combined with HLA class I and II haplotypes and correlated with therapeutic response and survival following ICI treatment. We examined rates of durable clinical benefit (DCB) for at least six months from ICI treatment initiation. Findings were validated utilizing whole exome sequence data from an independent cohort of ICI treated NSCLC.

Results

Analysis of whole exome sequence data from NSCLC tumors of females and males revealed that germline HLA class II diversity (≥9 unique HLA alleles) was associated with higher tumor class II IMM load in females (p=0.01) and not in males (p=0.64). Similarly, in tumors of female patients, somatic HLA class II loss of heterozygosity was associated with increased IMM load (p=0.01) while this association was not observed in tumors in males (p=0.20). In females, TMB (p=0.005), class I IMM load (p=0.005), class II IMM load (p=0.004), and mutational smoking signature (p<0.001) were significantly higher in tumors responding to ICI as compared to non-responding tumors. In contrast, among males, there was no significant association between DCB and any of these features. When IMM was considered in the context of HLA zygosity, high MHC-II restricted IMM load and high HLA class II diversity was significantly associated with overall survival in males (p=0.017).

Conclusions

Inherent sex-driven differences in immune surveillance affect the immunogenomic determinants of response to ICI and likely mediate the dimorphic outcomes with ICI therapy. Deeper understanding of the selective pressures and mechanisms of immune escape in tumors in males and females can inform patient selection strategies and can be utilized to further hone immunotherapy approaches in cancer.
Non-muscle invasive bladder cancer biomarkers beyond morphology
Authors: De Carlo Camilla , Valeri Marina , Corbitt Devin Nicole , Cieri Miriam , Colombo Piergiuseppe
Published: August 2022

Non-muscle invasive bladder cancer (NMIBC) still represents a challenge in decision-making and clinical management since prognostic and predictive biomarkers of response to treatment are still under investigation. In addition to the risk factors defined by EORTC guidelines, histological features have also been considered key variables able to impact on recurrence and progression in bladder cancer. Conversely, the role of genomic rearrangements or expression of specific proteins at tissue level need further assessment in NMIBC. As with muscle-invasive cancer, NMIBC is a heterogeneous disease, characterized by genomic instability, varying rates of mutation and a wide range of protein tissue expression. In this Review, we summarized the recent evidence on prognostic and predictive tissue biomarkers in NMIBC, beyond morphological parameters, outlining how they could affect tumor biology and consequently its behavior during clinical care. Our aim was to facilitate clinical evaluation of promising biomarkers that may be employed to better stratify patients. We described the most common molecular events and immunohistochemical protein expressions linked to recurrence and progression. Moreover, we discussed the link between available treatments and molecular drivers that could be predictive of clinical response. In conclusion, we foster further investigations with particular focus on immunohistochemical evaluation of tissue biomarkers, a promising and cost-effective tool for daily practice.
Intercalary reconstruction of long bones by massive allograft: Comparison of construct stability ensured by three different host-graft junctions and two types of fixations in a synthetic femur model
Authors: Baleani Massimiliano , Erani Paolo , Blaise Manon , Fognani Roberta , Palmas Marco , Manfrini Marco
Published: August 2022

An intercalary segmental allograft is an option for limb salvage in bone tumours. Stable and congruent intercalary reconstructions are a prerequisite for achieving host-graft union. However, a too rigid fixation could increase the risk of late complications correlated with negative bone remodelling. This study compared the reconstruction stiffness achieved by three different host-graft junctions, namely, end-to-end, modified step-cut, and taper. A low-stiffness bone plate was used as the fixation method, except for the taper junction where a low-stiffness intramedullary nail was also used to investigate the effects of different types of fixation on construct stiffness. Composite femora were tested under four loading conditions to determine coronal and sagittal bending stiffness, as well as torsional stiffness in opposite directions. Stiffness values were expressed as a percentage of intact host bone stiffness (%IBS). While a reduction of coronal bending stiffness was found with taper junctions (76%IBS) compared with the high values ensured by end-to-end (96%IBS) and modified step-cut junctions (92%IBS), taper junctions significantly increased stiffness under sagittal bending and torsion in intra- and extra-direction: end-to-end 29%IBS, 7%IBS, 7%IBS, modified step-cut 38%IBS, 20%IBS, 21%IBS, and taper junction 52%IBS, 55%IBS, 56%IBS, respectively. Construct stiffness with taper junctions was decreased by 11–41%IBS by replacing the bone plate with an intramedullary nail. Taper junctions can be an alternative to achieve intercalary reconstructions with more homogeneous and, in three out of four loading conditions, significantly higher construct stability without increasing bone plate stiffness. The risk of instability under high torsional loads increases when taper junctions are associated with a low-stiffness intramedullary nail.
Agreement between histopathological and intraoperative classifications for pediatric appendicitis and its relationship with the post-operative clinical outcome
Authors: Silva Camila de Paula , Ortolan Erika Veruska Paiva , Ribeiro Sergio Marrone , Tedesco Bruna Aliotto Nalin , Terra Simone Antunes , Rodrigues Maria Aparecida Marchesan , Lourenção Pedro Luiz Toledo de Arruda
Published: August 2022

Introduction

Some studies have shown poor agreement between intraoperative and histopathological classifications for appendicitis, despite their routine use in clinical practice.

Objective

To investigate the agreement between histopathological and intraoperative classifications for pediatric appendicitis and evaluate the predictive potential of these classifications for the post-operative outcome.

Methods

A retrospective, longitudinal, observational single-center study, carried out with 485 patients up to15 years of age, with a confirmed diagnosis of acute appendicitis by histopathological evaluation. The histopathological results classified the appendices as uncomplicated appendicitis when there was confirmation of the diagnosis of appendicitis without necrosis or perforation and complicated appendicitis when there was extensive necrotic tissue in the outer layer of the appendix or signs of perforation. The intraoperative findings were classified as uncomplicated appendicitis when the appendix presented with hyperemia and edema or fibrinous exudate and complicated appendicitis when the appendix showed necrosis, abscess, or perforation. The kappa index determined the agreement and the prediction relationships using a generalized linear model.

Results

43.9% of cases were classified as complicated appendicitis by histopathological evaluation and 49.7% by intraoperative classification. The agreement analysis between the histopathological and intraoperative classification showed a moderate agreement, with a Kappa index of 0.419 (0.337–0.501). There was an association (P < 0.05) between the intraoperative classification and the post-operative clinical outcomes (time to start feeding, fever, intraabdominal collection, length of stay, the need for antibiotic therapy changing, and need for ICU). There was no association between histopathological classification and post-operative outcomes.

Conclusion

The agreement between the two classifications was moderate, and the intraoperative classification was able to predict the post-operative clinical outcomes.
Epidemiological profile of dog attacks to patients under 14 years old assisted at the pediatric referral emergency unit of a tertiary hospital in Campinas, Brazil
Authors: Medeiros Michelle Marchi , Marson Fernando Augusto Lima , Marques Leonardo Souza , Peixoto Andressa Oliveira , Fraga Andrea de Melo Alexandre
Published: August 2022

Introduction

Accidents involving dog attacks are very common, which makes this type of accident a global public health issue. The estimates point to 20% of the victims of such accidents seeking care in health units, and half of them being children. In addition to acute injuries, dog attacks might result in fractures, infections, scars, and psychological traumas. This study aimed to describe the epidemiological profile of dog attacks to children under 14 years old assisted in a pediatric emergency service in Brazil.

Methods

The database of the Information and Toxicological Assistance Center of Campinas was surveyed to identify cases of children under 14 years old assisted after a dog attack in a 9-years period. Demographic data, number and type of lesions, type of exposure, part of the body affected, dog origin and condition, and the accident location and cause were analyzed. The data were presented in a descriptive way, and the age groups were classified as follows: 0–3 years old, 4–6 years old, and 7–14 years old. The different age groups were compared one to another regarding the markers evaluated using the chi-square test and the Fisher’s exact test. A 0.05 alpha was adopted in all analyses.

Results

The number of children assisted in the study period totaled 1,012. The 7–14-year-old group was the most affected (n = 498; 49.2%), male patients were also majority (n = 660; 65.2%). Most injuries were found on the head/neck area (n = 378; 37.4%). However, the older the patients were, the higher the frequency of lesions on upper and lower limbs was, as well as attacks occurred in external environments, thus involving animals that could not be observed. A significant increase in accidents with provoked causes was observed in younger patients.

Conclusion

Accidents involving dog attacks are more likely to happen among boys. Younger children run higher risks of becoming victims of these accidents inside homes, being attacked by pets, and showing a greater incidence of head and neck lesions. Older children present more injuries on their limbs, which are caused by dogs that cannot be observed.
Inhibition of Soybean 15-Lipoxygenase and Human 5-Lipoxygenase by Extracts of Leaves, Stem Bark, Phenols and Catechols Isolated From Lithraea caustica (Anacardiaceae)
Authors: Muñoz-Ramírez Alejandra , Mascayano-Collado Carolina , Barriga Andrés , Echeverría Javier , Urzúa Alejandro
Published: August 2022

Lithraea caustica(Molina) Hook. and Arn. (Anacardiaceae), common name Litre, is an evergreen endemic plant used in the Mapuche Chilean folk medicine. The stem juice ofL. causticamixed withRubus ulmifolius(blackberry) is used to treat cough and the infusion of leaves is used in baths to treat joint inflammations. In this study, the activities of 3-n-alk(en)yl-catechols, obtained from the dichloromethane extract of the epicuticular compounds of fresh leaves (DCME), stem bark petroleum ether extract (PEE), fractions of phenols and phenol-acid compounds obtained from the methanolic extract (methanolic extract) of defatted leaves and aqueous infusion (AE) from fresh leaves, were evaluated asin vitroinhibitors of soybean 15-lipoxygenase (15-sLOX) and human 5-lipoxygenase (5-hLOX), one of the inflammation pathways. The 3-n-alk(en)yl-catechols were characterized by gas chromatography-mass spectrometry and 1D and 2D nuclear magnetic resonance analysis as mixtures of 3-[(10E)-pentadec-10′-en-1-yl]-catechol, 3-[(10Z)-pentadec-10′-en-1-yl]-catechol and 3-n-pentadecylcatechol. In addition, two fractions, obtained from MeOHE, were characterized by liquid chromatography electrospray ionization tandem mass spectrometric as complex mixtures of known acids and phenolic compounds. DCME, MeOHE and ethyl acetate extract (AcOEtE) extracts showed inhibition against 15-sLOX, and the AE of fresh leaves, showed the best inhibition against 5-hLOX. The mixture of 3-n-alk(en)yl-catechols showed inhibition of 15-sLOX and 5-hLOX. The compounds 3-[(10Z)-pentadec-10′-en-1-yl]-catechol (IC502.09 µM) and 3-n-pentadecylcatechol (IC502.74 µM) showed inhibition against 5-hLOX. The inhibition values obtained for the 3-n-alk(en)yl-catechols are in the range of well-known inhibitors of 5-hLOX. Acetylation of the 3-n-alk(en)yl-catechols blocks the inhibitory activity, indicating that the free catechol function is necessary for the enzyme inhibition. In addition, the fractions of phenols and phenol-acid compounds showed inhibitory activity against 15-sLOX and the AE, showed a good inhibition against 5-hLOX. These results would be in agreement with the use ofL. caustica, as an anti-inflammatory in Mapuche ethnomedicine.
Chang qing formula ameliorates colitis-associated colorectal cancer via suppressing IL-17/NF-κB/STAT3 pathway in mice as revealed by network pharmacology study
Authors: Luo Qihan , Huang Shuo , Zhao Lisha , Liu Jingqun , Ma Qing , Wang Yiheng , Dong Yu , Li Changyu , Qiu Ping
Published: August 2022

Colitis-associated colorectal cancer (CAC) is a specific type of colorectal cancer (CRC) with high mortality and morbidity, the chronic inflammation in the intestinal mucosal is the characteristic of CAC. Chang Qing formula (CQF) is a Chinese herbal formula used clinically for the treatment of CAC with remarkable clinical efficacy, but its mechanism remains unclear. In the present work, Combined network pharmacology and transcriptomics were used to analyze the potential active ingredients and elucidate molecular mechanism of CQF in treating CAC. Firstly, the constituents migrating to blood of CQF were analyzed and identified by UPLC-Q-TOF-MS/MS, and core genes and pathways were screened by network pharmacology analysis. Encyclopedia of Genes and Genomes (KEGG) analysis showed that the IL-17 signaling pathway involved in CAC may be closely associated with the potential mechanismof action of CQF. Subsequently, the results from animal studies indicated that CQF profoundly reduced tumor numbers and tumor size in AOM/DSS mice. The RNA-seq data was analysed utilizing Ingenuity Pathway Analysis (IPA), and the results supported the idea that CQF exerts a tumour-suppressive effect via the IL-17 signalling pathway. Further studies demonstrated that CQF significantly reduced IL-17A levels, which in turn inhibited NF-κB/IL-6/STAT3 signaling cascade, suppressed MMP9 expression and promoted tumor cell apoptosis. In conclusion, the current study demonstrated that CQF remarkably improved inflammatory tumor microenvironment, and hindered the transformation of inflammation into cancer. These findings may help to design future strategies for the treatment of CAC.
Three main metabolites from Wolfiporia cocos (F. A. Wolf) Ryvarden & Gilb regulate the gut microbiota in mice: A comparative study using microbiome-metabolomics
Authors: Lai Yong , Yu Hailun , Deng Huiling , Fang Qi , Lei Hui , Liu Li , Wu Nannan , Guo Xiurong , Song Can
Published: August 2022

Wolfiporia cocos (F. A. Wolf) Ryvarden & Gilb, also known as Poria cocos is an ancient edible and medicinal mushroom that has been valued for thousands of years for its tranquilizing, diuretic, and spleen-enhancing properties. Because of the mushroom’s complex composition, its pharmacological effects have not been fully clarified. Therefore, to expand our knowledge of these effects from a pharmacological perspective and exploit potential medicinal value of fungal mushroom, we extracted three main metabolites from P. cocos, including water-soluble polysaccharides (PCX), water-insoluble polysaccharides (PCY), and triterpenoid saponins (PCZ) for intragastric injection into mice. These injections were made to explore the component’s effects on the mice’s gut microbiota and their metabolomics. The microbiota analysis showed that PCY had the strongest effect on regulating gut microbiota through altering its composition and increasing the number of Lactobacillus (p < 0.01). A total of 1,828 metabolites were detected using metabolomics methods, and the results showed that the three main active metabolites of P. cocos significantly changed the content of short-chain peptides in intestinal metabolites. In conclusion, our study further investigated the pharmacological functions of P. cocos, and revealed the differing effects of its three main metabolites on gut microbiota. The results suggested that PCY is a prominent prebiotic, and provided us with new insights into the potential development of fungal polysaccharides in Chinese traditional medicine.
Activation of TRPC6 by AngⅡ Induces Podocyte Injury and Participates in Proteinuria of Nephrotic Syndrome
Authors: Feng Ye , Li Manman , Wang Yunlai , Yang Mo , Shi Gaoxiang , Yin Dengke , Xuan Zihua , Xu Fan
Published: August 2022

Background: Nephrotic syndrome (NS) is a common glomerular disease, and podocyte injury is the character of primary NS, usually caused by minimal change disease and membranous nephropathy. Podocytopathy is primarily associated with glomerular proteinuria. Losartan, an angiotensin receptor blocker (ARB), is commonly used in the treatment of NS, and the AngiotensinⅡ (AngⅡ)–transient receptor potential ion channel 6 (TRPC6) axis has been reported to act on podocytes to regulate proteinuria in NS. Therefore, the purpose of this study was to explore the relationship in between AngⅡ–TRPC6, podocyte injury, and proteinuria based on the adriamycin (ADR) NS rat model.

Method: All male rats were divided into three groups: control group, model group, and ARB group. The rats in the model group were induced by ADR, and the rats in the ARB group received losartan after induction of renal injury for 4 weeks. The changes in parameters related to renal dysfunction, and glomerular and podocyte structural damage, such as AngⅡ, AngⅡ type I receptor (AT1R), TRPC6, CaN, Caspase-3, Nephrin, and Podocin, were analyzed. Furthermore, the kidneys were isolated for study via transmission electron microscopy (TEM), immunohistochemistry, and western blot (WB) after the rats were sacrificed. In vitro, immortalized mouse MPC5 podocytes were used to investigate the regulatory effect of flufenamic acid (Flu) and SAR7334 (SAR) on the AngⅡ-TRPC6 signaling axis. Flow cytometry and WB were conducted to determine the relationship between podocyte injury and AngⅡ-TRPC6.

Results:In vivo results showed that NS rats developed massive albuminuria and abnormal renal function, accompanied by abnormally increased levels of AngⅡ, TRPC6, AT1R, and CaN and a decreased expression of actin molecules in podocytes, extensive fusion of foot processes (FP), loss of glomerular structural integrity, collapse of podocyte structure, and skeletal reorganization. In vitro experiments indicated that both AngⅡ and Flu (the specific agonist of TRPC6) stimulated the expressions of TRPC6, AT1R, and Caspase-3 in podocytes. The AngⅡ receptor–blocker losartan and TRPC6-specific inhibitor SAR blocked the overexpression of the aforementioned proteins. In addition, SAR also attenuated the degradation of podocyte structural proteins and inhibited the fluorescence intensity of intracellular calcium (Ca2+) and cell apoptosis.

Conclusion: The involvement of AngⅡ in the occurrence of NS proteinuria may be related to podocyte injury induced by activated TRPC6.
Quantitative analysis of surface wave patterns of Min proteins
Authors: Meindlhumer Sabrina , Kerssemakers Jacob , Dekker Cees
Published: August 2022

The Min protein system is arguably the best-studied model system for biological pattern formation. It exhibits pole-to-pole oscillations in E. coli bacteria as well as a variety of surface wave patterns in in vitro reconstitutions. Such Min surface wave patterns pose particular challenges to quantification as they are typically only semi-periodic and non-stationary. Here, we present a methodology for quantitatively analysing such Min patterns, aiming for reproducibility, user-independence, and easy usage. After introducing pattern-feature definitions and image-processing concepts, we present an analysis pipeline where we use autocorrelation analysis to extract global parameters such as the average spatial wavelength and oscillation period. Subsequently, we describe a method that uses flow-field analysis to extract local properties such as the wave propagation velocity. We provide descriptions on how to practically implement these quantification tools and provide Python code that can directly be used to perform analysis of Min patterns.
CRISPR/Cas9-mediated Serine protease 2 disruption induces male sterility in Spodoptera litura
Authors: Bi Honglun , Xu Xia , Li Xiaowei , Wang Yaohui , Zhou Shutang , Huang Yongping
Published: August 2022

Male fertility is essential for reproduction and population growth in animals. Many factors affect male fertility, such as courtship behavior, sperm quantity, and sperm motility, among others. Seminal Fluid Proteins (SFPs) are vital components of seminal fluid in the male ejaculate, which affect male fertility, sperm activation, and female ovulation. However, the knowledge of SFPs is insufficient; the function of many SFPs remains unknown, and most described functions were mainly characterized in Drosophila or other laboratory models. Here, we focus on the Serine protease 2 (Ser2) gene in the lepidopteran pest Spodoptera litura. The Ser2 gene was specifically expressed in male adults. Disruption of the Ser2 gene mediated by CRISPR/Cas9 induced male sterility but females remained fertile. PCR-based detection of the next-generation mutants showed that male sterility was stably inherited. The qRT-PCR analysis of SlSer2 mutants showed that motor protein family genes and structural protein family genes were down-regulated, while protein modification family genes were up-regulated, suggesting that SlSer2 may be involved in sperm movement and activity. These results demonstrate that Ser2 is an important component of SFPs in seminal fluid and was identified for a useful sterile gene for pest control that may lead to new control strategies for lepidopteran insect pests such as S. litura.
Zinc oxide nanoparticles improved chlorophyll contents, physical parameters, and wheat yield under salt stress
Authors: Adil Muhammad , Bashir Safdar , Bashir Saqib , Aslam Zubair , Ahmad Niaz , Younas Tasaddaq , Asghar Rana Muhammad Ammar , Alkahtani Jawaher , Dwiningsih Yheni , Elshikh Mohamed S.
Published: August 2022

Nanotechnology has a wide range of applications. Nanotechnology refers to the particle in nanoscale used to improve agricultural productivity and to encounter the unsolved problems conventionally. Nanostructured formulation through mechanisms, such as targeted delivery or slow/controlled release mechanisms as well as conditional release, could release their active ingredients in response to the environmental conditions and biological demands more precisely. Nanotechnology has a great potential for achieving sustainable agriculture, especially in developing countries. Salinity is among the major abiotic stresses which limits the yield and quality of global crops. Zinc (Zn) is a vital micronutrient that is mandatory for the ideal growth of plants and has proved to reduce the hazardous effects of salt stress. To counter the salinity problem, a pot experiment was conducted at wire house of the Institute of Soil and Environmental Sciences (ISES), University of Agriculture, Faisalabad, Pakistan, to observe the effects of zinc oxide (ZnO) nanoparticles (NPs) on wheat variety “Gemmieza” imported from Egypt under salt stress. Notably, 10 dS m–1salinity was developed artificially, and different doses of Zn conventional fertilizer and ZnO NPs were applied to potted wheat. ZnO NPs (0.12 g pot–1) significantly increased the physical parameters of wheat compared to control under salt stress. Application of ZnO NPs (0.12 g pot–1) significantly increased chlorophyll A and B contents by 24.6 and 10%, plant height at vegetative and maturity stages by 34.6 and 37.4%, shoot and spike lengths by 30.7 and 27.6%, root fresh and dry weights by 74.5 and 63.1%, and wheat grain yield by 42.2%, respectively. ZnO NPs performed better compared to Zn conventional fertilizer under salt stress and could be used in place of Zn conventional fertilizer in salt-affected soils for attaining better crop production.
The key molecular pattern BxCDP1 of Bursaphelenchus xylophilus induces plant immunity and enhances plant defense response via two small peptide regions
Authors: Hu Long-Jiao , Wu Xiao-Qin , Wen Tong-Yue , Ye Jian-Ren , Qiu Yi-Jun , Rui Lin , Zhang Yan
Published: August 2022

The migratory plant-parasitic nematode Bursaphelenchus xylophilus is the pathogen of the pine wilt disease (PWD), causing serious damage to pine forests in China. During the process of plant resistance to multiple pathogens, plant immunity plays a key role. In this current study, the pathogen-associated molecular pattern (PAMP) BxCDP1 in B. xylophilus has been identified, but the host target protein of BxCDP1 and its key amino acid region inducing the plant immunity have yet to be elucidated. We found that BxCDP1 could trigger superoxide production, H2O2 production, and callose deposits. A RING-H2 finger protein 1 (RHF1) of Pinus thunbergii was screened and characterized as a target protein of BxCDP1 by yeast two-hybrid and co-immunoprecipitation (Co-IP). Moreover, two peptides (namely M9 and M16) proved to be key regions of BxCDP1 to induce PAMP-triggered immunity (PTI) in Nicotiana benthamiana, which also induced the expression of pathogenesis-related (PR) genes (PtPR-3, PtPR-4, and PtPR-5) in P. thunbergii and enhanced the resistance of the host to B. xylophilus. These results indicate that BxCDP1 plays a critical role in the interaction between B. xylophilus and P. thunbergii, and both peptides M9 and M16 have the potential to be developed and utilized as immune inducers of pines against B. xylophilus in future.
How Social Exclusion Affects Consumers’ Color Preference
Authors: Zong Lu , Wu Shali , Duan Shen
Published: August 2022

Social exclusion can cause negative changes on human beings both in the physiological and psychological aspects. Although considerable efforts have been devoted to study its effects on consumption behavior, little attention has been paid to the consequence that social exclusion might have on consumer’s color preference and the underlying mechanisms. Such social events can change individual’s behavior. This work examines the influence of social exclusion on consumers’ color preference as well as the moderation and mediation effects via three experiments: Experiment 1 studies the impacts of social exclusion on consumer color choice (warm color versus cold color). To further validate the robustness of the results, experiment 2 is designed by replicating the findings of experiment 1 in another product category and instructed the participants to choose products with different colors. Meanwhile, the mediation effect of self-threat is examined. In Experiment 3, the moderation effect of self-construal is investigated via a 2 (exclusion vs. inclusion) × 2 (independent vs. interdependent) × (warm color vs. cold color) between-subjects design. Our results indicate that social exclusion makes people prefer warm colors rather than cold colors. However, these effects would be mediated by self-threat, which could be further moderated by self-construal. The present study establishes the relationship between social exclusion and consumers’ color preference, which is expected to provide guidance for companies to improve product design and promotion strategies to adapt to various contexts.