bluuebunny/crossref_metadata_2025 huggingface dataset:
Frontline workers: Mediators of mucosal immunity in community acquired pneumonia and COVID-19
Authors: Hastak Priyanka S. , Andersen Christopher R. , Kelleher Anthony D. , Sasson Sarah C.
Published: September 2022

The current COVID-19 pandemic has highlighted a need to further understand lung mucosal immunity to reduce the burden of community acquired pneumonia, including that caused by the SARS-CoV-2 virus. Local mucosal immunity provides the first line of defence against respiratory pathogens, however very little is known about the mechanisms involved, with a majority of literature on respiratory infections based on the examination of peripheral blood. The mortality for severe community acquired pneumonia has been rising annually, even prior to the current pandemic, highlighting a significant need to increase knowledge, understanding and research in this field. In this review we profile key mediators of lung mucosal immunity, the dysfunction that occurs in the diseased lung microenvironment including the imbalance of inflammatory mediators and dysbiosis of the local microbiome. A greater understanding of lung tissue-based immunity may lead to improved diagnostic and prognostic procedures and novel treatment strategies aimed at reducing the disease burden of community acquired pneumonia, avoiding the systemic manifestations of infection and excess morbidity and mortality.
Glutaminolysis and CD4+ T-cell metabolism in autoimmunity: From pathogenesis to therapy prospects
Authors: Feng Xiaojin , Li Xue , Liu Na , Hou Ningning , Sun Xiaodong , Liu Yongping
Published: September 2022

The recent increase in the pathogenesis of autoimmune diseases revealed the critical role of T cells. Investigation into immunometabolism has drawn attention to metabolic processes other than glycometabolism. In rapidly dividing immune cells, including T lymphocytes, the consumption of glutamine is similar to or higher than that of glucose even though glucose is abundant. In addition to contributing to many processes critical for cellular integrity and function, glutamine, as the most abundant amino acid, was recently regarded as an immunomodulatory nutrient. A better understanding of the biological regulation of glutaminolysis in T cells will provide a new perspective for the treatment of autoimmune diseases. In this review, we summarized the current knowledge of glutamine catabolism in CD4+ T-cell subsets of autoimmunity. We also focused on potential treatments targeting glutaminolysis in patients with autoimmune diseases. Knowledge of immunometabolism is constantly evolving, and glutamine metabolism may be a potential therapeutic target for autoimmune disease therapy.
Biological drugs for systemic lupus erythematosus or active lupus nephritis and rates of infectious complications. Evidence from large clinical trials
Authors: Steiger Stefanie , Ehreiser Louisa , Anders Juliane , Anders Hans-Joachim
Published: September 2022

Systemic lupus erythematosus (SLE) is a multisystemic autoimmune disease that frequently affects the kidneys, known as lupus nephritis (LN). Such patients are treated with antimalarials, corticosteroids or immunosuppressive drugs, and more recently, target-specific biological drugs. Although efficacy of these therapies improved SLE-related outcomes, SLE remains associated with higher rates of infections. Here, we performed a comprehensive systemic review of infectious complications in clinical trials covering drug interventions for SLE or specifically for active LN. Our search in 15 online registries yielded a total of 1477 studies of which 14 matched our prespecified criteria. These covered the biological drugs anifrolumab, belimumab, and rituximab that were tested in patients with non-renal SLE and active LN.The available safety data from the SLE trials indicated that infectious complications such as herpes zoster, upper respiratory tract infection, nasopharyngitis, bronchitis, and urinary tract infection in patients receiving placebo were quite prevalent especially in the EXPLORER (rituximab) trial. Infections occurred mostly during the first year of LN therapy. Serious adverse events and infectious complications occurred more frequently in placebo-treated patients with active LN, especially in the BLISS-LN (belimumab) and LUNAR (rituximab) trials. Anifrolumab and rituximab increased the number of clinically relevant episodes of herpes zoster compared to belimumab in patients with active LN. Anifrolumab displayed a similar trend for influenza infections, which is consistent with the specific mechanisms-of-action of anifrolumab; highlighting drug-specific effects on infectious complications. In addition, standard-of-care therapy, e.g., MMF and immunosuppressants, as well as a longer SLE duration may also affect the incidence of serious adverse events and certain infectious complications in SLE patients with active LN.Infectious complications are common in SLE but even more common in patients with active LN, especially herpes zoster is strongly associated with active LN and anifrolumab therapy (OR 2.8, 95% CI 1.18 to 6.66, p = 0.018). Immunotherapy seems to impose unspecific and specific risks for infections. The latter may imply specific precautions such as preemptive vaccination and individual risk-benefit assessments.
Towards identification and development of alternative vaccines against pregnancy-associated malaria based on naturally acquired immunity
Authors: Rotich Alex K. , Takashima Eizo , Yanow Stephanie K. , Gitaka Jesse , Kanoi Bernard N.
Published: September 2022

Pregnant women are particularly susceptible to Plasmodium falciparum malaria, leading to substantial maternal and infant morbidity and mortality. While highly effective malaria vaccines are considered an essential component towards malaria elimination, strides towards development of vaccines for pregnant women have been minimal. The leading malaria vaccine, RTS,S/AS01, has modest efficacy in children suggesting that it needs to be strengthened and optimized if it is to be beneficial for pregnant women. Clinical trials against pregnancy-associated malaria (PAM) focused on the classical VAR2CSA antigen are ongoing. However, additional antigens have not been identified to supplement these initiatives despite the new evidence that VAR2CSA is not the only molecule involved in pregnancy-associated naturally acquired immunity. This is mainly due to a lack of understanding of the immune complexities in pregnancy coupled with difficulties associated with expression of malaria recombinant proteins, low antigen immunogenicity in humans, and the anticipated complications in conducting and implementing a vaccine to protect pregnant women. With the accelerated evolution of molecular technologies catapulted by the global pandemic, identification of novel alternative vaccine antigens is timely and feasible. In this review, we discuss approaches towards novel antigen discovery to support PAM vaccine studies.
Proton gradients across the coral calcifying cell layer: Effects of light, ocean acidification and carbonate chemistry
Authors: Venn Alexander A. , Tambutté Eric , Comeau Steeve , Tambutté Sylvie
Published: September 2022

In corals, pH regulation of the extracellular calcifying medium (ECM) by the calcifying cell layer is a crucial step in the calcification process and is potentially important to influencing how corals respond to ocean acidification. Here, we analyzed the growing edge of the reef coralStylophora pistillatato make the first characterization of the proton gradient across the coral calcifying epithelium. At seawater pH 8 we found that while the calcifying epithelium elevates pH in the ECM on its apical side above that of seawater, pH on its basal side in the mesoglea is markedly lower, highlighting that the calcifying cells are exposed to a microenvironment distinct from the external environment. Coral symbiont photosynthesis elevates pH in the mesoglea, but experimental ocean acidification and decreased seawater inorganic carbon concentration lead to large declines in mesoglea pH relative to the ECM, which is maintained relatively stable. Together, our results indicate that the coral calcifying epithelium is functionally polarized and that environmental variation impacts pHECMregulation through its effects on the basal side of the calcifying cells.
An update on the management of refractory cutaneous lupus erythematosus
Authors: Verdelli Alice , Corrà Alberto , Mariotti Elena Biancamaria , Aimo Cristina , Ruffo di Calabria Valentina , Volpi Walter , Quintarelli Lavinia , Caproni Marzia
Published: September 2022

Management of cutaneous lupus erythematosus (CLE) involves a combination of preventive measures, topical and systemic drugs, fairly similar for the different subtypes. Although guidelines exist, to date, no specific drugs have been specifically licensed for CLE. Antimalarials remain the first-line systemic treatment, but many patients do not respond, making refractory lupus a challenge for clinicians. The choice of alternative medication should be based on effectiveness, safety and cost. Most of the available drugs for CLE have been adapted from systemic lupus erythematosus (SLE) treatment but the existing literature is limited to small studies and evidence often lacks. As knowledge of pathogenesis of both CLE and SLE is improving, promising new therapies are emerging. In this review, we discuss the available medications, focusing on the novelties under development for CLE.
Characteristics of NtCCD1-3 from tobacco, and protein engineering of the CCD1 to enhance β-ionone production in yeast
Authors: Gong Xiaowei , Li Fan , Liang Yupeng , Han Xiulin , Wen Mengliang
Published: September 2022

Biosynthesis of β-ionone by microbial cell factories has become a promising way to obtain natural β-ionone. The catalytic activity of carotenoid cleavage dioxygenase 1 (CCD1) in cleavage of β-carotene to β-ionone severely limits its biosynthesis. In this study, NtCCD1-3 from Nicotiana tabacum with high ability to cleave β-carotene was screened. Multiple strategies for improving the β-ionone yield in Saccharomyces cerevisiae were performed. The results showed that NtCCD1-3 could cleave a variety of caroteniods at the 9,10 (9′,10′) double bonds and lycopene at the 5,6 (5′,6′) positions. The insertion site delta for NtCCD1-3 gene was more suitable for enhancing the yield of β-ionone, showing 19.1-fold increase compared with the rox1 site. More importantly, mutant K38A of NtCCD1-3 in membrane-bonding domains could greatly promote β-ionone production by more than 3-fold. We also found that overexpression of the NADH kinase Pos5 could improve β-ionone yield up to 1.5 times. These results may provide valuable references for biosynthesis of β-ionone.
Salicylic acid remodeling of the rhizosphere microbiome induces watermelon root resistance against Fusarium oxysporum f. sp. niveum infection
Authors: Zhu Feiying , Fang Yong , Wang Zhiwei , Wang Pei , Yang Kankan , Xiao Langtao , Wang Ruozhong
Published: September 2022

Fusarium wilt disease poses a severe threat to watermelon cultivation by affecting the yield and quality of the fruit. We had previously found that the rhizosphere microbiome has a significant impact on the ability of watermelon plants to resist Fusarium wilt development and that salicylic acid (SA) is closely related to this phenomenon. Therefore, in this study, the role of SA as a mediator between plants and microbes in activating resistance against Fusarium oxysporum f. sp. niveum (FON) infection was explored through physiological, biochemical, and metagenomic sequencing experiments. We demonstrated that exogenous SA treatment could specifically increase some beneficial rhizosphere species that can confer resistance against FON inoculation, such as Rhodanobacter, Sphingomonas, and Micromonospora. Functional annotation analysis indicated that SA application significantly increased the relative abundance of glycoside hydrolase and polysaccharide lyase genes in the microbiome, which may play an essential role in increasing plant lipids. Moreover, network interaction analysis suggested that the highly expressed AAC6_IIC gene may be manipulated through SA signal transduction pathways. In conclusion, these results provide a novel strategy for controlling Fusarium wilt in watermelons from the perspective of environmental ecology, that is, by manipulating the rhizosphere microbiome through SA to control Fusarium wilt.
The Isolation and Characterization of Rare Mycobiome Associated With Spacecraft Assembly Cleanrooms
Authors: Blachowicz Adriana , Mhatre Snehit , Singh Nitin Kumar , Wood Jason M. , Parker Ceth W. , Ly Cynthia , Butler Daniel , Mason Christopher E. , Venkateswaran Kasthuri
Published: September 2022

Ensuring biological cleanliness while assembling and launching spacecraft is critical for robotic exploration of the solar system. To date, when preventing forward contamination of other celestial bodies, NASA Planetary Protection policies have focused on endospore-forming bacteria while fungi were neglected. In this study, for the first time the mycobiome of two spacecraft assembly facilities at Jet Propulsion Laboratory (JPL) and Kennedy Space Center (KSC) was assessed using both cultivation and sequencing techniques. To facilitate enumeration of viable fungal populations and downstream molecular analyses, collected samples were first treated with chloramphenicol for 24 h and then with propidium monoazide (PMA). Among cultivable fungi, 28 distinct species were observed, 16 at JPL and 16 at KSC facilities, while 13 isolates were potentially novel species. Only four isolated species Aureobasidium melanogenum, Penicillium fuscoglaucum, Penicillium decumbens, and Zalaria obscura were present in both cleanroom facilities, which suggests that mycobiomes differ significantly between distant locations. To better visualize the biogeography of all isolated strains the network analysis was undertaken and confirmed higher abundance of Malassezia globosa and Cyberlindnera jadinii. When amplicon sequencing was performed, JPL-SAF and KSC-PHSF showed differing mycobiomes. Metagenomic fungal reads were dominated by Ascomycota (91%) and Basidiomycota (7.15%). Similar to amplicon sequencing, the number of fungal reads changed following antibiotic treatment in both cleanrooms; however, the opposite trends were observed. Alas, treatment with the antibiotic did not allow for definitive ascribing changes observed in fungal populations between treated and untreated samples in both cleanrooms. Rather, these substantial differences in fungal abundance might be attributed to several factors, including the geographical location, climate and the in-house cleaning procedures used to maintain the cleanrooms. This study is a first step in characterizing cultivable and viable fungal populations in cleanrooms to assess fungal potential as biocontaminants during interplanetary explorations. The outcomes of this and future studies could be implemented in other cleanrooms that require to reduce microbial burden, like intensive care units, operating rooms, or cleanrooms in the semiconducting and pharmaceutical industries.
A Bacterially Expressed SARS-CoV-2 Receptor Binding Domain Fused With Cross-Reacting Material 197 A-Domain Elicits High Level of Neutralizing Antibodies in Mice
Authors: Liu Liqin , Chen Tingting , Zhou Lizhi , Sun Jie , Li Yuqian , Nie Meifeng , Xiong Hualong , Zhu Yuhe , Xue Wenhui , Wu Yangtao , Li Tingting , Zhang Tianying , Kong Zhibo , Yu Hai , Zhang Jun , Gu Ying , Zheng Qingbing , Zhao Qinjian , Xia Ningshao , Li Shaowei
Published: September 2022

The Coronavirus disease 2019 (COVID-19) pandemic presents an unprecedented public health crisis worldwide. Although several vaccines are available, the global supply of vaccines, particularly within developing countries, is inadequate, and this necessitates a need for the development of less expensive, accessible vaccine options. To this end, here, we used the Escherichia coli expression system to produce a recombinant fusion protein comprising the receptor binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2; residues 319–541) and the fragment A domain of Cross-Reacting Material 197 (CRM197); hereafter, CRMA-RBD. We show that this CRMA-RBD fusion protein has excellent physicochemical properties and strong reactivity with COVID-19 convalescent sera and representative neutralizing antibodies (nAbs). Furthermore, compared with the use of a traditional aluminum adjuvant, we find that combining the CRMA-RBD protein with a nitrogen bisphosphonate-modified zinc-aluminum hybrid adjuvant (FH-002C-Ac) leads to stronger humoral immune responses in mice, with 4-log neutralizing antibody titers. Overall, our study highlights the value of this E. coli-expressed fusion protein as an alternative vaccine candidate strategy against COVID-19.
Antibiotic Potentiators Against Multidrug-Resistant Bacteria: Discovery, Development, and Clinical Relevance
Authors: Chawla Meenal , Verma Jyoti , Gupta Rashi , Das Bhabatosh
Published: September 2022

Antimicrobial resistance in clinically important microbes has emerged as an unmet challenge in global health. Extensively drug-resistant bacterial pathogens have cropped up lately defying the action of even the last resort of antibiotics. This has led to a huge burden in the health sectors and increased morbidity and mortality rate across the world. The dwindling antibiotic discovery pipeline and rampant usage of antibiotics has set the alarming bells necessitating immediate actions to combat this looming threat. Various alternatives to discovery of new antibiotics are gaining attention such as reversing the antibiotic resistance and hence reviving the arsenal of antibiotics in hand. Antibiotic resistance reversal is mainly targeted against the antibiotic resistance mechanisms, which potentiates the effective action of the antibiotic. Such compounds are referred to as resistance breakers or antibiotic adjuvants/potentiators that work in conjunction with antibiotics. Many studies have been conducted for the identification of compounds, which decrease the permeability barrier, expression of efflux pumps and the resistance encoding enzymes. Compounds targeting the stability, inheritance and dissemination of the mobile genetic elements linked with the resistance genes are also potential candidates to curb antibiotic resistance. In pursuit of such compounds various natural sources and synthetic compounds have been harnessed. The activities of a considerable number of compounds seem promising and are currently at various phases of clinical trials. This review recapitulates all the studies pertaining to the use of antibiotic potentiators for the reversal of antibiotic resistance and what the future beholds for their usage in clinical settings.
Dormancy and germination of microsclerotia of Verticillium longisporum are regulated by soil bacteria and soil moisture levels but not by nutrients
Authors: Sarenqimuge Sarenqimuge , Rahman Shahinoor , Wang Yao , von Tiedemann Andreas
Published: September 2022

The soil-borne pathogen Verticillium longisporum infects roots of its host plant, oilseed rape, and systemically colonizes stems where it finally forms microsclerotia at crop maturity. Once returned to the soil after harvest, microsclerotia undergo a stage of dormancy, in which they may survive for several years. Since there is neither efficient chemical control nor effective resistance in oilseed rape cultivars to control the disease, alternative control strategies may consist in regulating the germination and dormancy of microsclerotia in the soil. Therefore, a series of experiments were conducted to explore the effects of nutrients, soil moisture, and the soil microbiome on germination of dormant microsclerotia. Experiments with microsclerotia exposed in vitro to different nutrients indicated that under sterile conditions the stimulating effect of nutrients on microsclerotia germination was not enhanced as compared to water. Moreover, further assays revealed a strong inhibitory effect of unsterile soil on microsclerotia germination. Accordingly, oilseed rape plants inoculated with microsclerotia of V. longisporum showed severe infection with V. longisporum when grown in autoclaved soil, in contrast to plants grown in unsterile soil. These experiments indicate a crucial role of soil fungistasis and thus the soil microbiome on microsclerotia germination. Further bioassays demonstrated that viable soil bacteria obtained from the rhizosphere of oilseed rape plants and bulk field soil effectively inhibited microsclerotia germination, whereas dead bacteria and bacterial culture filtrates hardly suppressed germination. A putative inhibitory role of volatile organic compounds (VOCs) produced by soil bacteria was confirmed in two-compartment Petri dishes, where microsclerotia germination and colony growth were significantly inhibited. Bacterial VOCs were collected and analyzed by GC–MS. In total, 45 VOCs were identified, among which two acid and two alcohol compounds were emitted by all tested bacteria. A bioassay, conducted with corresponding pure chemicals in two-compartment Petri dishes, indicated that all acidic volatile compounds, including 3-methylbutanoic acid, 2-methylbutanoic acid, hexanoic acid, and 2-methylpropionic acid, induced strong inhibitory effects on microsclerotia. We conclude that bacterial acidic volatiles play a key role in the fungistatic effect on microsclerotia of V. longisporum in the soil and could thus be targeted for development of novel strategies to control this pathogen by artificially regulating dormancy of microsclerotia in soil.
Analysis of CT scan images for COVID-19 pneumonia based on a deep ensemble framework with DenseNet, Swin transformer, and RegNet
Authors: Peng Lihong , Wang Chang , Tian Geng , Liu Guangyi , Li Gan , Lu Yuankang , Yang Jialiang , Chen Min , Li Zejun
Published: September 2022

COVID-19 has caused enormous challenges to global economy and public health. The identification of patients with the COVID-19 infection by CT scan images helps prevent its pandemic. Manual screening COVID-19-related CT images spends a lot of time and resources. Artificial intelligence techniques including deep learning can effectively aid doctors and medical workers to screen the COVID-19 patients. In this study, we developed an ensemble deep learning framework, DeepDSR, by combining DenseNet, Swin transformer, and RegNet for COVID-19 image identification. First, we integrate three available COVID-19-related CT image datasets to one larger dataset. Second, we pretrain weights of DenseNet, Swin Transformer, and RegNet on the ImageNet dataset based on transformer learning. Third, we continue to train DenseNet, Swin Transformer, and RegNet on the integrated larger image dataset. Finally, the classification results are obtained by integrating results from the above three models and the soft voting approach. The proposed DeepDSR model is compared to three state-of-the-art deep learning models (EfficientNetV2, ResNet, and Vision transformer) and three individual models (DenseNet, Swin transformer, and RegNet) for binary classification and three-classification problems. The results show that DeepDSR computes the best precision of 0.9833, recall of 0.9895, accuracy of 0.9894, F1-score of 0.9864, AUC of 0.9991 and AUPR of 0.9986 under binary classification problem, and significantly outperforms other methods. Furthermore, DeepDSR obtains the best precision of 0.9740, recall of 0.9653, accuracy of 0.9737, and F1-score of 0.9695 under three-classification problem, further suggesting its powerful image identification ability. We anticipate that the proposed DeepDSR framework contributes to the diagnosis of COVID-19.
Repetitive transcranial magnetic stimulation combined with respiratory muscle training for pulmonary rehabilitation after ischemic stroke—A randomized, case-control study
Authors: Cao Haiyan , Chen Xiaoming , Ren Xuyan , Chen Zhiguo , Liu Chuandao , Ni Jianqiang , Liu Haoyu , Fan Yingjie , Xu Dandan , Jin Huaping , Bao Jie , Yulun Huang , Su Min
Published: September 2022

Respiratory muscle weakness often occurs after stroke, which can lead to pulmonary dysfunction (PD). Pulmonary dysfunction prolongs the length of hospital stay and increases the risk of death. In a prospective, randomized, case-control study, we used musculoskeletal ultrasonography (MSUS), and pulmonary function tester to objectively evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) combined with respiratory muscle training (RMT) in the treatment of PD in patients with acute ischemic stroke. Sixty-two stroke patients with PD were recruited and eventually 60 patients participated in this study. The control group was treated with RMT, and the treatment group was treated with rTMS on the basis of RMT. Treatment occurred five times a week for 8 weeks. Before and after treatment, diaphragmatic thickness (DT), diaphragmatic thickening fraction (DTF) and diaphragmatic mobility (DM) in patients, bilateral chest wall were measured by MSUS. Meanwhile, FVC, FEV1, FEV1/FVC, PEF, and MVV tested by pulmonary function tester was used to evaluate the improvement of lung functional. activities of daily living (ADL) was used as an objective criterion to evaluate the overall functional recovery of patients before and after treatment. After treatment, DT, DTF, and DM values improved significantly in both the affected and unaffected sides. The FVC, FEV1, FEV1/FVC, PEF, MVV, and ADL were all increased after the treatment. Combined treatment showed a stronger increase than that by RMT treatment alone. The study preliminarily shows that rTMS and RMT could improve lung functional after acute ischemic stroke.
The relationship between physical activity and trait anxiety in college students: The mediating role of executive function
Authors: Dong Zhiwei , Wang Peng , Xin Xin , Li Shufan , Wang Jing , Zhao Jinlei , Wang Xing
Published: September 2022

Objectives

Aimed to analyze the mediating effect of executive function between physical activity level and trait anxiety in college students.

Methods

The International Physical Activity Questionnaire, State-Trait Anxiety Inventory, Stroop task, 1-back task, and More-odd shifting task were used to analyze 248 college students.

Results

Trait anxiety were significantly correlated with shifting function (r = 0.182, P = 0.004) and inhibition function (r = 0.163, P = 0.010) and not with working memory (r = 0.056, P = 0.385). Vigorous physical activity (VPA) was most highly correlated with inhibition function (Beta = −0.144, P = 0.024) and working memory (Beta = −0.208, P = 0.001), and light physical activity (LPA) was most highly correlated with shifting function (Beta = −0.211, P = 0.001). Physical activity had a 72.31% association with trait anxiety (B = −0.195), with 11.79% mediated by inhibition function (B = −0.023) and 15.90% by shifting function (B = −0.031).

Conclusion

College students' physical activity promotes both inhibition and shifting functions, which in turn affect trait anxiety. VPA had a direct effect, while the effect of moderate physical activity (MPA) and LPA was completely mediated exclusively through executive functions, and the mediating effect of shifting function was the highest. It is recommended that college workers should motivate students with high trait anxiety to engage in more VPA and pay attention to changes in their inhibition and shifting functions.
Childhood socioeconomic status and adulthood dietary diversity among Indonesian adults
Authors: Isaura Emyr Reisha , Chen Yang-Ching , Yang Shwu-Huey
Published: September 2022

Food insecurity problems still exist among people in low-to-middle income countries. The long-term disadvantages of socioeconomic status may contribute to chronic food insecurity. However, whether childhood socioeconomic status factors are related to food insecurity in adulthood remains unclear. Thus, the aim of this study was to test the association between childhood socioeconomic status factors and one of the proxies for adulthood food security, dietary diversity. This study used the 2014 RAND Indonesia Family Life Survey dataset with 22,559 adult participants as study samples. The childhood socioeconomic status factors consisted of 16 questions about the participants’ conditions when they were 12 years old. Adult dietary diversity was assessed using the United Nations World Food Programme’s food consumption score. A linear regression model was used to analyze the association between variables. This study found that the number of owned books (β coef.: 3.713–7.846, p < 0.001), the use of safe drinking-water sources (β coef.: 0.707–5.447, p < 0.001–0.009) and standard toilets (β coef.: 1.263–4.955, p < 0.001–0.002), parents with the habit of alcohol consumption (β coef.: 2.983, p = 0.044) or the combination with smoking habits (β coef.: 1.878, p < 0.001), self-employed with the permanent worker (β coef.: 2.904, p = 0.001), still married biological parents (β coef.: 1.379, p < 0.001), the number of rooms (β coef.: 0.968, p < 0.001), people (β coef.: 0.231, p < 0.001), and younger siblings (β coef.: 0.209–0.368, p < 0.001–0.039) in the same house were positively and significantly associated with the outcome variable. Furthermore, in the order of childhood socioeconomic status factors, self-employment without permanent workers and casual work types (β coef.: –9.661 to –2.094, p < 0.001–0.001), houses with electricity facilities (β coef.: –4.007, p < 0.001), and parents with smoking habits (β coef.: –0.578, p = 0.006) were negatively and significantly associated with the food security proxy. In conclusion, childhood and early socioeconomic disadvantage is related to adult food security status and may lead to poor health.
MRI radiomics-based machine learning model integrated with clinic-radiological features for preoperative differentiation of sinonasal inverted papilloma and malignant sinonasal tumors
Authors: Gu Jinming , Yu Qiang , Li Quanjiang , Peng Juan , Lv Fajin , Gong Beibei , Zhang Xiaodi
Published: September 2022

Objective

To explore the best MRI radiomics-based machine learning model for differentiation of sinonasal inverted papilloma (SNIP) and malignant sinonasal tumor (MST), and investigate whether the combination of radiomics features and clinic–radiological features can produce a superior diagnostic performance.

Methods

The database of 247 patients with SNIP (n=106) or MST (n=141) were analyzed. Dataset from scanner A were randomly divided into training set (n=135) and test set 1 (n=58) in a ratio of 7:3, and dataset from scanner B and C were used as an additional independent test set 2 (n=54). Fourteen clinic-radiological features were analyzed by using univariate analysis, and those with significant differences were applied to construct clinical model. Based on the radiomics features extracted from single sequence (T2WI or CE-T1WI) and combined sequence, four commonly used classifiers (logistic regression (LR), support vector machine (SVM), decision tree (DT) and k-nearest neighbor (KNN)) were employed to constitute twelve different machine learning models, and the best-performing one was confirmed as the optimal radiomics model. Furthermore, a combined model incorporated best radiomics feature subsets and clinic-radiological features was developed. The diagnostic performances of these models were assessed by the area under the receiver operating characteristic (ROC) curve (AUC) and the calibration curves.

Results

Five clinic-radiological features (age, convoluted cerebriform pattern sign, heterogeneity, adjacent bone involvement and infiltration of surrounding tissue) were considered to be significantly different between the tumor groups (P < 0.05). Among the twelve machine learning models, the T2WI-SVM model exhibited optimal predictive efficacy for classification tasks on the two test sets, with the AUC of 0.878 and 0.914, respectively. For three types of diagnostic models, the combined model achieved highest AUC of 0.912 (95%CI: 0.807-0.970) and 0.927 (95%CI: 0.823-0.980) for differentiation of SNIP and MST in test 1 and test 2 sets, which performed prominently better than clinical model (P=0.011, 0.005), but not significantly different from the optimal radiomics model (P=0.100, 0.452).

Conclusion

The machine learning model based on T2WI sequence and SVM classifier achieved best performance in differentiation of SNIP and MST, and the combination of radiomics features and clinic-radiological features significantly improved the diagnostic capability of the model.
Prognostic value of receptor tyrosine kinases in malignant melanoma patients: A systematic review and meta-analysis of immunohistochemistry
Authors: Lei Xuan , Zhang Yiming , Mao Lianghao , Jiang Pan , Huang Yumeng , Gu Jia , Tai Ningzheng
Published: September 2022

Background

Substantial evidence suggests that receptor tyrosine kinases (RTKs) are overexpressed in tumors; however, few studies have focused on the prognostic value of RTKs in melanoma.

Objectives

The objective of this study is to evaluate the association between overexpression of RTKs and survival in melanoma patients based on immunohistochemistry (IHC) analysis.

Methods

Our review is registered on PROSPERO (http://www.crd.york.ac.uk/PROSPERO), registration number CRD42021261460. Seven databases were searched, and data were extracted. We used IHC to measure the association between overexpression of RTKs and overall survival (OS), disease-free survival (DFS), progression-free survival (PFS), and clinicopathology in melanoma patients. Pooled analysis was conducted to assess the differences between Hazard Ratios along with 95% confidence intervals.

Results

Of 5,508 publications examined following the database search, 23 publications were included in this study, which included data from a total of 2,072 patients. Vascular endothelial growth factor receptor 2 (VEGF-R2) overexpression was associated with worse OS and DFS in melanoma. Furthermore, there was an association between OS and the expression of several RTKs, including epidermal growth factor receptor (EGFR), mesenchymal-epithelial transition factor (MET), vascular endothelial growth factor receptor 1 (VEGF-R1), and insulin-like growth factor 1 receptor (IGF-1R). There were no significant correlations between EGFR overexpression and worse DFS or PFS. EGFR overexpression was associated with worse OS cutaneous and nasal melanoma, but not uveal melanoma. However, MET overexpression was related to worse OS in both cutaneous and uveal melanoma. Furthermore, EGFR overexpression was associated with a worse OS in Europe compared to other geographic areas. Moreover, EGFR and MET overexpression showed significant prognostic value in patients with the cut-off “≥10% staining”.

Conclusions

Our findings build concrete evidence that overexpression of RTKs is associated with poor prognosis and clinicopathology in melanoma, highlighting RTK expression has the potential to inform individualized combination therapies and accurate prognostic evaluation.
The Prognostic Value of Pretherapy Peripheral Blood Inflammatory Indices in Myelodysplastic Syndromes
Authors: Shi Cong , Gong Shengping , Niu Tingting , Li Tongyu , Wu An , Zheng Xiaojiao , Yang Shujun , Ouyang Guifang , Mu Qitian
Published: September 2022

Background

Inflammation appears to have a critical role in carcinogenesis tumor growth according to emerging research. The platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), and plasma C-reactive protein (CRP) are considered to reflect the systemic inflammatory response and clinical prognosis. The prognostic value of inflammatory indices in myelodysplastic syndrome (MDS) patients remains unclear.

Methods

A total of 213 MDS patients were enrolled for the study. Univariate and multivariate analyses were performed to determine the prognostic significance of various indicators, including PLR, NLR, and CRP.

Results

MDS patients with higher PLR, NLR, and CRP levels had significantly shorter overall survival (OS). Based on univariate analysis, age (≥60 years), gender (men), lower hemoglobin level (<10 g/dl), higher bone marrow blast percentage (>5%), poorer karyotype, and higher Revised International Prognostic Scoring System (IPSS-R) score were significantly associated with shorter OS. Patients with higher CRP levels had shorter leukemia-free survival (LFS,P= 0.041). However, higher PLR and NLR had no significant influence on LFS (P> 0.05). Multivariate Cox proportional hazards regression analysis indicated that high PLR and CRP were also independent adverse prognostic factors for OS in MDS.

Conclusions

Elevated PLR and CRP predict poor prognosis independent of the IPSS-R and provide a novel evaluation factor for MDS patients.
Wenzi Jiedu Recipe ameliorates colorectal cancer by remodeling the gut microbiota and tumor microenvironment
Authors: Qiu Wenli , Sang Tianqing , Chen Haibin , Zhou Hongli , Wang Zhongqiu , Zhou Hongguang
Published: September 2022

Introduction

Wenzi Jiedu Recipe (WJR), traditional Chinese medicine (TCM) formula, has been proven to be clinically useful in the treatment of colorectal cancer (CRC). However, its underlying mechanisms are still elusive, which limits its wider application. Thus, we aimed to evaluate the effect of WJR on CRC and elucidate mechanisms underlying its action.

Methods

Network pharmacology was employed to clarify the “herb-active ingredient-target” network of WJR. The 16S rDNA sequencing method was used to analyze the changes of gut microbes mediated by WJR in tumor-bearing mice with CRC. The proportions of CD4+ T cell and CD8+ T cell were measured by flow cytometry. Levels of the cytokines interleukin (IL)-10, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α were assessed by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA).

Results

WJR showed significant anti-CRC effects both in vitro and in vivo. Network pharmacology revealed that WJR exerts anti-CRC therapeutic effect on multiple targets and signaling pathways. Gut microbiota analysis revealed that WJR therapy significantly enriched for Oscillibacter and Bacteroides_acidifacien. In particular, we found that WJR significantly increased the proportion of CD8+ T cells and the expression of immune-associated cytokines IL-10, IFN-γ, and TNF-α.

Conclusion

The regulation of gut microbiota by WJR may be the breakthrough point to clarify its mechanism of action in the treatment of CRC, and it has a good prospect of clinical application.
Efficacy of erlotinib in NSCLC harboring rare EGFR extracellular domain mutation (T263P) and common mutations: Case report and literature review
Authors: Wang Qian , Wang Yong , Zhang Xinwei , Fang Chen , Qian Xiaoying , Li Yong
Published: September 2022

The epidermal growth factor receptor (EGFR) typically contains an extracellular domain (ECD), a transmembrane (TM) domain, and an intracellular kinase (KD) domain. ECD mutations of EGFR in NSCLC may affect its normal function and intrinsic resistance to tyrosine kinase inhibitors (TKIs) and the effectiveness of drugs for these patients is unsatisfactory. Recently, we found an EGFR T263P mutation located at the ECD, which has never been reported in Chinese non-small cell lung cancer (NSCLC). Hence, we reported that a patient with advanced lung adenocarcinoma harboring the EGFR T263P mutation, L858R mutation and MET amplification was resistant to osimertinib but significantly benefited from erlotinib and capmatinib treatment. This patient achieved a partial response and had progression-free survival (PFS) for more than 19 months. In summary, we are the first researchers to report in detail on a Chinese patient carrying the T263P mutation and summarize all the ECD mutations in NSCLC. We believe this finding will enlighten us to treat patients with EGFR ECD mutations and more patients deserve further study.
Gut microbiota composition in chemotherapy and targeted therapy of patients with metastatic colorectal cancer
Authors: Chen Yen-Cheng , Chuang Chia-Hsien , Miao Zhi-Feng , Yip Kwan-Ling , Liu Chung-Jung , Li Ling-Hui , Wu Deng-Chyang , Cheng Tian−Lu , Lin Chung-Yen , Wang Jaw-Yuan
Published: September 2022

Studies have reported the effects of the gut microbiota on colorectal cancer (CRC) chemotherapy, but few studies have investigated the association between gut microbiota and targeted therapy. This study investigated the role of the gut microbiota in the treatment outcomes of patients with metastatic CRC (mCRC). We enrolled 110 patients with mCRC and treated them with standard cancer therapy. Stool samples were collected before administering a combination of chemotherapy and targeted therapy. Patients who had a progressive disease (PD) or partial response (PR) for at least 12 cycles of therapy were included in the study. We further divided these patients into anti-epidermal growth factor receptor (cetuximab) and anti-vascular endothelial growth factor (bevacizumab) subgroups. The gut microbiota of the PR group and bevacizumab-PR subgroup exhibited significantly higher α-diversity. The β-diversity of bacterial species significantly differed between the bevacizumab-PR and bevacizumab-PD groups (P = 0.029). Klebsiella quasipneumoniae exhibited the greatest fold change in abundance in the PD group than in the PR group. Lactobacillus and Bifidobacterium species exhibited higher abundance in the PD group. The abundance of Fusobacterium nucleatum was approximately 32 times higher in the PD group than in the PR group. A higher gut microbiota diversity was associated with more favorable treatment outcomes in the patients with mCRC. Bacterial species analysis of stool samples yielded heterogenous results. K. quasipneumoniae exhibited the greatest fold change in abundance among all bacterial species in the PD group. This result warrants further investigation especially in a Taiwanese population.
Prognostic value of cachexia index in patients with colorectal cancer: A retrospective study
Authors: Wan Qianyi , Yuan Qian , Zhao Rui , Shen Xiaoding , Chen Yi , Li Tao , Song Yinghan
Published: September 2022

Background

Current diagnostic criteria for cancer cachexia are inconsistent, and arguments still exist about the impact of cachexia on the survival of patients with colorectal cancer. In this study, we aim to investigate the prognostic value of a novel cachexia indicator, the cachexia index (CXI), in patients with colorectal cancer.

Methods

The CXI was calculated as skeletal muscle index (SMI) × serum albumin/neutrophil-lymphocyte ratio. The cut-off value of CXI was determined by the receiver operating characteristic (ROC) curves and Youden’s index. The major outcomes were major complications, overall survival (OS), and recurrence-free survival (RFS).

Results

A total of 379 patients (234 men and 145 women) were included. The ROC curves indicated that CXI had a significantly diagnostic capacity for the detection of major complications. Based on Youden’s index, there were 231 and 148 patients in the low and high CXI groups, respectively. Patients in the low CXI group had significantly older age, lower BMI, and a higher percentage of cachexia and TNM stage II+III. Besides, Patients in low CXI group were associated with a significantly higher rate of major complications, blood transfusion, and longer length of stay. Logistic regression analysis indicated that low CXI, cachexia, and coronary heart disease were independent risk factors for the major complications. Kaplan Meier survival curves indicated that patients with high CXI had a significantly more favorable OS than those with low CXI, while no significant difference was found in RFS between the two groups. Besides, there were no significant differences in OS or RFS between patients with and without cachexia. The univariate and multivariate Cox regression analysis indicated that older age, low CXI, and coronary heart disease instead of cachexia were associated with a decreased OS.

Conclusion

CXI was better than cachexia in predicting OS and could be a useful prognostic indicator in patients with colorectal cancer, and greater attention should be paid to patients with low CXI.
A pulmonary enteric adenocarcinoma patient harboring a rare EGFR exon 19 P753S mutation: Case report and review
Authors: Xu Xiaohu , Chen Dong , Wu Xiao , Wang Qi
Published: September 2022

Pulmonary enteric adenocarcinoma (PEAC) is a rare subtype of non–small cell lung cancer (NSCLC), accounting for about 0.6% of all primary lung adenocarcinoma. Although epidermal growth factor receptor (EGFR) mutation is common in primary lung adenocarcinoma, it is rarely reported in PEAC. This case report describes a PEAC patient with co-mutations of EGFR, Kirsten rat sarcoma viral oncogene (KRAS), and TP53, being treated with immunotherapy combined with chemotherapy. A 69-year-old man complained of cough and expectoration with bloody sputum for 2 weeks. The lung-enhanced CT scan showed a massive soft tissue shadow, about 46 × 35 mm in the lower lobe of the right lung. The neoplasm sample in the lower lobe of the right lung was obtained using CT-guided fine-needle aspiration (FNA). Immunohistochemical assays showed that the tumor was positive for CK7, CDX-2, C-MET, and villin. Gastroscopy and rectal colonoscopy had been performed respectively to exclude a diagnosis of colorectal adenocarcinoma. The patient was finally diagnosed with pulmonary intestinal adenocarcinoma. Next-generation sequencing (NGS) analysis showed a rare EGFR exon 19 missense mutation (c.2257C>T, p.P753S), KRAS exon 2 missense mutation (c.35G>T, p.G12V), and TP53 exon 5 missense mutation (c.401T>C, p.F134S). The lung-enhanced CT scan showed that the tumor shrank after four cycles of chemotherapy combined with immunotherapy. We hope that this case report can increase the understanding of this rare type of tumor and provide new molecular indications for diagnosis and individualized treatment. Furthermore, the combination of chemotherapy and immunotherapy seems to be an effective therapy for PEAC. Whether the use of immunotherapy can provide clinical benefits needs to be further explored with more samples in future studies.
HIF-2α regulates proliferation, invasion, and metastasis of hepatocellular carcinoma cells via VEGF/Notch1 signaling axis after insufficient radiofrequency ablation
Authors: Yang Yongguang , Chen Weifeng , Mai Weiheng , Gao Yi
Published: September 2022

Background and Aims

Although insufficient radiofrequency ablation (RFA) promotes the recurrence and metastasis of liver cancer, the underlying mechanism remains unclear. This study aimed to investigate the role and mechanism of HIF-2α in hepatocellular carcinoma cells (HCCs) after Insufficient RFA.

Methods

We established a model of insufficient RFA in MHCC97H hepatoma cells and screened for stable sublines. We inhibited HIF-2α expression in the Insufficient RFA group using PT2385 and assessed the resulting changes in proliferation and biological function of HCCs. Cell viability and proliferation were detected by the MTT method, and scratch and Transwell chamber invasion tests detected migration and invasion abilities of HCCs. The mRNA and protein expression levels of VEGF, HIF-2α, and Notch1 were detected using qPCR, immunofluorescence, and western blotting.

Results

Compared with normal HCCs without RFA treatment, insufficient RFA enhanced the proliferation and invasion abilities of hepatocellular carcinoma subline MHCC97H (P < 0.001), as well as their migration ability (P = 0.046). The HIF-2α-specific inhibitor PT2385 downregulated the migration (P = 0.009) and invasion (P < 0.001) of MHCC97H cells but did not affect cell proliferation (P > 0.05). Insufficient ablation increased the mRNA and protein expression of VEGF, HIF-2α, and Notch1 in HCCs, whereas inhibition of HIF-2α reversed these changes.

Conclusions

Insufficient RFA increases the proliferation, migration, and invasion of HCCs via the HIF-2α/VEGF/Notch1 signaling axis; HIF-2α is a potential target for novel treatments of HCC after insufficient RFA.