bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated bioinformatics analysis for conducting a prognostic model and identifying immunotherapeutic targets in gastric cancer
Authors: Liu YaLing , Li Dan , Chen Yong , Liu YiJuan , Lin YiJuan , Huang XunRu , Wu Ting , Wang ChengDang , Ding Jian 
Published: May 2023

Abstract
Background
Gastric cancer is the third leading cause of death from cancer worldwide and has a poor prognosis. Practical risk scores and prognostic models for gastric cancer are lacking. While immunotherapy has succeeded in some cancers, few gastric cancer patients benefit from immunotherapy. Immune genes and the tumor microenvironment (TME) are essential for cancer progression and immunotherapy response. However, the roles of immune genes and the tumor microenvironment in immunotherapy remain unclear. The study aimed to construct a prognostic prediction model and identify immunotherapeutic targets for gastric cancer (GC) patients by exploring immune genes and the tumor microenvironment.

Results
An immune-related risk score (IRRS) model, including APOH, RNASE2, F2R, DEFB126, CXCL6, and CXCL3 genes, was constructed for risk stratification. Patients in the low-risk group, which was characterized by elevated tumor mutation burden (TMB) have higher survival rate. The risk level was remarkably correlated with tumor-infiltrating immune cells (TIICs), the immune checkpoint molecule expression, and immunophenoscore (IPS). CXCL3 and CXCL6 were significantly upregulated in gastric cancer tissues compared with normal tissues using the UALCAN database and RT-qPCR. The nomogram showed good calibration and moderate discrimination in predicting overall survival (OS) at 1-, 3-, and 5- year for gastric cancer patients using risk-level and clinical characteristics.

Conclusion
Our findings provided a risk stratification and prognosis prediction tool for gastric cancer patients and further the research into immunotherapy in gastric cancer.
Computational analysis of missense variant CYP4F2*3 (V433M) in association with human CYP4F2 dysfunction: a functional and structural impact
Authors: Farajzadeh-Dehkordi Mahvash , Mafakher Ladan , Samiee-Rad Fatemeh , Rahmani Babak 
Published: May 2023

Abstract
Background
Cytochrome P450 4F2 (CYP4F2) enzyme is a member of the CYP4 family responsible for the metabolism of fatty acids, therapeutic drugs, and signaling molecules such as arachidonic acid, tocopherols, and vitamin K. Several reports have demonstrated that the missense variant CYP4F2*3 (V433M) causes decreased activity of CYP4F2 and inter-individual variations in warfarin dose in different ethnic groups. However, the molecular pathogenicity mechanism of missense V433M in CYP4F2 at the atomic level has not yet been completely elucidated.

Methods and results
In the current study, we evaluated the effect of the V433M substitution on CYP4F2 using 14 different bioinformatics tools. Further molecular dynamics (MD) simulations were performed to assess the impact of the V433M mutation on the CYP4F2 protein structure, stability, and dynamics. In addition, molecular docking was used to illustrate the effect of V433M on its interaction with vitamin K1. Based on our results, the CYP4F2*3 variant was a damaging amino acid substitution with a destabilizing nature. The simulation results showed that missense V433M affects the dynamics and stability of CYP4F2 by reducing its compactness and stability, which means that it tends to change the overall structural conformation and flexibility of CYP4F2. The docking results showed that the CYP4F2*3 variant decreased the binding affinity between vitamin K1 and CYP4F2, which reduced the activity of CYP4F2*3 compared to native CYP4F2.

Conclusions
This study determined the molecular pathogenicity mechanism of the CYP4F2*3 variant on the human CYP4F2 protein and provided new information for understanding the structure-function relationship of CYP4F2 and other CYP4 enzymes. These findings will aid in the development of effective drugs and treatment options.
Leaves that walk and eggs that stick: comparative functional morphology and evolution of the adhesive system of leaf insect eggs (Phasmatodea: Phylliidae)
Authors: Büscher Thies H. , Bank Sarah , Cumming Royce T. , Gorb Stanislav N. , Bradler Sven 
Published: May 2023

AbstractPhylliidae are herbivorous insects exhibiting impressive cryptic masquerade and are colloquially called “walking leaves”. They imitate angiosperm leaves and their eggs often resemble plant seeds structurally and in some cases functionally. Despite overall morphological similarity of adult Phylliidae, their eggs reveal a significant diversity in overall shape and exochorionic surface features. Previous studies have shown that the eggs of most Phylliidae possess a specialised attachment mechanism with hierarchical exochorionic fan-like structures (pinnae), which are mantled by a film of an adhesive secretion (glue). The folded pinnae and glue respond to water contact, with the fibrous pinnae expanding and the glue being capable of reversible liquefaction. In general, the eggs of phylliids appear to exhibit varying structures that were suggested to represent specific adaptations to the different environments the eggs are deposited in. Here, we investigated the diversity of phylliid eggs and the functional morphology of their exochorionic structure. Based on the examination of all phylliid taxa for which the eggs are known, we were able to characterise eleven different morphological types. We explored the adhesiveness of these different egg morphotypes and experimentally compared the attachment performance on a broad range of substrates with different surface roughness, surface chemistry and tested whether the adhesion is replicable after detachment in multiple cycles. Furthermore, we used molecular phylogenetic methods to reconstruct the evolutionary history of different egg types and their adhesive systems within this lineage, based on 53 phylliid taxa. Our results suggest that the egg morphology is congruent with the phylogenetic relationships within Phylliidae. The morphological differences are likely caused by adaptations to the specific environmental requirements for the particular clades, as the egg morphology has an influence on the performance regarding the surface roughness. Furthermore, we show that different pinnae and the adhesive glue evolved convergently in different species. While the evolution of the Phylliidae in general appears to be non-adaptive judging on the strong similarity of the adults and nymphs of most species, the eggs represent a stage with complex and rather diverse functional adaptations including mechanisms for both fixation and dispersal of the eggs.
Metabolites and gene expression in the myocardium of fasting rats in an acute hypoxic environment
Authors: Zhao Ruzhou , Wang Xiaobo , Zhou Xiang , Jiang Shuai , Zhang Lin , Yu Zhibin 
Published: May 2023

AbstractWith the rising demand for entry to extremely high altitudes (HAs), rapid adaptability to extremely hypoxic environments is a challenge that we need to explore. Fasting was used to evaluate acute hypoxia tolerance at HA and was proven to be an effective method for improving the survival rate at extreme HA. Our experiments also showed that fasting pretreatment for 72 h significantly increased the 24 h survival rate of rats at 7620 m from 10 to 85% and protected the myocardium cells of rats. Here, we compared the metabolites and gene expression in the myocardium of SD rats pretreated with fasting and nonfasting at normal altitude and extreme HA. Our findings demonstrated that the dynamic contents of detected differential metabolites (DMs) between different rat groups were consistent with the expression of differentially expressed genes (DEGs), and DM clusters also showed strong correlations with DEG clusters. DM clusters related to amino acids and lipids were significantly lower in the fasting groups, and the correlated DEG clusters were enriched in mitotic pathways, including CDK1, CDC7, NUF2, and MCM6, suggesting that fasting can attenuate mitotic processes in cardiac tissues and reduce the synthesis of amino acids and lipids. L-Glutamine-related metabolites were particularly low at extreme HA without pretreatment but were normal in the fasting groups. The DEGs in the cluster related to L-glutamine-related metabolites were enriched for T-cell receptor V(D)J recombination, the Hippo signaling pathway, the Wnt signaling pathway, the cGMP-PKG signaling pathway, and the mTOR signaling pathway and were significantly downregulated, indicating that the content of L-glutamine decreased at extreme HA, while fasting increased it to adapt to the environment. Moreover, abundant fatty acids were detected when rats were exposed to extreme HA without pretreatment. Our study revealed the fasting and hypoxic environment-related factors in SD rats and provided new insights into the genetic and molecular characteristics in the myocardium, which is critical to developing more potential rapid adaptation methods to extreme HA.
Combined transcriptomic and metabolomic analyses elucidate key salt-responsive biomarkers to regulate salt tolerance in cotton
Authors: Han Mingge , Cui Ruifeng , Wang Delong , Huang Hui , Rui Cun , Malik Waqar Afzal , Wang Jing , Zhang Hong , Xu Nan , Liu Xiaoyu , Lei Yuqian , Jiang Tiantian , Sun Liangqing , Ni Kesong , Fan Yapeng , Zhang Yuexin , Wang Junjuan , Chen Xiugui , Lu Xuke , Yin Zujun , Wang Shuai , Guo Lixue , Zhao Lanjie , Chen Chao , Ye Wuwei 
Published: May 2023

Abstract
Background
Cotton is an important industrial crop and a pioneer crop for saline-alkali land restoration. However, the molecular mechanism underlying the cotton response to salt is not completely understood.

Methods
Here, we used metabolome data and transcriptome data to analyze the salt tolerance regulatory network of cotton and metabolic biomarkers.

Results
In this study, cotton was stressed at 400 m M NaCl for 0 h, 3 h, 24 h and 48 h. NaCl interfered with cotton gene expression, altered metabolite contents and affected plant growth. Metabolome analysis showed that NaCl stress increased the contents of amino acids, sugars and ABA, decreased the amount of vitamin and terpenoids. K-means cluster analysis of differentially expressed genes showed that the continuously up-regulated genes were mainly enriched in metabolic pathways such as flavonoid biosynthesis and amino acid biosynthesis.

Conclusion
The four metabolites of cysteine (Cys), ABA(Abscisic acid), turanose, and isopentenyladenine-7-N-glucoside (IP7G) were consistently up-regulated under salt stress, which may indicate that they are potential candidates for cotton under salt stress biomarkers. Combined transcriptome and metabolome analysis revealed accumulation of cysteine, ABA, isopentenyladenine-7-N-glucoside and turanose were important for salt tolerance in cotton mechanism. These results will provide some metabolic insights and key metabolite biomarkers for salt stress tolerance, which may help to understanding of the metabolite response to salt stress in cotton and develop a foundation for cotton to grow better in saline soil.
Efficacy and safety of bifidobacterium quadruple viable tablets in the treatment of Helicobacter pylori-infected peptic ulcer or gastritis patients: a systematic review and meta-analysis
Authors: Jiang Xueliang , Xu Chunjin , Liu Bo , Chen Ping , Xu Qinchang , Zhang Lu 
Published: May 2023

Abstract
Background
To better understand the efficacy and safety of Bifidobacterium quadruple viable tablets in the treatment of helicobacter pylori (H. pylori)-infected peptic ulcer or gastritis patients.

Methods
A systematic review of the studies published to June 2022 was performed in English database PubMed, Embase, Chinese database CNKI, Wanfang. There were 17 studies were included in this systematic review and meta-analysis. The outcomes measured included H. pylori eradication rate, changes in clinical symptoms of epigastric pain scores, and the incidence of adverse reactions.

Results
The results of the fixed effect model showed that the eradication rate of H. pylori in the combination of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was greater than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (OR = 3.73, 95%CI (2.79,5.00), Z = 2.78, P < 0.001; I2 = 0.0%, P > 0.999). The results of random effects model showed that the epigastric pain score of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was lower than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (WMD=-0.70, 95%CI (-1.06,-0.34), Z = 3.82, P < 0.001; I2 = 96.7%, P < 0.001). The results of random effects model showed that the acid reflux score of Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing conventional quadruple therapy was lower than that of bismuth-containing conventional quadruple therapy, and the difference was statistically significant (WMD=-0.98, 95%CI (-1.70,-0.26), Z = 2.66, P < 0.001; I2 = 99.7%, P < 0.001).

Conclusions
The eradication rate of H. pylori by Bifidobacterium quadruple viable bacteria tablets combined with bismuth-containing quadruple therapy is better than that of bismuth-containing quadruple therapy. The improvement of clinical symptoms of patients is better than that of bismuth-containing quadruple therapy, and the incidence of adverse reactions is lower than that of bismuth-containing quadruple therapy. Bifidobacterium quadruple viable bacteria tablet combined with bismuth-containing quadruple therapy was effective and safe. It provides a new way to treat patients with H. pylori.
HIV rapid test performance among health facilities enrolled in HIV rapid test quality improvement initiative (RTQII) in Ethiopia
Authors: Yenealem Dereje , Kedir Shemsu , MekonnenWubie Asmare , Melese Daniel , Molalign Tamirat , Yemanebirhan Nebiyou , Mohammed Awad , Nurahmed Negash , Liknaw Wondimeneh , Lakew Abrham Kerealeme , Asrat Habtamu , Hailu Getnet , Kebede Addisu , Sisay Abay , Desta Kassu , Tsegaye Aster 
Published: May 2023

Abstract
Background
As the Human Immunodeficiency Virus (HIV) rapid testing services expanded to reach the global target that 95% of people living with the virus will know their status by 2030, ensuring the quality of those services becomes critical. This study was conducted to assess the performance of HIV Rapid testing at sites in health facilities that were enrolled in the Rapid Test Quality Improvement Initiative (RTQII) in Ethiopia.

Methods
Characterized HIV proficiency testing (PT) panels of Dried Tube Specimen (DTS) were prepared, verified, and distributed to testing sites from August to December 2019. In addition on-site evaluation of HIV testing sites (HTSs) was conducted using a checklist to assess testing conditions. For proficiency testing, the study included 159 HIV testing sites (HTSs) in 41 Health facilities (HFs) in five administrative regions and two city administrations. The collected data was analyzed by SPSS version 20 and chi-square test was applied to identify the association between acceptable performance and contributing factors. Testing sites with 100% PT score as well as conducting the test with adherence to the National HIV Testing Algorithm were considered acceptable.

Results
The overall acceptable performance (100% PT score with the correct algorithm followed) was found to be 62% while 12% scored 80% and 11% scored between 20 and 60%. The rest 15% were not considered as acceptable due to failure to adhere to the National HIV Testing Algorithm. Testing sites that participated in External Quality Assessment/Proficiency Testing schemes have shown better performance than those that did not participate with 70% and 56% performance respectively (p = 0.057).
Prediction of pathologic complete response after single-dose MR-guided partial breast irradiation in low-risk breast cancer patients: the ABLATIVE-2 trial—a study protocol
Authors: Civil Yasmin A. , Oei Arlene L. , Duvivier Katya M. , Bijker Nina , Meijnen Philip , Donkers Lorraine , Verheijen Sonja , van Kesteren Zdenko , Palacios Miguel A. , Schijf Laura J. , Barbé Ellis , Konings Inge R. H. M. , -van der Houven van Oordt C. Willemien Menke , Westhoff Paulien G. , Meijer Hanneke J. M. , Diepenhorst Gwen M. P. , Thijssen Victor , Mouliere Florent , Slotman Berend J. , van der Velde Susanne , van den Bongard H. J. G. Desirée 
Published: May 2023

Abstract
Background
Partial breast irradiation (PBI) is standard of care in low-risk breast cancer patients after breast-conserving surgery (BCS). Pre-operative PBI can result in tumor downstaging and more precise target definition possibly resulting in less treatment-related toxicity. This study aims to assess the pathologic complete response (pCR) rate one year after MR-guided single-dose pre-operative PBI in low-risk breast cancer patients.

Methods
The ABLATIVE-2 trial is a multicenter prospective single-arm trial using single-dose ablative PBI in low-risk breast cancer patients. Patients ≥ 50 years with non-lobular invasive breast cancer ≤ 2 cm, grade 1 or 2, estrogen receptor-positive, HER2-negative, and tumor-negative sentinel node procedure are eligible. A total of 100 patients will be enrolled. PBI treatment planning will be performed using a radiotherapy planning CT and -MRI in treatment position. The treatment delivery will take place on a conventional or MR-guided linear accelerator. The prescribed radiotherapy dose is a single dose of 20 Gy to the tumor, and 15 Gy to the 2 cm of breast tissue surrounding the tumor. Follow-up MRIs, scheduled at baseline, 2 weeks, 3, 6, 9, and 12 months after PBI, are combined with liquid biopsies to identify biomarkers for pCR prediction. BCS will be performed 12 months after radiotherapy or after 6 months, if MRI does not show a radiologic complete response. The primary endpoint is the pCR rate after PBI. Secondary endpoints are radiologic response, toxicity, quality of life, cosmetic outcome, patient distress, oncological outcomes, and the evaluation of biomarkers in liquid biopsies and tumor tissue. Patients will be followed up to 10 years after radiation therapy.

Discussion
This trial will investigate the pathological tumor response after pre-operative single-dose PBI after 12 months in patients with low-risk breast cancer. In comparison with previous trial outcomes, a longer interval between PBI and BCS of 12 months is expected to increase the pCR rate of 42% after 6–8 months. In addition, response monitoring using MRI and biomarkers will help to predict pCR. Accurate pCR prediction will allow omission of surgery in future patients.

Trial registration
The trial was registered prospectively on April 28th 2022 at clinicaltrials.gov (NCT05350722).
Evaluation of factors related to maternal anxiety during pregnancy among women referred to Tabriz primary care centers
Authors: Mahini Elmira , Hakimi Sevil , Shahrokhi Hassan , Salahi Behnaz , Baniadam Khatereh Olad , Ranjbar Fatemeh 
Published: May 2023

Abstract
Background
Maternal anxiety during pregnancy is sometimes considered a normal mechanism to overcome the mother’s mental preoccupation with having a child. However, stress and anxiety might become a medical condition, becoming so severe as to affect the mother’s mental health. Therefore, the present study aimed to investigate factors related to maternal anxiety during pregnancy in women referring to prenatal primary care centers in Tabriz.

Methods
The target population in the present cross-sectional study was the pregnant women referring to primary care centers affiliated with Tabriz University of Medical Sciences in 2018–2019 (n = 533). Sampling was carried out using the random cluster technique (separately for municipal centers). The data were collected using the study tools, including a questionnaire on demographic data, prenatal anxiety screening scale (PASS), and researcher-made questions on maternal anxiety during pregnancy.

Results
In the present study, 37.5% of pregnant women had anxiety. Of all the demographic and background variables, income (P = 0.015), a history of preterm delivery (P = 0.018), and unintended pregnancy (P = 0.022) were significantly related to anxiety. Of the variables of income, a history of preterm delivery, and unintended pregnancy in the regression model, the odds of anxiety were 41% lower in pregnant women with somewhat adequate income than those with inadequate income after correcting for other variables (P = 0.011). In addition, the variable of unintended pregnancy increased the odds of anxiety up to 49% after correcting for other variables (P = 0.023).

Conclusion
The present study showed that income and unintended pregnancy significantly affect maternal anxiety during pregnancy.

Trial registration
The protocol of the study was approved by the Ethics Committee of Tabriz University of Medical Sciences under the code (IR.TBZMED.REC.1398.161).
Clustering of lifestyle and health behaviours in Australian adolescents and associations with obesity, self-rated health and quality of life
Authors: Ahmad Kabir , Keramat Syed Afroz , Ormsby Gail M. , Kabir Enamul , Khanam Rasheda 
Published: May 2023

Abstract
Objective
The primary aim of this study was to identify clusters of lifestyle and health behaviours and explore their associations with health outcomes in a nationally representative sample of Australian adolescents.

Methods
The study participants were 3127 adolescents aged 14–15 years who participated in the eighth wave of the birth cohort of the Longitudinal Study of Australian Children (LSAC). A latent class analysis (LCA) was performed to identify clusters based on the behaviours of physical activity, alcohol consumption, smoking, diet, eating disorders, sleep problems and weight consciousness. Multinomial logistic regression models were fitted to the following health outcome variables: obesity, self-rated general health and pediatric health-related quality of life, to investigate their associations with LCA clusters.

Results
Based on the prevalence of health behaviour related characteristics, LCA identified gender based distinct clusters of adolescents with certain outward characteristics. There were five clusters for male and four clusters for female participants which are named as: healthy lifestyle, temperate, mixed lifestyle, multiple risk factors, and physically inactive (male only). Adolescents in the healthy lifestyle and temperate clusters reported low and moderately active health risk behaviours, for example, low physical activity, inadequate sleep and so on, while these behaviours were prevailing higher among adolescents of other clusters. Compared to adolescents of healthy lifestyle clusters, male members of physically inactive (OR = 3.87, 95% CI: 1.12 – 13.33) or mixed lifestyle (OR = 5.57, 95% CI: 3.15 – 9.84) clusters were over three to five times more likely to have obesity; while for female adolescents, members of only multiple risk factors clusters (OR = 3.61, 95% CI: 2.00 – 6.51) were over three time more likely to have obesity compared to their counterpart of healthy lifestyle clusters. Adolescents of physically inactive (b = -9.00 for male only), mixed lifestyle (b = -2.77 for male; b = -6.72 for female) or multiple risk factors clusters (b = -6.49 for male; b = -6.59 for female) had a stronger negative association with health-related quality of life scores compared to adolescents of healthy lifestyle clusters.

Conclusion
The study offers novel insights into latent class classification through the utilisation of different lifestyles and health-related behaviours of adolescents to identify characteristics of vulnerable groups concerning obesity, general health status and quality of life. This classification strategy may help health policy makers to target vulnerable groups and develop appropriate interventions.