bluuebunny/crossref_metadata_2025_split huggingface dataset:
Non-Laboratory Project-Based Learning for Final Year Bioscience Students: Lessons From COVID-19
Authors: McKenna Declan J. 
Published: August 2023

Background:Provision of “dry-lab” final year honours projects, based outside the laboratory, have been proposed as a viable alternative to traditional “wet-lab” projects in bioscience subjects, but their value has not been widely evaluated to date. In 2020–21, the COVID-19 pandemic meant all students in the School of Biomedical Sciences at Ulster University (UU) undertook dry-lab projects, due to campus lockdown. Therefore, this provided an ideal opportunity to evaluate the provision of dry-lab projects in a large student cohort.Methods:A pilot group of final year students (n= 4) studying Biomedical Science at UU were interviewed to evaluate their experience of conducting a dry-lab project. This evaluation and the themes that emerged were subsequently used to inform the co-creation of a survey to appraise student experience of dry-lab research project learning across the final year student cohort in School of Biomedical Sciences (n= 140). Quantitative and qualitative data was collected and analysed for trends and themes.Results:The results of this project identified four main themes related to dry-lab projects; expectations, skills &amp; employability, quality of experience and choice. Student expectations about dry-lab projects were not dramatically changed, although initial negative opinions of some individuals were over-turned. Most students recognised that they had developed many useful employability skills through dry-lab projects, although lack of practical laboratory experience was still perceived as a drawback. Student experience was influenced by personal circumstances but students reporting poor project experience had significantly lower levels of communication with supervisor (p&lt; 0.05). Most students agreed that choice of dry- and wet-lab projects would be valuable for future cohorts.Conclusion:This report concludes that dry-lab project provision can be a suitable and equitable alternative for wet-lab projects. Dry-lab projects can be valuable for learning new skills and may be an attractive option for some students and supervisors who prefer to work outside the laboratory setting. A choice of both dry-lab and wet-lab projects is highly recommended as it provides more choice for students to tailor their final year experience to their individual circumstances, strengths and future career aspirations.
Parallel G-quadruplex recognition by neomycin
Authors: Ranjan Nihar , Arya Dev P. 
Published: August 2023

G-quadruplex-forming nucleic acids have evolved to have applications in biology, drug design, sensing, and nanotechnology, to name a few. Together with the structural understanding, several attempts have been made to discover and design new classes of chemical agents that target these structures in the hope of using them as future therapeutics. Here, we report the binding of aminoglycosides, in particular neomycin, to parallel G-quadruplexes that exist as G-quadruplex monomers, dimers, or compounds that have the propensity to form dimeric G-quadruplex structures. Using a combination of calorimetric and spectroscopic studies, we show that neomycin binds to the parallel G-quadruplex with affinities in the range of Ka ∼ 105–108 M-1, which depends on the base composition, ability to form dimeric G-quadruplex structures, salt, and pH of the buffer used. At pH 7.0, the binding of neomycin was found to be electrostatically driven potentially through the formation of ion pairs formed with the quadruplex. Lowering the pH resulted in neomycin’s association constants in the range of Ka ∼ 106–107 M-1 in a salt dependent manner. Circular dichroism (CD) studies showed that neomycin’s binding does not cause a change in the parallel conformation of the G-quadruplex, yet some binding-induced changes in the intensity of the CD signals were seen. A comparative binding study of neomycin and paromomycin using d(UG4T) showed paromomycin binding to be much weaker than neomycin, highlighting the importance of ring I in the recognition process. In toto, our results expanded the binding landscape of aminoglycosides where parallel G-quadruplexes have been discovered as one of the high-affinity sites. These results may offer a new understanding of some of the undesirable functions of aminoglycosides and help in the design of aminoglycoside-based G-quadruplex binders of high affinity.
Dynamic evolution of ceftazidime–avibactam resistance due to interchanges between blaKPC-2 and blaKPC-145 during treatment of Klebsiella pneumoniae infection
Authors: Chen Yili , Yang Runshi , Guo Penghao , Liu Pingjuan , Deng Jiankai , Wu Zhongwen , Wu Qingping , Huang Junqi , Liao Kang 
Published: August 2023

BackgroundThe emergence of ceftazidime–avibactam (CZA) resistance among carbapenem-resistant Klebsiella pneumoniae (CRKP) is of major concern due to limited therapeutic options.MethodsIn this study, 10 CRKP strains were isolated from different samples of a patient with CRKP infection receiving CZA treatment. Whole-genome sequencing (WGS) and conjugation experiments were performed to determine the transferability of the carbapenem resistance gene.ResultsThis infection began with a KPC-2-producing K. pneumoniae (CZA MIC = 2 μg/mL, imipenem MIC ≥ 16 μg/mL). After 20 days of CZA treatment, the strains switched to the amino acid substitution of T263A caused by a novel KPC-producing gene, blaKPC-145, which restored carbapenem susceptibility but showed CZA resistance (CZA MIC ≥ 256 μg/mL, imipenem MIC = 1 μg/mL). The blaKPC-145 gene was located on a 148,185-bp untransformable IncFII-type plasmid. The subsequent use of carbapenem against KPC-145-producing K. pneumoniae infection led to a reversion of KPC-2 production (CZA MIC = 2 μg/mL, imipenem MIC ≥ 16 μg/mL). WGS analysis showed that all isolates belonged to ST11-KL47, and the number of SNPs was 14. This implied that these blaKPC-positive K. pneumoniae isolates might originate from a single clone and have been colonized for a long time during the 120-day treatment period.ConclusionThis is the first report of CZA resistance caused by blaKPC-145, which emerged during the treatment with CZA against blaKPC-2-positive K. pneumoniae-associated infection in China. These findings indicated that routine testing for antibiotic susceptibility and carbapenemase genotype is essential during CZA treatment.
Transthoracic device closure of perimembranous ventricular septal defect via a small left intercostal incision in children
Authors: Xie Linfeng , Zhang Guican , He Jian , Shen Yanming , Liao Dongshan , Chen Liangwan , Xu Fan 
Published: August 2023

BackgroundIn children with perimembranous ventricular septal defect, surgical repair requires sternotomy and leaves unsightly scars, which can trigger long-term physical and psychological distress. However, transcatheter device closure is limited by vascular diameter, radiographic exposure, and expensive DSA equipment. We used an ultra-small left intercostal incision for transthoracic device closure to avoid the above problems and investigated its safety and feasibility by comparing it with surgical repair.MethodsThis study enrolled 358 children with perimembranous ventricular septal defect. Among them, 152 patients were treated by surgical closure and 206 by transthoracic device closure via an ultra-small left intercostal incision. Perioperative clinical data and postoperative follow-up results were collected and analyzed retrospectively.ResultsThe success rate was similar (P = 0.265) in the two groups: 203/206 patients in the device group vs. 152/152 patients in the surgical group. The operative time, intensive care unit time, mechanical ventilation time, and postoperative hospital stay were significantly shorter in the device group than in the surgical group. Although the incision length of the device group (1.1 ± 0.2 cm) was significant shorter (P &lt; 0.001) than that of the surgical group (6.7 ± 1.5 cm), there was no difference in hospitalization costs between the two groups (P = 0.099). Except for small residual shunt (16/206 vs. 3/152, P = 0.017), the incidence of complications in the device group was lower or equal to that in the surgical group, and all small residual shunt disappeared during follow-up. There was no thoracic deformity in the device group, compared with 11 cases in the surgery group during follow-up (P &lt; 0.001).ConclusionsTransthoracic device closure via an ultra-small left intercostal incision under transesophageal echocardiography guidance is safe and feasible. With appropriate indications, it can be a suitable alternative to surgical closure for treating perimembranous ventricular septal defect in children.
A study of effects of different impact loads on the dynamic and elastoplastic behavior in reservoir rocks at the beginning of hydraulic fracturing
Authors: Abulimiti Aibaibu , Wang Linsheng , Zang Chuanzhen , Chen Bo , Xiang Xinsheng , Jiang Peijia , Lin Jiaying 
Published: August 2023

Successful hydraulic fracturing is very important in the development of hydrocarbon-bearing formations. The loading introduced by hydraulic fracturing causes deformation and failure, which are related to the damage accumulation and hydraulic fracture initiation process. This study employs a numerical model that considers the dynamic and elastoplastic behaviors in rocks under the influence of impact loads. The acceleration and wave propagation behaviors are quantified using the model. A time integration algorithm is used to ensure numerical accuracy and stability. The effects of loading rate, loading location, and heterogeneity are quantified. Results show that the elastoplastic and dynamic can effectively capture the wavy mechanical responses in the domain. Strain rate, acceleration, and plasticity can all exhibit oscillatory distribution patterns. Increasing the loading rate can magnify acceleration, strain rate, and the maximum plastic strain, while it reduces the range experiencing these induced changes. Changing the loading types and introducing the heterogeneity consideration both largely alter the mechanical response in the domain, and the waveforms of the mechanical parameters are significantly changed. Failure can occur earlier in layers with more elastic mechanical properties. Exerting 50 MPa loading in 0.01 ms can effectively introduce deformation and failures in the reservoir rock. Doubling the loading rate can effectively improve the ability of creating rock failures, which facilitates the following fracture initiation and propagation processes. This study can be a reference for the understanding of near-well and instantaneous rock mechanical behaviors at the beginning of fracturing.
Endometrial thickness and early pregnancy complications after frozen-thawed embryo transfers
Authors: Song Lin , Bu Zhiqin , Sun Yingpu 
Published: August 2023

BackgroundThe relationship between endometrial thickness and pregnancy safety after in vitro fertilization treatment is an important topic that should provoke attention. The aim of this study was to demonstrate the relationship between endometrial thickness on day of embryo transfer and early pregnancy complications, including ectopic pregnancy and early miscarriage, in frozen thawed embryo transfer (FET) cycles.MethodsPatients undergoing their first FET cycles were included into this study from January 2010 to December 2021. Patients were divided into three groups according to endometrial thickness on day of embryo transfer: Thin, ≤ 7 mm; Medium, 7-14 mm; Thick, ≥ 14 mm. Ectopic pregnancy and early miscarriage were the two primary outcomes. Endometrial thickness was the main measured variable. The risk factors of these two compilations were determined based on univariate analysis and multivariate logistic regression analysis.ResultsA total of 11138 clinical pregnancies were included. The overall ectopic pregnancy and early spontaneous miscarriage rates were 2.62% and 13.40%. The ectopic pregnancy and early spontaneous miscarriage rates were significantly higher in patients with thin endometrium as compared with those in the other two groups (ectopic pregnancy rate: 5.06% vs. 2.62% vs. 1.05%; P &lt; 0.001; early spontaneous miscarriage rate: 15.18% vs. 13.45% vs. 11.53%; P &lt; 0.001). In multivariate logistic regression analysis, thin endometrium was an independent factor to predict ectopic pregnancy [adjusted odds ratio (aOR): 5.62; 95% confidence interval (CI): 2.51–12.58, P &lt; 0.001], and to predict early spontaneous miscarriage rate (aOR: 1.57; 95% CI: 1.21–1.74, P &lt; 0.001).ConclusionThin endometrium on day of embryo transfer in FET cycles is an independent predictor for early pregnancy compilations, including ectopic pregnancy and early spontaneous miscarriage.
A case report of membrane induction combined with RIA technique for the repair of distal humerus segmentary bone defect
Authors: Wang Guoliang , Zhu Zhenfeng , Lu Shuaikun , Wang Linhu , Gao Hao , Fu Congxiao , Ren Jun , Liu Xiang , Zhang Yong , Zhang Yunfei 
Published: August 2023

Bone nonunion and bone defect are common postoperative complications in clinic. Membrane induction or Ilizarov technique is often used to repair bone defect. Autologous bone is often used for bone defect repair and reconstruction, and the anterior superior iliac spine, posterior superior iliac spine or fibula bone is used as the donor area for bone extraction, but there are problems of donor area complications. In recent years, the development of bone marrow aspiration (RIA) has provided a new alternative way for the source of autogenous bone. We report a 48-year-old female patient with a comminuted supracondylar intercondylar fracture of the left humerus due to a car accident. After 8 months of emergency debridement and suture with Kirschner wire internal fixation, the fracture was found to be unhealed with extensive bone defects. We used membrane induction combined with RIA technology to repair and reconstruct the patients, and found good osteogenesis through late follow-up. In theory, membrane induction technique can realize the reconstruction of large segmental bone defects, but the scope of repair is often limited by the lack of autologous bone source. The emergence and development of RIA technology provides us with a new autologous bone donor area for bone repair and reconstruction surgery. It can provide a large amount of high-quality cancellar bone mud through minimally invasive means. Meanwhile, it can reduce patients’ pain, infection, fracture, aesthetics and other problems caused by iliac bone extraction, and shorten patients’ bed time. Maximize the preservation of the patient’s autologous bone source. For the first time in the world, we reported the combination of membrane induction technology and RIA technology in the treatment of segmental bone defects, providing a new idea for the treatment of bone defects.
Bioleptin as a useful marker of metabolic status in children with diabetes mellitus type 1
Authors: Jakubek-Kipa Katarzyna , Galiniak Sabina , Łagowska Katarzyna , Krupa Izabela , Ludwin Aleksandra , Tabarkiewicz Jacek , Mazur Artur 
Published: August 2023

IntroductionThe purpose of our study was tomeasure the level of leptin and biologically active leptin (bioLEP) in children with type 1 diabetes, depending on the duration of diabetes and its degree of metabolic control.MethodsThe study included 94 children (58 boys and 36 girls). In a group of children with diabetes, 40 patients were newly diagnosed with type 1 diabetes, 40 children who have diabetes for more than a year (20 with good metabolic control and 20 with poor metabolic control). The control group consisted of 14 healthy children. The serum level of leptin and bioLEP was measured using a sandwich enzyme-linked immunosorbent assay. To our knowledge, this is the first study to describe bioLEP levels among diabetic children with different forms of disease control.ResultsLower levels of leptin were found in children with diabetes compared to healthy children. Furthermore, we found a statistically higher concentration of leptin in the group of children with newly diagnosed diabetes compared to children from the diabetic group with poor metabolic control and lower than healthy children (11.19 vs. 7.84 and 20.94 ng/mL). Moreover, children in the metabolically well-controlled group had statistically lower levels of this hormone (5.11 ng/mL) than healthy children. Leptin concentrations differed significantly between underweight, overweight, and obese children.DiscussionIn our study, the level of bioLEP differed significantly between children in the newly diagnosed diabetes group and children in the long-term, poorly controlled diabetes group and healthy controls. Despite many studies published in recent years, many aspects of leptin secretion, action, and mechanisms of its influence on carbohydrate and fat metabolism are still to be clarified. In our opinion, studies evaluating the status of bioLEP in diabetes can also contribute to a better understanding of the mechanisms regulating metabolism.
Identification and verification of novel immune-related ferroptosis signature with excellent prognostic predictive and clinical guidance value in hepatocellular carcinoma
Authors: Jiang Wenxiu , Wang Lili , Zhang Yajuan , Li Hongliang 
Published: August 2023

Background: Immunity and ferroptosis often play a synergistic role in the progression and treatment of hepatocellular carcinoma (HCC). However, few studies have focused on identifying immune-related ferroptosis gene biomarkers.Methods: We performed weighted gene co-expression network analysis (WGCNA) and random forest to identify prognostic differentially expressed immune-related genes (PR-DE-IRGs) highly related to HCC and characteristic prognostic differentially expressed ferroptosis-related genes (PR-DE-FRGs) respectively to run co-expression analysis for prognostic differentially expressed immune-related ferroptosis characteristic genes (PR-DE-IRFeCGs). Lasso regression finally identified 3 PR-DE-IRFeCGs for us to construct a prognostic predictive model. Differential expression and prognostic analysis based on shared data from multiple sources and experimental means were performed to further verify the 3 modeled genes’ biological value in HCC. We ran various performance testing methods to test the model’s performance and compare it with other similar signatures. Finally, we integrated composite factors to construct a comprehensive quantitative nomogram for accurate prognostic prediction and evaluated its performance.Results: 17 PR-DE-IRFeCGs were identified based on co-expression analysis between the screened 17 PR-DE-FRGs and 34 PR-DE-IRGs. Multi-source sequencing data, QRT-PCR, immunohistochemical staining and testing methods fully confirmed the upregulation and significant prognostic influence of the three PR-DE-IRFeCGs in HCC. The model performed well in the performance tests of multiple methods based on the 5 cohorts. Furthermore, our model outperformed other related models in various performance tests. The immunotherapy and chemotherapy guiding value of our signature and the comprehensive nomogram’s excellent performance have also stood the test.Conclusion: We identified a novel PR-DE-IRFeCGs signature with excellent prognostic prediction and clinical guidance value in HCC.
GeNetOntology: identifying affected gene ontology terms via grouping, scoring, and modeling of gene expression data utilizing biological knowledge-based machine learning
Authors: Ersoz Nur Sebnem , Bakir-Gungor Burcu , Yousef Malik 
Published: August 2023

Introduction: Identifying significant sets of genes that are up/downregulated under specific conditions is vital to understand disease development mechanisms at the molecular level. Along this line, in order to analyze transcriptomic data, several computational feature selection (i.e., gene selection) methods have been proposed. On the other hand, uncovering the core functions of the selected genes provides a deep understanding of diseases. In order to address this problem, biological domain knowledge-based feature selection methods have been proposed. Unlike computational gene selection approaches, these domain knowledge-based methods take the underlying biology into account and integrate knowledge from external biological resources. Gene Ontology (GO) is one such biological resource that provides ontology terms for defining the molecular function, cellular component, and biological process of the gene product.Methods: In this study, we developed a tool named GeNetOntology which performs GO-based feature selection for gene expression data analysis. In the proposed approach, the process of Grouping, Scoring, and Modeling (G-S-M) is used to identify significant GO terms. GO information has been used as the grouping information, which has been embedded into a machine learning (ML) algorithm to select informative ontology terms. The genes annotated with the selected ontology terms have been used in the training part to carry out the classification task of the ML model. The output is an important set of ontologies for the two-class classification task applied to gene expression data for a given phenotype.Results: Our approach has been tested on 11 different gene expression datasets, and the results showed that GeNetOntology successfully identified important disease-related ontology terms to be used in the classification model.Discussion: GeNetOntology will assist geneticists and scientists to identify a range of disease-related genes and ontologies in transcriptomic data analysis, and it will also help doctors design diagnosis platforms and improve patient treatment plans.
Role of ICAM1 in tumor immunity and prognosis of triple-negative breast cancer
Authors: Zhou Qin , Xu Jiawei , Xu Yan , Sun Shaokun , Chen Jian 
Published: August 2023

BackgroundTreating triple-negative breast cancer (TNBC) is a difficult landscape owing to its short survival times and high risk of metastasis and recurrence among patients. Although involved in tumor invasion and metastasis, the mechanism of action of intercellular adhesion molecule 1 (ICAM1), a trans-membrane glycoprotein, in TNBC is ambiguous.MethodsWe examined ICAM1’s role in TNBC, focusing on its expression, cell survival, mutation, and tumor immunity. Then, a risk score model was created utilizing co-expressed genes associated with ICAM1. According to their respective risk scores, we divided patients into high- and low-risk groups. Immune function, drug susceptibility differences, and somatic variants were analyzed in the high-and low-risk groups. And we used the CMap database to predict potential medications. Then, TNBC cells with low expression of ICAM-1 were co-cultured with PMA-treated THP-1 cells and CD8 T cells. In addition, We detected the expression of PD-1 and CTLA4 of low ICAM-1 expressing TNBC cells when they were cocultured with CD8 T cells.ResultsICAM1 was found to be involved in leukocyte cell adhesion, motility, and immune activation. Patients with low-ICAM1 group had shorter disease-free survival (DFS) than those with high-ICAM1 group. The group with elevated levels of ICAM1 exhibited significantly increased levels of T-cell regulation, quiescence in natural killer (NK) cells, and M1 macrophage. ICAM1 expression was correlated with immune checkpoint drugs. The prognostic ability of the risk score model was found to be superior to that of individual genes. Patients categorized as high-risk exhibited elevated clinical stages, showed higher M1 macrophage numbers, and were able to benefit better from immunotherapy. Individuals belonging to the high-risk group exhibit significantly elevated mutation rates in TP53, TTN, and SYNE1 genes, along with increased TMB and PD-L1 levels and decreased TIDE scores. These findings suggest that immunotherapy may be advantageous for the high-risk group. Furthermore, low expression of ICAM1 was found to promote polarization to M2 macrophages along with T-cell exhaustion.ConclusionIn conclusion, Low ICAM1 expression may be related to immune escape, leading to poor treatment response and a worse prognosis.