bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated analysis of single-cell and Bulk RNA sequencing reveals a malignancy-related signature in lung adenocarcinoma
Authors: Wu Mengxi , Wu Zhenyu , Yan Jun , Zeng Jie , Kuang Jun , Zhong Chenghua , Zhu Xiaojia , Mo Yijun , Guo Quanwei , Li Dongfang , Tan Jianfeng , Zhang Tao , Zhang Jianhua 
Published: June 2023

BackgroundLung adenocarcinoma (LUAD), the most common histotype of lung cancer, may have variable prognosis due to molecular variations. The research strived to establish a prognostic model based on malignancy-related risk score (MRRS) in LUAD.MethodsWe applied the single-cell RNA sequencing (scRNA-seq) data from Tumor Immune Single Cell Hub database to recognize malignancy-related geneset. Meanwhile, we extracted RNA-seq data from The Cancer Genome Atlas database. The GSE68465 and GSE72094 datasets from the Gene Expression Omnibus database were downloaded to validate the prognostic signature. Random survival forest analysis screened MRRS with prognostic significance. Multivariate Cox analysis was leveraged to establish the MRRS. Furthermore, the biological functions, gene mutations, and immune landscape were investigated to uncover the underlying mechanisms of the malignancy-related signature. In addition, we used qRT-PCR to explore the expression profile of MRRS-constructed genes in LUAD cells.ResultsThe scRNA-seq analysis revealed the markers genes of malignant celltype. The MRRS composed of 7 malignancy-related genes was constructed for each patient, which was shown to be an independent prognostic factor. The results of the GSE68465 and GSE72094 datasets validated MRRS’s prognostic value. Further analysis demonstrated that MRRS was involved in oncogenic pathways, genetic mutations, and immune functions. Moreover, the results of qRT-PCR were consistent with bioinformatics analysis.ConclusionOur research recognized a novel malignancy-related signature for predicting the prognosis of LUAD patients and highlighted a promising prognostic and treatment marker for LUAD patients.
Monocyte anisocytosis corresponds with increasing severity of COVID-19 in children
Authors: Kane Abigail S. , Boribong Brittany P. , Loiselle Maggie , Chitnis Anagha P. , Chavez Hector , Moldawer Lyle L. , Larson Shawn D. , Badaki-Makun Oluwakemi , Irimia Daniel , Yonker Lael M. 
Published: June 2023

IntroductionAlthough SARS-CoV-2 infection can lead to severe COVID-19 in children, the role of biomarkers for assessing the risk of progression to severe disease is not well established in the pediatric population. Given the differences in monocyte signatures associated with worsening COVID-19 in adults, we aimed to determine whether monocyte anisocytosis early in the infectious course would correspond with increasing severity of COVID-19 in children.MethodsWe performed a multicenter retrospective study of 215 children with SARS-CoV-2 infection, Multisystem Inflammatory Syndrome in Children (MIS-C), convalescent COVID-19, and healthy age-matched controls to determine whether monocyte anisocytosis, quantified by monocyte distribution width (MDW) on complete blood count, was associated with increasing severity of COVID-19. We performed exploratory analyses to identify other hematologic parameters in the inflammatory signature of pediatric SARS-CoV-2 infection and determine the most effective combination of markers for assessing COVID-19 severity in children.ResultsMonocyte anisocytosis increases with COVID-19 severity and need for hospitalization. Although other inflammatory markers such as lymphocyte count, neutrophil/lymphocyte ratio, C-reactive protein, and cytokines correlate with disease severity, these parameters were not as sensitive as MDW for identifying severe disease in children. An MDW threshold of 23 offers a sensitive marker for severe pediatric COVID-19, with improved accuracy when assessed in combination with other hematologic parameters.ConclusionMonocyte anisocytosis corresponds with shifting hematologic profiles and inflammatory markers in children with COVID-19, and MDW serves as a clinically accessible biomarker for severe COVID-19 in children.
Antiprotozoal activity of natural products from Nigerien plants used in folk medicine
Authors: Sevik Kilicaslan Ozlem , Cretton Sylvian , Hausmann Estelle , Quirós-Guerrero Luis , Karimou Soumana , Kaiser Marcel , Mäser Pascal , Christen Philippe , Cuendet Muriel 
Published: June 2023

In the course of the screening of plants from Niger for antiprotozoal activity, the methanol extract of Cassia sieberiana, and the dichloromethane extracts of Ziziphus mauritiana and Sesamun alatum were found to be active against protozoan parasites, namely Trypanosoma brucei rhodesiense, Trypanosoma cruzi, Leishmania donovani and/or Plasmodium falciparum. Myricitrin (1), quercitrin (2) and 1-palmitoyl-lysolecithin (3) were isolated from C. sieberiana. From Z. mauritiana, the three triterpene derivatives 13, 15, and 16 are described here for the first time. Their chemical structures were determined by 1D and 2D NMR experiments, UV, IR and HRESIMS data. The absolute configurations were assigned via comparison of the experimental and calculated ECD spectra. In addition, eight known cyclopeptide alkaloids (4, 5, 7–12), and five known triterpenoids (6, 14, 17–19) were isolated. The antiprotozoal activity of the isolated compounds, as well as of eleven quinone derivatives (20–30) previously isolated from S. alatum was determined in vitro. The cytotoxicity in L6 rat myoblast cells was also evaluated. Compound 18 showed the highest antiplasmodial activity (IC50 = 0.2 µm) and compound 24 inhibited T. b. rhodesiense with an IC50 value of 0.007 µM. However, it also displayed significant cytotoxicity in L6 cells (IC50 = 0.4 µm).
Characterization of complex structural variation in the CYP2D6-CYP2D7-CYP2D8 gene loci using single-molecule long-read sequencing
Authors: Turner Amy J. , Derezinski Ashley D. , Gaedigk Andrea , Berres Mark E. , Gregornik David B. , Brown Keith , Broeckel Ulrich , Scharer Gunter 
Published: June 2023

Complex regions in the human genome such as repeat motifs, pseudogenes and structural (SVs) and copy number variations (CNVs) present ongoing challenges to accurate genetic analysis, particularly for short-read Next-Generation-Sequencing (NGS) technologies. One such region is the highly polymorphic CYP2D loci, containing CYP2D6, a clinically relevant pharmacogene contributing to the metabolism of &gt;20% of common drugs, and two highly similar pseudogenes, CYP2D7 and CYP2D8. Multiple complex SVs, including CYP2D6/CYP2D7-derived hybrid genes are known to occur in different configurations and frequencies across populations and are difficult to detect and characterize accurately. This can lead to incorrect enzyme activity assignment and impact drug dosing recommendations, often disproportionally affecting underrepresented populations. To improve CYP2D6 genotyping accuracy, we developed a PCR-free CRISPR-Cas9 based enrichment method for targeted long-read sequencing that fully characterizes the entire CYP2D6-CYP2D7-CYP2D8 loci. Clinically relevant sample types, including blood, saliva, and liver tissue were sequenced, generating high coverage sets of continuous single molecule reads spanning the entire targeted region of up to 52 kb, regardless of SV present (n = 9). This allowed for fully phased dissection of the entire loci structure, including breakpoints, to accurately resolve complex CYP2D6 diplotypes with a single assay. Additionally, we identified three novel CYP2D6 suballeles, and fully characterized 17 CYP2D7 and 18 CYP2D8 unique haplotypes. This method for CYP2D6 genotyping has the potential to significantly improve accurate clinical phenotyping to inform drug therapy and can be adapted to overcome testing limitations of other clinically challenging genomic regions.
Pharmacological interventions for preventing opioid-induced hyperalgesia in adults after opioid-based anesthesia: a systematic review and network meta-analysis
Authors: Xie Wei-Ji , Hong Ji-Shuang , Feng Cheng-Fei , Chen Hao-Feng , Li Wei , Li Yong-Chun 
Published: June 2023

Background: Opioid-induced hyperalgesia (OIH) is an adverse event of prolonged opioid use that increases pain intensity. The optimal drug to prevent these adverse effects is still unknown. We aimed to conduct a network meta-analysis to compare different pharmacological interventions for preventing the increase in postoperative pain intensity caused by OIH.Methods: Several databases were searched independently for randomized controlled trials (RCTs) comparing various pharmacological interventions to prevent OIH. The primary outcomes were postoperative pain intensity at rest after 24 h and the incidence of postoperative nausea and vomiting (PONV). Secondary outcomes included pain threshold at 24 h after surgery, total morphine consumption over 24 h, time to first postoperative analgesic requirement, and shivering incidence.Results: In total, 33 RCTs with 1711 patients were identified. In terms of postoperative pain intensity, amantadine, magnesium sulphate, pregabalin, dexmedetomidine, ibuprofen, flurbiprofen plus dexmedetomidine, parecoxib, parecoxib plus dexmedetomidine, and S (+)-ketamine plus methadone were all associated with milder pain intensity than placebo, with amantadine being the most effective (SUCRA values = 96.2). Regarding PONV incidence, intervention with dexmedetomidine or flurbiprofen plus dexmedetomidine resulted in a lower incidence than placebo, with dexmedetomidine showing the best result (SUCRA values = 90.3).Conclusion: Amantadine was identified as the best in controlling postoperative pain intensity and non-inferior to placebo in the incidence of PONV. Dexmedetomidine was the only intervention that outperformed placebo in all indicators.Clinical Trial Registration:https://www.crd.york.ac. uk/prospero/display_record.php?, CRD42021225361.
Association between genetic polymorphism, severity, and treatment response among COVID-19 infected Egyptian patients
Authors: Alaa Abdelrahman , Sarhan Neven , Lotfy El-Ansary Mohamed Gamal , Bazan Naglaa Samir , Farouk Khaled , Ismail Raed Shahat , Schalaan Mona Farag , Abd-Allah Adel R. A. 
Published: June 2023

Background: The world has been suffering from the Coronavirus Disease-2019 (COVID-19) pandemic since the end of 2019. The COVID-19-infected patients differ in the severity of the infection and the treatment response. Several studies have been conducted to explore the factors that affect the severity of COVID-19 infection. One of these factors is the polymorphism of the angiotensin converting enzyme 2 (ACE-2) and the type 2 transmembrane serine protease (TMPRSS2) genes since these two proteins have a role in the entry of the virus into the cell. Also, the ACE-1 regulates the ACE-2 expression, so it is speculated to influence the COVID-19 severity.Objective: This study investigates the relationship between the ACE-1, ACE-2, and TMPRSS2 genes single nucleotide polymorphism (SNPs) and the COVID-19 disease severity, treatment response, need for hospitalization, and ICU admission in Egyptian patients.Patients and Methods: The current study is an observational prospective, cohort study, in which 109 total COVID-19 patients and 20 healthy volunteers were enrolled. Of those 109 patients, 51 patients were infected with the non-severe disease and were treated in an outpatient setting, and 58 suffered from severe disease and required hospitalization and were admitted to the ICU. All 109 COVID-19 patients received the treatment according to the Egyptian treatment protocol.Results: Genotypes and allele frequencies among severe and non-severe patients were determined for ACE-1 rs4343, TMPRSS2 rs12329760, and ACE-2 rs908004. The GG genotype and the wild allele of the ACE-2 rs908004 and the mutant allele of the ACE-1 rs4343 were significantly more predominant in severe patients. In contrast, no significant association existed between the TMPRSS2 rs12329760 genotypes or alleles and the disease severity.Conclusion: The results of this study show that the ACE-1 and ACE-2 SNPs can be used as severity predictors for COVID-19 infection since also they have an effect on length of hospitalization.
Metasurface-generating high purity narrow linewidth cylindrical vector beams: power scaling and its limitation
Authors: Li Haokun , Xie Lianghua , Zhang Chun , Tao Rumao , Shu Qiang , Li Min , Shen Benjian , Feng Xi , Xu Lixin , Wang Jianjun 
Published: June 2023

1.89 kW cylindrical vector beams (CVBs) at 1,064 nm with the 3 dB linewidth being about 0.08 nm have been generated from a narrow linewidth all-fiber linearly-polarized laser by metasurface extra-cavity conversion. At the maximum output power, the transmission efficiency, mode purity of radially polarized cylindrical vector beams (RP-CVBs) are 97% and 92.7%, respectively. To the best of our knowledge, this is the highest power of narrow linewidth CVBs generated from fiber laser. The temperature of the metasurface is moderate, and the maximum temperature is 75.5°C at 1.89 kW, which means that the system can be further power scaled. The evolution of mode purity has been analyzed numerically, and the influence of high-order modes (HOM) in laser source and thermal effects of metasurface has been calculated, which reveals that the presence of high-order modes and the temperature rise of metasurface degrade the mode purity of the CVBs. Among them, HOM causes a degradation of 1.68%, thermal lensing effect contributes 2.32%, and the microstructure variation of the metasurface contributes the remaining 3.3%.
“Wading through the worst that humanity does to each other”: New Zealand Crown prosecutors’ experiences of working with potentially traumatic material in the criminal justice system
Authors: Kim Rachel , Tyler Nichola , Tinsley Yvette 
Published: June 2023

IntroductionOccupational exposure to trauma and its potential impacts on legal professionals working in the criminal justice system is an area that has historically been neglected and has only gained traction in recent years. Crown prosecutors, as a subset of practising criminal lawyers in New Zealand, are arguably at heightened risk of vicarious trauma (VT) due to their occupationally distinct exposure to potentially traumatic material (PTM). However, no research to date has explored the experiences of this group of working with PTM.MethodsThis qualitative study aimed to explore New Zealand Crown prosecutors’ experiences of working with PTM. Nineteen Crown prosecutors from four Crown Solicitor firms across New Zealand participated in individual semi-structured interviews. The data was analysed using reflexive thematic analysis.ResultsThree themes were developed that described Crown prosecutors’ experiences of work-related exposure to trauma: trauma is everywhere, enduring effects of PTM exposure, and coping in the moment. These findings add to the growing body of literature on legal professionals’ work-related wellbeing and highlights how they are an at-risk population for VT, which can be significant and enduring.DiscussionFurther research is needed to understand the unique etiological pathways for both the consequences of working with PTM and effective ways to reduce this occupational risk for legal professionals working in the criminal law.
Comparative study of accompaniment programs for undergraduate degree students in Spanish universities
Authors: García-Cardo Susana , Queiruga-Dios Marián , Queiruga-Dios Araceli 
Published: June 2023

IntroductionIn the last decade, higher education has undergone a transformation in different areas. The most recent and impactful one may have been the need to keep it updated during the COVID-19 pandemic and to be able to teach remotely and affect university life as little as possible. Another significant change is the emergence of personal attention, accompaniment, or mentoring programs, which have become the prevalent leitmotif in many universities.MethodsThis study compares the different programs at 60 Spanish universities. The relevant information collected during this research is related to the existence of an accompaniment program, and in this program, which plays the role of mentor, or what year is it for. Other information collected from the search is related to the type of mentoring programs, whether they are regulated, have a formal program, or are linked to specific courses. Finally, the assessment procedures are also indicated in case any evaluation is used. After the analysis developed during this research, the mentor-mentee program implemented at the Francisco de Vitoria University is detailed, highlighting differences from other programs, its advantages, and students' benefits.ResultsThe number of accompaniment and mentoring programs offered by Spanish universities continues to rise. In Spanish universities, some accompaniment and mentoring programs offer different and specific mentoring activities designed to enhance and further the kind of education and preparation institutions of higher learning should ideally provide. Accompaniment processes generally have a longer duration in private universities than in public universities, offering a wider range of programs for both current and incoming students and those with specific needs, such as international students.DiscussionThe authors found that not many studies have highlighted the value of the accompaniment, and even fewer have conducted comparative analyses of the diverse realities across various universities. Mentoring programs will have the potential to be part of a university's strategy to help students succeed when the shortcomings of mentoring programs. This study opens new avenues for research into the ideal profile of mentors to best accompany university students.
Trajectories and influencing factors in adolescent procrastination behavior throughout the COVID-19 pandemic: a four-wave prospective longitudinal study
Authors: Wu Yongmei , Bu Tianyi , Xie Yunjia , Wei Ping , Zhao Jinxin , Chen Lu , Qiao Kexin , Wang Yan , Yang Jiarun , Qiu Xiaohui , Yang Xiuxian , Zhou Jiawei , Qiao Zhengxue , Yang Yanjie 
Published: June 2023

BackgroundDespite the growing attention given to adolescent behavior problems, little is known about the trajectories and factors that have influenced adolescent procrastination during the COVID-19 pandemic. This study monitors changes in procrastination behavior among Chinese adolescents during the pandemic and identifies vulnerable groups.MethodsA four-wave study using a representative sample of 11-to 18-year-olds in China was conducted, with baseline data collected in June 2020 (n = 4,156; 49% girls) and follow-ups in December 2020 (n = 3,392; 50% girls), August 2021 (n = 2,380; 48% girls), and October 2021 (n = 1,485; 49% girls). Procrastination behavior was assessed using the General Procrastination Scale. Latent growth curve models, latent growth mixture modes, and multivariate logistic regression models were used to describe the trajectory of procrastination and identify predictors of deterioration.ResultsThe proportion and overall trends of adolescent procrastination increased with the pandemic. Higher parental over-protection was a contributing factor to the higher baseline levels leading to the faster growth of adolescent procrastination. The model identified three distinct trajectories of low-increasing [including 2,057 participants (49.5%)], moderate-stable [including 1,879 participants (45.2%)], and high-decreasing procrastination [including 220 participants (5.3%)]. More daily leisure screen-time, lower frequency of exercise weekly, and dissatisfaction with distance learning were the top three risk factors for moderate-stable and high-decreasing procrastination compared to low-increasing procrastination. Adolescents with mothers with a higher level of education were more liable to be high-decreasing procrastination than moderate-stable procrastination.ConclusionThe proportion and overall trends of adolescent procrastination increased with the pandemic. The categories of procrastination among adolescents during that time period were probed. Also, the study further clarified the risk factors for severe and moderate procrastination relative to no procrastination. Thus, effective procrastination prevention and intervention strategies need to be implemented to support adolescents, particularly those at risk.
Study protocol for a randomized trial of a supportive care mobile application to improve symptoms, coping, and quality of life in patients with advanced non-small cell lung cancer
Authors: Waldman Lauren P. , Centracchio Joely A. , Jacobs Jamie M. , Petrillo Laura A. , El-Jawahri Areej R. , Temel Jennifer S. , Greer Joseph A. 
Published: June 2023

Patients with advanced non-small cell lung cancer (NSCLC) often experience burdensome symptoms, emotional distress, and poor quality of life (QOL). While national guidelines recommend early palliative care to address these supportive care needs, most patients with advanced NSCLC lack access to such comprehensive care. Our aim in the current study is to test a novel model of palliative care delivery and use of innovative technology to evaluate the feasibility, acceptability, and preliminary efficacy of a supportive care mobile application (app) for improving symptom management and adaptive coping in patients with advanced NSCLC. We will enroll 120 patients with unresectable Stage III or IV NSCLC diagnosed within the past 12 weeks receiving care with palliative intent at a major academic comprehensive cancer center and its community affiliates. The study will take place in two phases, the first of which will be dedicated to adapting an evidence-based, early palliative care treatment guide and prior supportive care mobile app intervention to address the specific symptom management and coping needs of patients with advanced NSCLC. The second phase of the study will be a two-group, randomized controlled trial. Study patients will complete baseline self-report measures of symptoms, mood, coping skills, and QOL, after which they will be randomized to receive either the mobile app intervention combined with usual oncology care or usual oncology care alone. Intervention patients will use a tablet computer to self-administer the mobile app, which consists of six modules that teach evidence-based skills for managing burdensome symptoms and coping effectively with advanced cancer and its treatment. At 12 weeks follow up, patients in both groups will repeat the same self-report measures. We will use descriptive statistics to determine feasibility metrics of enrollment and retention rates. For secondary self-report measures, we will use linear regression controlling for baseline values. The results of the present study will contribute to a growing body of evidence regarding the supportive care needs of patients with advanced cancer and will have implications for how best to use innovative technology to widely disseminate comprehensive supportive care services to all patients who may benefit.Clinical Trial Registration: [www.ClinicalTrials.gov], identifier[NCT04629300].