bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impact of Amplification Efficiency Approaches on Telomere Length Measurement via Quantitative-Polymerase Chain Reaction
Authors: Hastings Waylon J. , Eisenberg Dan T. A. , Shalev Idan 
Published: September 2021

Background: Precise determination of amplification efficiency is critical for reliable conversion of within-sample changes in fluorescence occurring on a logarithmic scale to between-sample differences in DNA content occurring on a linear scale. This endeavor is especially challenging for the telomere length (TL) quantitative-PCR (qPCR) assay, where amplification efficiency can vary between reactions targeting telomeric repeats (T) and those targeting a single-copy gene (S) to calculate TL as the T/S ratio.Methods: We compared seven different approaches toward estimating amplification efficiency, including the standard-curve method utilized by the qPCR instrument software, and alternative approaches which estimate efficiency on a reaction-by-reaction basis using the stand-alone program LinRegPCR. After calculating T/S ratios using efficiency estimates from each approach (N = 363), we tested their relative performance on metrics of assay precision and correlates of external validity including chronological age (age range = 1–72 years), across tissues within-person (leukocyte-buccal), and between parents and offspring.Results: Estimated amplification efficiency for telomere reactions was significantly lower than estimates for single-copy gene reactions. Efficiency estimates for both reaction sets were significantly higher when estimated with the standard-curve method utilized by the qPCR instrument relative to estimates reconstructed during the log-linear phase with LinRegPCR. While estimates of single-copy gene efficiency reconstructed using LinRegPCR measured within 90% of perfect exponential doubling (E = 1.92), estimates generated using the standard-curve method were inflated beyond 100% (E = 2.10–2.12), indicating poor fidelity. Despite differences in raw value, TL measurements calculated with LinRegPCR efficiency estimates exhibited similar relationships with external validity correlates to measurements generated using the qPCR instrument software.Conclusion: Since methods to estimate amplification efficiency can vary across qPCR instruments, we suggest that future analyses empirically consider external methods of efficiency calculations such as LinRegPCR, and that already generated data be re-analyzed to glean possible improvements.
Recognition of Tumor-Associated Antigens and Immune Subtypes in Glioma for mRNA Vaccine Development
Authors: Ma Shuai , Ba Yixu , Ji Hang , Wang Fang , Du Jianyang , Hu Shaoshan 
Published: September 2021

BackgroundAlthough mRNA vaccines have been efficient for combating a variety of tumors, their effectiveness against glioma remains unclear. There is growing evidence that immunophenotyping can reflect the comprehensive immune status and microenvironment of the tumor, which correlates closely with treatment response and vaccination potency. The purpose of this research was to screen for effective antigens in glioma that could be used for developing mRNA vaccines and to further differentiate the immune subtypes of glioma to create an selection criteria for suitable patients for vaccination.MethodsGene expression profiles and clinical data of 698 glioma samples were extracted from The Cancer Genome Atlas, and RNA_seq data of 1018 glioma samples was gathered from Chinese Glioma Genome Atlas. Gene Expression Profiling Interactive Analysis was used to determine differential expression genes and prognostic markers, cBioPortal software was used to verify gene alterations, and Tumor Immune Estimation Resource was used to investigate the relationships among genes and immune infiltrating cells. Consistency clustering was applied for consistent matrix construction and data aggregation, Gene oncology enrichment was performed for functional annotation, and a graph learning-based dimensionality reduction method was applied to describe the subtypes of immunity.ResultsFour overexpressed and mutated tumor antigens associated with poor prognosis and infiltration of antigen presenting cells were identified in glioma, including TP53, IDH1, C3, and TCF12. Besides, four immune subtypes of glioma (IS1-IS4) and 10 immune gene modules were identified consistently in the TCGA data. The immune subtypes had diverse molecular, cellular, and clinical features. IS1 and IS4 displayed an immune-activating phenotype and were associated with worse survival than the other two subtypes, while IS2 and IS3 had lower levels of tumor immune infiltration. Immunogenic cell death regulators and immune checkpoints were also diversely expressed in the four immune subtypes.ConclusionTP53, IDH1, C3, and TCF12 are effective antigens for the development of anti-glioma mRNA vaccines. We found four stable and repeatable immune subtypes of human glioma, the classification of the immune subtypes of glioma may play a crucial role in the predicting mRNA vaccine outcome.
A Machine Learning Model to Predict the Triple Negative Breast Cancer Immune Subtype
Authors: Chen Zihao , Wang Maoli , De Wilde Rudy Leon , Feng Ruifa , Su Mingqiang , Torres-de la Roche Luz Angela , Shi Wenjie 
Published: September 2021

BackgroundImmune checkpoint blockade (ICB) has been approved for the treatment of triple-negative breast cancer (TNBC), since it significantly improved the progression-free survival (PFS). However, only about 10% of TNBC patients could achieve the complete response (CR) to ICB because of the low response rate and potential adverse reactions to ICB.MethodsOpen datasets from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) were downloaded to perform an unsupervised clustering analysis to identify the immune subtype according to the expression profiles. The prognosis, enriched pathways, and the ICB indicators were compared between immune subtypes. Afterward, samples from the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) dataset were used to validate the correlation of immune subtype with prognosis. Data from patients who received ICB were selected to validate the correlation of the immune subtype with ICB response. Machine learning models were used to build a visual web server to predict the immune subtype of TNBC patients requiring ICB.ResultsA total of eight open datasets including 931 TNBC samples were used for the unsupervised clustering. Two novel immune subtypes (referred to as S1 and S2) were identified among TNBC patients. Compared with S2, S1 was associated with higher immune scores, higher levels of immune cells, and a better prognosis for immunotherapy. In the validation dataset, subtype 1 samples had a better prognosis than sub type 2 samples, no matter in overall survival (OS) (p = 0.00036) or relapse-free survival (RFS) (p = 0.0022). Bioinformatics analysis identified 11 hub genes (LCK, IL2RG, CD3G, STAT1, CD247, IL2RB, CD3D, IRF1, OAS2, IRF4, and IFNG) related to the immune subtype. A robust machine learning model based on random forest algorithm was established by 11 hub genes, and it performed reasonably well with area Under the Curve of the receiver operating characteristic (AUC) values = 0.76. An open and free web server based on the random forest model, named as triple-negative breast cancer immune subtype (TNBCIS), was developed and is available from https://immunotypes.shinyapps.io/TNBCIS/.ConclusionTNBC open datasets allowed us to stratify samples into distinct immunotherapy response subgroups according to gene expression profiles. Based on two novel subtypes, candidates for ICB with a higher response rate and better prognosis could be selected by using the free visual online web server that we designed.
Disrupted Dynamic Functional Connectivity in Distinguishing Subjective Cognitive Decline and Amnestic Mild Cognitive Impairment Based on the Triple-Network Model
Authors: Xue Chen , Qi Wenzhang , Yuan Qianqian , Hu Guanjie , Ge Honglin , Rao Jiang , Xiao Chaoyong , Chen Jiu 
Published: September 2021

Background: Subjective cognitive decline and amnestic mild cognitive impairment (aMCI) were widely thought to be preclinical AD spectrum disorders, characterized by aberrant functional connectivity (FC) within the triple networks of the default mode network (DMN), the salience network (SN), and the executive control network (ECN). Dynamic FC (DFC) analysis can capture temporal fluctuations in brain FC during the scan, which static FC analysis cannot. The purpose of the current study was to explore the changes in dynamic FC within the triple networks of the preclinical AD spectrum and further reveal their potential diagnostic value in diagnosing preclinical AD spectrum disorders.Methods: We collected resting-state functional magnetic resonance imaging data from 44 patients with subjective cognitive decline (SCD), 49 with aMCI, and 58 healthy controls (HCs). DFC analysis based on the sliding time-window correlation method was used to analyze DFC variability within the triple networks in the three groups. Then, correlation analysis was conducted to reveal the relationship between altered DFC variability within the triple networks and a decline in cognitive function. Furthermore, logistic regression analysis was used to assess the diagnostic accuracy of altered DFC variability within the triple networks in patients with SCD and aMCI.Results: Compared with the HC group, the groups with SCD and aMCI both showed altered DFC variability within the triple networks. DFC variability in the right middle temporal gyrus and left inferior frontal gyrus (IFG) within the ECN were significantly different between patients with SCD and aMCI. Moreover, the altered DFC variability in the left IFG within the ECN was obviously associated with a decline in episodic memory and executive function. The logistic regression analysis showed that multivariable analysis had high sensitivity and specificity for diagnosing SCD and aMCI.Conclusions: Subjective cognitive decline and aMCI showed varying degrees of change in DFC variability within the triple networks and altered DFC variability within the ECN involved episodic memory and executive function. More importantly, altered DFC variability and the triple-network model proved to be important biomarkers for diagnosing and identifying patients with preclinical AD spectrum disorders.
Bleeding Risk Following Stereotactic Body Radiation Therapy for Localized Prostate Cancer in Men on Baseline Anticoagulant or Antiplatelet Therapy
Authors: Pepin Abigail , Shah Sarthak , Pernia Monica , Lei Siyuan , Ayoob Marilyn , Danner Malika , Yung Thomas , Collins Brian T. , Suy Simeng , Aghdam Nima , Collins Sean P. 
Published: September 2021

PurposePatients on anticoagulant/antiplatelet medications are at a high risk of bleeding following external beam radiation therapy for localized prostate cancer. SBRT may reduce the bleeding risk by decreasing the volume of bladder/rectum receiving high doses. This retrospective study sought to evaluate the rates of hematuria and hematochezia following SBRT in these patients.MethodsLocalized prostate cancer patients treated with SBRT from 2007 to 2017 on at least one anticoagulant/antiplatelet at baseline were included. The minimum follow-up was 3 years with a median follow-up of 72 months. Patients who had a rectal spacer placed prior to SBRT were excluded. Radiotherapy was delivered in 5 fractions to a dose of 35 Gy or 36.25 Gy utilizing the CyberKnife system. Hematuria and hematochezia were prospectively assessed before and after treatment using the Expanded Prostate Cancer Index Composite (EPIC-26). Toxicities were scored using the CTCAE v4. Cystoscopy and colonoscopy findings were retrospectively reviewed.ResultsForty-four men with a median age of 72 years with a history of taking at least one anticoagulant and/or antiplatelet medication received SBRT. Warfarin (46%), clopidogrel (34%) and rivaroxaban (9%) were the most common medications. Overall, 18.2% experienced hematuria with a median time of 10.5 months post-SBRT. Altogether, 38.6% experienced hematochezia with a median time of 6 months post-SBRT. ≥ Grade 2 hematuria and hematochezia occurred in 4.6% and 2.5%, respectively. One patient required bladder neck fulguration and one patient underwent rectal cauterization for multiple non-confluent telangiectasia. There were no grade 4 or 5 toxicities. Cystoscopy revealed bladder cancer (40%) and benign prostatic bleeding (40%) as the most common hematuria etiology. Colonoscopy demonstrated hemorrhoids (54.5%) and radiation proctitis (9.1%) as the main causes of hematochezia. There was no significant change from the mean baseline EPIC-26 hematuria and hematochezia scores at any point during follow up.ConclusionIn patients with baseline anticoagulant usage, moderate dose prostate SBRT was well tolerated without rectal spacing. High grade bleeding toxicities were uncommon and resolved with time. Baseline anticoagulation usage should not be considered a contraindication to prostate SBRT.
Preparation of Near-Infrared/Photoacoustic Dual-Mode Imaging and Photothermal/Chemo Synergistic Theranostic Nanoparticles and Their Imaging and Treating of Hepatic Carcinoma
Authors: Zhou Yun , Lin Bixia , Li Kai , Zhao Yufeng , Sun Zhuo , He Chenchen , Jha Rajiv Kumar 
Published: September 2021

At present, the clinical diagnosis of and treatment methods for hepatic carcinoma still fail to fully meet the needs of patients. The integrated theranostic system, in which functional materials are used to load different active molecules, created a new developmental direction for the combination treatment of hepatic carcinoma, realizing the synchronization of diagnosis and treatment. In this study, polydopamine (PDA), which has the functions of self-assembly, encapsulation, photothermal conversion, and photoacoustic interaction, was used as the carrier material. The IR780, a near-infrared fluorescence imaging (NIFI), photoacoustic imaging (PAI), and photothermal therapy (PTT) agent, and paclitaxel (PTX), a broad-spectrum chemotherapy drug, were selected to build the NIF/PA dual-mode imaging and PTT/chemo synergistic theranostic nanoparticles (DIST NPs). The DIST NPs have a 103.4 ± 13.3 nm particle size, a weak negative charge on the surface, good colloidal stability, slow and controlled drug release, and high photothermal conversion ability. The experiments results showed that the DIST NPs have a long circulation in vivo, high bioavailability, high biocompatibility, and low effective dose. DIST NPs showed an excellent NIFI/PAI dual-mode imaging and significant synergistic antitumor effect in hepatic carcinoma models. DIST NPs met the initial design requirements. A set of fast and low-cost preparation methods was established. This study provides an experimental basis for the development of new clinical theranostic methods for hepatic carcinoma.
Parent-Child Assessment of Strengths and Difficulties of German Children and Adolescents Born With Esophageal Atresia
Authors: Witt Stefanie , Dingemann Jens , Dellenmark-Blom Michaela , Quitmann Julia 
Published: September 2021

Introduction/Aim: Children and adolescents with a chronic somatic disease have a higher risk of developing psychological disorders than healthy peers. Therefore, we aim to investigate internalizing and behavioral problems in pediatric patients with esophageal atresia (EA) and compare this sample with German reference values using both childrens' self-reports and parents' proxy reports.Methods: The present cross-sectional study is part of the German-Swedish EA-QOL study developing a condition-specific instrument to assess Health-related Quality of Life in children and adolescents born with EA from both self and proxy perspectives. The current analyses use data from the German sample collected within the field test phase. Participants were enrolled from the Medical School Hannover and “Auf der Bult” Children's Hospital, Hannover. The cooperating clinicians provided the medical records while socio-demographic information was collected through the parent-report within the questionnaires. We used the Strengths and Difficulties Questionnaire (SDQ) to measure internalizing and behavioral problems of children and adolescents born with EA ranging from 2 to 18 years.Results: A total of 51 families participated in the field test phase. Eighty-eight parent reports and 22 child reports were included in the analyses. While the parents' perspective from the SDQ leads to a higher percentage of abnormal or borderline behavior, there is no difference to the reference group from the children's perspective.Conclusion: Incorporating routine psychological assessment into pediatric health care can help improve understanding of the burden of illness, examine treatment outcomes, assess the quality of care, and tailor interventions to meet patient and parent needs. Involving the whole family can help develop appropriate and functional coping strategies. From our point of view, it is necessary to address parental needs and concerns as well in order to provide the best possible holistic development in the family system. The family is the basis for the children's successful development, especially for children with special health care needs.
The Impact of Family Income on Body Mass Index and Self-Rated Health of Illiterate and Non-illiterate Rural Elderly in China: Evidence From a Fixed Effect Approach
Authors: Xin Yu , Ren Xiaohui 
Published: September 2021

Background: Rural communities worldwide are experiencing the most significant levels of aging. Most rural elderly have no stable pension, and leading family income plays an indispensable role in the life security of rural elderly. This study aims to investigate whether the association between annual family income per capita and body mass index (BMI) and self-rated health (SRH) in rural elderly is moderated by education during fast economic development.Methods: We chose the fixed-effects model to analyze the impact of the annual family income per capita change on BMI and SRH based on a large, nationally representative longitudinal dataset of rural respondents aged above 60 of the China Family Panel Studies (CFPS) from 2010 to 2018.Results: Six hundred and fifty-eight were eligible for inclusion in our analysis in CFPS. The median age of participants was 65 years in 2010, and 379 (57.60%) participants were male. Self-rated health increased with higher the logarithmized family income per capita among the rural illiterate elderly (β = 0.0770; 95% CI = 0.0065–0.1473). Body mass index increased with higher the logarithmized family income per capita among the rural elderly (β = 0.1614, 95% CI: 0.0325–0.2903), and it was more evident among the illiterate elderly (β = 0.2462, 95% CI: 0.05519–0.4372).Conclusion: Family income has an impact on BMI and SRH moderated by education level among rural elderly in China. These results contribute to developing more targeted strategies in the context of a developing country. In addition, it also reminds us to consider the differences in the educational level of the elderly in rural areas when examining the relationship between family income and health.
Conservation of Britain’s biodiversity: distribution and status of the Welsh endemic Hieracium apheles, Hepste hawkweed (Asteraceae)
Authors: Rich Timothy C. G. 
Published: September 2021

The conservation status of Hieracium apheles P. D. Sell (Asteraceae), Hepste hawkweed has been assessed. A lectotype for the basionym H. septentrionale Arv.-Touv. var. simplex Ley has been designated. It is a rare endemic restricted to the Hepste Glen in the Brecon Beacons (v.c. 42), Wales. Only one population of five plants is known it is assessed as ‘Critically Endangered’ under IUCN (2001) threat criteria.
SCIENTIFIC BASIS OF THE EDUCATIONAL DIALOGICAL INTERACTION IN THE HIGHER EDUCATION
Authors: Semenovska Larysa 
Published: September 2021

Based on analysis of the fundamental philosophical (M. Bakhtin, V. Kemerov,C. Frank et al.), psychological (V. Zinchenko, B. Meshcheryakov, A. Leontiev et al.) and pedagogical (I. Kolesnikova, O. Sydelkovskyy, E. Fedotova et al.) works found that the scientific basis for understanding the basics of interaction is a statement about the spiritual nature of man, the dialogical mode of existence in historical and cultural- educational and educational space. Proved that human interaction with the world and other people allows her to not only update the internal capacity, but also fill it structurally, meaningful, valuable and semantic aspects.The study found that immersion in this process allows comparison of thoughts, feelings and actions of the individual with their reflection in the minds of others, being the basis of its self-knowledge, self-fulfillment. Providing dialogic training interaction is extremely important for personal development and is the essence of educational activities. In the context of the study, this phenomenon is treated as a two-way process – learning and teaching that combines teacher and student as people made for a common goal, but are not identical in their social role, knowledge, experience, etc.Investigation of the nature and specifics of pedagogical interaction shows that it is a variant of social interaction, has its main features, the characteristics and at the same time realizing in the process of implementation specific, but very important for the formation of individual existence and purpose: to promote self-identity. Specificity dialogic educational interaction between teacher and students is that during the implementation of its self-study subjects interconnected phenomenon occurs largely contribute to this kind of phenomena and effects that arise. At the same time they can transform the content of educational interaction with the simple exchange of «exchange transformations» that gives new incentives for personal growth of participants this kind of contact. Proved that dialogic interaction study can be carried out only in the system of inter subjective relations. All this predetermines the presence of a specific inter subjective space, which intersect individual meanings and values. In the pedagogical process this space does not arises by itself, it's result of forming of the efforts of the teacher and student, adult and child, and so on.
ART OF PEDAGOGICAL ACTION IN THE FORMATION OF TEACHER’S CREATIVE INDIVIDUALITY
Authors: Adamiw Julia 
Published: September 2021

This article presents the essence of the concept of «creative individuality». It is proved that among educators confirms the idea that not only the identity of the teacher, his attitude, willingness and ability to act creatively is now the decisive factors of the institution, but for the education of the younger generation must be magnitude, brightness and uniqueness of each teacher’s personality, the autonomy of his actions. Based on the pedagogical and psychological theories, the development of teacher’s creative individuality is the process of his unique identity, based on positive quantitative and qualitative changes in the levels of formation components of his creative individuality; turning him into a distinctive, unique, self-effective person capable to realize himself fully in educational activities. It is noted that creative individuality of the teacher is the essential feature of his professional and pedagogical skills that characterizes the level of mastery of his educational process and art of pedagogical action. Nowadays when the world is rapidly changing, the problem of the professional’s creative personality becomes more urgent. A special role in this process belongs to vocational school teacher who makes impact on his students and creates a generation of modern professionals: creative, responsible, skilled, with innovative style of thinking and their own professional style.