bluuebunny/crossref_metadata_2025_split huggingface dataset:
Using online search activity for earlier detection of gynaecological malignancy
Authors: Barcroft Jennifer F , Yom-Tov Elad , Lampos Vasileios , Ellis Laura , Guzman David , Ponce-López Victor , Bourne Tom , Cox Ingemar , Saso Srdjan 
Published: April 2023

Abstract

Despite major advances in precision treatments and new biomarkers, only 55% of UK cancers are detected at an early stage. Ovarian cancer (OC) remains the most lethal gynaecological malignancy with survival, quality of life, and fertility implications, as most women present with advanced stage disease. Endometrial cancer (EC) is the most common gynaecological malignancy, with an incidence that is rising exponentially. Unfortunately, an effective screening program does not exist for EC and OC, to facilitate early detection.

Conventional healthcare cannot facilitate real-time monitoring of an individual’s health risks. However, digital footprints (e.g. online search activity) with their temporally dense nature could enable regular ‘health’ monitoring. The utilisation of online search data to identify those at risk of specific diseases has been suggested in other studies but were based on individuals with a proxy diagnosis, inferred through online search patterns, rather than confirmed clinical diagnosis.

We evaluated the use of online search data to detect gynaecological cancer in individuals with a known confirmed diagnosis. There was a difference in online search patterns between those with benign and malignant diagnoses, as early as 360 days prior to primary care (GP) referral with a suspected cancer. A classification model based on online search data achieved its highest AUC (0.82) using data 60 days before the GP referral, in individuals who routinely performed health-related online search queries. Our experiments indicate that online search data could provide individualised gynaecological cancer risk profiles, which are not reliant on individuals recognising key symptom patterns. Online search data could provide an accessible disease screening tool to facilitate the earlier detection of gynaecological malignancy, complementing currently established approaches. More generally, we advocate that online search data could provide early insights into numerous conditions including a range of cancers.
A Joint Frequency Space Design Approach for Efficient Planar Frequency Diverse Arrays
Authors: hasheminasab Maryam , cheldavi ahmed , kishk Ahmed 
Published: April 2023

Abstract
Antenna arrays benefit from spatial diversity, which enables the control of the pattern specifications in space. Adding frequency diversity to arrays provides an opportunity to control the beams in the Space-Time domain. Contrary to the conventional arrays, the added frequency diversity in the Frequency Diverse Arrays (FDA) leads to time-variant and range-dependent patterns. The time variation of the pattern affects both steering and auto-scanning applications. The array factor depends coherently on the frequency and spatial distributions of elements, in the same way, the spatial and time behavior of the FDA’s pattern is correlated. Due to this space-frequency coherency, an adjoint spatial-frequency design algorithm is the best approach for controlling the array's spatial and time behaviors. Although Due to the complexity of the array factor formulations in the FDA, the frequency and spatial distribution of the elements has been separately designed. This study proposes an algorithm to concurrently, allocate the location and frequency of the elements for a desired pattern. First, using some symmetry, a straightforward formulation for the array factor is obtained and used to design a symmetrical FDA for a stable and periodic scanning beam. Second, by analyzing the formulations, two important design parameters and some crucial design criteria of the FDA pattern for scanning applications are suggested, and using these parameters a designing algorithm is extracted. The novelty of the proposed approach is the simultaneous design of the location and frequency of the elements in the space-frequency plane, which results in meeting the time and spatial requirement of the pattern. Using this approach, two different planar arrays are designed, and their results are compared with those of other planar configurations. This study paves the way for a new approach to designing FDAs.
The factors affecting the HRQOL of kidney transplant recipients in the land of Gross National Happiness, Bhutan - A cross-sectional study.
Authors: Dorji Choki , Tobgay Tashi , Na-Bangchang Kesara 
Published: April 2023

Abstract
Background
Globally the prevalence of renal failure is on the rise. Kidney transplantation is the preferred and most affordable treatment for renal failure with improved health-related quality of life (HRQOL) compared to dialysis. In Bhutan, due to the lack of kidney transplant facilities in the country, patients are frequently referred to a neighbouring country. The HRQOL in kidney transplants in Bhutan has never been evaluated. The objective of the study was to investigate the relationships between different factors and HRQOL in kidney transplant recipients.
Methods
An observational study was conducted from January to July 2022. A kidney transplant recipient who underwent surgery until December 2021 and came for therapeutic drug monitoring (TDM) was recruited. Data on HRQOL were collected by face-to-face interviews using a structured questionnaire. A descriptive analysis was used to describe sociodemographic characteristics and HRQOL. Factors affecting HRQOL were analysed using Mann‒Whitney U and Kruskal‒Wallis tests. Linear regression was used to assess the link between factors and HRQOL.
Results
One hundred kidney transplant recipients were recruited in this study. Of these, 25 of them did not have a formal education, and 48 are employed. 53.0 % of kidney failures were due to hypertension, and 62 of them had dialysis for less than one year. Overall, physical symptoms contributed to poor HRQOL with a mean ± SD score of 4.9 ± (1.0) and the appearance dimension of better HRQOL at a mean ± SD of 4.0 ± (1.3). Unemployment was significantly associated with poor physical symptoms, uncertainty/fear and emotional dimension. Physical symptoms and age were found to be positive and statistically significant (r = .321, P<0.001).
Factors such as age, hematocrit and BMI are linked with physical symptoms, fatigue and appearance.
Conclusion
Hypertension is the leading cause of kidney failure in Bhutan. The physical symptoms are associated with poor HRQOL among transplant recipients affecting mostly the unemployed. Recipients who are employed and the related donor were found to have better HRQOL.
Consistency Between Student Self-Assessment and Faculty Assessment on Professional Behaviors Following a Patient Simulation Experience
Authors: Pottorf Ofra , Ward Jason 
Published: April 2023

Abstract
Purpose: The purpose of this study was to investigate if students’ perceived abilities on professional behavior performance were calibrated following participation in a patient simulated experience when the patient simulation experience was structured to mimic the natural environment where these skills are expected to be exhibited.
Methods: Quantitative statistical analysis compared two groups’ posttest assessment scores to determine if there was a consistency in students’ perceived abilities on 10 professional behaviors identified on the professional behaviors assessment instrument, following participation in a patient simulation experience. The sample of 50 participants were recruited who were matriculated in a post graduate healthcare program. Pearson’s correlation coefficient was used to analyze correlational relationships between the group scores.
Results: This study found a Pearson’s correlation of .884 indicating a strong positive relationship existed between students’ perceived abilities when self-assessing a set of 10 professional behaviors following a structured patient simulation experience and their abilities as assessed by their instructor.
Conclusions: This study found a strong positive correlation indicating consistency between students’ self-reported abilities and their abilities as reported by a faculty-rater, indicating that some degree of calibration took place in students’ perceived abilities after participation in a patient simulation experience.
High-dimensional deconstruction of pancreatic cancer identifies tumor microenvironmental and developmental stemness features that predict survival
Authors: Chaudhuri Aadel , Storrs Erik , Chati Prathamesh , Usmani Abul , Sloan Ian , Krasnick Bradley , Babbra Ramandeep Kaur , Harris Peter , Qaium Faridi , Chatterjee Deyali , Wetzel Chris , Goedegebuure Peter , Hollander Thomas , Anthony Hephzibah , Ponce Jennifer , Khaliq Ateeq , Badiyan Shahed , Kim Hyun , DeNardo David , Lang Gabriel , Cosgrove Natalie , Kushnir Vladimir , Early Dayna , Masood Ashiq , Lim Kian-Huat , Hawkins William , Ding Li , Fields Ryan , Das Koushik 
Published: April 2023

Abstract
Numerous cell states are known to comprise the pancreatic ductal adenocarcinoma (PDAC) tumor microenvironment (TME). However, the developmental stemness and co-occurrence of these cell states remain poorly defined. Here, we performed single-cell RNA sequencing (scRNA-seq) on a cohort of treatment-naive PDAC time-of-diagnosis endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) samples (n=25) and surgical resections (n=6), which were then combined with publicly available samples to increase statistical power (n=80). Following annotation into 25 distinct cell states, cells were scored for developmental stemness and a customized version of the Ecotyper tool was used to identify communities of co-occurring cell states in bulk RNA-seq samples (n=268). We discovered a tumor microenvironmental community comprised of aggressive basal-like malignant cells, tumor-promoting SPP1+ macrophages, and myofibroblastic cancer-associated fibroblasts associated with especially poor prognosis. We also found a developmental stemness continuum with implications for survival that is present in both malignant cells and cancer-associated fibroblasts (CAFs). We further demonstrated that high-dimensional analyses predictive of survival are feasible using standard-of-care, time-of-diagnosis EUS-FNB specimens. In summary, we identified novel tumor microenvironmental and developmental stemness characteristics from a high-dimensional gene expression analysis of PDAC using human tissue specimens including time-of-diagnosis EUS-FNB samples. These reveal new connections between tumor microenvironmental composition, CAF and malignant cell stemness, and patient survival that could lead to better upfront risk stratification and more personalized upfront clinical decision-making.
Genetic diversification of allohexaploid Brassica hybrids (AABBCC) using fertile octoploid with excessive C genome set
Authors: Shinke Teppei , Yamazaki Akira , Kudo Hiroshi , Hosokawa Munetaka 
Published: April 2023

Abstract
Even if somatic hybrids are produced, they are usually the end products and are difficult to develop as an innovative crop. In this study, we used somatic hybrids of Brassica juncea (AABB) and B. oleracea (CC) as model cases for the genetic diversification of the somatic hybrids. One cell of ‘Takana’ (B. juncea) and two cells of ‘Snow Crown’ (B. oleracea) were fused to create several somatic hybrids with excessive C genomes, AABBCCCC. Using AABBCCCC somatic hybrids as mother plants and crossbreeding with ‘Takana’, the AABBCC progenies were generated. When these AABBCC progenies were self-fertilized, and flow cytometric analysis was performed on the next generations, differences in the relative amount of genome size variation were observed, depending on the different individuals of AABBCCCC. In other words, somatic hybrid generations may be involved in the genetic stability/instability of generations produced by crossbreeding. Next, to obtain genetic diversification of the trigenomic hexaploid, different cultivars of B. juncea were crossed with AABBCCCC, resulting in a series of later generations with diverse AABBCC genomes. Genetic diversity can be further expanded by crossbreeding plants with different AABBCC genome sets. Although genetic stability is necessary to ensure in the later generations, the results obtained in this study show that the use of somatic hybrids with excess genomes is an effective strategy for creating innovative crops.
GCSF, A Diagnostic Marker and Potential Drug Target Candidate in Glioblastoma
Authors: Ahsan Hina , Asghar Muhammad , Malik Shaukat Iqbal 
Published: April 2023

Abstract
Glioblastoma multiforme (GBM) is the most prevalent brain malignancy in adults. However, molecular mechanisms, which leads to GBM have not been completely elucidated. Granulocyte colony-stimulating factor (GCSF), Granulocyte colony-stimulating factor receptor GCSFR, and Signal transducers and activators of transcription 3 (STAT3) have been involved in the occurrence and development of various cancers, but their role in GBM is little known. Herein, we have investigated the gene and protein expression of GCSF, GCSFR, and STAT3 in 21 tissue biopsy samples and also in tumor associated normal tissue (TANT) samples derived from glioblastoma patients, which revealed significantly differential expression of these genes. To validate our findings, we performed a comprehensive integrated analysis of transcriptomic and proteomic profiling of respective genes by retrieving Glioblastoma multiforme RNA-sequence data from Genome Atlas Databases. GO and KEGG analysis revealed enrichment in disease-related pathways, such as JAK/STAT pathway activation, which were associated with GBM progression. We further performed computational docking analysis of potential drug candidate Nisin against GCSF, and the results were validated in vitro through cytotoxic activity assay using a human glioblastoma cell line SF-767 in a dose-dependent manner. Our comprehensive analysis reveal that GCSF augments glioma progression, and its blockade with anticancer bacteriocin peptide Nisin can potentially inhibit the growth and metastasis of glioblastoma.
The Effect of pestle needle on Lumbar Disc Herniation: Study Protocol for a Randomized Controlled Trial
Authors: Liu Xuhao , Liao Tiannan , Zhong Lei , Dong Yuanwei , Zhang Di , Shen Yuquan , Fu Ping , Yuan Lei , Yu Yang , Fan Xiaohong 
Published: April 2023

Abstract
Background：Lumbar disc herniation (LDH) is a common and frequent disease in orthopedics. It is caused by degenerative changes of the lumbar spine and compression of the lumbar nerves, with the main clinical manifestation being painful involvement of the lumbar region and the legs，which in severe cases affects the patient's quality of life. The disease is treated in a variety of ways with varying degrees of efficacy, LDH is mainly treated conservatively with oral medication or external therapy of Traditional Chinese medicine (TCM) for mild cases, while surgery is required for severe cases. LDH surgical treatment is effective, but there are still some patients whose symptoms are difficult to improve after surgery and who are not suitable for surgical treatment. Pestle needle therapy is a unique external therapy of TCM method, which is non-invasive, non-painful, not easily infected, easy to operate, and easy for patients to accept. This study aimed to design a randomized controlled trial (RCT) to explore the effectiveness and safety of pestle needle in the treatment of LDH.
Methods：Sixty patients will be enrolled and randomly divided into one of two groups: the pestle needle group and the celecoxib group. The pestle needle group will be treated with pestle needle at Yaoyangguan bazhen, Heche-mingqiang section, BL23, BL25, GB30, BL40, BL57, BL60 for 30 minutes. 5 days is a course of treatment, with an interval of 2 days between courses, a total of 3 courses of treatment. The pestle needle manipulation is performed to the extent that the skin is flushed during the treatment. The celecoxib group participants will take one celecoxib capsule once a day for the duration of the study period. The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) score, Visual Analog Scale（VAS）score and Oswestry Disability Index（ODI）score were used as treatment outcome assessment indicators, while adverse events (AEs) were recorded. Patients were evaluated for efficacy at baseline, at the end of each course of treatment.
Discussion: This study will determine whether pestle needle is more effective and safer than celecoxib in the treatment of patients with LDH.
Trial registration The trial has been registered with the Chinese Clinical Trial Register (ChiCTR) under the Registration March ChiCTR2200057684.
Identification of F7 as a Hub Regulator in Hypertrophic Cardiomyopathy and Potential ceRNA Regulatory Network Based on Weighted Gene Co-expression Network Analysis
Authors: Pei Chong-Zhe , Meng Xinmin , dong yuxin , Sun Dongdong , Wu Xianming , Song Ningning , Zhou Xin , Yang Qing 
Published: April 2023

Abstract
Background. We identified a regulatory competing endogenous RNA (ceRNA) network and a hub gene for hypertrophic cardiomyopathy (HCM).
Methods. We obtained microarray datasets of HCM tissue from NCBI Gene Expression Omnibus (GEO) and identified differentially expressed genes using the R package “limma.” Subsequently, differentially expressed long non-coding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs were matched using online databases. We identified relationships between key modules and HCM using weighted gene co-expression network analysis, whereas protein–protein interaction networks were constructed in STRING. To verify hub genes, we performed a gene set enrichment analysis. Real-time quantitative PCR and western blotting were performed to examine hub-gene expression in a mouse model of Ang-II infusion-induced cardiac hypertrophy.
Results. We identified 271 upregulated and 368 downregulated lncRNAs in the GSE68316 dataset, along with 8 upregulated and 13 downregulated miRNAs in the GSE36946 dataset. We constructed a lncRNA–miRNA–mRNA ceRNA network in HCM using 6 downregulated lncRNAs, 1 upregulated miRNA, and 13 downregulated mRNAs. Another lncRNA–miRNA–mRNA ceRNA network in HCM was constructed with 15 upregulated lncRNAs, 1 downregulated miRNA, and 79 upregulated mRNAs. The results of WGCNA showed that black and turquoise modules were significantly related to HCM. Through Gene Ontology (GO) analysis, F7 was identified as a hub gene with network function enriched in neuroactive ligand–receptor interaction, cytokine–cytokine receptor interaction, and actin cytoskeleton regulation.
Conclusions. This study reveals a potential molecular regulatory mechanism that could improve HCM diagnosis and treatment. Furthermore, the hub gene F7 might play an important role in HCM progression and be a valuable biomarker.
Construction of a prognostic nomogram for early-onset colorectal cancer patients ： a population-based study in the SEER database and China
Authors: Chang Zewen , Xiong Huan , Wang Jiaqi , Li Xingyuan , Zhang Hao , Liu Yunxiao , Yuan Ziming , Hu Hanqing , Tang Qingchao 
Published: April 2023

Abstract
Background The prognosis of early-onset colorectal cancer (EOCRC) remains largely constrained by clinical heterogeneity. The aim of this paper was to construct a targeted prognostic nomogram combining multi-indicator to individually predict overall survival (OS) for EOCRC.Methods 6893 patients from the SEER database (SEER training set: n = 3447; SEER validation set: n = 3446) and 271 patients from the Second Affiliated Hospital of Harbin Medical University (External validation set) were included. Independent factors in the multivariate analysis were used to build the nomogram. The performance of nomogram was examined by calibration curves, net reclassification improvement (NRI) index and integrated discrimination improvement (IDI) index, decision curve analyses (DCA) and receiver operating characteristic (ROC) curves.Results Race, marital status, tumor location, histological type, tumor grade, T stage, N stage, M stage, preoperative CEA level, postoperative chemotherapy were identified as independent prognosticators for OS. The calibration curves of the nomogram showed good consistencies between predicted and observed OS. The AUCs, IDI and NRI indicated that the nomogram predicted prognosis with better accuracy than the TNM staging system. DCA also suggested that the proposed nomogram owned more excellent net benefits in guiding clinical decision than TNM staging system.Conclusion The current study conducted a prognostic analysis and built a prognostic nomogram for EOCRC patients, And the nomogram demonstrated superiority over the TNM staging system regrading to prediction capacity for EOCRC patients.
Exploring the Molecular Mechanisms of Asthma Across Multiple Datasets
Authors: Guo Lianshan , Huang Enhao , Wang Tongting , Song Jin , Li Zhengzhao 
Published: April 2023

Abstract
Objective: The aim of this research was to utilize bioinformatics techniques to explore the molecular mechanisms at the gene level that contribute to asthma, with the objective of discovering new treatment strategies and potential targets for addressing the condition.
Methods: The Series Matrix File data files of GSE43696 and GSE67940 were downloaded from the NCBI GEO public database, including expression profile data of 212 patients. Differential gene expression was functionally annotated using clusterProfiler to evaluate relevant functional categories with GO and KEGG. A gene co-expression network was constructed using MEGENA, and feature importance was evaluated by random forest algorithm. Fluorescent quantitative PCR was employed to validate the expression of essential genes, and the variations in KEGG signaling pathways among the groups with high and low expression were examined through GSEA. Asthma targeted therapeutic drugs were predicted using The Connectivity Map. Finally, single-cell sequencing data were annotated and analyzed using the Seurat and celldex packages.
Results: This study screened 267 differentially expressed genes between asthma patients and healthy controls from the GSE43696 dataset and further analyzed them using pathway analysis and multi-scale embedded gene co-expression network analysis, ultimately selecting 12 genes as the candidate gene set for random forest analysis. Based on this, five key genes were selected using random forest algorithm, and their expression was validated in the external dataset GSE67940. The expression of C1orf64 and C7orf26 genes was found to be different between the two groups of patients, and these two genes were found to be associated with immune regulatory factors, chemokines, and cell receptors. The mRNA expression levels of C1orf64 and C7orf26 were consistent with the results of the screening by PCR. Further analysis showed that C1orf64 and C7orf26 were enriched in ABC transporters, cell cycle, cell adhesion molecules, and Notch signaling pathways, and were related to other genes related to asthma. Finally, by classifying the differentially expressed genes using the Connectivity Map, potential clues were provided for finding candidate drugs for asthma treatment.
Conclusion: This study combined bioinformatics methods to identify key genes and pathways for asthma. C1orf64 and C7orf26 genes may be the core genes in the pathogenesis of asthma in asthma patients compared to healthy controls, providing potential targets for asthma treatment. These results also suggest the potential application of drug prediction analysis using CMap and single-cell sequencing analysis in understanding the molecular mechanisms of asthma.