bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative genomic landscape of patients with lung cancer with high-load versus low-load Epstein-Barr virus infection.
Authors: Liu Ming , Li Yingxiang , Chen Shifu , Mu Tianhao 
Published: June 2024

e20017 Background: As the first known oncogenic virus, Epstein–Barr virus (EBV) has been proven to be associated with nasopharyngeal carcinoma, gastric cancer, and lymphomas. Its relationship with lung cancer, however, remains ambiguous. Given that over 90% of adults globally harbor EBV infections and that EBV can be detected in the tumor cells of lung cancer patients, we hypothesize that lung cancer may be associated with high-load EBV infection, whereas low-load infection is less likely. Here, we compared the genomic landscapes of lung cancer patients with high-load and low-load EBV infections. Methods: We conducted a study on 2,268 Chinese lung cancer patients, collecting tumor tissue samples for analysis. Targeted sequencing of 680 cancer-related genes and EBV genome was performed using the HapOnco StarPanel NGS Assay (HaploX Biotechnology, Shenzhen). The EBV infection load was evaluated based on the proportion of reads aligned to the EBV reference genome in the total sequenced reads for each patient. 99% of these samples could be detected with at least two EBV reads. From them, we selected a total of 32 high-load EBV cases (2.1% - 64.3%) and 35 low-load EBV cases (0.1% - 1.7%). Their genomic profiles and altered signaling pathways were subsequently analyzed. Results: In the high-load EBV group, we identified 122 somatic mutations with no recurrent mutations between cases. As for genes, the most frequently mutated were TP53 (25.0%), LRP1B (15.6%), NFKBIA (12.5%), ERBB4 (9.4%), and CNTNAP5 (9.4%), with these mutations being notably enriched in EBV infection pathways according to KEGG, and IL−7 Signal Transduction pathways as per BioCarta. The most common copy number variation events were FGFR3 (12.5%), CDKN2A (12.5%) and FOXP1 (12.5%) gene deletions. In contrast, the low-load EBV group presented with 316 somatic mutations, with the most recurrent mutations being EGFR L858R (17.1%) and E746_A750del (17.1%). The top frequently mutated genes were TP53 (55.3%), EGFR (44.7%), ARID1A (10.5%) and KRAS (10.5%). Conclusions: The genomic profiles of lung cancer patients with high-load EBV infection differ significantly from those with low-load infection. Notably, the genomic mutations in the high-load EBV group are closely associated with EBV infection, suggesting that high-load EBV infection may be linked to lung cancer, unlike low-load infection.
Application of ctDNA sequencing in patients with metastasized lung cancer.
Authors: Zheng Zhi , Wen Jiale , Chen Yaru , Guo Wei , Zhou Yanqing 
Published: June 2024

e20033 Background: Circulating tumor DNA (ctDNA) is a form of cell-free DNA (cfDNA) found in blood that originates from tumor cells, which has emerged as a promising non-invasive biomarker in monitoring cancer prognosis and precision medicine with the advancement of deep sequencing. Here we compared the mutational landscape between solid tumor and cfDNA in metastasis-free and metastasized lung cancer patients using targeted NGS to investigate the feasibility of ctDNA sequencing in monitoring cancer prognosis. Methods: Blood-derived cfDNA samples and formalin-fixed paraffin embedded tissue were collected from 217 Chinese patients with metastatic lung cancer (n = 39) or metastasis-free lung cancer (n = 178). Blood samples were collected after surgery. Panel sequencing targeting 680 cancer-related genes was performed on both samples. Somatic single nucleotide variations and indels were analyzed. Results: Among the 178 metastasis-free patients, 89.3% of the patients have at least one mutation both detected in tumor and blood samples. On average, 50.4% of tumor mutations were detected in blood for each patients. EGFR, TP53, CSMD3, LRP1B and SYNE1 were the top five most frequently mutated genes, with the proportion of tumor mutation found in blood of 89.1%, 80.2%, 70.0%, 61.3% and 64.3% respectively. In the metastasized cohort, all 39 individuals have at least one tumor mutations found in blood, achieving a concordance of 100%. On average, 59.9% of tumor mutations were detected in blood for each patients. Notably, the proportion of tumor mutations detected in blood for each patients is significantly higher than the metastasis-free cohort (unpaired T-test, p = 0.0167). EGFR, TP53, RBM10, PIK3CA and CSMD3 were the top five most frequently mutated genes, with the proportion of tumor mutation found in blood of 93.5%, 80.8%, 57.1%, 83.3% and 42.9% respectively. Moreover, the proportion of patients having EGFR p.L858R mutation in metastasized cohort was higher than the metastasis-free cohort (54.3% vs 32.8%). While within the metastasized cohort, blood samples detected a higher proportion of EGFR p.T790M (12.9% vs 7.69%) but a lower proportion of EGFR exon19 deletion (p.E746_A750del, 19.4% vs 27.7%) comparing to tumor sample, which can indicate drug resistance. Conclusions: We demonstrated a high mutation detection concordance between tumor and blood using targeted NGS, with an exceptional performance especially in driver oncogenes like EGFR and TP53. Our findings showed that metastasized lung cancer patients exhibit a higher positive concordance rate compared to metastasis-free cohort using ctDNA. We also showed a varied mutational landscape between ctDNA and tumor sequencing in metastasized lung cancer patients. Overall, this study not only reaffirms the viability of using blood as an alternative of tissue biopsy, but also provides new insights on application of ctDNA monitoring lung cancer metastasis and its clinically targetable mutations.
Exploring the role of UMP as a molecular marker in the tumor microenvironment of lung adenocarcinoma.
Authors: Meng Yiran , Liu Yang , Zheng Liuqing , Wang Li 
Published: June 2024

e20064 Background: Currently, there is a relatively extensive research emphasis on tumor microenvironment based on single-cell transcriptomics. However, the investigation of the metabolic aspects of tumor microenvironment is relatively rare due to technological limitations. To address this gap, our study employes scFEA and MEBOCOST, which are metabolic level prediction tools based on single-cell transcriptomics, to explore the metabolic landscape of tumor microenvironment in lung adenocarcinoma(LUAD). Methods: This study utilized four single-cell sequencing (scRNA-seq) datasets, two targeted metabolomics datasets, and the TCGA-LUAD RNA sequencing dataset obtained from the Cancer Genomics Data Portal. To perform dimensionality reduction, the Seurat package was employed. Cell annotation was carried out using scType, followed by manual correction using the FindAllMarkers function. Tumor cell clusters were identified by utilizing tumor marker genes and the R package inferCNV. Single-cell metabolic levels were inferred using scFEA. The TCGA-LUAD datasets underwent analysis to estimate and analyze immune levels using estimate and cibersort algorithms. Additionally, scFEA was used for metabolic level analysis, and survival analysis was conducted. UMP differential expression analysis was performed on the targeted metabolomics datasets. Results: Across all four single-cell sequence datasets, metabolites such as (GlcNAc)4 (Man)3 (Asn)1[G00015], B-Alanine[C00099], and UMP[C00105] exhibited significantly higher levels in immune cells compared to tumor cells (P < 0.05). These findings were further validated using the TCGA-LUAD datasets. Cox regression analysis was performed using immune scores and tumor purity scores and based on the median value of risk scores, high and low-risk groups were distinguished. it was observed that UMP levels were higher in the low-risk group. Moreover, higher UMP levels were associated with elevated immune levels and decreased tumor purity. Analysis of targeted metabolomics datasets from various pan-cancer cell lines revealed that UMP expression level in tumor cells was lower than that in B and T cells. Furthermore, in different subtypes of LUAD, including AAH, AIS, MIA, and IAC, UMP expression in tissues gradually decreased as the severity of the subtype increased (P < 0.05). Conclusions: The study revealed that UMP metabolites are expressed at higher levels in immune cells compared to tumor cells within LUAD. Moreover, UMP expression levels showed significant variations among different disease severities of LUAD. These findings indicate that UMP has the potential to serve as a molecular marker for distinguishing between different disease severities. Further research is needed to investigate the underlying mechanisms and validate the diagnostic usefulness of UMP in LUAD.
Trends in malignant pleural mesothelioma prevalence in the United States from 2000 to 2020.
Authors: Ganesh Bharath , Micaily Ida 
Published: June 2024

e20094 Background: Malignant pleural mesothelioma (MPM) is a rare cancer that is closely associated with prolonged asbestos exposure. Its incidence has steadily declined over time with decreasing prevalence of asbestos-related lung disease. Our study aims to provide an update on recent MPM trends in the United States from 2000 to 2020. Methods: This is a retrospective cohort study design. The primary endpoints of this study are age-adjusted MPM rates and annual percentage change (APC) in rates from 2000-2020. We queried the Surveillance, Epidemiology, and End Results (SEER) 17 database for information about demographics, cause of death, and survival time for patients diagnosed with MPM from 2000-2020. For rate analysis, we used the SEER 22 database which covers 22 national cancer registries and approximately 41.9% of the US population. Age-adjusted rate analysis was performed using the National Cancer Institute (NCI) joinpoint regression program. Results: We identified 13,018 patients diagnosed with MPM from 2000-2020 who were eligible for analysis in the SEER 17 database. Individuals with MPM were primarily male (78.2%) and belonged to Non-Hispanic White (80.7%) ancestry. The mean age at diagnosis overall was 72.4 (SD +/- 10.6) years. The overall age-adjusted rate of MPM for all groups decreased from 0.97 (cases per 100,000 population) in 2000 to 0.55 in 2020. When stratified by sex, the MPM rate in males decreased from 1.91 to 0.93. The rate decrease in females over the same period was more modest, from 0.33 to 0.27. Overall APC for all groups from 2000-2013 was -1.45 (95% CI -2.01 to -0.40, p<.05), and from 2013-2020 it was -5.22 (95% CI -8.92 to -3.76, p<.05). The APC for males from 2000-2013 was -1.88 (95% CI -2.62 to -0.62, p<.05) and -6.46 (95% CI -10.49 to -4.57, p<.05) from 2013-2020. The rate decrease for females demonstrated a consistent APC of -0.87 (95% CI -1.54 to -0.26, p<.05) from 2000-2020. Conclusions: MPM is a disease that is best managed at large academic cancer centers due to its rarity. Our study demonstrates an accelerated decline in overall MPM rates since 2013, mainly driven by a similar fall in rates in males over the same period. MPM rates are lower in females and continue to decline, albeit slowly. The continued and reassuring decrease in rates of MPM likely reflects the effectiveness of regulations targeting widespread industrial and residential asbestos use that have been in place since the 1990s. [Table: see text]
Cutaneous Pneumocystis jirovecii infection in an allogeneic stem cell transplant recipient
Authors: Sood Nikhil , Vadnerkar Aniket , Kodali Murali , Hamacher Lyn K. 
Published: June 2024

Pneumocystis jirovecii is an opportunistic fungus that infects the lungs but can involve other organs, including the skin and lymph nodes. Risk factors include human immunodeficiency virus (HIV), solid organ/haematological malignancies and a CD4 cell count of fewer than 200 cells/µl. Pneumocystis jirovecii pneumonia (PJP) infection is reported less frequently these days with the advent of prophylaxis with trimethoprim-sulfamethoxazole (TMP-SMX). We report a case of extrapulmonary PJP infection in a patient while receiving pentamidine prophylaxis in a T-cell prolymphocytic leukaemia, who underwent an allogeneic stem cell transplant. There are plenty of reported cases of PJP on pentamidine prophylaxis; however, none had cutaneous PJP infection. Cutaneous P. jirovecii infection (CPJ) is an extrapulmonary infection that is rarely reported. Our patient’s skin biopsy was inconclusive, but the skin nodules improved once he was initiated on TMP-SMX. Many transplant patients cannot tolerate TMP-SMX for various reasons and are placed on second-line prophylaxis for PJP, which does not prevent extrapulmonary PJP infections. Our case highlights the challenges of diagnosing such a rare infection in immunocompromised patients. Extrapulmonary PJP should be suspected in patients with a history of pulmonary PJP and persistent elevated Fungitell® levels in low CD4 counts.
A rare case of membranous nephropathy complicated by chylothorax
Authors: Farouji Abdelhadi , Kloub Mohammad N. , Haddad Ahmad W. , Ahmad Amaar S. , Chow Priscilla , Miller Richard 
Published: June 2024

Background: Chylothorax can be classified into traumatic and nontraumatic based on the etiology. Nephrotic syndrome is a very rare cause of nontraumatic chylothorax in adults. Case presentation: A 66-year-old woman with membranous nephropathy who was non-compliant with her management, presented with dyspnea, and was found to have a large right sided chylothorax. Her chylothorax was secondary to membranous nephropathy after excluding other causes, which has been rarely reported in literature. Conclusion: This case highlights the possibility of nephrotic syndrome causing chylothorax, especially in patients with undiagnosed nephrotic syndrome or patients non-compliant with their management. When evaluating a patient with chylothorax, providers should consider nephrotic syndrome in the differential diagnosis.
Community-Led Growth als Markteintrittsstrategie für Software-Startups im B2B-Umfeld
Authors: Grimm Ramona , Durst Carolin 
Published: June 2024

ZusammenfassungCommunity-gesteuerte Marketing- und Vertriebsaktivitäten nehmen seit dem Pandemiejahr stetig zu und etablieren sich in den USA bereits als vielversprechende Markteintrittsstrategie für Software-Startups. Innerhalb der Entrepreneurial Marketing Forschung ist der Ansatz bislang wenig diskutiert, birgt aber großes Potenzial wertschöpfende Interaktionen mit Nutzern und Kunden zu generieren, indem frühzeitig eine Community aufgebaut wird. Mit dem Community-Led Growth Ansatz können insbesondere Herausforderungen von Software-Startups im B2B-Umfeld adressiert werden. Da die Kundenakquise hier besonders langwierig und komplex ist, kann mithilfe einer Community eine kundenzentrierte Produktentwicklung mit vielen direkten Berührungspunkten fokussiert werden. Somit können Markteintrittsbarrieren reduziert, Expertise und Kredibilität aufgebaut und erste Kontakte zu potenziellen Kunden oder späteren Vertriebskanälen und Multiplikatoren geknüpft werden. Dieser Artikel liefert einen konzeptionellen Beitrag zu Community-Led Growth und reflektiert, wie die Dynamik von Communities entlang der Customer Journey Wert für Unternehmen wie z. B. geringere Servicekosten oder eine stärkere Produktaffinität und daraus resultierend eine stärkere Kundenzufriedenheit und -bindung schaffen kann. Basierend auf dem Orbit Model und dem Community Grid wird zunächst aufgezeigt, wie Community-Mitglieder segmentiert werden können und wer zum initialen Kern einer Community gehört. Ein Vergleich von drei Modellen zum Aufbau von Communities (Community Canvas, Community-Led Growth Model und Community Experience) zeigt auf, welche internen und externen Voraussetzungen für den Aufbau einer Community notwendig sind. Abschließend werden auf Basis einer Minimum Viable Community Canvas Handlungsempfehlungen für Software-Startups abgeleitet und ein erweitertes Framework mit iterativen und zielorientierten Komponenten skizziert.
Contribution to the biosystematics of the wild Vaccinium species distributed in Turkey
Authors: Yılmaz Gülşah , Coşkunçelebi Kamil , Güzel Murat Erdem , Makbul Serdar 
Published: June 2024

The genus Vaccinium L. (Ericaceae) consists of shrubs or dwarf shrubs species widely distributed in Southeast Asia, America, and Europe. In the present paper, members of the genus (V. arctostaphylos, V. myrtillus, V. uliginosum, V. vitis-idaea) naturally grown in Northeast Anatolia were compared in terms of leaf venation, seed micromorphology, and palynological properties based on 16 populations in detail. Present findings revealed that number of areoles (the small area bounded by secondary veinlet) is 8–9 for V. arctostaphylos, 5–7 for V. myrtillus, 3–4 for V. uliginosum and V. vitis-idaea. Scanning electron microscope observation shows that the leaf adaxial surface is fiber-fluted in V. arctostaphylos, ruminate in V. myrtillus, V. uliginosum, and V. vitis-idaea due to epicuticular waxes. In addition, the seed shape of V. arctostaphylos in outline varies from triangular, tetragonal to oval, whereas they are lunate to reniform or falcate in the rest of the examined taxa. Epidermal cells of the seed are quadrilateral with straight anticlinal walls in V. arctostaphylos, however, they are most elongate rectangle with weakly undulate anticlinal walls in the rest species. The mean tetrad diameter (D) of pollen belonging to all examined species is 29.89 (21.47–43.22) μm while the lowest mean D was found in V. uliginosum (24.59 μm) and the highest mean D was found in V. arctostaphylos (36.74 μm). Principal component analysis based on 47 traits (flower: 9, leaf: 18, seed and fruit: 9 and pollen: 11) showed that the leaf length and width, teeth numbers, tetrad diameter, equatorial axis, and polar axis were the most valuable characters to distinguish the examined taxa in the present paper.
Patient result monitoring of HbA1c shows small seasonal variations and steady decrease over more than 10 years
Authors: Rollborn Niclas , Kultima Kim , Larsson Anders 
Published: June 2024

Abstract

Objectives
Internal and external quality assurance materials often use highly processed matrixes. This can render the materials non-commutable. Monitoring laboratory methods with patient medians helps in identifying and correcting systematic errors that may affect diagnostic accuracy. The aim of the present study was to use HbA1c patient results for monitoring of method performance over time.

Methods
Test HbA1c results from 2010 to 2022 was analyzed (n=722,553) regarding changes over time and seasonal variation. The HbA1c testing was initially performed on a Cobas 501 instrument using immunological detection but in May 2017 the method was replaced by capillary electrophoresis on Capillarys 3 Tera.

Results
There was a steady decrease in HbA1c values. From 2011 to 2021 the decrease was for 0.10 percentile 6.6 %, lower quartile 7.9 %, median 10.2 %, mean values 9 %, upper quartile 11.2 %, and 0.90 percentile 9.3 %. No clear shift in HbA1c levels was observed due to the shift in methods. The median HbA1c values per month was approximately 44 mmol/mol (6.2 %, DCCT/NGSP). The only month with a median HbA1c that differed by more than 1 mmol/mol was July with a median value of 42 mmol/mol (6.0 %).

Conclusions
The patient data showed a similar decrease as in the National Diabetes Register which indicates that the method is stable over time without any sudden changes and that the seasonal variation is low. The continuous decrease in HbA1c values over time is most likely to a shift towards earlier detection of patient with diabetes and improved treatment.
Stress relaxation experimental research and prediction of GFRP pipes under ring deflection condition
Authors: Shen Tong , Chen Jianzhong , Lv Yong , Zhang Xiaoyu , Huang Li 
Published: June 2024

Abstract
Glass fiber-reinforced plastic (GFRP) pipes are widely used as buried pipes in petrochemical and other industries. At present, in-depth studies have been conducted on GFRP pipes in terms of internal hydrostatic pressure, axial compression, and cyclic internal pressure, especially limited research has been carried out on transverse load, especially stress relaxation behavior. In this study, GFRP pipes with three different component contents were subjected to different initial deflections at different temperatures and subjected to stress relaxation tests for 1000 h. The findings demonstrate that the stress relaxation behavior of GFRP pipes is not affected by the initial deflection. Rather, it is primarily influenced by temperature and sand entrapment content, which are identified as the key factors determining the stress relaxation behavior of GFRP pipes. In addition, the time-temperature superposition principle (TTSP) was used to pass the test results to obtain a smooth master curve and verify the applicability of TTSP on GFRP pipes. Subsequently, the relaxation performance of GFRP pipes was predicted after 50 years. This research result contributes to a more comprehensive understanding of the stress relaxation behavior of GFRP through accelerated testing and offers crucial insights into the application of GFRP pipes.
Study of fractional telegraph equation via Shehu homotopy perturbation method
Authors: Kapoor Mamta , Bin Turki Nasser , Shah Nehad Ali 
Published: June 2024

Abstract
The iterative Shehu transform homotopy perturbation method (HPM) is used in the present research to address fractional telegraph equations in different dimensions, respectively. Considered equations particularly stand out in the field of material science and certain other significant fields. A graphic comparison of estimated and actual results is used to assess the validity and efficacy of the suggested technique. Graphs show a match of approximate to exact findings. Without any linearization or discretization, the iterative Shehu HPM offers a reliable and efficient way to deliver approximations and accurate outcomes that is also error-free. The development of numerical regimes based on discretization is difficult and expensive computationally. Additionally, discretization error is produced as a result of discretization in purely numerical regimes. The present regime has produced robust results and is time-efficient. Also, no discretization error was produced.
Kein Schlaraffenland, nirgends: Rekonstruktive Analysen von Kinderzeichnungen im historischen Vergleich
Authors: Kleeberg-Niepage Andrea , Marx Marie Theres 
Published: June 2024

Zusammenfassung
Die bis heute selten genutzten Kinderzeichnungen waren zu Beginn des 20. Jahrhunderts Gegenstand eines intensiven Forschungsstrangs in der psychologischen und pädagogischen Kindheitsforschung. Unter anderem der Psychologe William Stern führte umfangreiche Sammlungen von Kinderzeichnungen durch, verbunden mit der Hoffnung, Einblicke in das kindliche Seelenleben zu gewinnen. In diesem Beitrag re-analysieren wir zwei historische Kinderzeichnungen aus der Schlaraffenland-Sammlung Sterns von 1905 mit der dokumentarischen Bildanalyse und vergleichen sie mit zwei Zeichnungen aus einer Replikationsstudie von 2019. Die Befunde zeigen den Gewinn der Analyse von Kinderzeichnungen und insbesondere eines rekonstruktiven Vorgehens für die Elaboration kindlicher Perspektiven jenseits sprachlicher Zugänge. Zudem wird das Potential von Kinderzeichnungen für die historische Kindheitsforschung deutlich, die bislang vorrangig mit Quellen über Kinder und weniger von Kindern arbeitet. Hier kann die Bearbeitung bisher unberücksichtigter Kinderzeichnungen mit rekonstruktiven Methoden Einblicke in kindliche Erfahrungsräume aus früheren Epochen ermöglichen.