bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated study on the conservation of ecocultural heritage in the Tiantai Mountain area, China
Authors: Zhao Yanxuan , Wu Hui , Fan Yingjia , Jin Hexian , Wang Yifan , Lu Lei 
Published: August 2024

Abstract
This study deeply analyzes the ecocultural heritage of the Tiantai Mountain area in Eastern China, assesses its current status and explores effective mechanisms for its conservation and construction. Employing remote sensing technology, kernel density analysis and Minimum Cumulative Resistance Model, the study comprehensively evaluated the environmental characteristics of the region and its role in historical and modern conservation efforts. The results demonstrate the unique distribution patterns of ecocultural heritage in various conservation zones, such as restoration, controlled construction and core conservation zone. Furthermore, the study highlights the importance of religious beliefs and clan systems in the preservation of traditional knowledge and practices, with significant impacts of local community participation on conservation strategies. This research provides new theoretical and practical support for the implemention of ecocultural heritage conservation and development within religiously significant areas, highlights the need for conservation measures and synergistic strategies between ecological and cultural practices.
High-precision GPS orbit determination by integrating the measurements from regional ground stations and LEO onboard receivers
Authors: Li Kai , Tang Chengpan , Zhou Shanshi , Hu Xiaogong , Zhou Xuhua 
Published: August 2024

AbstractHigh-precision Global Navigation Satellite System (GNSS) orbit and clock products are crucial for precise applications. An evenly distributed global network enables continuous tracking for GNSS satellites, while a regional network may result in tracking gaps in the areas where monitoring stations are not deployed. This also means that the orbit determination accuracy based on a regional network is not comparable to that with a global network. Integrating the measurements from regional ground stations and Low Earth Orbit (LEO) satellites onboard receivers is a potential approach for generating GNSS orbit and clock products with centimeter-level accuracy, which is particularly important for BDS and the local commercial providers relying on a regional network. In the integrated Precise Orbit Determination (POD), LEO satellites are used to compensate for the drawback of regional ground stations in the precise orbit and clock determination of GNSS satellites. To validate the role of LEO satellites in the orbit determination with a regional network, 6 International GNSS Service stations around China and 13 LEO satellites from January 20 to 26, 2019, including GRACE-C/D, SWARM-A/B/C, Jason-3, Sentinel-3A/B, and SAT-A/B/C/D/E are selected in this study to perform the integrated POD. The orbit and clock accuracies of GPS and LEO satellites are evaluated by comparison with precise products. The average Root Mean Square (RMS)of GPS orbit errors in the radial (R), along-track (T) and cross-track (N) directions are 2.27 cm, 3.45 cm, and 3.08 cm, respectively, and the clock accuracy is better than 0.15 ns based on a comparison with the final products provided by Center for Orbit Determination in Europe (CODE). The LEO orbit accuracy is better than 2 cm in the R direction, and the position errors are mostly within 4 cm. The results indicate that the integrated POD can generate high-precision orbit and clock products for GPS and LEO satellites based on regional network stations. Finally, the integrated POD products are assessed for Precise Point Positioning (PPP). Simulated kinematic PPP has a comparable performance in terms of the convergence time and positioning accuracy. With more LEO satellites available, the orbit and clock determination accuracy and PPP positioning accuracy can be improved.
Case series on neuroimaging spectrum of Wilson’s disease: knowing the known and the uncommonly known
Authors: Patel Kunal , Bhayana Aanchal , Bagri Neha , Malik Amita 
Published: August 2024

Abstract
Background
Wilson’s disease is an inherited disease characterized by impaired copper metabolism that causes damage to many organs, including the brain. Patients having neurological involvement usually present with varied neuropsychiatric symptoms. Magnetic resonance imaging (MRI) Brain plays an indispensable role in identifying the structural involvement in these patients, aiding in early accurate diagnosis and timely management. Typically, basal ganglia, thalami and brainstem are involved, with bright claustrum sign, face of giant panda sign and miniature panda signs on MRI.

Conclusions
Having knowledge about the commonly encountered and known MRI brain findings in Wilson’s disease are essential in aiding accurate diagnosis and initiating early management. However, identifying the Atypical MRI brain characteristics is all the more imperative and should be considered in patients with prolonged or severe disease or in patients with rapid clinical progression and in patients showing poor response to treatment.
Microbial remediation of polluted environment by using recombinant E. coli: a review
Authors: Sharma Samriti , Pathania Shruti , Bhagta Suhani , Kaushal Neha , Bhardwaj Shivani , Bhatia Ravi Kant , Walia Abhishek 
Published: August 2024

AbstractAn increased amount of toxins has collected in the environment (air, water, and soil), and traditional methods for managing these pollutants have failed miserably. Advancement in modern remediation techniques could be one option to improve bioremediation and waste removal from the environment. The increased pollution in the environment prompted the development of genetically modified microorganisms (GEMs) for pollution abatement via bioremediation. The current microbial technique focuses on achieving successful bioremediation with engineered microorganisms. In the present study, recombination in E. coli will be introduced by either insertion or deletion to enhance the bioremediation properties of the microbe. Bioremediation of domestic and industrial waste performed using recombinant microbes is expensive but effectively removes all the waste from the environment. When compared to other physicochemical approaches, using microbial metabolic ability to degrade or remove environmental toxins is a cost-effective and safe option. These synthetic microorganisms are more effective than natural strains, having stronger degradative capacities and the ability to quickly adapt to varied contaminants as substrates or co-metabolites. This review highlights the recent developments in the use of recombinant E. coli in the biodegradation of a highly contaminated environment with synthetic chemicals, petroleum hydrocarbons, heavy metals, etc. It also highlights the mechanism of bioremediation in different pollution sources and the way in which this genetically altered microbe carries out its function. Additionally, addressed the benefits and drawbacks of genetically engineered microbes.
Investigation of the effect of macrophage and epithelial cell interaction in the progression of different subtypes of breast cancer.
Authors: Majumdar Banani , Dolui Barnali , Basu Anupam 
Published: August 2024

10 Background: In the realm of tumor progression, the immunosuppressive role of macrophages has been well-established. However, a significant lacuna persists concerning the mechanisms through which epithelial cells regulate macrophages. Furthermore, the precise manner in which macrophages modulate breast cancer cells remains unclear. Hence, the primary objective of the current investigation is to delve into the influence of macrophages on the progression of distinct subtypes of breast cancer. Methods: Human monocyte cell-derived macrophages (M0) were cultivated in the presence of conditioned media (CM) from various subtypes of breast cancer cells. Conversely, human luminal breast cancer cell line T47D, and basal cell line MDA MB 231 were cultured in the presence of CM from macrophages. Results: When macrophages were incubated with CM of T47D, they exhibited a spindle-shaped morphology with pseudopodia. Conversely, exposure to CM of MDA MB 231 induced macrophages to adopt a foamy, round shape with numerous filopodia. Flow cytometry analysis revealed that T47D-CM promoted a higher proportion of CD80+ cells, while MDA MB 231-CM led to an increase in both CD206+ and CD80+ cells. Moreover, both T47D and MDA MB 231-CM escalated the production of various cytokines including IL-1β, IL-2, IL-4, IL-5, IL-7, IL-12(p70), IL-13, IL-17, G-CSF, IFN-γ, and MIP-1β. Intriguingly, MDA MB 231-CM induced a significant increase in IL-6, GM-CSF, and TNF-α. Subsequent cultivation of cancer cells in the presence of macrophage-CM resulted in a marked proliferation of MDA MB 231 cells, while T47D cell proliferation decreased significantly. Correspondingly, there was a notable increase in apoptosis among T47D cells. Scratch wound healing assays revealed heightened migration of MDA MB 231 cells following treatment with macrophage-CM, whereas there was negligible alteration in T47D cell migration. Proteomic analysis unveiled dysregulation of 247 and 596 proteins in MDA MB 231 and T47D cells, respectively. Particularly noteworthy were three proteins—MDHM, H1.5, and LEG8—abundant in MDA MB 231 cells, yet scarce in T47D cells. These proteins have been implicated in promoting tumor growth across various cancer types. Conclusions: This study first time elucidates subtype specific role of macrophage in breast tumour. In triple-negative breast cancer, infiltrating macrophages induce an immunosuppressive effect, altering cytokine expression and fostering the expression of tumor-promoting factors in epithelial cells, thereby facilitating cellular proliferation and metastasis. Conversely, in luminal breast cancer, infiltrating macrophages exhibit a predominantly pro-inflammatory profile, resulting in minimal tumor-promoting effects. Key Words: Breast Cancer, Macrophage polarization, Conditioned Media, Cytokines, Proteomics. Acknowledgements, DBT – Govt of India, NIBMG, Kalyani.
Comprehensive validation of a cell-free DNA-based assay for multi-cancer detection: A Vietnamese longitudinal prospective cohort study of 9,024 participants.
Authors: Tran Le Son , Nguyen Thi Hue Hanh , Nguyen Luu Hong Dang , Nguyen Trong Hieu , Nguyen Thanh Dat , Giang Hoa , Phan Minh Duy , Nguyen Duy Sinh , Tang Hung Sang , Nguyen Hoai-Nghia 
Published: August 2024

102 Background: Blood-based multi-cancer early detection (MCED) has emerged as a promising method for enhancing early cancer detection efficiency and benefiting population health. However, the lack of evidence regarding their clinical utility across diverse populations has hindered their routine use. To address this, we conducted a comprehensive analytical and clinical validation of an MCED test, SPOT-MAS (Screening for the Presence Of Tumor by DNA Methylation And Size). Methods: Analytical validation was conducted on a retrospective cohort of 96 healthy and 169 cancer-confirmed individuals to determine the limit of detection, reproducibility, and potential interferents. Additionally, we launched a multi-center prospective study, named K-DETEK (ClinicalTrials.gov identifier: NCT05227261), to clinically validate the diagnostic performance. Our study recruited 10,027 asymptomatic individuals aged 40 years or older across 75 major hospitals in Vietnam, following them up for 12 months. Results: SPOT-MAS test demonstrated the capability to detect over 50% of cancer samples with 98% specificity at a tumor fraction of 0.049 (95% CI: 0.043-0.059). These results were consistent across intra- and inter-batch analyses. The test remained robust even with hemoglobin contamination up to 500 mg/dL and genomic DNA contamination of up to 100%. In the K-DETEK study, among 9,024 eligible participants, 43 (0.48%) showed a positive cancer signal. Of those, 25 were diagnosed with cancer through standard imaging and biopsy tests, with 21 matching tumor types with our predictions, resulting in a positive predictive value of 58.14% (95% CI: 43.33-71.62) and tumor-tissue-origin accuracy of 84%. 8,981 participants (99.52%) had a negative cancer signal, and 8,974 were confirmed cancer-free, indicating a negative predictive value of 99.92% (95% CI: 99.84-99.96). The test showed an overall sensitivity of 78.13% (95% CI: 61.25-88.98) and a specificity of 99.80% (95% CI: 99.68-99.87) for cases with tumors at all stages, with slightly lower sensitivity (74.05%, 95% CI: 56.64-87.32) for precancerous and early clinical stages. Conclusions: Our study represents the most comprehensive and largest validation study in Asia supporting the utility of SPOT-MAS as a multi-cancer blood test for early cancer detection. Its potential significance is underscored, particularly in low- and middle-income countries, emphasizing the need for accessible and effective screening tools. Clinical trial information: NCT05227261 .
A novel cell-free multi-omics approach for enhancing multi-cancer early detection.
Authors: Nguyen Thien-Chi Van Van , Nguyen Anh-Nhu , Nguyen Thien-Phuc Hoang , Nguyen Hanh Thi-Hue , Tran Trung-Hieu , Nguyen Tien-Anh , Tran Trang Thi , Nguyen Trong Hieu , Giang Hoa , Phan Minh-Duy , Nguyen Hoai-Nghia , Tran Le Son 
Published: August 2024

103 Background: While circulating tumor DNA (ctDNA)-based assays for multi-cancer early detection (MCED) have shown significant potential, their performance is hindered by the limited amount and inherent variability of ctDNA, particularly in cancer types with low ctDNA shedding. To enhance the accuracy of MCED, recent studies have focused on profiling cell-free RNA (cfRNA), which is secreted not only by tumor cells but also by other cell types to reflect the systemic tumor responses. Herein, we developed a novel cell-free multi-omics approach integrating cfDNA and cfRNA analyses from a single blood draw to improve the sensitivity of an MCED assay, especially for detecting low-shedding ctDNA cancer types. Methods: We recruited 535 healthy subjects and 287 patients across five cancer types (77 breast cancers, 102 colorectal cancers, 35 gastric cancers, 34 liver cancers, and 42 lung cancers). We established a multi-omics workflow to comprehensively profile cfDNA signatures (methylation, fragment length, motif ends, and copy number alterations), and cfRNA signatures (cfmRNA). Distinctive signatures were identified to differentiate cancers from healthy subjects and used for constructing robust machine learning classifiers. Results: We identified multiple significantly different features distinguishing cancer from healthy individuals, with 81% originating from cfDNA. Notably, cfmRNA features, accounting for 19% of total significant features, were mainly enriched in immune-related pathways, reflecting tumor-immune cell interactions. The cfDNA-based model achieved 81.2% accuracy, with highest performance in detecting liver cancer (100%) and 64%, 42%, and 36.4% for breast, colorectal, and gastric cancers, respectively, at 93% specificity. Combining cfDNA and cfRNA signatures increased sensitivity to 73%, 71%, and 46% for breast, colorectal, and gastric cancers. Overall, the multi-omic model achieved 85.6% accuracy and 72.7% sensitivity for detecting five cancer types at 92.6% specificity. Conclusions: The cell-free multi-omics approach holds potential for improving ctDNA-based MCED tests by simultaneously profiling both cfDNA and transcriptomic cfmRNA from a single blood draw. Validation on larger cohorts could lead to a paradigm shift in cancer screening practices.
Lenvatinib and pembrolizumab in patients with metastatic papillary renal cell carcinoma: A phase 2 pilot study.
Authors: Tsimafeyeu Ilya , Sultanbaev Alexander , Vilkov Sergey 
Published: August 2024

109 Background: Traditionally, metastatic papillary renal cell carcinoma (papillary mRCC) has been treated with tyrosine kinase inhibitors, resulting in a 23% objective response rate and a progression-free survival of 9 months (SWOG 1500 trial). Combinations of immunotargeted therapy have shown improved outcomes in clear-cell mRCC. This prospective pilot study aimed to evaluate the preliminary efficacy of combining lenvatinib with pembrolizumab in patients with papillary mRCC. Methods: At study entry in August 2021, patients with papillary mRCC types 1 or 2, multiple measurable lesions per RECIST 1.1 criteria, and no prior therapy for advanced disease were included. The primary endpoint was the objective response rate. The study employed Simon's two-stage design (Simon, 1989) to test the null hypothesis that the true response rate is 23% against a one-sided alternative. In the first stage, 5 patients were enrolled. If there were 1 or fewer responses among these initial 5 patients, the study would be halted. The null hypothesis would be rejected if 6 or more responses were observed in the entire cohort of 12 patients. This design yields a type I error rate of 0.05 and power of 0.8 when the true response rate is 63%. Results: As planned, 5 patients were enrolled in the stage 1. The median age was 57.4 years. Among them, 4 patients were diagnosed with papillary RCC type 2, and 3 patients had an unresected primary tumor. Additionally, 1 patient presented with brain metastases. The objective response rate was 100%, of which there was 1 complete and 4 partial responses. As of the last follow-up, the status of patients on therapy was as follows: i) three patients remained on therapy for more than 12 months; ii) one patient experienced disease progression after 14.3 months of treatment; iii) one patient who initially had an ongoing response developed grade 3 uncontrolled diarrhea after 5.5 months from the start of therapy. Despite the positive outcomes observed in stage 1 of the study, the enrollment was stopped. This decision was influenced by emerging results from the large phase 2 trial KEYNOTE-B61, as reported by Chung-Han Lee et al. (ASCO 2023). Conclusions: All patients responded to lenvatinib and pembrolizumab therapy. These results suggest promising efficacy of the combination in metastatic papillary RCC. Clinical trial information: KCRB01012021 .
Prevalence of pathogenic or likely pathogenic germline mutations in patients with metastatic renal cell cancer.
Authors: Batra Atul , Nayak Brusabhanu , Sahoo Ranjit Kumar , Kaushal Seema , Sharma Aparna , Kumar Akash , Seth Amlesh , Shamim Shamim Ahmed 
Published: August 2024

110 Background: Data from the West suggests that 5-10% of patients with metastatic renal cell cancer (RCC) are known to harbor a pathogenic/likely pathogenic mutation in the RCC-associated genes. However, there are no data from the Indian subcontinent in this regard. Methods: This study was a prospective single-center cohort study conducted at a large tertiary care cancer center in northern India. Patients newly diagnosed with metastatic RCC were eligible to participate and, if willing, were offered pretest counseling and germline genetic testing. We performed whole exome sequencing on blood samples using next-generation sequencing on the Illumina platform. The frequency and spectrum of pathogenic/likely pathogenic (P/LP) variants were determined and classified using the ACMG guidelines, and clinical characteristics associated with mutation status were analyzed using a Fisher's exact test. Results: A total of 156 patients with metastatic RCC were enrolled in this study from October 2023 to February 2024. The median age at diagnosis was 44 years, and 67% were men. Histologically, 64% had clear cells, 12% had papillary, and 8% had unknown histology. In RCC-associated genes, 6 patients (3.8%) had P/Lp mutations, of which 4 had mutations in FH and 2 in VHL. Further P/LP variants in the non-RCC genes were detected in 12 additional patients (7.7%), of which 4 were in ATM, 2 in BRIP1, and one each in BRCA1, BARD1, PALB2, MUTYH, MSH6, and PMS2, respectively. The presence of germline P/LP mutation was associated with non-clear histology but not with age and sex. Patients with a P/LP mutation were more likely to have a family history of other cancers (most common, breast cancer) in first and second-degree relatives. Conclusions: 11.5% of patients with metastatic RCC were detected with germline P/LP variants, of which one-third had one of the RCC genes, and the rest had non-RCC gene mutations. Patients with mRCC should have access to germline genetic testing, and the gene panel for patients needs to be expanded to include genes previously classified as non-RCC genes.
Differences in the expression heterogeneity of ADC-related markers between primary tumors and metastatic lymph nodes in advanced urothelial cancers.
Authors: Tan Xingliang , Liu Zhicheng , Zhou Qianghua , Yao Kai 
Published: August 2024

111 Background: The booming development of antibody‒drug conjugates (ADCs), which represent a novel, effective and low-toxicity therapeutic approach, has dramatically improved clinical outcomes in urothelial cancers, especially those with advanced disease. However, previous studies focused less on the targeted genes expression pattern and heterogeneity in metastatic tissues, which are more critical to inhibit tumor progression. Here, we aimed to explore the expression of potential ADC-related genes, including HER2, HER3, Nectin4 and Trop2 in advanced urothelial cancers between primary tumors and metastatic lymph nodes (mLN) in pairs. Methods: A large cohort of 306 urothelial cancer patients (292 patients, pN+), including 65 renal pelvis, 38 ureter, 179 bladder and 24 urethral cancer patients (10 patients, pN+), from SYSUCC was enrolled. Paraffin-embedded primary tumors and corresponding mLN sections were subjected to immunohistochemistry (IHC) to detect ADC-related gene expression. HER2 IHC scores of 2/3+ were defined as high expression as previously described. HER3, Nectin4 and Trop2 were evaluated by H-scores (range 0-300, rank 0 to 3+) multiplied by the extent and intensity of the staining, and H-scores >15 were considered positive. Results: A total of 74.8% of advanced urothelial cancer patients were HER2 positive (1-3+), and 49.4% had high HER2 expression. High HER2 expression was detected in 33.8%, 42.2%, 56.5% and 50% of renal pelvis, ureter, bladder and urethral primary tumors, respectively. The rate of high HER2 expression in mLNs slightly decreased to 30.1%, 41.7%, 51.9% and 50%, and the concordance rate of HER2 expression between primary and mLNs was 71.9%. Similarly, 27.7%, 42.1%, 52%, and 66.7% of primary tumors were positive for HER3 expression; 72.3%, 89.5%, 77.7%, and 87.5% were positive for Nectin4; and 89.2%, 94.7%, 83.2%, and 95.8% were positive for Trop2 in renal pelvis, ureter, bladder and urethral cancers, respectively. Overall, 71.9%, 50.7%, and 65.3% of patients had consistent expression of HER3, Nectin4 and Trop2 in mLNs, respectively. Survival analysis indicated that the overexpression of HER2, HER3 and Trop2 in advanced urothelial cancers was associated with poor OS (p=0.001, 0.025 and 0.022, respectively). More importantly, we found that patients with higher HER2 expression in mLNs at primary sites had a worse prognosis (p=0.006). Conclusions: We first investigated the heterogeneity of ADC-related marker expression in primary urothelial tumors and mLNs in a large single cohort, especially in patients who underwent radical lymphadenectomy. Therapy targeting HER2-ADCs might show better homogeneity in advanced disease, but it is more recommended to detect IHC staining both in primary and metastatic tissues if possible.