bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inverse FASN and LDHA correlation drives metabolic resistance in breast cancer
Authors: Papulino Chiara , Chianese Ugo , Ali Ahmad , Favale Gregorio , Tuccillo Concetta , Ciardiello Fortunato , Di Mauro Annabella , Mignogna Chiara , Ferrara Gerardo , Budillon Alfredo , Megchelenbrink Wouter Leonard , Del Gaudio Nunzio , Conte Mariarosaria , Merciai Fabrizio , Campiglia Pietro , Altucci Lucia , Carafa Vincenzo , Sommella Eduardo , Benedetti Rosaria 
Published: July 2024

Abstract
Background
Breast cancer manifests as a heterogeneous pathology marked by complex metabolic reprogramming essential to satisfy its energy demands. Oncogenic signals boost the metabolism, modifying fatty acid synthesis and glucose use from the onset to progression and therapy resistant-forms. However, the exact contribution of metabolic dependencies during tumor evolution remains unclear.

Methods
In this study, we elucidate the connection between FASN and LDHA, pivotal metabolic genes, and their correlation with tumor grade and therapy response using datasets from public repositories. Subsequently, we evaluated the metabolic and proliferative functions upon FASN and LDHA inhibition in breast cancer models. Lastly, we integrated metabolomic and lipidomic analysis to define the contributions of metabolites, lipids, and precursors to the metabolic phenotypes.

Results
Collectively, our findings indicate metabolic shifts during breast cancer progression, unvealling two distinct functional energy phenotypes associated with aggressiveness and therapy response. Specifically, FASN exhibits reduced expression in advance-grade tumors and therapy-resistant forms, whereas LDHA demonstrates higher expression. Additionally, the biological and metabolic impact of blocking the enzymatic activity of FASN and LDHA was correlated with resistant conditions.

Conclusions
These observations emphasize the intrinsic metabolic heterogeneity within breast cancer, thereby highlighting the relevance of metabolic interventions in the field of precision medicine.
Survey of knowledge on calcium carbide use in fruit ripening and associated health risks among fruit sellers and consumers in Ado-Ekiti Nigeria
Authors: Orok Edidiong , Okeke Uchenna , Williams Tonfamoworio , Adeniyi Funmilayo , Ikpe Favour , Femi-Oyewo Mbang 
Published: July 2024

Abstract
Background
This study aimed to assess the methods used for ripening fruits by sellers and to examine the knowledge regarding the health risks associated with the use of calcium carbide (CaC2) among both fruit sellers and consumers in Ado-Ekiti.

Methods
The study employed a cross-sectional design, utilizing a semi-structured questionnaire administered in major markets within Ado-Ekiti. Knowledge levels were categorized into good (> 70% score), fair (50–69% score), and poor (< 50% score). One way Analysis of variance (ANOVA) and Independent sample t-test was used to indicate knowledge score difference with respect to socio demographic characteristics.

Results
The study involved 357 consumers and 20 fruit sellers, with a majority being females (54.9% of consumers; 80.0% of sellers) and aged predominantly between 18–27 years and 28–39 years. The findings revealed that the use of CaC2 (50%) and natural ripening methods (100%) were common among fruit sellers. Sellers cited cancer (60%), bacterial infections (35%), and chest tightness (15%) as associated risks with CaC2 usage. Similarly, consumers expressed concerns about consuming CaC2-ripened fruits, attributing risks such as abdominal burns (70%), cancer (70.6%), and diarrhoea (67.3%). A significant proportion of sellers (90%) exhibited poor knowledge regarding the risks associated with CaC2, while 24.6% of consumers demonstrated fair knowledge on the subject.

Conclusion
The study identified common fruit ripening practices among sellers. Fruit sellers showed poor knowledge, while consumers displayed fair to poor understanding of health risks linked to calcium carbide use in artificial fruit ripening.
Elucidating the nature of acinic cell carcinoma of the breast with high-grade morphology: evidence from case report
Authors: Ge Yunjie , Wei Xianping , Liu Jing-Nan , Sun Ping-Li , Gao Hongwen 
Published: July 2024

Abstract
Background
Acinic cell carcinoma (AciCC) of the breast is a rare subtype of breast cancer. It was considered a low-grade triple-negative breast cancer (TNBC) with the potential to progress or transform into a high-grade lesion because of the molecular similarities with conventional aggressive TNBC in several genetic studies. Microscopically, the coexistence of classical low-grade and high-grade triple-negative components in breast AciCC is not uncommon. However, there is a scarcity of research on the comparative histopathological and genetic aspects of both components.

Case presentation
A 34-year-old woman with a nontender mass in the upper outer quadrant of the left breast was initially diagnosed with a malignant small round cell tumor (undifferentiated or poorly differentiated carcinoma) based on a preoperative biopsy, which was later identified as breast AciCC with a high-grade solid component. Left breast-conserving surgery with sentinel lymph node biopsy was performed. Microscopically, the breast AciCC consisted of a classical acinic component and a high-grade component. The latter demonstrated a solid sheet-like pattern characterized by large, round, pleomorphic or vesicular nuclei, prominent nucleoli, and frequent mitotic activities. Classical acinic architectures focally merged together to form solid nests and transited into high-grade areas. Remarkably, in the high-grade lesion, conventional immunochemical markers for breast AciCC, such as α1-antitrypsin (AAT), Lysozyme (LYS), Epithelial membrane antigen (EMA), S100 protein (S100), and cytokeratin (CK) were negative, whereas cell cycle protein D1 (cyclin D1) and vimentin showed diffuse expression. Next‑generation sequencing (NGS) revealed that 43.5% of variants were identical in both components. Furthermore, PAK5 mutation; copy number (CN) loss of CDH1, CHEK1, and MLH1; and CN gains of CDK6, HGF, and FOXP1 were identified in the high-grade lesion. The patient was treated with eight cycles of adjuvant chemotherapy (epirubicin combined with cyclophosphamide) and radiotherapy after surgery, and she is currently alive for 43 months with no metastases or recurrences.

Conclusions
This case demonstrates a comparative analysis of the histopathological and genetic characteristics of classical low-grade and high-grade components of AciCC within the same breast. This information may serve as a morphological and molecular basis for further investigation into the molecular mechanisms underlying high-grade lesions in breast AciCC.
Feasibility of dose calculation for treatment plans using electron density maps from a novel dual-layer detector spectral CT simulator
Authors: Zhu Qizhen , Wei Shuoyang , Wang Zhiqun , Xu Haoran , Zhou Bing , Qu Huiying , Nie Mingming , Guo Ning , Wang Wenshuai , Yang Bo , Qiu Jie 
Published: July 2024

Abstract
Background
Conventional single-energy CT can only provide a raw estimation of electron density (ED) for dose calculation by developing a calibration curve that simply maps the HU values to ED values through their correlations. Spectral CT, also known as dual-energy CT (DECT) or multi-energy CT, can generate a series of quantitative maps, such as ED maps. Using spectral CT for radiotherapy simulations can directly acquire ED information without developing specific calibration curves. The purpose of this study is to assess the feasibility of utilizing electron density (ED) maps generated by a novel dual-layer detector spectral CT simulator for dose calculation in radiotherapy treatment plans.

Methods
30 patients from head&neck, chest, and pelvic treatment sites were selected retrospectively, and all of them underwent spectral CT simulation. Treatment plans based on conventional CT images were transplanted to ED maps with the same structure set, including planning target volume (PTV) and organs at risk (OARs), and the dose distributions were then recalculated. The differences in dose and volume histogram (DVH) parameters of the PTV and OARs between the two types of plans were analyzed and compared. Besides, gamma analysis between these plans was performed by using MEPHYSTO Navigator software.

Results
In terms of PTV, the homogeneity index (HI), gradient index (GI), D2%, D98%, and Dmean showed no significant difference between conventional plans and ED plans. For OARs, statistically significant differences were observed in parotids D50%, brainstem in head&neck plans, spinal cord in chest plans and rectum D50% in pelvic plans, whereas the variance remained minor. For the rest, the DVH parameters exhibited no significant difference between conventional plans and ED plans. All of the mean gamma passing rates (GPRs) of gamma analysis were higher than 90%.

Conclusion
Compared to conventional treatment plans relying on CT images, plans utilizing ED maps demonstrated similar dosimetric quality. However, the latter approach enables direct utilization in dose calculation without the requirements of establishing and selecting a specific Hounsfield unit (HU) to ED calibration curve, providing an advantage in clinical applications.
Bridging cultures: Chinese elements in scientific illustrations
Authors: Gu Jianyou , Zhang Wenying , Wang Xianxing , Zhou Qiang , Zhang Junfeng , Xie Fuming , Xia Renpei , Chen Zhe-Sheng , Wang Huaizhi 
Published: July 2024

AbstractIn the context of globalization, the integration of cultural elements into scientific research, particularly through the incorporation of traditional Chinese cultural motifs in scientific illustrations, represents a novel frontier in enhancing the universality and appeal of scientific discoveries. This paper explores the innovative practice of embedding traditional Chinese cultural elements into scientific paper illustrations, highlighting its significant role in augmenting the global appeal of research findings, promoting diversity and innovation in scientific inquiry, and facilitating cross-cultural understanding. Through a series of case studies, including symbolic representations of ancient myths and the use of traditional themes to elucidate complex scientific phenomena, we demonstrate how this cultural integration not only makes scientific content more accessible and engaging but also fosters a deeper appreciation of Chinese heritage among international audiences. This approach not only bridges the gap between science and culture but also contributes to a more inclusive and interconnected global scientific community, underscoring the importance of cultural diversity in enriching scientific exploration and communication.
Targeting RBM39 through indisulam induced mis-splicing of mRNA to exert anti-cancer effects in T-cell acute lymphoblastic leukemia
Authors: Ji Tongting , Yang Yang , Yu Juanjuan , Yin Hongli , Chu Xinran , Yang Pengju , Xu Ling , Wang Xiaodong , Hu Shaoyan , Li Yizhen , Wu Xiaochen , Liu Wengyuan , Zhou Bi , Wang Wenjuan , Zhang Shuqi , Cheng Wei , Chen Yanling , Shi Lei , Li Zhiheng , Zhuo Ran , Zhang Yongping , Tao Yanfang , Wu Di , Li Xiaolu , Zhang Zimu , Fan Jun-jie , Pan Jian , Lu Jun 
Published: July 2024

Abstract
Background
Despite the use of targeted therapeutic approaches, T-cell acute lymphoblastic leukemia (T-ALL) is still associated with a high incidence of complications and a poor prognosis. Indisulam (also known as E7070), a newly identified molecular glue compound, has demonstrated increased therapeutic efficacy in several types of cancer through the rapid degradation of RBM39. This study aimed to evaluate the therapeutic potential of indisulam in T-ALL, elucidate its underlying mechanisms and explore the role of the RBM39 gene.

Methods
We verified the anticancer effects of indisulam in both in vivo and in vitro models. Additionally, the construction of RBM39-knockdown cell lines using shRNA confirmed that the malignant phenotype of T-ALL cells was dependent on RBM39. Through RNA sequencing, we identified indisulam-induced splicing anomalies, and proteomic analysis helped pinpoint protein changes caused by the drug. Comprehensive cross-analysis of these findings facilitated the identification of downstream effectors and subsequent validation of their functional roles.

Results
Indisulam has significant antineoplastic effects on T-ALL. It attenuates cell proliferation, promotes apoptosis and interferes with cell cycle progression in vitro while facilitating tumor remission in T-ALL in vivo models. This investigation provides evidence that the downregulation of RBM39 results in the restricted proliferation of T-ALL cells both in vitro and in vivo, suggesting that RBM39 is a potential target for T-ALL treatment. Indisulam’s efficacy is attributed to its ability to induce RBM39 degradation, causing widespread aberrant splicing and abnormal translation of the critical downstream effector protein, THOC1, ultimately leading to protein depletion. Moreover, the presence of DCAF15 is regarded as critical for the effectiveness of indisulam, and its absence negates the ability of indisulam to induce the desired functional alterations.

Conclusion
Our study revealed that indisulam, which targets RBM39 to induce tumor cell apoptosis, is an effective drug for treating T-ALL. Targeting RBM39 through indisulam leads to mis-splicing of pre-mRNAs, resulting in the loss of key effectors such as THOC1.
Streamlining electronic reporting of serious adverse events (SAEs) using the REDCap data collection system: the eSAE Project
Authors: Black Joanna , Julier Patrick , Eldridge Lucy , Barber Vicki S. 
Published: July 2024

Abstract
Background
It is essential that electronic data collection (EDC) systems are both compliant with regulations and the principles of Good Clinical Practice (GCP) to allow for the timely and accurate reporting of data including safety data. For clinical trials of investigational medicinal products (CTIMPs), investigators must immediately report to the sponsor any serious adverse event (SAE) that occurs in a site for which they are responsible. It is therefore expected that sponsors provide systems for timely review and reporting should a SAE be classified as a suspected unexpected serious adverse reaction (SUSAR). Challenges arise when data related to adverse events (AEs) needs to be re-entered for SAEs; this can be prone to error and may delay reporting. Additionally, recognising what has changed from an initial SAE report when an investigator responds to queries raised can cause errors.

Method
A multi-disciplinary working group came together from a UK academic clinical trials unit (CTU) to establish if an electronic system could be created in the unit’s open-source EDC system—REDCap, to manage SAEs in an efficient way.

Results
A module has been created in REDCap to facilitate electronic SAE reporting: enabling an AE form to automatically trigger an SAE form for any AE which is also a SAE, prepopulating relevant fields of the SAE form, reducing the risk of delay and error when entering data into the SAE form. The system has also been developed with an embedded code to allow for instant visual recognition of any data updated following reporting to allow the sponsor to immediately review and resolve SAEs in a timely manner, complying with UK regulatory reporting. This functionality ‘The eSAE Project’ is now an active project for all of our new trials where data collection is undertaken using the REDCap system.

Conclusion
The eSAE Project coded into REDCap offers a unique way of populating SAE forms with information already entered in the initial AE forms as applicable, coupled with highlighting any updates during the lifetime of the SAE for sponsors to identify any new information that needs to be reassessed to process and report the SAE.
Effect of CdS loading on the properties and photocatalytic activity of MoS2 nanosheets
Authors: Rahman Ashmalina , Khan Fazlurrahman , Jennings James Robert , Tan Ai Ling , Kim Young-Mog , Khan Mohammad Mansoob 
Published: July 2024

AbstractMolybdenum sulfide (MoS2) and modified MoS2 with different percentages of CdS (10%, 30%, and 50% CdS@MoS2) were successfully synthesized and characterized. The photocatalytic performance of the MoS2 and CdS@MoS2 was evaluated by degrading brilliant green (BG), methylene blue (MB), and rhodamine B (RhB) dyes under visible light irradiation. Amongst the synthesized photocatalysts, 50% CdS@MoS2 exhibited the highest photocatalytic activity, degrading 97.6%, 90.3%, and 75.5% of BG, MB, and RhB dyes, respectively within 5 h. The active species involved in the degradation processes were investigated. All trapping agents inhibited BG and MB degradation to a similar extent, indicating that all of the probed active species play an important role in the degradation of BG and MB. In contrast, h+ and O2•− were found to be the main reactive species in the photocatalytic RhB degradation. A potential mechanism for the photocatalytic degradation of dyes using CdS@MoS2 has been proposed. This work highlights the potential of CdS@MoS2 as a photocatalyst for more efficient water remediation applications.
Usability of a novel Hounsfield units measurement procedure to quantify intercorporal bone graft remodeling in patients after posterior lumbar interbody fusion: a case series
Authors: Reijmer Joey F. H. , van Susante Job L. C. , Kruijt Moyo C. , van Gorp Maarten J. , de Jong Lex D. 
Published: July 2024

Abstract
Background
There is a lack of knowledge about the biological process of intercorporal bone graft remodeling after posterior lumbar interbody fusion surgery and whether this process is associated with changes in back pain and intercorporal fusion status. As an alternative to the commonly used but unreliable fusion criteria, Hounsfield units can be used to quantify biological activity and changes in bone mineral content. However, studies assessing Hounsfield units conducted to date do not provide sufficient details about how the bone grafts were segmented to measure the Hounsfield units to allow for replication, and did not assess individual patient trends in graft changes over time. Using the data of nine patients after posterior lumbar interbody fusion, a novel Hounsfield units measurement procedure was developed and used to explore its usability to quantify the bone graft remodeling process.

Case details
We report a case series of nine patients (six male, three female, mean age 64 years, all Caucasian) who all had computed tomography scans performed at 1 and 2 years after posterior lumbar interbody fusion surgery. Overall, seven out of the nine (78%) cases had a 3–41% increase in their bone grafts’ Hounsfield units between 1 and 2 years after surgery. The cases showed large interindividual variability in their Hounsfield units values over time, which coincided with varying levels of back pain and intercorporal fusion status.

Conclusion
The Hounsfield units measurement procedure used for this case series may be useful to quantify intercorporal bone graft remodeling in patients after posterior lumbar interbody fusion, and may be used as an adjunct diagnostic measure to monitor bone graft remodeling over time. Future research is warranted to explore how to interpret bone graft Hounsfield units-values and Hounsfield units trajectories in light of clinical variables or intercorporal fusion status.
CACTI: an in silico chemical analysis tool through the integration of chemogenomic data and clustering analysis
Authors: Godinez-Macias Karla P. , Winzeler Elizabeth A. 
Published: July 2024

AbstractIt is well-accepted that knowledge of a small molecule’s target can accelerate optimization. Although chemogenomic databases are helpful resources for predicting or finding compound interaction partners, they tend to be limited and poorly annotated. Furthermore, unlike genes, compound identifiers are often not standardized, and many synonyms may exist, especially in the biological literature, making batch analysis of compounds difficult. Here, we constructed an open-source annotation and target hypothesis prediction tool that explores some of the largest chemical and biological databases, mining these for both common name, synonyms, and structurally similar molecules. We used this Chemical Analysis and Clustering for Target Identification (CACTI) tool to analyze the Pathogen Box collection, an open-source set of 400 drug-like compounds active against a variety of microbial pathogens. Our analysis resulted in 4,315 new synonyms, 35,963 pieces of new information and target prediction hints for 58 members.Scientific contributionsWith the employment of this tool, a comprehensive report with known evidence, close analogs and drug-target prediction can be obtained for large-scale chemical libraries that will facilitate their evaluation and future target validation and optimization efforts.
Identification of the most relevant aspects of spinal muscular atrophy (SMA) with impact on the quality of life of SMA patients and their caregivers: the PROfuture project, a qualitative study
Authors: de Lemus Mencía , Cattinari Maria G. , Pascual Samuel I. , Medina Julita , García Mar , Magallón Ana , Dumont María , Rebollo Pablo 
Published: July 2024

Abstract
Background
SMA is a hereditary neuromuscular disease that causes progressive muscle weakness and atrophy. Several studies have shown that the burden of SMA is very high at many levels. Functional assessment tools currently used do not completely address the impact of the disease in patients’ life. The objective of this qualitative study was to identify aspects of SMA that are relevant to patients and to design items useful for assessment purposes.

Results
Five focus group sessions were run during an annual SMA families meeting in Madrid, Spain. Focus groups were composed by parents of SMA type I children, sitter children type II-III, parents of sitter children type II-III, adult patients, and parents of walker children. Two trained facilitators conducted the focus groups using a semi-structured guideline to cover previously agreed topics based on the input of a Scientific and Patient Advisory Committee. The guideline was adapted for the different groups. According to what was communicated by participants, SMA entails a high burden of disease for both patients and their parents. Burden was perceived in physical, psychological, and social areas. Patient’s physical domain was the most relevant for participants, especially for parents of non-ambulant children, followed by limitations of motor scales to capture all changes, parents psychological burden, treatment expectations and patient’s psychological burden. Ten domains were the main areas identified as impacted by the disease: mobility and independence, fatigue and fatigability, infections and hospital consultations, scoliosis and contractures, vulnerability, pain, feeding, time spent in care, breathing, and sleep and rest.

Conclusions
This study confirms the necessity of evaluating other aspects of the disease that are not assessed in the functional motor scale. Measures of other aspects of the disease, such as pain, fatigue, feeding, should be also considered. A patient-reported outcomes instrument measuring such aspects in a valid and reliable way would be very useful. This study generated a list of new items relevant to be systematically measured in the assessment of the impact of SMA on the patients’ everyday life.