bluuebunny/crossref_metadata_2025_split huggingface dataset:
To stay civil during the carnage: Feeling rules for soldiers in British military memoirs from the Napoleonic Wars (1803–15)
Authors: Pahl Kerstin Maria 
Published: December 2024

Abstract
During the Napoleonic Wars (1803–15), an unprecedented number of soldiers wrote “military memoirs,” firsthand accounts of the “first total war.” Next to private forms of recording experiences and keeping contact with those at home, such as letters or diaries, these memoirs were part of a larger shift in the relations between the army and civil society: soldiers wrote, at least partly, to change what non-combatants thought about them. As Britain did not see battles on home soil, war was both omnipresent and far away. Moreover, the reputation of the British armed forces was notorious, with common soldiers famously called “the scum of the earth” by Wellington. In conveying the battlefield experience to a sheltered audience, military memoirs, especially those written during or shortly after the wars, aimed at bridging the emotional divide between military and civil life, between the callous soldier and the compassionate citizen. Soldiers, too, these texts argued, were men of feeling, able to preserve a moral sense of respectability despite all the killing, blood, and trauma. Many memoirs communicated viscerally and in graphic detail about the horrors of war, both to make the traumatizing experience understandable and to show the heights of their emotional self-discipline. Bringing together the history of biography, reading, and emotions, this article argues that, by writing frankly about their horrific experiences, British soldiers fighting during the Napoleonic Wars contributed to changing civil society’s feeling rules about the army, reproaching the civilians’ contempt, and soliciting their compassion.
Thermal Adaptation of Enzyme‐Mediated Processes Reduces Simulated Soil CO2 Fluxes Upon Soil Warming
Authors: Van de Broek Marijn , Riley William J. , Tang Jinyun , Frey Serita D. , Schmidt Michael W. I. 
Published: December 2024

AbstractUnderstanding factors influencing carbon effluxes from soils to the atmosphere is important in a world experiencing climatic change. Two important uncertainties related to soil organic carbon (SOC) stock responses to a changing climate are (a) whether soil microbial communities acclimate or adapt to changes in soil temperature and (b) how to represent this process in SOC models. To further explore these issues, we included thermal adaptation of enzyme‐mediated processes in a mechanistic SOC model (ReSOM) using the macromolecular rate theory. Thermal adaptation is defined here to encompass all potential responses of soil microbes and microbial communities following a change in temperature. To assess the effects of thermal adaptation of enzyme‐mediated processes on simulated SOC losses, ReSOM was applied to data collected from a 13‐year soil warming experiment. Results show that a model omitting thermal adaptation of enzyme‐mediated processes substantially overestimates observed CO2 effluxes during the initial years of soil warming. The bias against observed CO2 effluxes was lower for models including thermal adaptation of enzyme‐mediated processes. In addition, for a simulated linear 3°C soil warming over 100 years, models including thermal adaptation of enzyme‐mediated processes simulated SOC losses of a factor of three smaller than models omitting this process. As thermal adaptation of microbial community characteristics is generally not included in models simulating feedback between the soil, biosphere and atmosphere, we encourage future studies to assess the potential impact that microbial adaptation has on soil carbon – climate feedback representations in models.
Improving the rehabilitation of individuals admitted to England’s National Spinal Injuries Centre with traumatic brain injury
Authors: Falshaw Lawson , King Nigel , Cotter Imogen 
Published: December 2024

Abstract
Study design
Mixed methods service improvement project. Retrospective analysis of clinical documentation and qualitative focus group with clinicians.

Objectives
Although traumatic brain injury (TBI) and spinal cord injury (SCI) often co-occur, many barriers have been found to identifying TBI in SCI rehabilitation and adapting treatment accordingly. This study aimed to compare the number of individuals with a TBI detected at England’s National Spinal Injuries Centre to figures found in previous research and understand the barriers to adapting SCI rehabilitation in the presence of TBI.

Setting
England’s National Spinal Injuries Centre at Stoke Mandeville Hospital.

Methods
This mixed methods study assessed the documentation at each stage of 88 patients’ treatment where a TBI could be detected and used to inform rehabilitation, and subsequently, a focus group was conducted with staff to explore the barriers to detecting TBI and adapting SCI rehabilitation.

Results
Results suggested that data related to TBI were inconsistently recorded, the number of individuals recorded as having a TBI at the centre was lower than a recent study, and several barriers were interpreted from the focus group.

Conclusions
TBI in SCI populations may be an invisible unmet need. Several barriers may exist which prevent clinicians from detecting TBI in this population and adapting rehabilitation accordingly. Findings have implications for rehabilitation for individuals with TBI and SCI admitted to the service.
Oleanolic acid combined with aspirin plays antitumor roles in colorectal cancer via the Akt/NFκB/IκBα/COX2 pathway
Authors: Zhou Yulv , Lin Shengnan , Zhong Xinzhu , Huang Fang , Huang Jinxiang , Xu Luning 
Published: December 2024

AbstractAmong the common malignancies, colorectal cancer (CRC) is often resistant to chemotherapy because of drug resistance and severe toxicity. Currently, aspirin is one of the most promising CRC chemopreventive drugs, both for primary prevention and for reducing the chance of recurrence and metastasis following radical surgery in patients with early-stage CRC. Oleanolic acid is a potential antineoplastic drug that has an antagonistic effect on many kinds of tumors. Network pharmacology, molecular docking, and in vitro experiments were performed to investigate whether OA combined with aspirin can enhance the anticancer effects of aspirin. As indicated by the network pharmacology results, oleanolic acid and aspirin can regulate multiple signaling pathways through multiple target proteins, including NFκB1\IκBα\PTGS2\MAPK3\PIK3CA. A series of cellular experiments demonstrated for the first time that oleanolic acid synergistically enhances aspirin to inhibit the proliferation and invasion of HCT116 and HT29 cells and induce S-phase arrest by regulating Akt/NFκB/IκBα/COX2 signaling pathway, thus synergistically enhancing the ability of aspirin to promote apoptosis of colorectal cancer cells. This study provides a novel approach to the use of fresh medications for the treatment of colorectal cancer and offers a theoretical foundation for the potential creation of aspirin derivatives based on oleanolic acid.
GALNTL5, which is restricted to mouse spermatids, impairs endoplasmic reticulum (ER) function through direct interaction with ER chaperone proteins
Authors: Takasaki Nobuyoshi , Koya Yoshihiro , Yamashita Mamoru , Nawa Akihiro 
Published: December 2024

AbstractPolypeptide N-acetylgalactosaminyltransferase-like protein 5 (GALNTL5) was identified as a pp-GalNAc-T family gene. Nevertheless, GALNTL5 has no glycosyltransferase activity. In mice, Galntl5 expression is restricted to differentiating spermatids, and haploinsufficiency leads to immotile spermatozoa with an aberrant protein composition. Moreover, heterozygotic deletions of human GALNTL5 have been detected in patients diagnosed with asthenozoospermia (low sperm motility). Although these findings indicate that GALNTL5 is a functional molecule essential for mature sperm formation in mammals, the exact function of GALNTL5 in spermiogenesis remains unknown. To clarify this role, we established the mouse spermatocyte cell line GC-2spd(ts), which exhibits drug-inducible GALNTL5 expression. Interestingly, continuous GALNTL5 expression in the resultant cell lines caused apoptosis with cell shrinkage, and GALNTL5 was localized in the endoplasmic reticulum (ER) and was associated with two ER-resident chaperone proteins, calnexin and BiP (GRP78). Calnexin recognized and strongly bound to the N-glycans on GALNTL5 molecules modified in the ER. In contrast, ER-resident BiP likely attached to GALNL5 regardless of its glycosylation. GALNTL5 expression abolished the binding between calnexin and misfolded substrate proteins, indicating that GALNTL5 directly blocks calnexin function. Furthermore, the interaction between GALNTL5 and calnexin decreased the level of BiP protein, and consequently also the expression levels of proteins that are resident in the ER, Golgi apparatus, and cytoplasm. These reduced protein levels were confirmed by loss of calnexin or BiP function in the GC-2spd(ts) cell line using siRNA knockdown. Further, sustained expression of GALNTL5 resulted in cell structure changes, including the position of the cis-Golgi apparatus and alterations in the ER network. These results strongly suggest that GALNTL5 contributes to alteration of the cell structure specific to differentiating spermatids by blocking ER function.
Phytochemical-mediated efferocytosis and autophagy in inflammation control
Authors: Vafadar Asma , Tajbakhsh Amir , Hosseinpour-Soleimani Fatemeh , Savardshtaki Amir , Hashempur Mohammad Hashem 
Published: December 2024

AbstractEfferocytosis, the clearance of apoptotic cells, is a critical process that maintains tissue homeostasis and immune regulation. Defective efferocytosis is linked to the development of chronic inflammatory conditions, including atherosclerosis, neurological disorders, and autoimmune diseases. Moreover, the interplay between autophagy and efferocytosis is crucial for inflammation control, as autophagy enhances the ability of phagocytic cells. Efficient efferocytosis, in turn, regulates autophagic pathways, fostering a balanced cellular environment. Dysregulation of this balance can contribute to the pathogenesis of various disorders. Phytochemicals, bioactive compounds found in plants, have emerged as promising therapeutic agents owing to their diverse pharmacological properties, including antioxidant, anti-inflammatory, and immunomodulatory effects. This review aims to highlight the pivotal role of phytochemicals in enhancing efferocytosis and autophagy and explore their potential in the prevention and treatment of related disorders. This study examines how phytochemicals influence key aspects of efferocytosis, including phagocytic cell activation, macrophage polarization, and autophagy induction. The therapeutic potential of phytochemicals in atherosclerosis and neurological diseases is highlighted, emphasizing their ability to enhance efferocytosis and autophagy and reduce inflammation. This review also discusses innovative approaches, such as nanoformulations and combination therapies to improve the targeting and bioavailability of phytochemicals. Ultimately, this study inspires further research and clinical applications in phytochemical-mediated efferocytosis enhancement for managing chronic inflammatory and autoimmune conditions.
USP21-EGFR signaling axis is functionally implicated in metastatic colorectal cancer
Authors: Shin Ji Hye , Kim Mi-Jeong , Kim Ji Young , Choi Bongkum , Kang Yeeun , Kim Seo Hyun , Lee Ha-Jeong , Kwon Dohee , Cho Yong Beom , Kim Kyeong Kyu , Chun Eunyoung , Lee Ki-Young 
Published: December 2024

AbstractThe emerging role of ubiquitin-specific peptidase 21 (USP21) in stabilizing Fra-1 (FOSL1) highlights its involvement in promoting colorectal cancer (CRC) metastasis. Additionally, a reciprocal link between EGFR signaling and Fra-1 activation has been identified, mediated through matrix metalloproteinases (MMPs). However, the functional implications of the USP21-EGFR signaling axis in metastatic CRC (mCRC) are not fully understood. To investigate the clinical correlation between USP21 and EGFR expression, RNA-Seq data from tumor tissues (n = 27) and matched normal tissues (n = 27) of 27 mCRC patients were analyzed. Functional studies were performed, including the use of CRISPR/Cas9 to generate USP21-knockout (USP21-KO) CRC cells, in vitro assays for cancer progression and tumor formation, in vivo xenograft assays in NSG mice. Additionally, the therapeutic effect of the USP21 inhibitor, BAY-805, was evaluated. We found that elevated levels of USP21 and EGFR expression in mCRC patients were associated with poorer survival outcomes. Mechanistically, USP21 was found to enhance EGFR stability by deubiquitinating EGFR, leading to reduced EGFR degradation. USP21-KO colon cancer cells exhibited significantly reduced proliferation, migration, colony formation, and 3D tumor spheroid formation in response to EGF. Furthermore, the tumorigenic activity in vivo was markedly diminished in NSG mice xenografted with USP21-KO colon cancer cells. Importantly, BAY-805 demonstrated a notable inhibitory effect on the formation of 3D tumor spheroids in colorectal cancer cells stimulated with EGF. These findings suggest that USP21 could be a valuable therapeutic target and predictive biomarker for managing mCRC driven by EGF.
SLC50A1 inhibits the doxorubicin sensitivity in hepatocellular carcinoma cells through regulating the tumor glycolysis
Authors: Wang Ganggang , Jin Wenzhi , Zhang Lianmei , Dong Meiyuan , Zhang Xin , Zhou Zhijie , Wang Xiaoliang 
Published: December 2024

AbstractMetabolic reprogramming has been found to be closely associated with the occurrence and development of hepatocellular carcinoma (HCC). The relationship between SLC50A1, a member of the SLC family involved in glucose transmembrane transport, and HCC remains unclear. This study aims to investigate the function and underlying mechanisms of SLC50A1 in the occurrence and progression of HCC. Based on bioinformatics analysis and clinical sample testing, we observed a significant upregulation of SLC50A1 in HCC, which is correlated with unfavorable prognosis in HCC patients. Additionally, there is a noticeable correlation between the expressions of SLC50A1 and METTL3. Further in vitro and in vivo experiments confirmed that SLC50A1 can regulate cellular glycolysis and the cell cycle, thereby promoting the proliferation of HCC cells while reducing apoptosis. Moreover, our findings indicate that SLC50A1 enhances resistance of HCC cells to DOX and 2-DG. Furthermore, we discovered that the m6A methyltransferase METTL3 mediates the methylation modification of SLC50A1. The recognition and binding of the modified SLC50A1 by IGF2BP2 subsequently promote its stability and translational expression. Consequently, our research identifies the METTL3/SLC50A1 axis as a novel therapeutic target in the context of HCC.
Cardiocutaneous syndrome is caused by aggregation of iASPP mutants
Authors: Lotz Rebecca , Osterburg Christian , Schäfer Birgit , Lu Xin , Dötsch Volker 
Published: December 2024

AbstractThe ASPP (apoptosis-stimulating protein of p53) family of proteins is involved in many cellular interactions and is starting to emerge as a major scaffolding hub for numerous proteins involved in cancer biology, inflammation and cellular integrity. It consists of the three members ASPP1, ASPP2 and iASPP which are best known for modulating the apoptotic function of p53, thereby directing cell fate decision. Germline mutations in iASPP have been shown to cause cardiocutaneous syndromes, a combination of heart and skin defects usually leading to death before the age of five. Mutations in iASPP causing these syndromes do not cluster in hot spots but are distributed throughout the protein. To understand the molecular mechanism(s) of how mutations in iASPP cause the development of cardiocutaneous syndromes we analysed the stability and solubility of iASPP mutants, characterized their interaction with chaperones and investigated their influence on NF-ĸB activity. Here we show that three different mechanisms are responsible for loss of function of iASPP: loss of the complete C-terminal domain, mutations resulting in increased auto-inhibition and aggregation due to destabilization of the C-terminal domain. In contrast to these germline mutations causing cardiocutaneous syndromes, missense mutations found in cancer do not result in aggregation.
Role of N6-methyladenosine methylation in nasopharyngeal carcinoma: current insights and future prospective
Authors: Zhao YaYan , Li Jie , Dian MeiJuan , Bie YaNan , Peng ZhiTao , Zhou Ying , Zhou BingQian , Hao WeiChao , Wang XiCheng 
Published: December 2024

AbstractNasopharyngeal carcinoma (NPC) is a distinct type of head and neck squamous cell carcinoma prevalent in Southern China, Southeast Asia, and North Africa. Despite advances in treatment options, the prognosis for advanced NPC remains poor, underscoring the urgent need to explore its underlying mechanisms and develop novel therapeutic strategies. Epigenetic alterations have been shown to play a key role in NPC progression. Recent studies indicate that dysregulation of RNA modifications in NPC specifically affects tumor-related transcripts, influencing various oncogenic processes. This review provides a comprehensive overview of altered RNA modifications and their regulators in NPC, with a focus on m6A and its regulatory mechanisms. We discuss how m6A RNA modification influences gene expression and affects NPC initiation and progression at the molecular level, analyzing its impact on cancer-related biological functions. Understanding these modifications could reveal new biomarkers and therapeutic targets for NPC, offering promising directions for future research and precision medicine.
Hexamethylene amiloride induces lysosome-mediated cell death in multiple myeloma through transcription factor E3
Authors: Yang Nianhui , Dong Zexuan , Xiao Weihao , Deng Suqi , Li Yizhen , Hua Lei , Li Yue , Wu Yingying , Huang Kexiu , Zhou Wei , Wang Hua , Li Yonghua , Du Juan , Zeng Hui 
Published: December 2024

AbstractMultiple myeloma (MM) is the second common hematological malignancy characterized by the abnormal proliferation of plasma cells. Although advances in the past decades have led to improved outcomes and longer survival, MM remains largely incurable. New targets and targeted therapy may help to achieve better outcomes. Proton exporter NHE1 is highly expressed by tumor cells to maintain pH gradient for their survival and its inhibitor Hexamethylene amiloride (HA) has been demonstrated anti-tumor effect. However, whether HA could inhibit MM remains unknown. In this study, we firstly demonstrated that elevated expression level of NHE1 is associated with poor prognosis of MM. Moreover, the NHE1 inhibitor HA inhibited growth and induced apoptosis effectively in both MM cell lines and primary bone marrow cells from MM patients. Mechanistically, inhibitory effect was achieved partially through TFE3-mediated lysosomal production. With a MM xenograft mouse model, we verified that HA has a significant anti MM effect in vivo. Importantly, HA induced apoptosis of the carfilzomib-resistant MM cells and enhanced the effect of carfilzomib in MM. In summary, we demonstrated that NHE1 inhibitor HA can effectively inhibit MM growth both in vitro and in vivo, providing a new therapeutic strategy for improved outcome of de novo and resistant MM.
Genomic predictors of radiation response: recent progress towards personalized radiotherapy for brain metastases
Authors: Harary Paul M. , Rajaram Sanjeeth , Chen Maggie S. , Hori Yusuke S. , Park David J. , Chang Steven D. 
Published: December 2024

AbstractRadiotherapy remains a key treatment modality for both primary and metastatic brain tumors. Significant technological advances in precision radiotherapy, such as stereotactic radiosurgery and intensity-modulated radiotherapy, have contributed to improved clinical outcomes. Notably, however, molecular genetics is not yet widely used to inform brain radiotherapy treatment. By comparison, genetic testing now plays a significant role in guiding targeted therapies and immunotherapies, particularly for brain metastases (BM) of lung cancer, breast cancer, and melanoma. Given increasing evidence of the importance of tumor genetics to radiation response, this may represent a currently under-utilized means of enhancing treatment outcomes. In addition, recent studies have shown potentially actionable mutations in BM which are not present in the primary tumor. Overall, this suggests that further investigation into the pathways mediating radiation response variability is warranted. Here, we provide an overview of key mechanisms implicated in BM radiation resistance, including intrinsic and acquired resistance and intratumoral heterogeneity. We then discuss advances in tumor sampling methods, such as a collection of cell-free DNA and RNA, as well as progress in genomic analysis. We further consider how these tools may be applied to provide personalized radiotherapy for BM, including patient stratification, detection of radiotoxicity, and use of radiosensitization agents. In addition, we describe recent developments in preclinical models of BM and consider their relevance to investigating radiation response. Given the increase in clinical trials evaluating the combination of radiotherapy and targeted therapies, as well as the rising incidence of BM, it is essential to develop genomically informed approaches to enhance radiation response.
Overexpression of PDSS2-Del2 in HCC promotes tumor metastasis by interacting with macrophages
Authors: Li Guanghui , Suo Daqin , Ma Yuanzhen , Zeng Tingting , Zhan Jiarong , Yuan Yunfei , Guan Xin-Yuan , Li Yan 
Published: December 2024

AbstractHepatocellular carcinoma (HCC) is one of the most frequent solid tumors worldwide. According to the Global Cancer Statistics 2020, liver cancer remains the third cause of cancer death globally. Despite significant advances in systemic therapy, HCC still has one of the worst prognoses due to its frequent recurrence and metastasis. Previously we found that PDSS2-Del2 (prenyl diphosphate synthase subunit 2 with exon 2 deletion), a novel variant of PDSS2, could promote HCC metastasis and angiogenesis via activating NF-κB. In this study, we elucidate a novel mechanism by which PDSS2-Del2 enhances HCC metastasis. The overexpression of PDSS2-Del2 in HCC cells promotes the ubiquitination and degradation of SKOR1, consequently heightening SMAD3 phosphorylation. Subsequently, the expression and secretion of MST1 (macrophage stimulatory protein 1) are upregulated, resulting in enhanced recruitment of macrophages into tumor tissues where they differentiate into M2-type macrophages. Co-culture with PDSS2-Del2 overexpressed HCC cells activated the PI3K/AKT signaling pathway in macrophages, and more MMP2 and MMP9 were secreted, which facilitated HCC cell dissemination. Our study elucidates a novel molecular mechanism by which PDSS2-Del2 promotes HCC metastasis, which may contribute to the development of effective HCC clinical treatment and prevent tumor metastasis. Furthermore, MST1 could be a potential therapeutic target, and MST1 inhibitors might be integrated into clinical practice for HCC patients with high expression of PDSS2-Del2.