bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mismatch repair protein deficiency and its implications on distant metastasis in colorectal cancer: A comprehensive analysis
Authors: Fan Chuanwen , Fang Chao , Wang Wei , Lv Zhaoying , Zhang Xueli , Long Feiwu , Jiang Zongze , Li Yuan , Zhang Hong , Zhou Zong‐Guang , Wang Cun , Sun Xiao‐Feng 
Published: March 2024

AbstractBackgroundWhile previous studies have indicated variability in distant metastatic potential among different mismatch repair (MMR) states in colorectal cancer (CRC), their findings remain inconclusive, especially considering potential differences across various ethnic backgrounds. Furthermore, the gene regulatory networks and the underlying mechanisms responsible for these variances in metastatic potential across MMR states have yet to be elucidated.MethodsWe collected 2058 consecutive primary CRC samples from the South West of China and assessed the expression of MMR proteins (MLH1, MSH2, MSH6, and PMS2) using immunohistochemistry. To explore the inconsistencies between different MMR statuses and recurrence, we performed a meta‐analysis. To delve deeper, we employed Weighted Gene Co‐expression Network Analysis (WGCNA), ClueGo, and iRegulon, pinpointing gene expression networks and key regulatory molecules linked to metastasis and recurrence in CRC. Lastly, both univariate and multivariate Cox regression analyses were applied to determine the impact of core regulatory molecules on metastasis.ResultsOf the samples, 8.2% displayed deficient MMR (dMMR), with losses of MLH1 and PSM2 observed in 40.8% and 63.9%, respectively. A unique 24.3% isolated loss of PMS2 without concurrent metastasis was identified, a result that diverges from established literature. Additionally, our meta‐analysis further solidifies the reduced recurrence likelihood in dMMR CRC samples compared to proficient MMR (pMMR). Two gene expression networks tied to distant metastasis and recurrence were identified, with a majority of metastasis‐related genes located on chromosomes 8 and 18. An IRF1 positive feedback loop was discerned in the metastasis‐related network, and IRF1 was identified as a predictive marker for both recurrence‐free and distant metastasis‐free survival across multiple datasets.ConclusionGeographical and ethnic factors might influence peculiarities in MMR protein loss. Our findings also highlight new gene expression networks and crucial regulatory molecules in CRC metastasis, enhancing our comprehension of the mechanisms driving distant metastasis.
Effect of galectin‐1 on prognosis and responsiveness of immune checkpoint plus tyrosine kinase inhibition in renal cell carcinoma
Authors: Wang Jiajun , Zhang Sihong , Wang Ying , Zhu Yanjun , Xu Xianglai , Guo Jianming 
Published: March 2024

AbstractBackgroundIn renal cell carcinoma (RCC), no clinically available biomarker has been utilized for checkpoint inhibitor immunotherapy (IO) + tyrosine kinase inhibitor (TKI) combinations. Galectin‐1 overexpression is found in tumors, with potential immune‐regulating roles.MethodsRNA‐sequencing was performed in two cohorts of RCC treated with IO/TKI combination therapy (ZS‐MRCC, JAVELIN‐101). Immunohistochemistry and flow cytometry were performed to investigate immune cell infiltration and function in the tumor microenvironment of RCC. The RECIST criteria were used to define response and progression‐free survival (PFS).ResultsGalectin‐1 expression was elevated in RCC with higher stage (p < 0.001) and grade (p < 0.001). Galectin‐1 expression was also elevated in non‐responders of IO/TKI therapy (p = 0.047). High galectin‐1 was related with shorter PFS in both ZS‐MRCC cohort (p = 0.036) and JAVELIN‐101 cohort (p = 0.005). Multivariate Cox analysis defined galectin‐1 as an independent factor for PFS (HR 2.505; 95% CI 1.116–5.622; p = 0.026). In the tumor microenvironment, high galectin‐1 was related with decreased GZMB+CD8+ T cells (Speraman's ρ = −0.31, p = 0.05), and increased PD1 + CD8+ T cells (Speraman's ρ = 0.40, p = 0.01). Besides, elevated number of regulatory T cells (p = 0.039) and fibroblasts (p = 0.011) was also found in high galectin‐1 tumors. Finally, a random‐forest score (RFscore) was built for predicting IO/TKI benefit. IO/TKI therapy showed benefit only in low‐RFscore patients (HR 0.489, 95% CI 0.358–0.669, p < 0.001), rather than high‐RFscore patients (HR 0.875, 95% CI 0.658–1.163, p = 0.357).ConclusionsHigh galectin‐1 indicated therapeutic resistance and shorter PFS of IO/TKI therapy. High galectin‐1 also indicated CD8+ T cell dysfunction. High galectin‐1 could be applied for patient selection of IO/TKI therapy in RCC.
The death burden of colorectal cancer attributable to modifiable risk factors, trend analysis from 1990 to 2019 and future predictions
Authors: Zhu Ning , Zhang Yan , Mi Mi , Ding Yuwei , Weng Shanshan , Zheng Jia , Tian Yang , Yuan Ying 
Published: March 2024

AbstractBackgroundThe death burden attributable to modifiable risk factors is key to colorectal cancer (CRC) prevention. This study aimed to assess the prevalence and regional distribution of attributable CRC death burden worldwide from 1990 to 2019.MethodsWe extracted data from the Global Burden of Disease Study in 2019 and assessed the mortality, age‐standardized death rate (ASDR), population attributable fractions, and time trend in CRC attributable to risk factors by geography, socio‐demographic index (SDI) quintile, age, and sex.ResultsOver the past 30 years, from high to low SDI region, the number of deaths increased by 46.56%, 103.55%, 249.64%, 231.89%, 163.11%, and the average annual percentage change (AAPC) for ASDR were −1.06%, −0.01%, 1.32%, 1.19%, and 0.65%, respectively. ASDR in males was 1.88 times than in females in 2019; ASDR in males showed an increasing trend (AAPC 0.07%), whereas ASDR in females showed a decreasing trend (AAPC −0.69%) compared to figures in 1990. In 2019, from high to low SDI region, the 15–49 age group accounted for 3%, 6%, 10%, 11%, and 15% of the total population; dietary and metabolic factors contributed 43.4% and 20.8% to CRC‐attributable death worldwide. From high to low SDI region, ASDRs caused by dietary and metabolic factors increased by −23.4%, −5.5%, 25.8%, 29.1%, 13.5%, and 1.4%, 33.3%, 100.8%, 128.4%, 77.7% respectively, compared to 1990.ConclusionsThe attributable CRC death burden gradually shifted from higher SDI to lower SDI regions. The limitation in males was more significant, and the gap is expected to be further expanded. In lower SDI regions, the death burden tended to affect younger people. The leading cause of CRC‐attributable deaths was the inadequate control of dietary and metabolic risk factors.
Trauma plays an important role in acral melanoma: A retrospective study of 303 patients
Authors: Huang Rong , Zhao Mengke , Zhang Guiying , Yang Yueling , Wang Jiayu , Zheng Kelin , Li Lin , Su Xinyu , Zhao Lianjun , Wu Yirong , Zou Zhengyun 
Published: March 2024

AbstractIntroductionAcral melanoma (AM) is the most common subtype of malignant melanoma in China, with a very poor prognosis. Despite the frequent reporting of trauma events in AM cases, the precise etiology of AM remains elusive.MethodsA retrospective analysis was conducted on a cohort of 303 AM patients at Nanjing Drum Tower Hospital. The patients were categorized into four distinct groups based on different patterns of disease onset: trauma type (Type 1), pigmented nevus type (Type 2), pigmented nevi with trauma (Type 3), and pigmented nevi with natural ulceration (Type 4). Differences in clinicopathological features, genetic alterations, and tumor immune microenvironment (TIME) were analyzed.ResultsTraumatic events accounted for a large proportion of AM cases. Among these categories, Type 1 patients displayed the least favorable pathological traits and an immunosuppressive TIME. Common copy number variations (CNVs) were observed in CCND1, RB1, FGF19, and IL7R, while CNVs in CDK4 and TERT occurred less frequently in patients with a history of trauma (Type 1 and Type 3). Type 2 patients exhibited the most favorable pathological characteristics and genetic profiles, and demonstrated the lowest incidence of CCDN1 and RB1 CNVs but had the highest CDK4 CNVs. In contrast, the pathological behavior of Type 3 and Type 4 patients was in between Type 1 and Type 2. And patients in Type 3 and Type 4 displayed a more favorable overall microenvironment.ConclusionThis study provides a clinical classification of Chinese AM based on diverse clinical onset characteristics and highlights the important role of trauma in AM. These findings may help to guide the diagnosis, treatment, and prognosis of AM patients. Further investigations are imperative to elucidate the underlying mechanisms governing the association between trauma and AM.
Synthesis and Molecular Docking of some new Thiazolidinone and Thiadiazole Derivatives as Anticancer Agents
Authors: Saeed Ali , Soliman Ahbarah M. , Abdullah Mahmood M. S. , Abdel‐Latif Ehab , El‐Demerdash Amr 
Published: March 2024

AbstractNew sets of functionalized thiazolidinone and thiadiazole derivatives were synthesized, and their cytotoxicity was evaluated on HepG2, MCF‐7, HTC‐116, and WI38 cells. The synthetic approach is based on the preparation of 4‐(4‐acetamidophenyl)thiosemicarbazide (4) and their thiosemicarbazones 5 a–e, which are converted to the corresponding thiazoldin‐4‐one compounds 6 a–e upon cyclization with ethyl bromoacetate. The thiadiazole compounds 9 and 12 were obtained by reacting 4‐(4‐acetamidophenyl)thiosemicarbazide with isothiocyanates and/or ethyl 2‐cyano‐3,3‐bis(methylthio)acrylate, respectively. The thiazolidinone compounds 6 c and 6 e exhibited strong cytotoxicity against breast cancer cells, with an IC50 (6.70±0.5 μM) and IC50 (7.51±0.8 μM), respectively, very close to that of doxorubicin (IC50: 4.17±0.2 μM). In addition, the anti‐cancer properties of the tested thiazolidinone and thiadiazole scaffolds were further explored by the molecular docking program (MOE)‐(PDB Code‐1DLS). Compounds 5 d, 5 e, 6 d, 6 e, and 7 have the best binding affinity, ranging from −8.5386 kcal.mol−1 to −8.2830 kcal.mol−1.
Glutamic Acid Modified Gold Nanorod Sensor for the Detection of Calcium ions in Neuronal Cells
Authors: Pathiriparambath Muhammed Shafeeque Rahman , Joseph Merin , Manog Mithun , Thomas Vinoy , Tharayil Hanas , Nair Lakshmi V. 
Published: March 2024

AbstractCalcium (Ca2+) ions play a crucial role in the functioning of neurons, governing various aspects of neuronal activity such as rapid modulation and alterations in gene expression. Ca2+ signaling has a significant impact on the development of diseases and the impairment of neuronal functions. Herein, the study reports a Ca2+ ion sensor in neuronal cells using a gold nanorod. The gold nanorod (GA‐GNR) conjugated glutamic acid developed in the study was used as a nano‐bio probe for the experimental and in vitro detection of calcium. The nanosensor is colloidally stable, preserves plasmonic properties, and shows good viability in neuronal cells, as well as promoting neuron cell line growth. The cytotoxicity and cell penetration of the nanosensor are studied using Raman spectroscopy, brightfield and darkfield microscopy imaging, and MTT assays. The quantification of Ca2+ ions in neuronal cells is determined by monitoring the surface plasmon resonance (SPR) of the GA‐GNR. The change in the intensity profile in the presence of Ca2+ incubated neurons was effectively used to develop a portable prototype of an optical Ca2+ sensor, proposing it as a tool for neurodegenerative disease diagnosis and neuromodulation evaluation.
Phosphoramide‐Based Metal‐Organic Frameworks for Effective Gas Adsorption
Authors: Sugamata Koh , Kobayashi Sho , Amanokura Natsuki , Shirai Akihiro , Minoura Mao 
Published: March 2024

AbstractCost‐effective and facile synthetic routes to organic ligands, along with porous materials that exhibit exceptional gas‐storage properties, promise significant industrial applications. Here, a two‐step synthesis of novel organophosphorus ligands without metal catalysts is reported. These ligands serve as versatile linkers for the construction of metal‐organic frameworks (MOFs) incorporating various metal ions, including zinc and copper. One of the zinc‐based MOFs demonstrates remarkable gas‐storage properties, with a hydrogen (H2) capacity exceeding 2.5 wt% at 77 K and 100 kPa as well as a carbon dioxide (CO2) capacity exceeding 20 wt% at 298 K and 100 kPa. Furthermore, this zinc‐based MOF can be synthesized through a solvothermal process on the gram scale that yields high‐quality single crystals.
MiRNA research—The potential for understanding the multiple facets of anorexia nervosa
Authors: Voelz Clara , Trinh Stefanie , Käver Larissa , Tran Mai‐Tam , Beyer Cordian , Seitz Jochen 
Published: March 2024

AbstractAnorexia nervosa (AN) has a multifaceted and complex pathology, yet major gaps remain in our understanding of factors involved in AN pathology. MicroRNAs (miRNAs) play a regulatory role in translating genes into proteins and help understand and treat diseases. An extensive literature review on miRNAs with AN and comorbidities has uncovered a significant lack in miRNA research. To demonstrate the importance of understanding miRNA deregulation, we surveyed the literature on depression and obesity providing examples of relevant miRNAs. For AN, no miRNA sequencing or array studies have been found, unlike other psychiatric disorders. For depression and obesity, screenings and mechanistic studies were conducted, leading to clinical studies to improve understanding of their regulatory influences. MiRNAs are promising targets for studying AN due to their role as signaling molecules, involvement in psychiatric‐metabolic axes, and potential as biomarkers. These characteristics offer valuable insights into the disease's etiology and potential new treatment options. The first miRNA‐based treatment for rare metabolic disorders has been approved by the FDA and it is expected that these advancements will increase in the next decade. MiRNA research in AN is essential to examine its role in the development, manifestation, and progression of the disease.Public SignificanceThe current understanding of the development and treatment of AN is insufficient. miRNAs are short regulatory sequences that influence the translation of genes into proteins. They are the subject of research in various diseases, including both metabolic and psychiatric disorders. Studying miRNAs in AN may elucidate their causal and regulatory role, uncover potential biomarkers, and allow for future targeted treatments.
Environmental DNA–RNA dynamics provide insights for effective monitoring of marine invasive species
Authors: Scriver Michelle , von Ammon Ulla , Pochon Xavier , Arranz Vanessa , Stanton Jo‐Ann L. , Gemmell Neil J. , Zaiko Anastasija 
Published: March 2024

AbstractEnvironmental DNA and RNA (eDNA/eRNA) can serve as molecular tools for biodiversity monitoring and biosecurity surveillance. However, uncertainties still exist regarding the persistence and dynamics of marine nucleic acids in the environment and the effects of post‐sampling storage on species detectability. To bridge these gaps, an experiment was conducted in an Auckland marina, a known New Zealand entry point for marine non‐indigenous species (NIS). We targeted a prominent invader, the Mediterranean fanworm Sabella spallanzanii, for eDNA/eRNA‐based detection. Permeable dialysis bags filled with seawater collected near an S. spallanzanii colony were deployed in the marina to simulate environmental conditions, with a subset of bags stored on ice to mimic field storage conditions. Sabella spallanzanii eDNA/eRNA signal was quantified using droplet digital PCR on samples collected over 24 h of dialysis bag deployment. Results challenged traditional first‐order decay models, showing inconsistent eDNA/eRNA signal patterns and no significant concentration changes between 0 and 24 h. Consequently, total eDNA fragmentation was assessed using the Agilent 2100 Bioanalyzer® electrophoresis system, which revealed a rise in the number of total eDNA fragments and an unexpected increase in the median fragment size of total eDNA under field conditions over time, likely originating from the ambient microbiome. Additional analysis using long‐read sequencing (Oxford Nanopore Technologies, UK) revealed an increase in microbial eDNA reads within the in‐field samples, suggesting potential microbial growth within the dialysis bags. In contrast, the ice‐stored samples exhibited no significant changes in the number of reads assigned to microbial taxa, implying limited microbial growth in cold storage. These findings provide insights into total eDNA dynamics and its potential impact on targeted eDNA concentration and detection. Further comprehensive research on eDNA/eRNA dynamics, particularly focused on eRNA, is essential, as this understanding is crucial for refining survey interpretation and sampling design for effective environmental management.
Interlaboratory validation of the ToxTracker assay: An in vitro reporter assay for mechanistic genotoxicity assessment
Authors: Hendriks Giel , Adriaens Els , Allemang Ashley , Clements Julie , Cole Gabrielle , Derr Remco , Engel Maria , Hamel Annie , Kidd Darren , Kellum Stephanie , Kiyota Tomomi , Myhre Abby , Naëssens Valerie , Pfuhler Stefan , Roy Marise , Settivari Raja , Schuler Maik , Zeller Andreas , van Benthem Jan , Vanparys Philippe , Kirkland David 
Published: March 2024

AbstractToxTracker is a mammalian cell reporter assay that predicts the genotoxic properties of compounds with high accuracy. By evaluating induction of various reporter genes that play a key role in relevant cellular pathways, it provides insight into chemical mode‐of‐action (MoA), thereby supporting discrimination of direct‐acting genotoxicants and cytotoxic chemicals. A comprehensive interlaboratory validation trial was conducted, in which the principles outlined in OECD Guidance Document 34 were followed, with the primary objectives of establishing transferability and reproducibility of the assay and confirming the ability of ToxTracker to correctly classify genotoxic and non‐genotoxic compounds. Reproducibility of the assay to predict genotoxic MoA was confirmed across participating laboratories and data were evaluated in terms of concordance with in vivo genotoxicity outcomes. Seven laboratories tested a total of 64 genotoxic and non‐genotoxic chemicals that together cover a broad chemical space. The within‐laboratory reproducibility (WLR) was up to 98% (73%–98% across participants) and the overall between‐laboratory reproducibility (BLR) was 83%. This trial confirmed the accuracy of ToxTracker to predict in vivo genotoxicants with a sensitivity of 84.4% and a specificity of 91.2%. We concluded that ToxTracker is a robust in vitro assay for the accurate prediction of in vivo genotoxicity. Considering ToxTracker's robust standalone accuracy and that it can provide important information on the MoA of chemicals, it is seen as a valuable addition to the regulatory in vitro genotoxicity battery that may even have the potential to replace certain currently used in vitro battery assays.
Titanium oxide aerogel/graphene oxide based electrode for electrochemical supercapacitors
Authors: Hanif Md. Abu , Kim Young‐Soon , Kwac Lee Ku , Ameen Sadia , Abdullah Abdulmuin M. , Akhtar M. Shaheer 
Published: March 2024

AbstractIn order to build electrochemical energy storage electrodes, carbon composite materials containing nanosized metal oxides might be desirable. This article describes the designing of TiO2 aerogel/graphene oxide (TiO2‐A/GO) composites for electrochemical supercapacitors. TiO2‐A was synthesized by a simple sol‐gel process followed by annealing at 250°C and thereafter, different concentrations of GO were mixed to prepare TiO2‐A/GO composites via sonochemical method. The intermixing of GO and TiO2‐A in composite was confirmed by observing the structural and crystalline characterizations. Two electrode electrochemical system was used to elucidate the capacitive characteristics of TiO2‐A/GO composite electrode by cyclic voltammetry analysis. In comparison with TiO2‐A electrode, high specific capacitances (Cs) were recorded for TiO2‐A/GO composite electrode. TiO2‐A/2GO composite electrode attained the highest Cs value of ~338.2 Fg−1 at 10 mVs−1 with excellent cycle stability after 2000 cycles. Thus, the prepared TiO2‐A/GO composites‐based electrode can be a promising material to achieve good capacitive properties.
The myelination‐associated G protein‐coupled receptor 37 is regulated by Zfp488, Nkx2.2, and Sox10 during oligodendrocyte differentiation
Authors: Schmidt Antonia L. , Kremp Marco , Aratake Takaaki , Cui Siying , Lin Yifeng , Zhong Xiaowen , Lu Q. Richard , Zhang Chengfu , Qiu Mengsheng , Aberle Tim , Wegner Michael 
Published: March 2024

AbstractOligodendrocyte differentiation and myelination in the central nervous system are controlled and coordinated by a complex gene regulatory network that contains several transcription factors, including Zfp488 and Nkx2.2. Despite the proven role in oligodendrocyte differentiation little is known about the exact mode of Zfp488 and Nkx2.2 action, including their target genes. Here, we used overexpression of Zfp488 and Nkx2.2 in differentiating CG4 cells to identify aspects of the oligodendroglial expression profile that depend on these transcription factors. Although both transcription factors are primarily described as repressors, the detected changes argue for an additional function as activators. Among the genes activated by both Zfp488 and Nkx2.2 was the G protein‐coupled receptor Gpr37 that is important during myelination. In agreement with a positive effect on Gpr37 expression, downregulation of the G protein‐coupled receptor was observed in Zfp488‐ and in Nkx2.2‐deficient oligodendrocytes in the mouse. We also identified several potential regulatory regions of the Gpr37 gene. Although Zfp488 and Nkx2.2 both bind to one of the regulatory regions downstream of the Gpr37 gene in vivo, none of the regulatory regions was activated by either transcription factor alone. Increased activation by Zfp488 or Nkx2.2 was only observed in the presence of Sox10, a transcription factor continuously present in oligodendroglial cells. Our results argue that both Zfp488 and Nkx2.2 also act as transcriptional activators during oligodendrocyte differentiation and cooperate with Sox10 to allow the expression of Gpr37 as a modulator of the myelination process.