bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protocol Development: Effectivity and Safety evaluation between topical L-ascorbic acid 15% serum compared to Retinol 0.1% serum in Anti Aging Therapy: A double blinded, randomized controlled trial, split face study in Indonesia
Authors: Yolanda Keiko , Novianto Endi , Agustin Triana , Friska Dewi 
Published: October 2024

Abstract

Background
The process of aging in which a progressive decrease in both the function and capacity of the body, which includes the skin may cause the skin surface to appear pale, fine wrinkles and atrophy of the epidermis and dermis layer which leads to a thinner, transparent and fragile appearance of the skin. A variety of methods have been developed to prevent and treat skin aging, including the use of vitamin C as an potent antioxidant which is found to be beneficial skin aging therapy.
Objective
This study aims to investigate the effectivity and safety of topical L-ascorbic acid 15% serum towards skin aging using the parameters such as wrinkle, spots, ultraviolet spots, pores and skin moisture.
Methods
The study is a randomized clinical trial with double disguise and split-face carried out at the Dermatology and Venereology outpatient clinic, Dr. Cipto Mangkunkusumo Hospital in January – February 2024. Subjects includes woman and man aged 35–65 years outpatient clinic. Vitamin C serum containing L-ascorbic acid 15% and retinol 0.1% serum, were given to the patients to apply, and skin analysis profile measuring instrument using the JANUS III, examining eight skin parameters: age, hyperpigmentation, UV spots, wrinkles, pores, elasticity, porphyrin, sebum, and moisture before and after application of the vitamin C serum and retinol.
Discussion
Ascorbic Acid is expected to attenuate photoaging and the natural aging of the skin by reducing oxidative stress caused by external and internal factors and by promoting collagen gene expression and maturation. The data acquired from this study will be used to make recommendations for anti-aging therapy that has superior results than standard therapies but produces minimal side effects.
Joint Association of Systemic Inflammatory Response Index and Sarcopenia with Mortality Among Cancer Survivors
Authors: Huang Zhifei , Peng Wenjia , Zhao Mengdie , Gao Bo , Qian Jing , Zhu Shuangqiu , Ren Mingdong , Jiang Tao , Yusuf Sulaiman Abdulahi Yusuf , He Zelai , jiang hao 
Published: October 2024

Abstract

Purpose
The aim of this study was to investigate the joint association of systemic inflammatory response index (SIRI) and sarcopenia with cancer-specific and all-cause mortality in cancer survivors.
Methods
The study cohort comprised US cancer survivors from the NHANES database, with data collected between 1999–2006 and 2011–2018. The researchers tracked deaths up to 31 December 2019 by linking the relevant records to those held by the (NDI). A weighted sampling design was employed, with participants stratified according to the median value of the SIRI. Cox regression models were employed to assess the association between SIRI, sarcopenia, all-cause mortality, and cancer-specific mortality.
Results
The study cohort comprised 1316 cancer survivors. Over a median follow-up period of 9.21 years, 523 all-cause deaths were recorded, including 163 cancer-specific and 360 non-cancer deaths. Adjusting for multiple confounders, elevated SIRI levels were significantly associated with increased risks of all-cause (HR = 1.90 [1.58–2.28], P < 0.001), cancer (HR = 1.88 [1.26–2.78], P = 0.002), and non-cancer mortality (HR = 1.93 [1.54–2.41], P < 0.001). Sarcopenia also emerged as a significant predictor of mortality. Individuals with sarcopenia faced a 50% higher risk of all-cause mortality (HR = 1.50 [1.18–1.91], P < 0.001) and a 54% higher risk of non-cancer mortality (HR = 1.54 [1.11–2.12], P = 0.009). However, the association with cancer mortality was not significant in the fully adjusted model. When both sarcopenia and elevated SIRI were present, the risk was the highest for all-cause (HR = 2.54 [1.92–3.37], P < 0.001), cancer (HR = 2.29 [1.19–4.40], P = 0.014), and non-cancer mortality (HR = 2.63 [1.78–3.89], P < 0.001). Elevated SIRI alone was linked to significant risks for all-cause (HR = 1.91 [1.51–2.42], P < 0.001), cancer (HR = 1.95 [1.28–2.97], P = 0.002), and non-cancer mortality (HR = 1.92 [1.46–2.53], P < 0.001). Sarcopenia alone significantly increased the risk of all-cause mortality (HR = 1.63 [1.01–2.56], P = 0.043) but not cancer mortality.
Conclusion
Our study is the first to demonstrate the joint association between the SIRI and sarcopenia with mortality among cancer survivors. These findings underscore the importance of assessing and managing these two factors in cancer survivors to reduce the risk of death and improve survival outcomes.
Identification of a GII.P21-GII.13 recombinant norovirus strain, mutations shift its binding spectra to host receptor glycans
Authors: Yu yongxin , Chen Yunfei , Zhou Zexian , Dong Lei , Jin Miao , Wang Yongjie 
Published: October 2024

Abstract

Norovirus is a pervasive pathogen that causes global outbreaks of viral gastroenteritis. Previous studies suggest that histo-blood group antigens (HBGAs) can interact with norovirus, facilitating its entry of host cells and significantly impacting its evolution. In this study, a complete genome of recombinant GII.13[GII.P21] norovirus from fecal samples was analyzed, revealing a weak effect of genomic recombination on the replication efficiency of GII.13[GII.P21]. Molecular dynamics simulations of GII.13 norovirus P proteins from 1978 to 2019 showed changes in binding capacity with HBGAs. Initially, GII.13 proteins bound A or B/H-type HBGAs, but subsequent residue mutations resulted in a loss of this binding capacity, favoring binding to the HBGA type I precursor (Lec) over A or B/H and Lewis antigens.
Single-Cell Analysis Reveals Ide-cel and Cilta-cel Characteristics That Influence Efficacy
Authors: Freeman Ciara , Noble Jerald , Song Xiaofei , Menges Meghan , Abraham-Miranda Julieta , Corallo Salvatore , De Avila Gabriel , Castaneda Omar , Liu Hien , Alsina Melissa , Nishihori Taiga , Shain Kenneth , Baz Rachid , Blue Brandon , Cruz Ariel Grajales , Hansen Doris , Atkins Reginald , Locke Frederick 
Published: October 2024

Abstract

Chimeric antigen receptor T-cells targeting BCMA have revolutionized the treatment of relapsed/refractory multiple myeloma (RRMM) with two approved products, idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel). To explore biological differences, we analyzed pre-infusion products (IP) and CAR-enriched peripheral blood mononuclear cells (PBMCs) at expansion using single-cell RNA sequencing (scRNAseq) from 52 samples. Post-quality control 247,500 cells (117,530 CD4, 80,939 CD8) were analyzed. We found that ide-cel IPs from durable responders (DR) had higher construct expression, enhanced NFKB signaling, and anti-apoptotic signatures, correlating with improved progression free survival. CAR + ide-cel PBMCs in DRs showed upregulated ribosomal genes and higher CD27, KLF2, TCF7 expression. Relative to ide-cel, cilta-cel CAR + cells showed higher expression of CD27, GZMK, TCF7, and a 4-fold increase in CAR expression. In addition, the TCR repertoire was less clonal and more diverse. This study elucidates the distinct characteristics of ide-cel and cilta-cel, offering insights into their differing clinical efficacy.
Stabilization of cyclo-N6 by insertion into [18]-annulene: a DFT study
Authors: Pichierri Fabio 
Published: October 2024

Abstract

The elusiveness of hexazine (a.k.a. hexaazabenzene) and its perhydrogenated derivative, hexazinane, prompted the author to investigate the possibility of stabilizing the six-membered nitrogen ring by inserting it into [18]-annulene. The resulting compound is made of a central N6 ring surrounded by an outer ring of 18 carbon atoms that prevents its decomposition into dinitrogen. The N6 ring is non-planar and with a chair-like conformation that does not undergo conformational isomerization. The designed molecule can be stabilized either by oxidation to a hexa-oxide derivative or by coordination of ZnCl+. Furthermore, a triangle-shaped macrocyclic isomer made of three pyridazine moieties connected to each other by ethylene bridges represents a possible precursor in the synthesis of the N6-embedded hydrocarbon. By employing an alkali or alkaline-earth metal cation that coordinates the three pyridazine monomers it becomes possible to bring their nitrogen atoms in close proximity so that a subsequent aromatic fusion reaction could be attempted.
Mechanical properties and damage characterization of cracked granite after cyclic temperature action
Authors: Bao Xiankai , Wang Lingyu , Cui Guangqin , Qiao Jianlong , Tian Baolong , Huang Shunjia , Wang Lizhi 
Published: October 2024

Abstract

To study investigates the mechanical properties and damage characteristics of granite under the influence of cyclic temperature and crack inclination, uniaxial compression tests were conducted on granite with prefabricated cracks at cyclic temperatures of 30 °C, 50 °C, 70 °C, 100 °C, and 130 °C. The mechanical properties and damage characteristics of the granite were analyzed using characteristic stress, acoustic emission parameters, damage variables, fractal dimensions, and SEM. The results indicate that: (1) At the same cyclic temperature, the granite with a 45 ° prefabricated crack exhibits the lowest peak stress, elastic modulus, and σci/σm, resulting in a significant reduction in the specimen's load-bearing capacity. At the same crack inclination, the granite at 70 °C shows the highest peak stress, elastic modulus, σcc/σm, and σci/σm, with a noticeable reduction in internal microcracks. (2) At the same cyclic temperature, the b-value drop point of acoustic emissions in the 45 ° prefabricated crack specimen occurs earlier, indicating the earlier formation of the main crack inside the specimen. At the same crack inclination, the cumulative ring count and total energy of acoustic emissions are the lowest at 70 °C, indicating the least thermal damage to the specimen. (3) At the same cyclic temperature, the damage in the 45 ° prefabricated crack granite specimen develops more rapidly, with the damage variable reaching above 0.8 at the damage stress point, and the fluctuation in fractal dimension is minimal, indicating strong orderliness in the development of internal microcracks. At the same crack inclination, the fractal dimension of the granite specimen significantly increases at 70 °C, and the dispersion of damage proportion increases significantly after 70 °C. (4) At a cyclic temperature of 70 °C, the changes in cracks and pores in the granite uniaxial compression specimen are evident, with relatively mild damage; the final failure modes of specimens under various cyclic temperatures and crack inclinations differ significantly, transitioning from tensile-shear failure to shear failure and tensile failure as the crack inclination increases. The research results can provide theoretical references for understanding the mesoscopic damage and failure mechanisms of granite under different cyclic temperatures and crack inclinations.
Skew-pair fusion theory: An interpretable multimodal fusion framework
Authors: Hu Zhiwen , Hong HaiBo , Cai Xuqiang , Li Linxiang , Ren Zichu , Ma Xi-Ao , Jiang Haihua , Wang Xun 
Published: October 2024

Abstract

Multimodal fusion models have the potential to harness the homogeneity and heterogeneity of multimodal data as a performance turbocharger in multifaceted domains. Nonetheless, a formal fusion theory for fusion-pair alignment and sparsity assignment in latent representation spaces remain underdeveloped. Here we disentangle a dual cross-modal heterogeneity paradigm ingrained within the fabric of the involved models and present a universal skew-pair fusion theory. This holistic framework formalizes a dual interpretable mechanism—universal skew-layer alignment and bootstrapping sparsity—to bolster fusion gain in hybrid neural networks. Our comprehensive validation experiments across text-audio, audio-video, image-text, and text-text fusion tasks, demonstrating its empirical advantages over conventional late- and pairwise-fusion strategies. Inspired by multisensory integration, we further curate a sparsest skew-pair fusion network (SSFN) that outperforms late- and pairwise-fusion counterparts, even in seemingly “unimodal” fusion scenarios such as text-text fusion. Our findings suggest that this bioinspired framework could serve as a benchmark for reframing the multidisciplinary perspective on multimodal fusion and multisensory integration.
N88S seipin-related seipinopathy is a lipidopathy associated with loss of iron homeostasis
Authors: Ribeiro Mariana O. , Oliveira Mafalda , Nogueira Verónica , Costa Vítor , Teixeira Vitor 
Published: October 2024

Abstract

Background
Seipin is a protein encoded by the BSCL2 gene in humans and SEI1 gene in yeast, forming an Endoplasmic Reticulum (ER)-bound homo-oligomer. This oligomer is crucial in targeting ER-lipid droplet (LD) contact sites, facilitating the delivery of triacylglycerol (TG) to nascent LDs. Mutations in BSCL2, particularly N88S and S90L, lead to seipinopathies, which correspond to a cohort of motor neuron diseases (MNDs) characterized by the accumulation of misfolded N88S seipin into inclusion bodies (IBs) and cellular dysfunctions.
Methods
Quantitative untargeted mass spectrometric proteomic and lipidomic analyses were conducted to examine changes in protein and lipid abundance in wild-type (WT) versus N88S seipin-expressing mutant cells. Differentially expressed proteins were categorized into functional networks to highlight altered protein functions and signaling pathways. Statistical comparisons were made using unpaired, two-tailed Student's t-tests or two-way ANOVA. P-values < 0.05 are considered significant.
Results
In a well-established yeast model of N88S seipinopathy, misfolded N88S seipin forms IBs and exhibits higher levels of ER stress, leading to decreased cell viability due to increased reactive oxygen species (ROS), oxidative damage, lipid peroxidation, and reduced antioxidant activity. Proteomic and lipidomic analyses revealed alterations in phosphatidic acid (PA) levels, associated with disrupted inositol metabolism and decreased flux towards phospholipid biosynthesis. Importantly, deregulation of lipid metabolism contributed to ER stress beyond N88S seipin misfolding and IB formation. Additionally, the model exhibited deregulated iron (Fe) homeostasis during lifespan. N88S seipin-expressing cells showed impaired ability to cope with iron deficiency. This was linked to changes in the expression of Aft1p-controlled iron regulon genes, including the mRNA-binding protein CTH2 and the high-affinity iron transport system member FET3, in a p38/Hog1p- and Msn2p/Msn4p-dependent manner. Importantly, we unraveled a novel link between inositol metabolism and activation of the iron regulon in cells expressing the N88S seipin mutation. Despite iron accumulation, this was not associated with oxidative stress.
Conclusions
The study highlights that the effects of N88S seipin mutation extend beyond protein misfolding, with significant disruptions in lipid metabolism and iron homeostasis. This research marks a significant advance in understanding and defining the roles of proteins and signaling pathways that contribute to human seipinopathy. Altered cellular processes, as well as potential therapeutic targets and biomarkers, were identified and can be explored in translational studies using human cell models.
Transcriptomic Analyses and Novel Organoid and Xenograft Modeling Reveals Potential Drug Sensitivities in a KRAS G12V-Mutant Colorectal Cancer Brain Metastasis
Authors: Panovska Dena , Nasajpour Emon , Xing Yao Lulu , Gwyn Alexa , Morales Daniella , Chaudhary Suhani , Sathe Anuja , Tran Caitlynn To-Duyen , Feng Zhi-Ping , Rada Cara Coleen , Nakano Michitaka , Habib Pardes , Rabin Leif , Chang Steven D. , Kuo Calvin J. , Gui Chloe , Zadeh Gelareh , Nirschl Jeffrey J. , Vogel Hannes , Gephart Melanie Hayden , Ji Hanlee P. , Petritsch Claudia K. 
Published: October 2024

Abstract

Brain metastases (BM) occur in 2.3% of patients with colorectal cancer (CRC), which is the second leading cause of cancer deaths globally. Despite aggressive treatment like surgery and chemo-irradiation, median survival for patients with BM originating from CRC (CRC-BM) remains poor at 5.3 months, highlighting the need for improved therapies. Next-generation sequencing has identified KRAS mutations in approximately 40% of metastatic CRC cases. Therapies targeting mutant KRAS and downstream MAPK pathway components exist, but their effectiveness is often limited by therapy resistance, underscoring the need for novel drug targets beyond the MAPK pathway. Additionally, there is a lack of accurate preclinical models for CRC-BM. In this study, we generated a patient-derived organoid model (PDO) from a KRAS G12V mutant CRC-BM surgical sample. PDO consistently formed intracranial tumors in both male and female mice, indicative of their stable malignant potential. Both the PDO and PDO-derived xenografts (PDoX) retained the KRAS G12Vmutation and key epithelial and mesenchymal markers, closely resembling the original BM. Spatial transcriptome analysis of the patient BM revealed six distinct functional tumor epithelial cells, with features such as enhanced MAPK signaling and upregulated ER-stress. Bulk RNA sequencing analyses showed differences between PDO and PDoX, which reflected in vitro growth conditions. PDO, PDoX, and patient BM shared pathways including ER-stress and unfolded protein response (UPR) pathway. DNA methylation profiling revealed a varying number of differentially methylated regions between samples derived from primary CRC and BM, and comparable numbers of these regions between PDO and PDoX. Proof-of-concept was demonstrated by pharmacologically inhibiting RAS-RAF-MAPK signaling, and more effectively key molecules in the ER-stress sensor/UPR pathways. In conclusion, we developed a patient-derived organoid (PDO) model from a KRAS G12V mutant CRC-BM, closely mirroring the tumor’s clinical characteristics. Targeting the MAPK and ER/UPR pathways significantly reduced PDO viability, revealing key therapeutic vulnerabilities.
The Relations between Ethical Reasoning, Moral Intuitions, and Foreign Language among Engineering Students in the US, Netherlands, and China
Authors: Clancy Rockwell , Zhu Qin , Streiner Scott , Gammon Andrea , Thorpe Ryan 
Published: October 2024

Abstract

Background: Ethical knowledge and reasoning have been adopted as the goals of engineering ethics education, and measures of ethical reasoning have been developed by researchers and with participants in mostly the US. But US participants are global outliers on various psychological and social characteristics, and engineering is increasingly global. Further, it is also unclear whether ethical reasoning results in more ethical judgments or behaviors. To address these issues, this study sought to better understand the natures of and relations between ethical reasoning, moral intuitions, and foreign language among engineering students across multiple countries. Students at universities in the US, Netherlands, and China completed the ESIT (Engineering and Science Issues Test), MFQ (Moral Foundations Questionnaire), and demographics items online. Statistical hypothesis testing and correlation analysis were used to examine relations between study variables.
Results: (1) Students in the US evidenced higher rates of ethical reasoning than those in the Netherlands or China. (2) Ethics education was associated with lower rates of self-based reasoning. (3) Ethical reasoning was positively related to intuitions about care and fairness, and negatively relations to intuitions about loyalty, authority, and sanctity. (4) Students in China care more about loyalty, authority, and sanctity, and less about care and fairness, than those in the US or Netherlands. (5) Foreign language was associated with higher rates of ethical reasoning and less concern with sanctity.
Conclusions: Rather than ethical reasoning, education should aim at reducing self-based reasoning, and researchers must study a broader range of national groups to better understand how language affect ethics education.
Urea and Thiourea Derivatives of Salinomycin as Agents Targeting Malignant Colon
Cancer Cells
Authors: Antoszczak Michal , Mielczarek-Puta Magdalena , Struga Marta , Huczynski Adam 
Published: October 2024

Background:
Since it was discovered that a natural polyether ionophore called salinomycin (SAL)
selectively inhibits human cancer cells, the scientific world has been paying special attention to this compound. It
has been studied for nearly 15 years.

Objective:
Thus, a very interesting research direction is the chemical modification of SAL structure, which could
give more biologically active agents.

Methods:
We evaluated the anticancer activity of (thio)urea analogues class of C20-epi-aminosalinomycin (compound
3b). The studies covered the generation of reactive oxygen species (ROS), proapoptotic activity, cytotoxic
activity, and lipid peroxidation in vitro.

Results:
Thioureas 5a-5d showed antiproliferative activity against selected human colon cancer cell lines greater
than that of chemically unmodified SAL, with a 2~10-fold higher potency towards a metastatic variant of colon
cancer cells (SW620). Mechanistically, SAL derivatives showed proapoptotic activity in primary colon cancer
cells and induced the production of reactive oxygen species (ROS) in these cells. In SW620 cells, SAL derivatives
increased lipid peroxidation with a weak effect on apoptosis and low ROS formation with cytotoxic effects
followed by cytostatic ones, suggesting different modes of action of the compounds against primary and metastatic
colon cancer cells.

Conclusion:
The results of this study suggested that urea and thiourea derivatives of SAL provide promising
leads for the rational development of new anticancer active agents.