bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a novel disulfidptosis-related lncRNA signature for prognostic and immune response prediction in clear cell renal cell carcinoma
Authors: Wang Ning , Hu Yifeng , Wang Shasha , Xu Qin , Jiao Xiaojing , Wang Yanliang , Yan Lei , Cao Huixia , Shao Fengmin 
Published: January 2024

AbstractDisulfidptosis, a novel form of regulated cell death, occurs due to the aberrant accumulation of intracellular cystine and other disulfides. Moreover, targeting disulfidptosis could identify promising approaches for cancer treatment. Long non-coding RNAs (lncRNAs) are known to be critically implicated in clear cell renal cell carcinoma (ccRCC) development. Currently, the involvement of disulfidptosis-related lncRNAs in ccRCC is yet to be elucidated. This study primarily dealt with identifying and validating a disulfidptosis-related lncRNAs-based signature for predicting the prognosis and immune landscape of individuals with ccRCC. Clinical and RNA sequencing data of ccRCC samples were accessed from The Cancer Genome Atlas (TCGA) database. Pearson correlation analysis was conducted for the identification of the disulfidptosis-related lncRNAs. Additionally, univariate Cox regression analysis, Least Absolute Shrinkage and Selection Operator Cox regression, and stepwise multivariate Cox analysis were executed to develop a novel risk prognostic model. The prognosis-predictive capacity of the model was then assessed using an integrated method. Variation in biological function was noted using GO, KEGG, and GSEA. Additionally, immune cell infiltration, the tumor mutational burden (TMB), and tumor immune dysfunction and exclusion (TIDE) scores were calculated to investigate differences in the immune landscape. Finally, the expression of hub disulfidptosis-related lncRNAs was validated using qPCR. We established a novel signature comprised of eight lncRNAs that were associated with disulfidptosis (SPINT1-AS1, AL121944.1, AC131009.3, AC104088.3, AL035071.1, LINC00886, AL035587.2, and AC007743.1). Kaplan–Meier and receiver operating characteristic curves demonstrated the acceptable predictive potency of the model. The nomogram and C-index confirmed the strong correlation between the risk signature and clinical decision-making. Furthermore, immune cell infiltration analysis and ssGSEA revealed significantly different immune statuses among risk groups. TMB analysis revealed the link between the high-risk group and high TMB. It is worth noting that the cumulative effect of the patients belonging to the high-risk group and having elevated TMB led to decreased patient survival times. The high-risk group depicted greater TIDE scores in contrast with the low-risk group, indicating greater potential for immune escape. Finally, qPCR validated the hub disulfidptosis-related lncRNAs in cell lines. The established novel signature holds potential regarding the prognosis prediction of individuals with ccRCC as well as predicting their responses to immunotherapy.
Plasma proteome profiling reveals the therapeutic effects of the PPAR pan-agonist chiglitazar on insulin sensitivity, lipid metabolism, and inflammation in type 2 diabetes
Authors: Wang Xingyue , Wang You , Hou Junjie , Liu Hongyang , Zeng Rong , Li Xiangyu , Han Mei , Li Qingrun , Ji Linong , Pan Desi , Jia Weiping , Zhong Wen , Xu Tao 
Published: January 2024

AbstractChiglitazar is a novel peroxisome proliferator-activated receptor (PPAR) pan-agonist, which passed phase III clinical trials and was newly approved in China for use as an adjunct to diet and exercise in glycemic control in adult patients with Type 2 Diabetes (T2D). To explore the circulating protein signatures associated with the administration of chiglitazar in T2D patients, we conducted a comparative longitudinal study using plasma proteome profiling. Of the 157 T2D patients included in the study, we administered chiglitazar to a specific group, while the controls were given either placebo or sitagliptin. The plasma proteomes were profiled at baseline and 12 and 24 weeks post-treatment using data-independent acquisition mass spectrometry (DIA-MS). Our study indicated that 13 proteins were associated with chiglitazar treatment in T2D patients, including 10 up-regulated proteins (SHBG, TF, APOA2, APOD, GSN, MBL2, CFD, PGLYRP2, A2M, and APOA1) and 3 down-regulated proteins (PRG4, FETUB, and C2) after treatment, which were implicated in the regulation of insulin sensitivity, lipid metabolism, and inflammation response. Our study provides insight into the response of chiglitazar treatment from a proteome perspective and demonstrates the multi-faceted effects of chiglitazar in T2D patients, which will help the clinical application of chiglitazar and further study of its action mechanism.
Selenoprotein P expression in glioblastoma as a regulator of ferroptosis sensitivity: preservation of GPX4 via the cycling-selenium storage
Authors: Zheng Xi , Toyama Takashi , Siu Stephanie , Kaneko Takayuki , Sugiura Hikari , Yamashita Shota , Shimoda Yoshiteru , Kanamori Masayuki , Arisawa Kotoko , Endo Hidenori , Saito Yoshiro 
Published: January 2024

AbstractGlioblastoma (GBM) is one of the most aggressive and deadly brain tumors; however, its current therapeutic strategies are limited. Selenoprotein P (SeP; SELENOP, encoded by the SELENOP gene) is a unique selenium-containing protein that exhibits high expression levels in astroglia. SeP is thought to be associated with ferroptosis sensitivity through the induction of glutathione peroxidase 4 (GPX4) via selenium supplementation. In this study, to elucidate the role of SeP in GBM, we analyzed its expression in GBM patients and found that SeP expression levels were significantly higher when compared to healthy subjects. Knock down of SeP in cultured GBM cells resulted in a decrease in GPX1 and GPX4 protein levels. Under the same conditions, cell death caused by RSL3, a ferroptosis inducer, was enhanced, however this enhancement was canceled by supplementation of selenite. These results indicate that SeP expression contributes to preserving GPX and selenium levels in an autocrine/paracrine manner, i.e., SeP regulates a dynamic cycling-selenium storage system in GBM. We also confirmed the role of SeP expression in ferroptosis sensitivity using patient-derived primary GBM cells. These findings indicate that expression of SeP in GBM can be a significant therapeutic target to overcome anticancer drug resistance.
Clinical predictors of prognosis in stroke patients after endovascular therapy
Authors: Wang Yugang , Yuan Xingyun , Kang Yonggang , Yu Liping , Chen Wanhong , Fan Gang 
Published: January 2024

AbstractEndovascular therapy (EVT) is effective in the treatment of large vascular occlusive stroke. However, many factors are associated with the outcomes of acute ischemic stroke (AIS) after EVT. This study aimed to identify the main factors related to the prognosis of AIS patients after EVT. We analyzed the clinical data of AIS patients in the neurology department of our medical center from June 2017 to August 2021 following treatment with EVT. The data included the patients’ blood pressure upon admission, blood glucose concentration, National Institutes of Health Stroke Scale (NIHSS) score, 90-day modified Rankin scale (mRs) score follow-up data, and time from LKN to the successful groin puncture (GP). A good outcome was defined as a 90-day mRs score of 0–2, and a poor outcome was defined as a 90-day mRs score of 3–6. A total of 144 patients were included in the study. Admission, smoking, and LKN-to-GP time, NIHSS score of 6–12 was found to be relevant to the prognosis. The results of multivariate analysis showed that prognosis was significantly influenced by baseline NIHSS (odds ratio = 3.02; 95% confidence interval, 2.878–4.252; P = 0.001), LKN-to-GP time (odds ratio = 2.17; 95% confidence interval, 1.341–2.625; P = 0.003), and time stratification (6–12 h) (odds ratio = 4.22; 95% confidence interval, 2.519–5.561; P = 0.001). Our study indicated that smoking, baseline NIHSS score, and LKN-to-GP time were the risk factors for a poor outcome in stroke patients following an EVT. Quitting smoking and shortening LKN time to GP should improve the outcome of AIS after EVT.
A destabilizing Y891D mutation in activated EGFR impairs sensitivity to kinase inhibition
Authors: Lenchner Daniel S. , Petrova Zaritza O. , Hunihan Lisa , Ashtekar Kumar D. , Walther Zenta , Wilson Frederick H. 
Published: January 2024

AbstractEGFR tyrosine kinase inhibitors (TKIs) have transformed the treatment of EGFR-mutated non-small cell lung carcinoma (NSCLC); however, therapeutic resistance remains a clinical challenge. Acquired secondary EGFR mutations that increase ATP affinity and/or impair inhibitor binding are well-described mediators of resistance. Here we identify a de novo EGFR Y891D secondary alteration in a NSCLC with EGFR L858R. Acquired EGFR Y891D alterations were previously reported in association with resistance to first generation EGFR TKIs. Functional studies in Ba/F3 cells demonstrate reduced TKI sensitivity of EGFR L858R + Y891D, with the greatest reduction observed for first and second generation TKIs. Unlike other EGFR mutations associated with TKI resistance, Y891D does not significantly alter ATP affinity or promote steric hindrance to inhibitor binding. Our data suggest that the Y891D mutation destabilizes EGFR L858R, potentially generating a population of misfolded receptor with preserved signaling capacity but reduced sensitivity to EGFR inhibitors. These findings raise the possibility of protein misfolding as a mechanism of resistance to EGFR inhibition in EGFR-mutated NSCLC.
LiLA: lipid lung-based ATLAS built through a comprehensive workflow designed for an accurate lipid annotation
Authors: Fernández Requena Belén , Nadeem Sajid , Reddy Vineel P. , Naidoo Vanessa , Glasgow Joel N. , Steyn Adrie J. C. , Barbas Coral , Gonzalez-Riano Carolina 
Published: January 2024

AbstractAccurate lipid annotation is crucial for understanding the role of lipids in health and disease and identifying therapeutic targets. However, annotating the wide variety of lipid species in biological samples remains challenging in untargeted lipidomic studies. In this work, we present a lipid annotation workflow based on LC-MS and MS/MS strategies, the combination of four bioinformatic tools, and a decision tree to support the accurate annotation and semi-quantification of the lipid species present in lung tissue from control mice. The proposed workflow allowed us to generate a lipid lung-based ATLAS (LiLA), which was then employed to unveil the lipidomic signatures of the Mycobacterium tuberculosis infection at two different time points for a deeper understanding of the disease progression. This workflow, combined with manual inspection strategies of MS/MS data, can enhance the annotation process for lipidomic studies and guide the generation of sample-specific lipidome maps. LiLA serves as a freely available data resource that can be employed in future studies to address lipidomic alterations in mice lung tissue.
Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma
Authors: Liu Zhiwei , Luo Yang , Kirimunda Samuel , Verboom Murielle , Onabajo Olusegun O. , Gouveia Mateus H. , Ogwang Martin D. , Kerchan Patrick , Reynolds Steven J. , Tenge Constance N. , Were Pamela A. , Kuremu Robert T. , Wekesa Walter N. , Masalu Nestory , Kawira Esther , Kinyera Tobias , Otim Isaac , Legason Ismail D. , Nabalende Hadijah , Dhudha Herry , Ayers Leona W. , Bhatia Kishor , Goedert James J. , Cole Nathan , Luo Wen , Liu Jia , Manning Michelle , Hicks Belynda , Prokunina-Olsson Ludmila , Chagaluka George , Johnston W. Thomas , Mutalima Nora , Borgstein Eric , Liomba George N. , Kamiza Steve , Mkandawire Nyengo , Mitambo Collins , Molyneux Elizabeth M. , Newton Robert , Hsing Ann W. , Mensah James E. , Adjei Anthony A. , Hutchinson Amy , Carrington Mary , Yeager Meredith , Blasczyk Rainer , Chanock Stephen J. , Raychaudhuri Soumya , Mbulaiteye Sam M. 
Published: January 2024

AbstractBurkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum. However, whether human leukocyte antigen (HLA) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10−6), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10−8), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10−6). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.
Two somatic mutations in the androgen receptor N-terminal domain are oncogenic drivers in hepatocellular carcinoma
Authors: Ren Qian-Nan , Huang Dan-Hui , Zhang Xiao-Nan , Wang Yue-Ning , Zhou Yu-Feng , Zhang Mei-Yin , Wang Shuo-Cheng , Mai Shi-Juan , Wu De-Hua , Wang Hui-Yun 
Published: January 2024

AbstractThe androgen receptor (AR) plays an important role in male-dominant hepatocellular carcinoma, and specific acquired somatic mutations of AR have been observed in HCC patients. Our previous research have established the role of AR wild type as one of the key oncogenes in hepatocarcinogenesis. However, the role of hepatic acquired somatic mutations of AR remains unknown. In this study, we identify two crucial acquired somatic mutations, Q62L and E81Q, situated close to the N-terminal activation function domain-1 of AR. These mutations lead to constitutive activation of AR, both independently and synergistically with androgens, making them potent driver oncogene mutations. Mechanistically, these N-terminal AR somatic mutations enhance de novo lipogenesis by activating sterol regulatory element-binding protein-1 and promote glycogen accumulation through glycogen phosphorylase, brain form, thereby disrupting the AMPK pathway and contributing to tumorigenesis. Moreover, the AR mutations show sensitivity to the AMPK activator A769662. Overall, this study establishes the role of these N- terminal hepatic mutations of AR as highly malignant oncogenic drivers in hepatocarcinogenesis and highlights their potential as therapeutic targets for patients harboring these somatic mutations.
A biphenotypic lymphocyte subset displays both T- and B-cell functionalities
Authors: zhang Yifan , Guo Cuiyuan , Zhou Yigong , Zhang Wenhong , Zhu Zhaoqin , Wang Wanhai , Wan Yanmin 
Published: January 2024

AbstractT cell/B cell mixed phenotypic lymphocytes have been observed in different disease contexts, yet their presence and function in physiological conditions remain elusive. Here, we provide evidence for the existence of a lymphocyte subset endogenously expressing both T- and B-cell lineage markers in mice. The majority of these T/B phenotypic lymphocytes (CD3+CD19+) show an origin of pro/pre B cells and distribute widely in mouse bone marrow, lymph nodes, spleen, and peripheral blood. Functional assays show that these biphenotypic lymphocytes can be activated through stimulating TCR or BCR signaling pathways. Moreover, we show that these cells actively participate both the humoral and cellular immune responses elicited by vaccination. Compared to conventional T cells, these biphenotypic lymphocytes can secrete a higher level of IL-2 but a lower level of TNF-α upon antigen specific stimulation. An equivalent lymphocyte subset is found in freshly isolated human PBMCs and exhibits similar functionality, albeit at a lower frequency than in mice.
Dimerization of the 4Ig isoform of B7-H3 in tumor cells mediates enhanced proliferation and tumorigenic signaling
Authors: Sutton Margie N. , Glazer Sarah E. , Muzzioli Riccardo , Yang Ping , Gammon Seth T. , Piwnica-Worms David 
Published: January 2024

AbstractB7-H3 (CD276) has two isoforms (2Ig and 4Ig), no confirmed cognate receptor, and physiological functions that remain elusive. While differentially expressed on many solid tumors correlating with poor survival, mechanisms of how B7-H3 signals in cis (tumor cell) versus in trans (immune cell co-regulator) to elicit pro-tumorigenic phenotypes remain poorly defined. Herein, we characterized a tumorigenic and signaling role for tumor cell-expressed 4Ig-B7-H3, the dominant human isoform, in gynecological cancers that could be abrogated upon CRISPR/Cas9 knockout of B7-H3; tumorigenesis was rescued upon re-expression of 4Ig-B7-H3. Size exclusion chromatography revealed dimerization states for the extracellular domains of both human 4Ig- and murine 2Ig-B7-H3. mEGFP lifetimes of expressed 4Ig-B7-H3-mEGFP fusions determined by FRET-FLIM assays confirmed close-proximity interactions of 4Ig-B7-H3 and identified two distinct homo-FRET lifetime populations, consistent with monomeric and homo-dimer interactions. In live cells, bioluminescence imaging of 4Ig-B7-H3-mediated split luciferase complementation showed dimerization of 4Ig-B7-H3. To separate basal from dimer state activities in the absence of a known receptor, C-terminus (cytosolic) chemically-induced dimerization of 4Ig-B7-H3 increased tumor cell proliferation and cell activation signaling pathways (AKT, Jak/STAT, HIF1α, NF-κβ) significantly above basal expression of 4Ig-B7-H3 alone. These results revealed a new, dimerization-dependent intrinsic tumorigenic signaling role for 4Ig-B7-H3, likely acting in cis, and provide a therapeutically-actionable target for intervention of B7-H3-dependent tumorigenesis.
Sudden change of the photon output field marks phase transitions in the quantum Rabi model
Authors: Chen Ye-Hong , Qiu Yuan , Miranowicz Adam , Lambert Neill , Qin Wei , Stassi Roberto , Xia Yan , Zheng Shi-Biao , Nori Franco 
Published: January 2024

AbstractThe experimental observation of quantum phase transitions predicted by the quantum Rabi model in quantum critical systems is usually challenging due to the lack of signature experimental observables associated with them. Here, we describe a method to identify the dynamical critical phenomenon in the quantum Rabi model consisting of a three-level atom and a cavity at the quantum phase transition. Such a critical phenomenon manifests itself as a sudden change of steady-state output photons in the system driven by two classical fields, when both the atom and the cavity are initially unexcited. The process occurs as the high-frequency pump field is converted into the low-frequency Stokes field and multiple cavity photons in the normal phase, while this conversion cannot occur in the superradiant phase. The sudden change of steady-state output photons is an experimentally accessible measure to probe quantum phase transitions, as it does not require preparing the equilibrium state.
Three-path quantum Cheshire cat observed in neutron interferometry
Authors: Danner Armin , Geerits Niels , Lemmel Hartmut , Wagner Richard , Sponar Stephan , Hasegawa Yuji 
Published: January 2024

AbstractAlthough our every-day experience rejects it, the quantum Cheshire Cat suggests a potential spatial separation between different properties of a single particle in an interferometer. The first experiment with neutrons confirmed the quantum Cheshire Cat effect by using the path and spin degrees of freedom. The locations of each property are determined qualitatively through reactions to locally applied perturbations. Yet, no consensus on the interpretation has been reached. To clarify the origin of the effect, in the present experiment the energy degree of freedom is used as the third property; the three properties of neutrons appear to be separated in different paths in the interferometer. The analysis of the experiment suggests the strong involvement of the inner product between the state vectors, one evolved from the initial state through the perturbation and the other being the final state. The inner product results in amplitudes from two sub-beams which contribute to the intensity. The cross-term between amplitudes gives rise to the quantum Cheshire Cat.
Non-collinear magnetism driven by a hidden multipolar order in PrO2
Authors: Khmelevskyi Sergii , Pourovskii Leonid V. 
Published: January 2024

AbstractStandard microscopic approach to magnetic orders is based on assuming a Heisenberg form for inter-atomic exchange interactions. These interactions are considered as the driving force for the ordering transition with magnetic moments serving as the primary order parameter. Any higher-rank multipoles appearing simultaneously with such magnetic order are typically treated as auxiliary order parameters rather than a principal cause of the transition. In this study, we show that these traditional assumptions are violated in the case of PrO2. Evaluating a full set of Pr-Pr superexchange interactions from a first-principles many-body technique we find that its unusual non-collinear 2k magnetic structure stems from high-rank multipolar interactions, and that the corresponding contribution of the Heisenberg interactions is negligible. The observed magnetic order in PrO2 is thus auxiliary to high-rank “hidden” multipoles. Within this picture we consistently account for previously unexplained experimental observations like the magnitude of exchange splitting and the evolution of magnetic structure in external field. Our findings challenge the standard paradigm of observable magnetic moments being the driving force for magnetic transitions.
Galilean invariant dynamics in an emergent spin-orbit coupled Zeeman lattice
Authors: Ome M. K. H. , He Huaxin , Mukhopadhyay A. , Crowell E. , Mossman S. , Bersano T. , Zhang Yongping , Engels P. 
Published: January 2024

AbstractPeriodic band structures are a hallmark phenomenon of condensed matter physics. While often imposed by external potentials, periodicity can also arise through the interplay of couplings that are not necessarily spatially periodic on their own, but this option is generally less explored than the fully-periodic counterpart. Here, we investigate dynamics in a lattice structure that emerges from the simultaneous application of Raman and radio frequency coupling to a dilute-gas Bose-Einstein condensate. We elaborate on the role of Galilean invariance in this system and demonstrate a variety of techniques, including Bloch oscillations and lattice shaking with spin and momentum resolved measurements. This combined coupling scheme allows for tunability and control, enabling future investigations into unconventional band structures such as quasi-flat ground bands and those with semimetal-like band gaps.