bluuebunny/crossref_metadata_2025_split huggingface dataset:
A novel identified epithelial ligand-receptor-associated gene signature highlights POPDC3 as a potential therapy target for non-small cell lung cancer
Authors: Zhu Xiao-Ren , Zhu Jia-Qi , Gu Qian-Hui , Liu Na , Lu Jing-Jing , Li Xiao-Hong , Liu Yuan-Yuan , Zheng Xian , Chen Min-Bin , Ji Yong 
Published: February 2025

Abstract
The tumor microenvironment (TME) is pivotal in non-small cell lung cancer (NSCLC) progression, influencing drug resistance and immune cell behavior through complex ligand-receptor (LR) interactions. This study developed an epithelial LR-related prognostic risk score (LRrisk) to identify biomarkers and targets in NSCLC. We identified twenty epithelial LRs with significant prognostic implications and delineated three molecular NSCLC subtypes with distinct outcomes, pathological characteristics, biological pathways, and immune profiles. The LRrisk model was constructed using twelve differentially expressed ligand-receptor interaction-related genes (LRGs), with a focus on POPDC3 (popeye domain-containing protein 3), which was overexpressed in NSCLC cells. Functional assays revealed that POPDC3 knockdown reduced cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT), while its overexpression promoted cancerous activities. In vivo, POPDC3 silencing hindered, and its overexpression accelerated the growth of NSCLC xenografts in nude mice. Additionally, high expression levels of POPDC3 in NSCLC tissues were associated with enhanced CD4+ T cell infiltration and increased PD-1 expression within the TME. Moreover, ectopic POPDC3 overexpression in C57BL/6 J mouse Lewis lung carcinoma (LLC) xenografts enhanced CD4+ T cell infiltration and PD-1 expression in the TME. This research establishes a robust epithelial LR-related signature, highlighting POPDC3 as a critical facilitator of NSCLC progression and a potential therapeutic target.
CDK6 kinase inhibition unmasks metabolic dependencies in BCR::ABL1+ leukemia
Authors: Scheiblecker Lisa , Klampfl Thorsten , Doma Eszter , Nebenfuehr Sofie , Torres-Quesada Omar , Strich Sophie , Heller Gerwin , Werdenich Daniela , Tschulenk Waltraud , Zojer Markus , Bellutti Florian , Schirripa Alessia , Zöchbauer-Müller Sabine , Valent Peter , Walter Ingrid , Stefan Eduard , Sexl Veronika , Kollmann Karoline 
Published: February 2025

Abstract
Metabolic reprogramming and cell cycle deregulation are hallmarks of cancer cells. The cell cycle kinase CDK6 has recently been implicated in a wide range of hematopoietic malignancies. We here investigate the role of CDK6 in the regulation of cellular metabolism in BCR::ABL1+ leukemic cells. Our study, using gene expression data and ChIP-Seq analysis, highlights the contribution of CDK6 kinase activity in the regulation of oxidative phosphorylation. Our findings imply a competition for promoter interaction of CDK6 with the master regulator of mitochondrial respiration, NRF-1. In line, cells lacking kinase active CDK6 display altered mitochondria morphology with a defective electron transport chain. The enhanced cytoplasm/mitochondria ATP ratio paralleled by high pyruvate and lactate levels indicate a metabolic switch to glycolysis. Accordingly, combinatorial treatment of leukemic cells including imatinib resistant cells with the CDK4/6 inhibitor palbociclib and the glycolysis inhibitor 2-deoxyglucose (2-DG) enhanced apoptosis, while blocking cell proliferation in leukemic cells. These data may open a new therapeutic avenue for hematologic malignancies with high CDK6 expression by exploiting metabolic vulnerabilities unmasked by blocking CDK6 kinase activity that might even be able to overcome imatinib resistance.
Engineered mesenchymal stem/stromal cells against cancer
Authors: Shi Yuzhu , Zhang Jia , Li Yanan , Feng Chao , Shao Changshun , Shi Yufang , Fang Jiankai 
Published: February 2025

Abstract
Mesenchymal stem/stromal cells (MSCs) have garnered attention for their potential in cancer therapy due to their ability to home to tumor sites. Engineered MSCs have been developed to deliver therapeutic proteins, microRNAs, prodrugs, chemotherapy drugs, and oncolytic viruses directly to the tumor microenvironment, with the goal of enhancing therapeutic efficacy while minimizing off-target effects. Despite promising results in preclinical studies and clinical trials, challenges such as variability in delivery efficiency and safety concerns persist. Ongoing research aims to optimize MSC-based cancer eradication and immunotherapy, enhancing their specificity and efficacy in cancer treatment. This review focuses on advancements in engineering MSCs for tumor-targeted therapy.
Hemiphosphoindigos as a platform for chiroptical or water soluble photoswitching
Authors: Kohl Fabien , Vogl Theresa , Hampel Frank , Dube Henry 
Published: February 2025

Abstract
Photoswitches are important molecular tools to precisely control the behavior of matter by using light irradiation. They have found application in virtually all applied chemical fields from chemical biology to material sciences. However, great challenges remain in advanced property design including tailored chiroptical responses or water solubility. Here, hemiphosphoindigo (HPI) photoswitches are presented as capable phosphorus-based photoswitches and a distinct addition to the established indigoid chromophore family. Phosphinate is embedded in the core indigoid chromophore and the resulting optimized photoswitches display high thermal stabilities, excellent fatigue resistance and high isomer enrichment. A series of planar, twisted and heterocyclic HPIs are investigated to probe design strategies for advantageous photophysical properties. The phosphinate provides a platform for easily accessible, water-soluble photoswitches, especially interesting for biological applications. Its chiral nature further allows light-induced modulation of chiroptical properties. HPIs therefore open up a distinct structural space for photoswitch generation and advanced light-responsive applications.
Lipogenic enzyme FASN promotes mutant p53 accumulation and gain-of-function through palmitoylation
Authors: Liu Juan , Shen Yiyun , Liu Jie , Xu Dandan , Chang Chun-Yuan , Wang Jianming , Zhou Jason , Haffty Bruce G. , Zhang Lanjing , Bargonetti Jill , De Subhajyoti , Hu Wenwei , Feng Zhaohui 
Published: February 2025

Abstract
The tumor-suppressive function of p53 is frequently disrupted by mutations in cancers. Missense mutant p53 (mutp53) protein often stabilizes and accumulates to high levels in cancers to promote tumorigenesis through the gain-of-function (GOF) mechanism. Currently, the mechanism of mutp53 accumulation and GOF is incompletely understood. Here, we identify the lipogenic enzyme FASN as an important regulator of mutp53 accumulation and GOF. FASN interacts with mutp53 to enhance mutp53 palmitoylation, which inhibits mutp53 ubiquitination to promote mutp53 accumulation and GOF. Blocking FASN genetically or by small-molecule inhibitors suppresses mutp53 palmitoylation to inhibit mutp53 accumulation, which in turn inhibits the growth of mutp53 tumors in orthotopic and subcutaneous xenograft tumor models and transgenic mice, as well as the growth of human tumor organoids carrying mutp53. Our results reveal that mutp53 palmitoylation is an important mechanism underlying mutp53 accumulation and GOF, and targeting FASN is a potential therapeutic strategy for cancers carrying mutp53.
Plasmodium blood stage development requires the chromatin remodeller Snf2L
Authors: Watzlowik Maria Theresia , Silberhorn Elisabeth , Das Sujaan , Singhal Ritwik , Venugopal Kannan , Holzinger Simon , Stokes Barbara , Schadt Ella , Sollelis Lauriane , Bonnell Victoria A. , Gow Matthew , Klingl Andreas , Marti Matthias , Llinás Manuel , Meissner Markus , Längst Gernot 
Published: February 2025

Abstract
The complex life cycle of the malaria parasite Plasmodium falciparum involves several major differentiation stages, each requiring strict control of gene expression. Fundamental changes in chromatin structure and epigenetic modifications during life cycle progression suggest a central role for these mechanisms in regulating the transcriptional program of malaria parasite development1–6. P. falciparum chromatin is distinct from other eukaryotes, with an extraordinarily high AT content (>80%)7 and highly divergent histones resulting in atypical DNA packaging properties8. Moreover, the chromatin remodellers that are critical for shaping chromatin structure are not conserved and are unexplored in P. falciparum. Here we identify P. falciparum Snf2L (PfSnf2L, encoded by PF3D7_1104200) as an ISWI-related ATPase that actively repositions P. falciparum nucleosomes in vitro. Our results demonstrate that PfSnf2L is essential, regulating both asexual development and sexual differentiation. PfSnf2L globally controls just-in-time transcription by spatiotemporally determining nucleosome positioning at the promoters of stage-specific genes. The unique sequence and functional properties of PfSnf2L led to the identification of an inhibitor that specifically kills P. falciparum and phenocopies the loss of correct gene expression timing. The inhibitor represents a new class of antimalarial transmission-blocking drugs, inhibiting gametocyte formation.
Activated type 17 helper T cells affect tofacitinib treatment outcomes
Authors: Ito Yuki , Watanabe Daisuke , Okamoto Norihiro , Miyazaki Haruka , Tokunaga Eri , Ku Yuna , Ooi Makoto , Hoshi Namiko , Kohashi Michitaka , Kanzawa Maki , Kodama Yuzo 
Published: February 2025

Abstract
The incidence of ulcerative colitis (UC) is on the rise also in Japan. Simultaneously, therapeutic options, including biologics and Janus kinase (JAK) inhibitors, have significantly expanded over the past decade. Although tofacitinib (TOF), one of JAK inhibitors, is a viable option for patients with moderate to severe UC, there is insufficient data to predict responsiveness of TOF treatment. The present study aimed to determine whether the infiltration of IL-17 A-positive mononuclear cells into the colonic mucosa can predict responsiveness to TOF treatment. Patients with UC who underwent TOF treatment were divided into responder and failure groups. Subsequently, we conducted a comparative analysis to identify differences in the infiltration of IL-17 A-positive cells into the colonic mucosa through immunohistochemical examination of colon biopsy samples. The proportion of IL-17 A positive mononuclear cells in colon biopsy samples was significantly higher in the failure group than among responders (38.2% vs. 21.2%). Consistent with this finding, our re-analysis of RNA sequence datasets available in the Gene Expression Omnibus (GEO) database suggested that TOF exerts a more pronounced influence on Th1 cells compared with IL-17-producing Th17 cells. In summary, an abundance of IL-17 A-positive mononuclear cells in the colonic mucosa has the potential to predict the responsiveness to TOF treatment.
Bias in data-driven replicability analysis of univariate brain-wide association studies
Authors: Burns Charles D. G. , Fracasso Alessio , Rousselet Guillaume A. 
Published: February 2025

Abstract
Recent studies have used big neuroimaging datasets to answer an important question: how many subjects are required for reproducible brain-wide association studies? These data-driven approaches could be considered a framework for testing the reproducibility of several neuroimaging models and measures. Here we test part of this framework, namely estimates of statistical errors of univariate brain-behaviour associations obtained from resampling large datasets with replacement. We demonstrate that reported estimates of statistical errors are largely a consequence of bias introduced by random effects when sampling with replacement close to the full sample size. We show that future meta-analyses can largely avoid these biases by only resampling up to 10% of the full sample size. We discuss implications that reproducing mass-univariate association studies requires tens-of-thousands of participants, urging researchers to adopt other methodological approaches.
Sensor-assessed grasping time as a biomarker of functional impairment in rheumatoid arthritis
Authors: Coppers Birte , Heinrich Simon , Tascilar Koray , Phutane Uday , Kleyer Arnd , Simon David , Bräunig Johanna , Penner Johann , Vossiek Martin , Schönau Verena , Bayat Sara , Schett Georg , Leyendecker Sigrid , Liphardt Anna-Maria 
Published: February 2025

Abstract
Quantifying physical impairment in rheumatoid arthritis (RA) is important to determine disease burden and disability. Therefore, we aimed to define hand function impairments in RA patients using an opto-electronic measurement system (OMS). In this cross-sectional pilot study, spatio-temporal and hand segment data were collected during the fine motor skill Moberg Picking-Up Test (MPUT) and two elementary hand movement tasks in RA patients and healthy controls (HC) using a marker-based OMS. The duration of two MPUT movement phases (grasping, transporting 12 objects) and kinematic characteristics during the elementary movements were evaluated. We analyzed between-group differences using linear mixed-effects models accounting for within-participant clustering of hands and adjusting for age and sex. Measurements were obtained from 24 RA and 23 HC. The mean duration of the grasping phase of MPUT was longer in RA patients compared to HC while transporting times were identical, showing a significant group-phase interaction (p < 0.001). Interphalangeal joint angle ratios were similar in RA and HC (p > 0.05) with a lower ratio in both groups for the task thumb-finger opposition compared to flexion of joints. In RA patients especially grasping objects was impaired, and performance time for a subset of objects may serve as a quantitative biomarker of functional impairment.
Targeting fatty acid synthase reduces aortic atherosclerosis and inflammation
Authors: Meade Rodrigo , Ibrahim Dina , Engel Connor , Belaygorod Larisa , Arif Batool , Hsu Fong-Fu , Adak Sangeeta , Catlett Ryan , Zhou Mingzhou , Ilagan Ma. Xenia G. , Semenkovich Clay F. , Zayed Mohamed A. 
Published: February 2025

Abstract
Fatty acid synthase (FAS) is predominantly expressed in the liver and adipose tissue. It plays vital roles in de novo synthesis of saturated fatty acids and regulates insulin sensitivity. We previously demonstrated that serum circulating FAS (cFAS) is a clinical biomarker for advanced atherosclerosis, and that it is conjugated to low-density lipoproteins (LDL). However, it remains unknown whether cFAS can directly impact atheroprogression. To investigate this, we evaluate whether cFAS impacts macrophage foam cell formation – an important cellular process leading to atheroprogression. Macrophages exposed to human serum containing high levels of cFAS show increased foam cell formation as compared to cells exposed to serum containing low levels of cFAS. This difference is not observed using serum containing either high or low LDL. Pharmacological inhibition of cFAS using Platensimycin (PTM) decreases foam cell formation in vitro. In Apoe
−/− mice with normal FAS expression, administration of PTM over 16 weeks along with a high fat diet decreases cFAS activity and aortic atherosclerosis without affecting circulating total cholesterol. This effect is also observed in Apoe
−/− mice with liver-specific knockout of hepatic Fasn. Reductions in aortic root plaque are associated with decreased macrophage infiltration. These findings demonstrate that cFAS plays an important role in arterial atheroprogression.
Collaborative Referencing Intervention (CRI) in Aphasia: A Replication and Extension of the Phase II Efficacy Study
Authors: Devanga Suma R. 
Published: February 2025

Purpose:
A Phase II study on collaborative referencing intervention (CRI) documented significant positive treatment effects on a traditional confrontation naming measure in four participants with aphasia (PWAs). We replicated the 2021 study and extended it by studying the treatment effect on dyadic conversations and perceptions of communication confidence.

Method:

Three PWAs participated in this multiple-probe, single-case experimental study composed of (a) three preparatory sessions, (b) five baseline sessions, (c) 15 CRI sessions with five treatment probes, and (d) five maintenance sessions. The dependent variables included a collaborative confrontation naming (CCN) probe, the Communication Confidence Rating Scale for Aphasia (CCRSA; Babbitt et al., 2011), and 10-min conversations each with clinician and a communication partner. Each CRI session (i.e., independent variable) consisted of a photo-matching game with the participant and clinician taking alternative turns identifying and matching personally relevant treatment cards. CCN probes were scored using a multidimensional rating scale. Analyses of correct information units
conv
(CIU
conv
), trouble sources, and repairs were conducted on the conversations across the study. The CCRSA scores were also analyzed across the study.

Results:

Multiple-probe analysis revealed significant positive treatment effects on (a) confrontation naming (consistent with the previous study), (b) conversations (on trouble sources and repairs with clinician only, with no significant changes in CIU
conv
across partners), and (c) perceived communication confidence across participants.

Conclusions:
CRI emerges as a promising intervention for individuals with aphasia with potential impacts on conversations and perceived communication confidence. Future research endeavors will further augment our understanding and evidence base regarding this treatment.
An empirical model of the extragalactic radio background
Authors: Gao Fangyou , Wang Tao , Wang Yijun 
Published: February 2025

Aims. Radio observations provide a powerful tool for constraining the assembly of galaxies over cosmic time. Recent deep and wide radio continuum surveys have significantly improved our understanding of the radio emission properties of active galactic nuclei (AGNs) and star-forming galaxies (SFGs) across 0 < z < 4. These findings have allowed us to derive an empirical model of the radio continuum emission of galaxies, based on their star formation rates and the probability of their hosting radio AGNs. In this work, we verify how well this empirical model can reproduce the extragalactic radio background (ERB), which can provide new insights into the contribution to the ERB from galaxies of different masses and redshfits.
Methods. We made use of the Empirical Galaxy Generator (EGG) code to generate a near-infrared (NIR) selected, flux-limited, multiwavelength catalog to mimic real observations. Then we assigned radio continuum flux densities to galaxies based on their star formation rates and the probability that they would host a radio-AGN of a specific 1.4 GHz luminosity. We also applied special treatments to reproduce the clustering signal of radio AGNs.
Results. Our empirical model successfully recovers the observed 1.4 GHz radio luminosity functions (RLFs) of both AGN and SFG populations, as well as the differential number counts at various radio bands. The uniqueness of this approach also allows us to directly link the radio flux densities of galaxies to other properties, including redshifts, stellar masses, and magnitudes at various photometric bands. We find that roughly half of the radio continuum sources to be detected by the Square Kilometer Array (SKA) at z ∼ 4 − 6 will be too faint to be detected in the optical survey (r ∼ 27.5) carried out by Rubin Observatory.
Conclusions. Unlike previous studies, which utilized (extrapolations of) RLFs to reproduce the ERB, our work starts from a simulated galaxy catalog with realistic physical properties. It has the potential to simultaneously and self-consistently reproduce physical properties of galaxies across a wide range of wavelengths, from the optical, NIR, and far-infrared (FIR) to radio wavelengths. Our empirical model can shed light on the contribution of different galaxies to the extragalactic background light and would greatly facilitate the design of future multiwavelength galaxy surveys.
Women and Hereditary Bleeding Disorders
Authors: Bosch Alessandra , Moussaoui Dehlia , Casini Alessandro 
Published: February 2025

AbstractHereditary bleeding disorders encompass a range of hemostasis defects that impair the blood coagulation process. Although these disorders affect both men and women, research and clinical management have historically been predominantly focused on male patients, particularly those with hemophilia. Consequently, the impact of these disorders on women has been undervalued and frequently overlooked. The intricate relationship between a woman's tendency to bleed and the various gynecological and obstetric processes gives rise to distinctive health challenges for women with hereditary bleeding disorders. Heavy menstrual bleeding (HMB), excessive bleeding during miscarriages, postpartum hemorrhage, and hemorrhagic ovarian cysts represent some of the most common complications. Despite the high prevalence and significant impact of these symptoms, many women experience delays in diagnosis and treatment, which in turn may result in iron-deficiency anemia, anxiety, influence on reproductive decisions, and a decreased quality of life. This review aims to summarize the distinctive characteristics of hereditary bleeding disorders in women, emphasizing the clinical challenges and hormonal management strategies for HMB.
Signal Transduction and Transformation by the Platelet Activation Cascade: Systems Biology Insights
Authors: Sveshnikova Anastasia N. , Panteleev Mikhail Aleksandrovich 
Published: February 2025

AbstractBinding of platelet activators to their receptors initiates a signal transduction network, where intracellular signal is filtered, amplified, and transformed. Computational systems biology methods could be a powerful tool to address and analyze dynamics and regulation of the crucial steps in this cascade. Here we review these approaches and show the logic of their use for a relatively simple case of SFLLRN-induced procoagulant activity. Use of a typical model is employed to track signaling events along the main axis, from the binding of the peptide to PAR1 receptor down to the mPTP opening. Temporal dynamics, concentration dependence, formation of calcium oscillations and their deciphering, and role of stochasticity are quantified for all essential signaling molecules and their complexes. The initial step-wise activation stimulus is transformed to a peak at the early stages, then to oscillation calcium spikes, and then back to a peak shape. The model can show how both amplitude and width of the peak encode the information about the activation level, and show the principle of decoding calcium oscillations via integration of the calcium signal by the mitochondria. Use of stochastic algorithms can reveal that the complexes of Gq, in particular the complex of phospholipase C with Gq, which are the limiting steps in the cascade with their numbers not exceeding several molecules per platelet at any given time; it is them that cause stochastic appearance of the signals downstream. Application of reduction techniques to simplify the system is demonstrated.