bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative proteome and serum analysis identified FSCN1 as a marker of abiraterone resistance in castration-resistant prostate cancer
Authors: Csizmarik Anita , Nagy Nikolett , Keresztes Dávid , Váradi Melinda , Bracht Thilo , Sitek Barbara , Witzke Kathrin , Puhr Martin , Tornyi Ilona , Lázár József , Takács László , Kramer Gero , Sevcenco Sabina , Maj-Hes Agnieszka , Hadaschik Boris , Nyirády Péter , Szarvas Tibor 
Published: August 2023

Abstract
Background
Abiraterone (Abi) is an androgen receptor signaling inhibitor that significantly improves patients’ life expectancy in metastatic prostate cancer (PCa). Despite its beneficial effects, many patients have baseline or acquired resistance against Abi. The aim of this study was to identify predictive serum biomarkers for Abi treatment.

Methods
We performed a comparative proteome analysis on three Abi sensitive (LNCaPabl, LAPC4, DuCaP) and resistant (LNCaPabl-Abi, LAPC4-Abi, DuCaP-Abi) PCa cell lines using liquid chromatography tandem mass spectrometry (LC-MS/MS) technique. Two bioinformatic selection workflows were applied to select the most promising candidate serum markers. Serum levels of selected proteins were assessed in samples of 100 Abi-treated patients with metastatic castration-resistant disease (mCRPC) using ELISA. Moreover, FSCN1 serum concentrations were measured in samples of 69 Docetaxel (Doc) treated mCRPC patients.

Results
Our proteome analysis identified 68 significantly, at least two-fold upregulated proteins in Abi resistant cells. Using two filtering workflows four proteins (AMACR, KLK2, FSCN1 and CTAG1A) were selected for ELISA analyses. We found high baseline FSCN1 serum levels to be significantly associated with poor survival in Abi-treated mCRPC patients. Moreover, the multivariable analysis revealed that higher ECOG status (>1) and high baseline FSCN1 serum levels (>10.22 ng/ml by ROC cut-off) were independently associated with worse survival in Abi-treated patients (p < 0.001 and p = 0.021, respectively). In contrast, no association was found between serum FSCN1 concentrations and overall survival in Doc-treated patients.

Conclusions
Our analysis identified baseline FSCN1 serum levels to be independently associated with poor survival of Abi-treated, but not Doc-treated mCRPC patients, suggesting a therapy specific prognostic value for FSCN1.
Hydrogenotrophic methanogenesis is the key process in the obligately syntrophic consortium of the anaerobic ameba Pelomyxa schiedti
Authors: Treitli Sebastian C , Hanousková Pavla , Beneš Vladimír , Brune Andreas , Čepička Ivan , Hampl Vladimír 
Published: August 2023

Abstract
Pelomyxa is a genus of anaerobic amoebae that live in consortia with multiple prokaryotic endosymbionts. Although the symbionts represent a large fraction of the cellular biomass, their metabolic roles have not been investigated. Using single-cell genomics and transcriptomics, we have characterized the prokaryotic community associated with P. schiedti, which is composed of two bacteria, Candidatus Syntrophus pelomyxae (class Deltaproteobacteria) and Candidatus Vesiculincola pelomyxae (class Clostridia), and a methanogen, Candidatus Methanoregula pelomyxae. Fluorescence in situ hybridization and electron microscopy showed that Ca. Vesiculincola pelomyxae is localized inside vesicles, whereas the other endosymbionts occur freely in the cytosol, with Ca. Methanoregula pelomyxae enriched around the nucleus. Genome and transcriptome-based reconstructions of the metabolism suggests that the cellulolytic activity of P. schiedti produces simple sugars that fuel its own metabolism and the metabolism of a Ca. Vesiculincola pelomyxae, while Ca. Syntrophus pelomyxae energy metabolism relies on degradation of butyrate and isovalerate from the environment. Both species of bacteria and the ameba use hydrogenases to transfer the electrons from reduced equivalents to hydrogen, a process that requires a low hydrogen partial pressure. This is achieved by the third endosymbiont, Ca. Methanoregula pelomyxae, which consumes H2 and formate for methanogenesis. While the bacterial symbionts can be successfully eliminated by vancomycin treatment without affecting the viability of the amoebae, treatment with 2-bromoethanesulfonate, a specific inhibitor of methanogenesis, killed the amoebae, indicating the essentiality of the methanogenesis for this consortium.
Targeted inhibition of protein synthesis renders cancer cells vulnerable to apoptosis by unfolded protein response
Authors: Gsottberger Franziska , Meier Christina , Ammon Anna , Parker Scott , Wendland Kerstin , George Rebekka , Petkovic Srdjan , Mellenthin Lisa , Emmerich Charlotte , Lutzny-Geier Gloria , Metzler Markus , Mackensen Andreas , Chandramohan Vidyalakshmi , Müller Fabian 
Published: August 2023

AbstractCellular stress responses including the unfolded protein response (UPR) decide over the fate of an individual cell to ensure survival of the entire organism. During physiologic UPR counter-regulation, protective proteins are upregulated to prevent cell death. A similar strategy induces resistance to UPR in cancer. Therefore, we hypothesized that blocking protein synthesis following induction of UPR substantially enhances drug-induced apoptosis of malignant cells. In line, upregulation of the chaperone BiP was prevented by simultaneous arrest of protein synthesis in B cell malignancies. Cytotoxicity by immunotoxins—approved inhibitors of protein synthesis—was synergistically enhanced in combination with UPR-inducers in seven distinct hematologic and three solid tumor entities in vitro. Synergistic cell death depended on mitochondrial outer membrane permeabilization via BAK/BAX, which correlated with synergistic, IRE1α-dependent reduction of BID, accompanied by an additive fall of MCL-1. The strong synergy was reproduced in vivo against xenograft mouse models of mantle cell lymphoma, Burkitt’s lymphoma, and patient-derived acute lymphoblastic leukemia. In contrast, synergy was absent in blood cells of healthy donors suggesting a tumor-specific vulnerability. Together, these data support clinical evaluation of blocking stress response counter-regulation using inhibitors of protein synthesis as a novel therapeutic strategy.
The DDUP protein encoded by the DNA damage-induced CTBP1-DT lncRNA confers cisplatin resistance in ovarian cancer
Authors: Ren Liangliang , Qing Xingrong , Wei Jihong , Mo Haixin , Liu Yuanji , Zhi Yaofeng , Lu Wenjie , Zheng Mingzhu , Zhang Weijian , Chen Yuan , Zhang Yuejiao , Pan Taijin , Zhong Qian , Li Ronggang , Zhang Xin , Ruan Xiaohong , Yu Ruyuan , Li Jun 
Published: August 2023

AbstractSustained activation of DNA damage response (DDR) signaling has been demonstrated to play vital role in chemotherapy failure in cancer. However, the mechanism underlying DDR sustaining in cancer cells remains unclear. In the current study, we found that the expression of the DDUP microprotein, encoded by the CTBP1-DT lncRNA, drastically increased in cisplatin-resistant ovarian cancer cells and was inversely correlated to cisplatin-based therapy response. Using a patient-derived human cancer cell model, we observed that DNA damage-induced DDUP foci sustained the RAD18/RAD51C and RAD18/PCNA complexes at the sites of DNA damage, consequently resulting in cisplatin resistance through dual RAD51C-mediated homologous recombination (HR) and proliferating cell nuclear antigen (PCNA)-mediated post-replication repair (PRR) mechanisms. Notably, treatment with an ATR inhibitor disrupted the DDUP/RAD18 interaction and abolished the effect of DDUP on prolonged DNA damage signaling, which resulted in the hypersensitivity of ovarian cancer cells to cisplatin-based therapy in vivo. Altogether, our study provides insights into DDUP-mediated aberrant DDR signaling in cisplatin resistance and describes a potential novel therapeutic approach for the management of platinum-resistant ovarian cancer.
USP14 governs CYP2E1 to promote nonalcoholic fatty liver disease through deubiquitination and stabilization of HSP90AA1
Authors: Wei Dongqin , Tian Xin , Zhu Longbo , Wang Han , Sun Chao 
Published: August 2023

AbstractNonalcoholic fatty liver disease (NAFLD) begins with excessive triglyceride accumulation in the liver, and overly severe hepatic steatosis progresses to nonalcoholic steatohepatitis (NASH), which is characterized by lipid peroxidation, inflammation, and fibrosis. Ubiquitin-specific proteinase 14 (USP14) regulates inflammation, hepatocellular carcinoma and viral infection, but the effect of USP14 on NAFLD is unknown. The aim of this study was to reveal the role of USP14 in the progression of NAFLD and its underlying mechanism. We demonstrated that hepatic USP14 expression was significantly increased in NAFLD in both humans and mice. Hepatic USP14 overexpression exacerbated diet-induced hepatic steatosis, inflammation and fibrosis in mice, in contrast to the results of hepatic USP14 knockdown. Furthermore, palmitic/oleic acid-induced lipid peroxidation and inflammation in hepatocytes were markedly increased by USP14 overexpression but decreased by USP14 knockdown. Notably, in vivo or in vitro data show that USP14 promotes NAFLD progression in a cytochrome p4502E1 (CYP2E1)-dependent manner, which exacerbates hepatocyte oxidative stress, impairs the mitochondrial respiratory chain and inflammation by promoting CYP2E1 protein levels. Mechanistically, we demonstrated by immunoprecipitation and ubiquitination analysis that USP14 inhibits the degradation of heat shock protein 90 alpha family class A member 1 (HSP90AA1) by decreasing its lysine 48-linkage ubiquitination. Meanwhile, upregulation of HAP90AA1 protein promotes CYP2E1 protein accumulation. Collectively, our data indicate that an unknown USP14-HSP90AA1-CYP2E1 axis contributes to NAFLD progression, and we propose that inhibition of USP14 may be an effective strategy for NASH treatment.
Assembly landscape for the bacterial large ribosomal subunit
Authors: Sheng Kai , Li Ning , Rabuck-Gibbons Jessica N. , Dong Xiyu , Lyumkis Dmitry , Williamson James R. 
Published: August 2023

AbstractAssembly of ribosomes in bacteria is highly efficient, taking ~2-3 min, but this makes the abundance of assembly intermediates very low, which is a challenge for mechanistic understanding. Genetic perturbations of the assembly process create bottlenecks where intermediates accumulate, facilitating structural characterization. We use cryo-electron microscopy, with iterative subclassification to identify intermediates in the assembly of the 50S ribosomal subunit from E. coli. The analysis of the ensemble of intermediates that spans the entire biogenesis pathway for the 50 S subunit was facilitated by a dimensionality reduction and cluster picking approach using PCA-UMAP-HDBSCAN. The identity of the cooperative folding units in the RNA with associated proteins is revealed, and the hierarchy of these units reveals a complete assembly map for all RNA and protein components. The assembly generally proceeds co-transcriptionally, with some flexibility in the landscape to ensure efficiency for this central cellular process under a variety of growth conditions.
Universal patterns in egocentric communication networks
Authors: Iñiguez Gerardo , Heydari Sara , Kertész János , Saramäki Jari 
Published: August 2023

AbstractTie strengths in social networks are heterogeneous, with strong and weak ties playing different roles at the network and individual levels. Egocentric networks, networks of relationships around an individual, exhibit few strong ties and more weaker ties, as evidenced by electronic communication records. Mobile phone data has also revealed persistent individual differences within this pattern. However, the generality and driving mechanisms of social tie strength heterogeneity remain unclear. Here, we study tie strengths in egocentric networks across multiple datasets of interactions between millions of people during months to years. We find universality in tie strength distributions and their individual-level variation across communication modes, even in channels not reflecting offline social relationships. Via a simple model of egocentric network evolution, we show that the observed universality arises from the competition between cumulative advantage and random choice, two tie reinforcement mechanisms whose balance determines the diversity of tie strengths. Our results provide insight into the driving mechanisms of tie strength heterogeneity in social networks and have implications for the understanding of social network structure and individual behavior.
Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype
Authors: Oh Ki , Yoo Yun Jae , Torre-Healy Luke A. , Rao Manisha , Fassler Danielle , Wang Pei , Caponegro Michael , Gao Mei , Kim Joseph , Sasson Aaron , Georgakis Georgios , Powers Scott , Moffitt Richard A. 
Published: August 2023

AbstractBulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. However, understanding of underlying signals driving distinct immune and stromal landscapes is still incomplete. Here we integrate 92 single cell RNA-seq samples from seven independent studies to build a reproducible PDAC atlas with a focus on tumor-TME interdependence. Patients with activated stroma are synonymous with higher myofibroblastic and immunogenic fibroblasts, and furthermore show increased M2-like macrophages and regulatory T-cells. Contrastingly, patients with ‘normal’ stroma show M1-like recruitment, elevated effector and exhausted T-cells. To aid interoperability of future studies, we provide a pretrained cell type classifier and an atlas of subtype-based signaling factors that we also validate in mouse data. Ultimately, this work leverages the heterogeneity among single-cell studies to create a comprehensive view of the orchestra of signaling interactions governing PDAC.
The challenge of population aging for mitigating deaths from PM2.5 air pollution in China
Authors: Xu Fangjin , Huang Qingxu , Yue Huanbi , Feng Xingyun , Xu Haoran , He Chunyang , Yin Peng , Bryan Brett A. 
Published: August 2023

AbstractEstimating the health burden of air pollution against the background of population aging is of great significance for achieving the Sustainable Development Goal 3.9 which aims to substantially reduce the deaths and illnesses from air pollution. Here, we estimated spatiotemporal changes in deaths attributable to PM2.5 air pollution in China from 2000 to 2035 and examined the drivers. The results show that from 2019 to 2035, deaths were projected to decease 15.4% (6.6%–20.7%, 95% CI) and 8.4% (0.6%–13.5%) under the SSP1-2.6 and SSP5-8.5 scenario, respectively, but increase 10.4% (5.1%–20.5%) and 18.1% (13.0%–28.3%) under SSP2-4.5 and SSP3-7.0 scenarios. Population aging will be the leading contributor to increased deaths attributable to PM2.5 air pollution, which will counter the positive gains achieved by improvements in air pollution and healthcare. Region-specific measures are required to mitigate the health burden of air pollution and this requires long-term efforts and mutual cooperation among regions in China.
Nanocompartment-confined polymerization in living systems
Authors: Chen Yun , Zuo Mengxuan , Chen Yu , Yu Peiyuan , Chen Xiaokai , Zhang Xiaodong , Yuan Wei , Wu Yinglong , Zhu Wei , Zhao Yanli 
Published: August 2023

AbstractPolymerization in living systems has become an effective strategy to regulate cell functions and behavior. However, the requirement of high concentrations of monomers, the existence of complicated intracorporal interferences, and the demand for extra external stimulations hinder their further biological applications. Herein, a nanocompartment-confined strategy that provides a confined and secluded environment for monomer enrichment and isolation is developed to achieve high polymerization efficiency, reduce the interference from external environment, and realize broad-spectrum polymerizations in living systems. For exogenous photopolymerization, the light-mediated free-radical polymerization of sodium 4-styrenesulfonate induces a 2.7-fold increase in the reaction rate with the protection of a confined environment. For endogenous hydrogen peroxide-responsive polymerization,p‑aminodiphenylamine hydrochloride embedded in a nanocompartment not only performs a 6.4-fold higher reaction rate than that of free monomers, but also activates an effective second near-infrared photoacoustic imaging-guided photothermal immunotherapy at tumor sites. This nanocompartment-confined strategy breaks the shackles of conventional polymerization, providing a universal platform for in vivo synthesis of polymers with diverse structures and functions.
Design of stretchable and self-powered sensing device for portable and remote trace biomarkers detection
Authors: Huang Wenxi , Ding Qiongling , Wang Hao , Wu Zixuan , Luo Yibing , Shi Wenxiong , Yang Le , Liang Yujie , Liu Chuan , Wu Jin 
Published: August 2023

AbstractTimely and remote biomarker detection is highly desired in personalized medicine and health protection but presents great challenges in the devices reported so far. Here, we present a cost-effective, flexible and self-powered sensing device for H2S biomarker analysis in various application scenarios based on the structure of galvanic cells. The sensing mechanism is attributed to the change in electrode potential resulting from the chemical adsorption of gas molecules on the electrode surfaces. Intrinsically stretchable organohydrogels are used as solid-state electrolytes to enable stable and long-term operation of devices under stretching deformation or in various environments. The resulting open-circuit sensing device exhibits high sensitivity, low detection limit, and excellent selectivity for H2S. Its application in the non-invasive halitosis diagnosis and identification of meat spoilage is demonstrated, emerging great commercial value in portable medical electronics and food security. A wireless sensory system has also been developed for remote H2S monitoring with the participation of Bluetooth and cloud technologies. This work breaks through the shortcomings in the traditional chemiresistive sensors, offering a direction and theoretical foundation for designing wearable sensors catering to other stimulus detection requirements.
Characterizing SARS-CoV-2 neutralization profiles after bivalent boosting using antigenic cartography
Authors: Rössler Annika , Netzl Antonia , Knabl Ludwig , Bante David , Wilks Samuel H. , Borena Wegene , von Laer Dorothee , Smith Derek J. , Kimpel Janine 
Published: August 2023

AbstractSince emergence of the initial SARS-CoV-2 BA.1, BA.2 and BA.5 variants, Omicron has diversified substantially. Antigenic characterization of these new variants is important to analyze their potential immune escape from population immunity and implications for future vaccine composition. Here, we describe an antigenic map based on human single-exposure sera and live-virus isolates that includes a broad selection of recently emerged Omicron variants such as BA.2.75, BF.7, BQ, XBB and XBF variants. Recent Omicron variants clustered around BA.1 and BA.5 with some variants further extending the antigenic space. Based on this antigenic map we constructed antibody landscapes to describe neutralization profiles after booster immunization with bivalent mRNA vaccines based on ancestral virus and either BA.1 or BA.4/5. Immune escape of BA.2.75, BQ, XBB and XBF variants was also evident in bivalently boosted individuals, however, cross-neutralization was improved for those with hybrid immunity. Our results indicate that future vaccine updates are needed to induce cross-neutralizing antibodies against currently circulating variants.
Hydrodynamic finite-size scaling of the thermal conductivity in glasses
Authors: Fiorentino Alfredo , Pegolo Paolo , Baroni Stefano 
Published: August 2023

AbstractIn the past few years, the theory of thermal transport in amorphous solids has been substantially extended beyond the Allen-Feldman model. The resulting formulation, based on the Green-Kubo linear response or the Wigner-transport equation, bridges this model for glasses with the traditional Boltzmann kinetic approach for crystals. The computational effort required by these methods usually scales as the cube of the number of atoms, thus severely limiting the size range of computationally affordable glass models. Leveraging hydrodynamic arguments, we show how this issue can be overcome through a simple formula to extrapolate a reliable estimate of the bulk thermal conductivity of glasses from finite models of moderate size. We showcase our findings for realistic models of paradigmatic glassy materials.
A decade of urban fires: Portuguese events between 2013 and 2022
Authors: Bispo Regina , Marques Filipe J. , Penha Alexandre , Espadinha-Cruz Pedro , Grilo António 
Published: August 2023

AbstractThis study describes a dataset containing urban fire events that took place in mainland Portugal between 2013 and 2022. The Regulation n.º3317-A/2018, established by the Portuguese National Emergency and Civil Protection Authority (Autoridade Nacional de Emergência e Proteção Civil, ANEPC), defines the Operations Management System (Sistema de Gestão de Operações, SGO). Among other attributions, this system allows to manage the lyfe-cycle of the urban fire events, from ignition to extinction, through the Operations Decision Support System (Sistema de Apoio Ã Decisão Operacional, SADO). This system supports the systematic collection of a minimum set of data on each event. All instances included in the dataset were retrieved from SADO. To make the data suitable for analytic purposes, several pre-processing actions were taken, including the steps of data transformation and cleaning. The dataset was further validated by a set of technical procedures aiming to verify both data correctness and utility. The final dataset provides the most recent multi-year record of Portuguese urban fires including 27 variables on 72641 events.
A randomized trial that compared brain activity, efficacy and plausibility of open-label placebo treatment and cognitive reappraisal for reducing emotional distress
Authors: Schienle Anne , Kogler Wolfgang , Wabnegger Albert 
Published: August 2023

AbstractPlacebo pills can reduce emotional distress even when recipients have been informed about the inert nature of the treatment. However, before such open-label placebos (OLPs) can be recommended for general clinical use, their efficacy and acceptability need to be further investigated and compared with established methods for emotion regulation, such as cognitive reappraisal (CR). The current study with functional magnetic resonance imaging compared the effects of an OLP pill with CR for reducing a specific form of emotional distress: disgust. Participants (150 healthy females) were randomly allocated to one of three groups, all of which were exposed to disgusting and neutral images (OLP, CR, PV: passive viewing). It was tested whether the three groups would differ in brain activity and reported disgust. Ratings for the perceived efficacy and plausibility of treatment were also compared between OLP and CR. Both OLP and CR increased the activity in a cognitive control region, the ventrolateral prefrontal cortex. Relative to PV and OLP, CR reduced activity in the putamen and pallidum. These regions play an important role in decoding disgust signals from different modalities. Self-reports indicated that CR was perceived as a more effective and plausible intervention strategy than OLP. In conclusion, CR was a superior method for disgust regulation compared to OLP, both on the subjective as well as the neurobiological level. Future OLP studies are needed to test whether the observed effects generalize to other forms of emotional distress.