bluuebunny/crossref_metadata_2025_split huggingface dataset:
Colorectal cancer detected by liquid biopsy 2 years prior to clinical diagnosis in the HUNT study
Authors: Brenne Siv S. , Madsen Poul Henning , Pedersen Inge Søkilde , Hveem Kristian , Skorpen Frank , Krarup Henrik Bygum , Giskeødegård Guro F. , Laugsand Eivor A. 
Published: July 2023

Abstract
Background
Colorectal cancer (CRC) is often diagnosed in advanced stages. Circulating tumour DNA (ctDNA) has been proposed as an early diagnostic biomarker. However, as a screening tool, ctDNA has mainly been studied in selected populations at the time of clinical diagnosis. The aim of this study was to detect CRC by known ctDNA markers up to 2 years prior to clinical diagnosis.

Methods
In this case–control study, methylated ctDNA markers were detected in plasma samples from 106 healthy controls and 106 individuals diagnosed with CRC within 24 months following participation in The Trøndelag Health Study.

Results
The most specific single markers were BMP3, FLI1, IKZF1, SFRP1, SFRP2, NPTX2, SLC8A1 and VIM (specificity >70%). When combining these into a panel, the CRC sensitivity was 43% (95% CI 42.7–43.4) and the CRC specificity was 86% (95% CI 85.7–86.2). The findings were reproduced in an independent validation set of samples.

Conclusions
Detection of known methylated ctDNA markers of CRC is possible up to 2 years prior to the clinical diagnosis in an unselected population resembling the screening setting. This study supports the hypothesis that some patients could be diagnosed earlier, if ctDNA detection was part of the CRC screening programme.
Transcriptome profiling and network enrichment analyses identify subtype-specific therapeutic gene targets for breast cancer and their microRNA regulatory networks
Authors: Elango Ramesh , Rashid Sameera , Vishnubalaji Radhakrishnan , Al-Sarraf Reem , Akhtar Mohammed , Ouararhni Khalid , Decock Julie , Albagha Omar M. E. , Alajez Nehad M. 
Published: July 2023

AbstractPrevious studies have suggested that breast cancer (BC) from the Middle East and North Africa (MENA) is presented at younger age with advanced tumor stage, indicating underlying biological differences. Given the scant transcriptomic data on BC from the MENA region and to better understand the biology of this disease, we performed mRNA and microRNA (miRNA) transcriptomic profiling on a local cohort of BC (n = 96) from Qatar. Our data revealed the differentially expressed genes and miRNAs as function of BC molecular subtypes (HR+, HER2+, HER2+HR+, and TNBC), tumor grade (GIII vs GI-II), patients’ age (young (≤40) vs old (>40)), and ethnicity (MENA vs non-MENA). Our profiling data revealed close similarity between TNBC and HER2+, while the transcriptome of HER2+HR+tumor was resemblant of that from HR+tumors. Network analysis identified complex miRNA-mRNA regulatory networks in each BC molecular subtype, in highvslow grade tumors, in tumors from young vs old patients, and in tumors from MENA vs non-MENA, thus implicating miRNA-mediated gene regulation as an essential mechanism in shaping the transcriptome of BC. Integration of our transcriptomic data with CRISPR-Cas9 functional screen data and the OncoKB database identified numerous dependencies and therapeutic vulnerabilities in each BC molecular subtype, while CDC123 was functionally validated as potential therapeutic target for TNBC. Cox regression survival analyses identified mRNA and miRNA-based signatures predicative of worse and better relapse free survival (RFS), which were validated in larger BC cohorts. Our data provides comprehensive transcriptomic profiling and unraveled the miRNA-mRNA regulatory networks in BC patients from the region and identified novel actionable gene targets, employing integrated approach. Findings from the current study have potential implications to improve the current standard-of-care for BC from the MENA as well as patients from other ethnicities.
METTL3-mediated m6A modification of LINC00839 maintains glioma stem cells and radiation resistance by activating Wnt/β-catenin signaling
Authors: Yin Jianxing , Ding Fangshu , Cheng Zhangchun , Ge Xin , Li Yanhui , Zeng Ailiang , Zhang Junxia , Yan Wei , Shi Zhumei , Qian Xu , You Yongping , Ding Zhiliang , Ji Jing , Wang Xiefeng 
Published: July 2023

AbstractLong noncoding RNAs (lncRNAs) are involved in glioma initiation and progression. Glioma stem cells (GSCs) are essential for tumor initiation, maintenance, and therapeutic resistance. However, the biological functions and underlying mechanisms of lncRNAs in GSCs remain poorly understood. Here, we identified that LINC00839 was overexpressed in GSCs. A high level of LINC00839 was associated with GBM progression and radiation resistance. METTL3-mediated m6A modification on LINC00839 enhanced its expression in a YTHDF2-dependent manner. Mechanistically, LINC00839 functioned as a scaffold promoting c-Src-mediated phosphorylation of β-catenin, thereby inducing Wnt/β-catenin activation. Combinational use of celecoxib, an inhibitor of Wnt/β-catenin signaling, greatly sensitized GSCs to radiation. Taken together, our results showed that LINC00839, modified by METTL3-mediated m6A, exerts tumor progression and radiation resistance by activating Wnt/β-catenin signaling.
IF1 ablation prevents ATP synthase oligomerization, enhances mitochondrial ATP turnover and promotes an adenosine-mediated pro-inflammatory phenotype
Authors: Domínguez-Zorita Sonia , Romero-Carramiñana Inés , Santacatterina Fulvio , Esparza-Moltó Pau B. , Simó Carolina , del-Arco Araceli , Núñez de Arenas Cristina , Saiz Jorge , Barbas Coral , Cuezva José M. 
Published: July 2023

AbstractATPase Inhibitory Factor 1 (IF1) regulates the activity of mitochondrial ATP synthase. The expression of IF1 in differentiated human and mouse cells is highly variable. In intestinal cells, the overexpression of IF1 protects against colon inflammation. Herein, we have developed a conditional IF1-knockout mouse model in intestinal epithelium to investigate the role of IF1 in mitochondrial function and tissue homeostasis. The results show that IF1-ablated mice have increased ATP synthase/hydrolase activities, leading to profound mitochondrial dysfunction and a pro-inflammatory phenotype that impairs the permeability of the intestinal barrier compromising mouse survival upon inflammation. Deletion of IF1 prevents the formation of oligomeric assemblies of ATP synthase and alters cristae structure and the electron transport chain. Moreover, lack of IF1 promotes an intramitochondrial Ca2+ overload in vivo, minimizing the threshold to Ca2+-induced permeability transition (mPT). Removal of IF1 in cell lines also prevents the formation of oligomeric assemblies of ATP synthase, minimizing the threshold to Ca2+-induced mPT. Metabolomic analyses of mice serum and colon tissue highlight that IF1 ablation promotes the activation of de novo purine and salvage pathways. Mechanistically, lack of IF1 in cell lines increases ATP synthase/hydrolase activities and installs futile ATP hydrolysis in mitochondria, resulting in the activation of purine metabolism and in the accumulation of adenosine, both in culture medium and in mice serum. Adenosine, through ADORA2B receptors, promotes an autoimmune phenotype in mice, stressing the role of the IF1/ATP synthase axis in tissue immune responses. Overall, the results highlight that IF1 is required for ATP synthase oligomerization and that it acts as a brake to prevent ATP hydrolysis under in vivo phosphorylating conditions in intestinal cells.
Differential associations between body composition indices and neurodevelopment during early life in term-born infants: findings from the Pakistan cohort: Multi-Center Body Composition Reference Study
Authors: Ariff Shabina , Aamir Almas , Young Aneurin , Sikanderali Laila , Rizvi Arjumand , Shaheen Fariha , Khan Gul Nawaz , Soofi Sajid , Fernandes Michelle 
Published: July 2023

Abstract
Objective
We examined associations between fat free mass (FFM) and fat mass (FM) accretion during the first 1000 days of life and neurodevelopment in term-born, low-risk infants from Karachi, Pakistan.

Design
Prospective, observational study nested within the larger Multi-Center Body Composition Reference Study. FFM, FM, and fat% were estimated using measured deuterium dilution method. Neurodevelopmental outcomes were assessed at 24 months on the INTER-NDA (INTERGROWTH-21st Project Neurodevelopment Assessment) (n = 132).

Results
Children with gross motor delays had significantly lower FFM at 18 months (8.01 ± 0.97 kg vs. 7.55 ± 0.20 kg). Children with positive and negative behavior problems had significantly higher fat% at 24 months (20.62 ± 4.30% vs. 18.23 ± 5.46%) and 20.89 ± 4.24% vs. 18.54 ± 5.38%). No associations remained significant after adjusting for covariates. Trajectory modeling showed that between 12 and 18 months, negative behavior scores changed by 13.8 points for every standard deviation change in fat accretion.

Conclusions
Our findings highlight the importance of balancing neurodevelopment and metabolic risk when designing nutritional interventions for young children.
Mixed strain pathogen populations accelerate the evolution of antibiotic resistance in patients
Authors: Diaz Caballero Julio , Wheatley Rachel M. , Kapel Natalia , López-Causapé Carla , Van der Schalk Thomas , Quinn Angus , Shaw Liam P. , Ogunlana Lois , Recanatini Claudia , Xavier Basil Britto , Timbermont Leen , Kluytmans Jan , Ruzin Alexey , Esser Mark , Malhotra-Kumar Surbhi , Oliver Antonio , MacLean R. Craig 
Published: July 2023

AbstractAntibiotic resistance poses a global health threat, but the within-host drivers of resistance remain poorly understood. Pathogen populations are often assumed to be clonal within hosts, and resistance is thought to emerge due to selection for de novo variants. Here we show that mixed strain populations are common in the opportunistic pathogenP. aeruginosa. Crucially, resistance evolves rapidly in patients colonized by multiple strains through selection for pre-existing resistant strains. In contrast, resistance evolves sporadically in patients colonized by single strains due to selection for novel resistance mutations. However, strong trade-offs between resistance and growth rate occur in mixed strain populations, suggesting that within-host diversity can also drive the loss of resistance in the absence of antibiotic treatment. In summary, we show that the within-host diversity of pathogen populations plays a key role in shaping the emergence of resistance in response to treatment.
AI-designed NMR spectroscopy RF pulses for fast acquisition at high and ultra-high magnetic fields
Authors: Manu V. S. , Olivieri Cristina , Veglia Gianluigi 
Published: July 2023

AbstractNuclear magnetic resonance (NMR) spectroscopy is a powerful high-resolution tool for characterizing biomacromolecular structure, dynamics, and interactions. However, the lengthy longitudinal relaxation of the nuclear spins significantly extends the total experimental time, especially at high and ultra-high magnetic field strengths. Although longitudinal relaxation-enhanced techniques have sped up data acquisition, their application has been limited by the chemical shift dispersion. Here we combined an evolutionary algorithm and artificial intelligence to design 1H and 15N radio frequency (RF) pulses with variable phase and amplitude that cover significantly broader bandwidths and allow for rapid data acquisition. We re-engineered the basic transverse relaxation optimized spectroscopy experiment and showed that the RF shapes enhance the spectral sensitivity of well-folded proteins up to 180 kDa molecular weight. These RF shapes can be tailored to re-design triple-resonance experiments for accelerating NMR spectroscopy of biomacromolecules at high fields.
Expanded quantum vortex liquid regimes in the electron nematic superconductors FeSe1−xSx and FeSe1−xTex
Authors: Čulo M. , Licciardello S. , Ishida K. , Mukasa K. , Ayres J. , Buhot J. , Hsu Y.-T. , Imajo S. , Qiu M. W. , Saito M. , Uezono Y. , Otsuka T. , Watanabe T. , Kindo K. , Shibauchi T. , Kasahara S. , Matsuda Y. , Hussey N. E. 
Published: July 2023

AbstractThe quantum vortex liquid (QVL) is an intriguing state of type-II superconductors in which intense quantum fluctuations of the superconducting (SC) order parameter destroy the Abrikosov lattice even at very low temperatures. Such a state has only rarely been observed, however, and remains poorly understood. One of the key questions is the precise origin of such intense quantum fluctuations and the role of nearby non-SC phases or quantum critical points in amplifying these effects. Here we report a high-field magnetotransport study of FeSe1−xSx and FeSe1−xTex which show a broad QVL regime both within and beyond their respective electron nematic phases. A clear correlation is found between the extent of the QVL and the strength of the superconductivity. This comparative study enables us to identify the essential elements that promote the QVL regime in unconventional superconductors and to demonstrate that the QVL regime itself is most extended wherever superconductivity is weakest.
The MOM1 complex recruits the RdDM machinery via MORC6 to establish de novo DNA methylation
Authors: Li Zheng , Wang Ming , Zhong Zhenhui , Gallego-Bartolomé Javier , Feng Suhua , Jami-Alahmadi Yasaman , Wang Xinyi , Wohlschlegel James , Bischof Sylvain , Long Jeff A. , Jacobsen Steven E. 
Published: July 2023

AbstractMORPHEUS’ MOLECULE1 (MOM1) is an Arabidopsis factor previously shown to mediate transcriptional silencing independent of major DNA methylation changes. Here we find that MOM1 localizes with sites of RNA-directed DNA methylation (RdDM). Tethering MOM1 with an artificial zinc finger to an unmethylated FWA promoter leads to establishment of DNA methylation and FWA silencing. This process is blocked by mutations in components of the Pol V arm of the RdDM machinery, as well as by mutation of MICRORCHIDIA 6 (MORC6). We find that at some endogenous RdDM sites, MOM1 is required to maintain DNA methylation and a closed chromatin state. In addition, efficient silencing of newly introduced FWA transgenes is impaired in the mom1 mutant. In addition to RdDM sites, we identify a group of MOM1 peaks at active chromatin near genes that colocalized with MORC6. These findings demonstrate a multifaceted role of MOM1 in genome regulation.
Three-dimensional images reveal the impact of the endosymbiont Midichloria mitochondrii on the host mitochondria
Authors: Uzum Zerrin , Ershov Dmitry , Pavia Michael J. , Mallet Adeline , Gorgette Olivier , Plantard Olivier , Sassera Davide , Stavru Fabrizia 
Published: July 2023

AbstractThe hard tick, Ixodes ricinus, a main Lyme disease vector, harbors an intracellular bacterial endosymbiont. Midichloria mitochondrii is maternally inherited and resides in the mitochondria of I. ricinus oocytes, but the consequences of this endosymbiosis are not well understood. Here, we provide 3D images of wild-type and aposymbiotic I. ricinus oocytes generated with focused ion beam-scanning electron microscopy. Quantitative image analyses of endosymbionts and oocyte mitochondria at different maturation stages show that the populations of both mitochondrion-associated bacteria and bacterium-hosting mitochondria increase upon vitellogenisation, and that mitochondria can host multiple bacteria in later stages. Three-dimensional reconstructions show symbiosis-dependent morphologies of mitochondria and demonstrate complete M. mitochondrii inclusion inside a mitochondrion. Cytoplasmic endosymbiont located close to mitochondria are not oriented towards the mitochondria, suggesting that bacterial recolonization is unlikely. We further demonstrate individual globular-shaped mitochondria in the wild type oocytes, while aposymbiotic oocytes only contain a mitochondrial network. In summary, our study suggests that M. mitochondrii modulates mitochondrial fragmentation in oogenesis possibly affecting organelle function and ensuring its presence over generations.
Reconstructed Ir‒O‒Mo species with strong Brønsted acidity for acidic water oxidation
Authors: Chen Shiyi , Zhang Shishi , Guo Lei , Pan Lun , Shi Chengxiang , Zhang Xiangwen , Huang Zhen-Feng , Yang Guidong , Zou Ji-Jun 
Published: July 2023

AbstractSurface reconstruction generates real active species in electrochemical conditions; rational regulating reconstruction in a targeted manner is the key for constructing highly active catalyst. Herein, we use the high-valence Mo modulated orthorhombic Pr3Ir1−xMoxO7 as model to activate lattice oxygen and cations, achieving directional and accelerated surface reconstruction to produce self-terminated Ir‒Obri‒Mo (Obri represents the bridge oxygen) active species that is highly active for acidic water oxidation. The doped Mo not only contributes to accelerated surface reconstruction due to optimized Ir‒O covalency and more prone dissolution of Pr, but also affords the improved durability resulted from Mo-buffered charge compensation, thereby preventing fierce Ir dissolution and excessive lattice oxygen loss. As such, Ir‒Obri‒Mo species could be directionally generated, in which the strong Brønsted acidity of Obri induced by remaining Mo assists with the facilitated deprotonation of oxo intermediates, following bridging-oxygen-assisted deprotonation pathway. Consequently, the optimal catalyst exhibits the best activity with an overpotential of 259 mV to reach 10 mA cmgeo−2, 50 mV lower than undoped counterpart, and shows improved stability for over 200 h. This work provides a strategy of directional surface reconstruction to constructing strong Brønsted acid sites in IrOx species, demonstrating the perspective of targeted electrocatalyst fabrication under in situ realistic reaction conditions.
Detecting diagnostic features in MS/MS spectra of post-translationally modified peptides
Authors: Geiszler Daniel J. , Polasky Daniel A. , Yu Fengchao , Nesvizhskii Alexey I. 
Published: July 2023

AbstractPost-translational modifications are an area of great interest in mass spectrometry-based proteomics, with a surge in methods to detect them in recent years. However, post-translational modifications can introduce complexity into proteomics searches by fragmenting in unexpected ways, ultimately hindering the detection of modified peptides. To address these deficiencies, we present a fully automated method to find diagnostic spectral features for any modification. The features can be incorporated into proteomics search engines to improve modified peptide recovery and localization. We show the utility of this approach by interrogating fragmentation patterns for a cysteine-reactive chemoproteomic probe, RNA-crosslinked peptides, sialic acid-containing glycopeptides, and ADP-ribosylated peptides. We also analyze the interactions between a diagnostic ion’s intensity and its statistical properties. This method has been incorporated into the open-search annotation tool PTM-Shepherd and the FragPipe computational platform.
Slab gliding, a hidden factor that induces irreversibility and redox asymmetry of lithium-rich layered oxide cathodes
Authors: Song Jun-Hyuk , Yu Seungju , Kim Byunghoon , Eum Donggun , Cho Jiung , Jang Ho-Young , Park Sung-O , Yoo Jaekyun , Ko Youngmin , Lee Kyeongsu , Lee Myeong Hwan , Kang Byungwook , Kang Kisuk 
Published: July 2023

AbstractLithium-rich layered oxides, despite their potential as high-energy-density cathode materials, are impeded by electrochemical performance deterioration upon anionic redox. Although this deterioration is believed to primarily result from structural disordering, our understanding of how it is triggered and/or occurs remains incomplete. Herein, we propose a theoretical picture that clarifies the irreversible transformation and redox asymmetry of lithium-rich layered oxides by introducing a series of global and local dynamic structural evolution processes involving slab gliding and transition-metal migration. We show that slab gliding plays a key role in trigger/initiating the structural disordering and consequent degradation of the anionic redox reaction. We further reveal that the ‘concerted disordering mechanism’ of slab gliding and transition-metal migration produces spontaneously irreversible/asymmetric lithiation and de-lithiation pathways, causing irreversible structural deterioration and the asymmetry of the anionic redox reaction. Our findings suggest slab gliding as a crucial, yet underexplored, method for achieving a reversible anionic redox reaction.
Abrupt perturbation and delayed recovery of the vaginal ecosystem following childbirth
Authors: Costello Elizabeth K. , DiGiulio Daniel B. , Robaczewska Anna , Symul Laura , Wong Ronald J. , Shaw Gary M. , Stevenson David K. , Holmes Susan P. , Kwon Douglas S. , Relman David A. 
Published: July 2023

AbstractThe vaginal ecosystem is closely tied to human health and reproductive outcomes, yet its dynamics in the wake of childbirth remain poorly characterized. Here, we profile the vaginal microbiota and cytokine milieu of participants sampled longitudinally throughout pregnancy and for at least one year postpartum. We show that delivery, regardless of mode, is associated with a vaginal pro-inflammatory cytokine response and the loss of Lactobacillus dominance. By contrast, neither the progression of gestation nor the approach of labor strongly altered the vaginal ecosystem. At 9.5-months postpartum—the latest timepoint at which cytokines were assessed—elevated inflammation coincided with vaginal bacterial communities that had remained perturbed (highly diverse) from the time of delivery. Time-to-event analysis indicated a one-year postpartum probability of transitioning to Lactobacillus dominance of 49.4%. As diversity and inflammation declined during the postpartum period, dominance by L. crispatus, the quintessential health-associated commensal, failed to return: its prevalence before, immediately after, and one year after delivery was 41%, 4%, and 9%, respectively. Revisiting our pre-delivery data, we found that a prior live birth was associated with a lower odds of L. crispatus dominance in pregnant participants—an outcome modestly tempered by a longer ( > 18-month) interpregnancy interval. Our results suggest that reproductive history and childbirth in particular remodel the vaginal ecosystem and that the timing and degree of recovery from delivery may help determine the subsequent health of the woman and of future pregnancies.
Analysis of DIA proteomics data using MSFragger-DIA and FragPipe computational platform
Authors: Yu Fengchao , Teo Guo Ci , Kong Andy T. , Fröhlich Klemens , Li Ginny Xiaohe , Demichev Vadim , Nesvizhskii Alexey I. 
Published: July 2023

AbstractLiquid chromatography (LC) coupled with data-independent acquisition (DIA) mass spectrometry (MS) has been increasingly used in quantitative proteomics studies. Here, we present a fast and sensitive approach for direct peptide identification from DIA data, MSFragger-DIA, which leverages the unmatched speed of the fragment ion indexing-based search engine MSFragger. Different from most existing methods, MSFragger-DIA conducts a database search of the DIA tandem mass (MS/MS) spectra prior to spectral feature detection and peak tracing across the LC dimension. To streamline the analysis of DIA data and enable easy reproducibility, we integrate MSFragger-DIA into the FragPipe computational platform for seamless support of peptide identification and spectral library building from DIA, data-dependent acquisition (DDA), or both data types combined. We compare MSFragger-DIA with other DIA tools, such as DIA-Umpire based workflow in FragPipe, Spectronaut, DIA-NN library-free, and MaxDIA. We demonstrate the fast, sensitive, and accurate performance of MSFragger-DIA across a variety of sample types and data acquisition schemes, including single-cell proteomics, phosphoproteomics, and large-scale tumor proteome profiling studies.