bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the potential of water channels for developing MRI reporters and sensors without the need for exogenous contrast agents
Authors: Chacko Asish N. , Miller Austin D.C. , Dhanabalan Kaamini M. , Mukherjee Arnab 
Published: January 2024

AbstractGenetically encoded reporters for magnetic resonance imaging (MRI) offer a valuable technology for making molecular-scale measurements of biological processes within living organisms with high anatomical resolution and whole-organ coverage without relying on ionizing radiation. However, most MRI reporters rely on contrast agents, typically paramagnetic metals and metal complexes, which often need to be supplemented exogenously to create optimal contrast. To eliminate the need for contrast agents, we previously introduced aquaporin-1, a mammalian water channel, as a new reporter gene for the fully autonomous detection of genetically labeled cells using diffusion-weighted MRI. In this study, we aimed to expand the toolbox of diffusion-based genetic reporters by modulating aquaporin membrane trafficking and harnessing the evolutionary diversity of water channels across species. We identified a number of new water channels that functioned as diffusion-weighted reporter genes. In addition, we show that loss-of-function variants of yeast and human aquaporins can be leveraged to design first-in-class diffusion-based sensors for detecting the activity of a model protease within living cells.
CAT Bridge: An Efficient Toolkit for Gene-Metabolite Association Mining from Multi-Omics Data
Authors: Yang Bowen , Meng Tan , Wang Xinrui , Li Jun , Zhao Shuang , Wang Yingheng , Yi Shu , Zhou Yi , Zhang Yi , Li Liang , Guo Li 
Published: January 2024

AbstractBackgroundWith advancements in sequencing and mass spectrometry technologies, multi-omics data can now be easily acquired for understanding complex biological systems. Nevertheless, substantial challenges remain in determining the association between gene-metabolite pairs due to the non-linear and multifactorial interactions within cellular networks. The complexity arises from the interplay of multiple genes and metabolites, often involving feedback loops and time-dependent regulatory mechanisms that are not easily captured by traditional analysis methods.FindingsHere, we introduce Compounds And Transcripts Bridge (abbreviated as CAT Bridge, available athttps://catbridge.work), a free user-friendly platform for longitudinal multi-omics analysis to efficiently identify transcripts associated with metabolites using time-series omics data. To evaluate the association of gene-metabolite pairs, CAT Bridge is a pioneering work benchmarking a set of statistical methods spanning causality estimation and correlation coefficient calculation for multi-omics analysis. Additionally, CAT Bridge features an artificial intelligence (AI) agent to assist users interpreting the association results.ConclusionsWe applied CAT Bridge to experimentally obtainedCapsicum chinense(chili pepper) and public human andEscherichia coli(E. coli) time-series transcriptome and metabolome datasets. CAT Bridge successfully identified genes involved in the biosynthesis of capsaicin inC. chinense. Furthermore, case study results showed that the convergent cross mapping (CCM) method outperforms traditional approaches in longitudinal multi-omics analyses. CAT Bridge simplifies access to various established methods for longitudinal multi-omics analysis, and enables researchers to swiftly identify associated gene-metabolite pairs for further validation.
MR-link-2: pleiotropy robustcisMendelian randomization validated in four independent gold-standard datasets of causality
Authors: van der Graaf Adriaan , Warmerdam Robert , Auwerx Chiara ,   eQTLGen Consortium, Võsa Urmo , Borges Maria Carolina , Franke Lude , Kutalik Zoltán 
Published: January 2024

AbstractMendelian randomization (MR) can identify causal relationships from observational data but has increased Type 1 error rates (T1E) when genetic instruments are limited to a single associated region, a typical scenario for molecular exposures. To address this, we developed MR-link-2, which uses summary statistics and linkage disequilibrium (LD) information to simultaneously estimate a causal effect and pleiotropy in a single associated region. We extensively compare MR-link-2 to othercisMR methods: i) In realistic simulations, MR-link-2 has calibrated T1E and high power. ii) We replicate causal relationships derived from three metabolic pathway references using four independent metabolite quantitative trait locus studies as input to MR. Compared to other methods, MR-link-2 has a superior area under the receiver operator characteristic curve (AUC) (up to 0.80). iii) Applied to canonical causal relationships between complex traits, MR-link-2 has a lower per-locus T1E rate than competing methods (0.09 vs 0.15, at a nominal 5% level) and has several fold less heterogeneous causal effect estimates. iv) Testing the correct causal direction between blood cell type compositions and gene expression of their marker genes reveals that MR-link has superior AUC 0.90 (best competing: 0.67). Finally, when testing for causality between metabolites that are not connected by canonical reactions, MR-link-2 exclusively identifies a link between glycine and pyrroline-5-carboxylate, corroborating results for hypomyelinating leukodystrophy-10, otherwise only found in model systems. Overall, MR-link-2 is the first method to identify pleiotropy-robust causality from summary statistics in single associated regions, making it ideally suited for applications on molecular phenotypes.
Circulating blood circular RNA in Parkinson’s Disease; a systematic study
Authors: Beric Aleksandra , Sun Yichen , Sanchez Santiago , Martin Charissa , Powell Tyler , Pardo Jose Adrian , Sanford Jessie , Botia Juan A. , Cruchaga Carlos , Ibanez Laura 
Published: January 2024

ABSTRACTWe aimed to identify circRNAs associated with Parkinson’s disease (PD) by leveraging 1,848 participants and 1,789 circRNA from two of the largest publicly available studies with longitudinal clinical and blood transcriptomic data. To comprehensively understand changes in circRNAs we performed a cross-sectional study utilizing the last visit of each participant, and a longitudinal (mix model) analysis that included 1,166 participants with at least two time points. We identified 192 circRNAs differentially expressed in PD participants compared to healthy controls, with effects that were consistent in the mixed models, mutation carriers, and diverse ancestry. Finally, we included the 149 circRNA in a model with a ROC AUC of 0.825, showing that have the potential to aid the diagnosis of PD. Overall, we demonstrated that circRNAs play an important role in PD and can be leveraged as biomarkers.
Agriculturally developed areas reduce genetic connectivity for a keystone neotropical ungulate
Authors: Baptista Mozart Sávio Pires , Keuroghlian Alexine , Tambosi Leandro Reverberi , Côrtes Marina Corrêa , Maciel Fernanda de Góes , Cirino Douglas William , Shmaedecke Gabriela , Biondo Cibele 
Published: January 2024

AbstractModified landscapes can restrict the movement of organisms, leading to isolation and reduced population viability, particularly for species with extensive home ranges and long-distance travel, such as white-lipped peccaries (WLPs,Tayassu pecari). Previous studies have indicated that forested areas favor WLP herd movements, but the impact of the non-forested areas on their genetic connectivity is unknown. In this study, we used land cover, the Brazilian Roads Map, and population genetic data to investigate the impact of non-forested matrices on WLP’s genetic connectivity in the Pantanal floodplain and surrounding Cerrado plateau of central-west Brazil. We compared isolation-by-distance (IBD), isolation-by-barrier, and isolation-by-resistance models and tested 39 hypotheses within a modeling framework. Finally, we identified the optimal areas for ecological corridors based on the most effective landscape model. Barrier and landscape resistance were more strongly correlated with genetic relatedness than the IBD model. The model that received the most robust support considered only forest as habitat. All other classes formed a matrix that impeded gene flow, including agriculture, grassland, savannah, and paved and unpaved roads. WLP herds living in landscapes with reduced forest cover are more vulnerable to the effects of genetic isolation. To maintain gene flow, it is essential to establish connections between habitats throughout the landscape. Conservation programs should prioritize strategies that strengthen connections between habitats, including facilitating wildlife road-crossing structures and creating/restoring ecological corridors to link isolated habitat fragments.
The SUbventral-Gland master Regulator (SUGR) of nematode virulence
Authors: Pellegrin Clement , Damm Anika , Sperling Alexis L. , Molloy Beth , Shin Dio S. , Long Jonathan , Brett Paul , Bravo Andrea Díaz-Tendero , Lynch Sarah Jane , Senatori Beatrice , Vieira Paulo , Mejias Joffrey , Kumar Anil , Masonbrink Rick E. , Maier Tom R. , Baum Thomas J. , Eves-van den Akker Sebastian 
Published: January 2024

AbstractAll pathogens must tailor their gene expression to their environment. Therefore, targeting host:parasite biology that regulates these changes in gene expression could open up routes to pathogen control. Here, we show that in the plant-parasitic nematodeHeterodera schachtii,host signals (termed effectostimulins) within plant roots activate the master regulatorsugr1. SUGR1, then, directly binds effector promoters, and orchestrates their production. Effector production, in turn, facilitates host entry, releasing more effectostimulins. These data show that gene expression during the very earliest stages of parasitism is defined by a feed forward loop for host entry. Importantly, we demonstrate that blocking SUGR1 blocks parasitism, underlining the SUGR1 signalling cascade as a valuable target for crop protection. Given that nematodes also parasitise humans and other animals, the potential impact is broad: disrupting effector production could, in principle, be applied to any pathogen that secrets effectors.Graphical abstract
Cryopreservation of the collector urchin embryo,Tripneustes gratilla
Authors: Westbrook Charley E. , Daly Jonathan , Bowen Brian , Hagedorn Mary 
Published: January 2024

AbstractThe collector urchin,Tripneustes gratilla, is an ecologically important member of the grazing community of Hawaii’s coral reefs. Beyond its ability to maintain balance between native seaweeds and corals,T. gratillahas also been used as a food source and a biocontrol agent against alien invasive algae species. Due to overexploitation, habitat degradation, and other stressors, their populations face local extirpation. However, artificial reproductive techniques, such as cryopreservation, could provide more consistent seedstock throughout the year to supplement aquaculture efforts. Although the sperm and larvae of temperate urchins have been successfully cryopreserved, tropical urchins living on coral reefs have not. Here, we investigated the urchin embryos’ tolerance to various cryoprotectants and cooling rates to develop a cryopreservation protocol forT. gratilla. We found that using 1M Me2SO with a cooling rate of 9.7°C/min on gastrula stage embryos produced the best results with survival rates of up to 85.5% and up to 50.8% maturation to the 4-arm echinopluteus stage, assessed three days after thawing. Continued research could see cryopreservation added to the repertoire of artificial reproductive techniques forT. gratilla, thereby assisting in the preservation of this ecologically important urchin, all while augmenting aquaculture efforts that contribute to coral reef restoration.
High-throughput selection of humande novo-emerged sORFs with high folding potential
Authors: Aubel Margaux , Buchel Filip , Heames Brennen , Jones Alun , Honc Ondrej , Bornberg-Bauer Erich , Hlouchova Klara 
Published: January 2024

AbstractDe novogenes emerge from previously non-coding stretches of the genome. Their en-codedde novoproteins are generally expected to be similar to random sequences and, accordingly, with no stable tertiary fold and high predicted disorder. However, structural properties ofde novoproteins and whether they differ during the stages of emergence and fixation have not been studied in depth and rely heavily on predictions. Here we generated a library of short human putativede novoproteins of varying lengths and ages and sorted the candidates according to their structural compactness and disorder propensity. Using Förster resonance energy transfer (FRET) combined with Fluorescence-activated cell sorting (FACS) we were able to screen the library for most compact protein structures, as well as most elongated and flexible structures. Compactde novoproteins are on average slightly shorter and contain lower predicted disorder than less compact ones. The predicted structures for most and least compactde novoproteins correspond to expectations in that they contain more secondary structure content or higher disorder content, respectively. Our experiments indicate that olderde novoproteins have higher compactness and structural propensity compared to young ones. We discuss possible evolutionary scenarios and their implications underlying the age-dependencies of compactness and structural content of putativede novoproteins.
Autism spectrum disorders: an impaired glycolysis induces an ATP deficiency and a reduced cell respiration
Authors: Féron Francois , Caillol Damien , Fourel Laure , Leimkuhler Silke , Iranzo Olga , Gepner Bruno , Guiraudie-Capraz Gaelle 
Published: January 2024

AbstractIn two previous studies, based on human olfactory ecto-mesenchymal stem cells (OE-MSC) of 11 patients with autism spectrum disorders (ASD) and 11 healthy individuals, we demonstrated that the lower abundance of the enzyme MOCOS (MOlybdenum COfactor Sulfurase) and its associated lower expression of the long non-coding RNA, COSMOC, induces neurotransmission and synaptic defects as well as an exacerbated oxidative stress sensitivity. To move a step further, we assessed whether these defects were associated to a disturbed mitochondrial homeostasis. For that purpose, we used cellular and molecular techniques to quantitfy mitochondrial metabolism and biogenesis, ATP production and cell respiration in OE-MSCs from the 8 ASD patients of the cohort that display the most severe symptoms. We show here that OE-MSCs from ASD patients, when compared to control individuals, display i) a reduced expression/abundance of glycolysis-associated transcripts and metabolites, ii) an overall reduced ATP, mainly due to the impaired glycolysis, iii) a reduced basal cell respiration and iv) a modified mitochondrial network. These results are in accordance with some of our previously published data and may explain some of the symptoms – stress, overarousal, seizures, increased or decreased muscle tone, fatigue - observed in autism spectrum disorders.
Interplay ofMycobacterium abscessusandPseudomonas aeruginosain coinfection: Biofilm Dynamics and Host Immune Response
Authors: Campo-Pérez Víctor , Julián Esther , Torrents Eduard 
Published: January 2024

AbstractThe incidence of infection by nontuberculous mycobacteria, mainlyMycobacterium abscessus, in patients with cystic fibrosis and other chronic pulmonary illnesses is increasing, translating into an acceleration in the decline of lung function. In most cases,M. abscessuscoinfects withPseudomonas aeruginosa, the most common pathogen in these chronic diseases. However, it is unknown how these two bacterial species interact when coinfecting. This study aims to explore the behavior of both species in three relevant pathogenic settings: dual-species biofilm development using a recently developed method to monitor individual species in dual-species biofilms; coinfection in bronchial epithelial cells usingin vitroassays; andin vivocoinfection using theGalleria mellonellamodel. The results demonstrate the capability of both species to form stable mixed biofilms and to reciprocally inhibit single-biofilm progression. Coinfections in bronchial epithelial cells were correlated with significantly decreased cell viability, while inG. mellonella,coinfections induced lower survival rates than individual infections. Outstandingly, the analysis of the immune response triggered by each bacterium in bronchial epithelial cell assays andG. mellonellalarvae revealed thatP. aeruginosainduces the overexpression of proinflammatory and melanization cascade responses, respectively. In contrast,M. abscessusandP. aeruginosacoinfection significantly inhibited the immune response in both models, resulting in worse consequences for the host than those generated by singleP. aeruginosainfection. Overall, the presence ofM. abscessusproduces a decline in the immune responses that worsens the infection and compromises the host.ImportanceThe appearance of bacterial infections in the respiratory tract of patients with chronic respiratory diseases suppose a serious and difficult to treat health problem. This complication is exacerbated by the increase resistance against antibiotics generated by pathogenic microorganisms. The most common and virulent pathogenic bacteria reported in the respiratory airway isPseudomonas aeruginosa. It is a Gram-negative, ubiquitous, and intrinsic resistant to antibiotics bacteria. However, the incidence of a rapidly growing, multi-drug resistant mycobacteria;Mycobacterium abscessus, is growing worldwide. The pulmonary coinfection by both pathogens is directly related with higher rates of morbidity and mortality of patients. The significance of our research is characterizing the behavior of these two pathogens when they coinfects together, exploring the immune response triggered by the host and its impact in the survival. The purpose is enhancing the limited understanding we have of this clinically relevant coinfection to favor the development of new effective treatments.
Implementation of the Short-Form 36 (SF-36) in childhood cancer survivors: An analysis on measurement properties across 5 European countries
Authors: Baust Katja , Calaminus Gabriele , Berger Claire , Byrne Julianne , Grabow Desiree , van den Heuvel-Eibrink Marry M. , Kaiser Melanie , Kepak Tomas , Kremer Leontien C.M. , Kruseova Jarmila , Kuonen Rahel , Roser Katharina , Spix Claudia , Maurice-Stam Heleen , Kuehni Claudia E. , Sommer Grit 
Published: January 2024

ABSTRACTPurposeThe Short Form-36 (SF-36) is widely used in many research contexts and cultures to assess health-related quality of life (HRQOL). We investigated the measurement properties of the SF-36 in a large cohort study among childhood cancer survivors living in 5 European countries.MethodsThe PanCareLIFE project includes adult survivors of childhood cancer living in the Czech Republic, France, Germany, The Netherlands, and Switzerland. We invited 19,268 survivors aged >18 years, and 10,077 (53%) returned questionnaires. Of these, 9,871 (98%) were included in the analyses. We assessed HRQOL with the SF-36 version 1 (V1) or version 2 (V2) and investigated its performance. We analysed data completeness, floor and ceiling effects, item-internal consistency, item-discriminant validity, reliability, and scaling assumptions focusing on country-and version-specific differences.ResultsData completeness was high but differed between countries (90% in the Czech Republic to 96% in France). Floor effects were negligible, but ceiling effects in 5 out of 8 SF-36 scales were present (50-70%). V2 had slightly fewer ceiling effects than V1 in 2 scales. Item-internal consistency, item-discriminant validity, and reliability were good. Scaling assumptions were met, with 4 scales representing strong mental health content, and the other 4 representing strong physical health content.ConclusionThe SF-36 (V1 and V2) provided robust measurement properties among childhood cancer survivors, and differences in study design across the 5 European countries did not affect measurement properties. Researchers need to take into account that ceiling effects exist which might limit sensitivity among participants who fared particularly well.PLAIN ENGLISH SUMMARYThis study investigated how well the Short Form-36 (SF-36), a commonly used tool for assessing health-related quality of life, performs in childhood cancer survivors from five different European countries. We looked at the amount of survivors answering to all of the SF-36 questions, how many indicated the most positive or the most negative answer category, whether the questions were consistent within the different aspects of the questionnaire and how consistent and dependable it measured quality of life in the survivors. We found that overall, the SF-36 measured health-related quality of life well in all the countries. This is reassuring for researchers considering its use in studies involving multiple centers across Europe.
RMS: A ML-based system for ICU Respiratory Monitoring and Resource Planning
Authors: Hüser Matthias , Lyu Xinrui , Faltys Martin , Pace Alizée , Berger David , Hoche Marine , Hyland Stephanie L , Yèche Hugo , Burger Manuel , Merz Tobias M , Rätsch Gunnar 
Published: January 2024

AbstractAcute hypoxemic respiratory failure (RF) occurs frequently in critically ill patients and is associated with substantial morbidity, mortality and increased resource use. We used machine learning to create a comprehensive monitoring system to assist intensive care unit (ICU) physicians in managing acute RF. The system encompasses early detection and ongoing monitoring of acute hypoxemic RF, assessment of readiness for tracheal extubation and prediction of the risk of extubation failure. In study patients, the model predicted 80% of RF events at a precision of 45%, with 65% of RF events identified more than 10 hours before RF onset. System predictive performance was significantly higher than standard clinical monitoring based on the patient’s oxygenation index and was successfully validated in an external cohort of ICU patients. We have demonstrated how the estimated risk of extubation failure (EF) could facilitate prevention of both, extubation failure and unnecessarily prolonged mechanical ventilation. Furthermore, we illustrated how machine-learning-based monitoring of RF risk, along with the necessity for mechanical ventilation and extubation readiness on a patient-by-patient basis, can facilitate resource planning for mechanical ventilation in the ICU. Specifically, our model predicted ICU-level ventilator use within 8 to 16 hours into the future, with a mean absolute error of 0.4 ventilators per 10 patients of effective ICU capacity.