bluuebunny/crossref_metadata_2025_split huggingface dataset:
Turn ‘noise’ to signal: accurately rectify millions of erroneous short reads through graph learning on edit distances
Authors: Ping Pengyao , Su Shuquan , Cai Xinhui , Lan Tian , Zhang Xuan , Peng Hui , Pan Yi , Liu Wei , Li Jinyan 
Published: April 2024

AbstractAlthough the per-base erring rate of NGS is very low at 0.1% to 0.5%, the percentage/probability oferroneous readsin a short-read sequencing dataset can be as high as 10% to 15% or in the number of millions. Correction of these wrongly sequenced reads to retrieve their huge missing value will improve many downstream applications. As current methods correct only some of the errors at the cost of introducing many new errors, we solve this problem by turning erroneous reads into their original states, without bringing up any non-existing reads to keep the data integrity. The novelty of our method is originated in a computable rule translated from PCR erring mechanism that: a rare read is erroneous if it has a neighbouring read of high abundance. With this principle, we construct a graph to link every pair of reads of tiny edit distances to detect a solid part of erroneous reads; then we consider them as training data to learn the erring mechanisms to identify possibly remaining hard-case errors between pairs of high-abundance reads. Compared with state-of-the-art methods on tens of datasets of UMI-based ground truth, our method has made a remarkably better performance under 19 metrics including two entropy metrics that measure noise levels in a dataset. Case studies found that our method can make substantial impact on genome abundance quantification, isoform identification, SNP profiling, and genome editing efficiency estimation. For example, the abundance level of the reference genome of SARS-CoV-2 can be increased by 12% and that of Monkeypox can be boosted by 52.12% after error correction. Moreover, the number of distinct isomiRs is decreased by 31.56%, unveiling there are so many previously identified isomiRs that are actually sequencing errors.Author summaryDetecting short-read sequencing errors and correcting the related erroneous reads is a long-standing problem in bioinformatics. Current error correction algorithms correct only small parts of the errors but simultaneously introduce thousands of non-existing sequences. We present a new method to rectify erroneous reads under 300 bp produced by PCR-involved miRNA-sequencing, small RNA sequencing, or paired-end RNA sequencing, regardless of platform or sample type. Our method is the first kind considering the PCR erring mechanism and machine learning technique to improve sequencing data quality by turning millions of erroneous short reads into their original state without bringing up any non-existing sequences into the read set. Our error correction method can make a significant impact on a wide range of cutting-edge downstream applications. The observations and advantages in the case studies lay down strong evidence to question the accuracies of current downstream research outcomes and open new avenues to conduct downstream analysis whenever short-read data are adopted.
Physiological bias governs neutrophil inflammatory threat perception
Authors: Pajonczyk Denise , Pauli Lina , Pünt Charlotte , Sternschulte Merle F. , Fehler Olesja , Vogl Thomas , Soehnlein Oliver , Bermudez Marcel , Raabe Carsten Alexander , Rescher Ursula 
Published: April 2024

AbstractBackground and PurposeThe functional G protein-coupled receptor (GPCR) signalling unit consists of an agonist acting on a receptor that is coupled to a G protein that transduces the signals to effectors within a complex cellular environment. While much attention is given to GPCR-agonist or GPCR-transducer relationships, the contribution of the cellular environment remains significantly unexplored.Experimental ApproachHere, we juxtaposed the signalling responses triggered by the activation of two GPCR pattern recognition receptors, Formyl peptide receptor 1 and Formyl peptide receptor 2, in a recombinant cell system against their signalling dynamics in the native neutrophilic environment.Key resultsWe observed that agonist activation leads to cell context-dependent substantial differences in the receptor signalling texture. While the impact of receptor activation onde novocAMP formation varied depending on the cell type, MAPK activation was similar in both systems. This physiological bias was conserved across species. Expression analysis unveiled the absence of the Gαi-sensitive adenylyl cyclases ADCY5 and ADCY6 in neutrophils, implying that cAMPde novosynthesis cannot be inhibited by Gαi-coupled receptors. The signalling behaviour of the Gαi-coupled LTB4 high-affinity receptor BLT1 in neutrophils corroborated our findings.Conclusion and ImplicationsOur data underscore the profound impact of the specific cellular environment on GPCR signalling, causing physiological bias in GPCR signalling, thereby affecting drug efficacy and therapeutic targeting.
Harnessing molecular mechanism for precision medicine in dilated cardiomyopathy caused by a mutation in troponin T
Authors: Greenberg Lina , Stump W. Tom , Lin Zongtao , Bredemeyer Andrea L. , Blackwell Thomas , Han Xian , Greenberg Akiva E. , Garcia Benjamin A. , Lavine Kory J. , Greenberg Michael J. 
Published: April 2024

AbstractFamilial dilated cardiomyopathy (DCM) is frequently caused by autosomal dominant point mutations in genes involved in diverse cellular processes, including sarcomeric contraction. While patient studies have defined the genetic landscape of DCM, genetics are not currently used in patient care, and patients receive similar treatments regardless of the underlying mutation. It has been suggested that a precision medicine approach based on the molecular mechanism of the underlying mutation could improve outcomes; however, realizing this approach has been challenging due to difficulties linking genotype and phenotype and then leveraging this information to identify therapeutic approaches. Here, we used multiscale experimental and computational approaches to test whether knowledge of molecular mechanism could be harnessed to connect genotype, phenotype, and drug response for a DCM mutation in troponin T, deletion of K210. Previously, we showed that at the molecular scale, the mutation reduces thin filament activation. Here, we used computational modeling of this molecular defect to predict that the mutant will reduce cellular and tissue contractility, and we validated this prediction in human cardiomyocytes and engineered heart tissues. We then used our knowledge of molecular mechanism to computationally model the effects of a small molecule that can activate the thin filament. We demonstrate experimentally that the modeling correctly predicts that the small molecule can partially rescue systolic dysfunction at the expense of diastolic function. Taken together, our results demonstrate how molecular mechanism can be harnessed to connect genotype and phenotype and inspire strategies to optimize mechanism-based therapeutics for DCM.Significance statementDilated cardiomyopathy (DCM), a leading cause of heart failure, is characterized by the inability of the heart to perfuse the body at normal filling pressures. There are multiple causes of DCM, including point mutations in sarcomeric proteins, but most patients receive similar courses of treatment, regardless of the underlying cause of the DCM. Many patients remain unserved by current therapies, and there is a need for new approaches. Here, we use multiscale experimental and computational approaches to demonstrate how knowledge of molecular mechanism can be harnessed to accurately predict the effects of a patient-specific mutation and responses to presumptive therapeutics. Our approach lays the foundation for a precision medicine approach to DCM.
Oriented Cell Dataset: efficient imagery analyses using angular representation
Authors: Kirsten LN , Angonezi AL , Oliveira FD , Faccioni JL , Cassel CB , de Sousa DC Santos , Vedovatto S , Jung CR , Lenz G 
Published: April 2024

AbstractIn this work, we propose a new public dataset for cell detection in bright-field microscopy images annotated with Oriented Bounding Boxes (OBBs), named Oriented Cell Dataset (OCD). We show that OBBs provide a more accurate shape representation compared to standard Horizontal Bounding Boxes (HBBs), with slight overhead of one extra click in the annotation process. Our dataset also contains a subset of images with five independent expert annotations, which allows inter-annotation analysis to determine if the results produced by algorithms are within the expected variability of human experts. We investigated how to automate cell biology microscopy images by training seven popular OBB detectors in the proposed dataset, and focused our analyses on two main problems in cancer biology: cell confluence and polarity determination, the latter not possible through HBB representation. All models achieved statistically similar results to the biological applications compared to human annotation, enabling the automation of cell biology and cancer cell biology microscopy image analysis. Our code and dataset are available athttps://github.com/LucasKirsten/Deep-Cell-Tracking-EBB.
Childhood Ocular Inflammation Sensations and Symptoms Reporting Questionnaire (ChOIR-Q): Development and assessment of a paediatric self-report tool
Authors: Solebo Ameenat L , Kellett Salomey , Rahi Jugnoo , Dick Andrew D , Ashworth Jane , Cooper Gisella , McLoone Eibhlin , Muthusamy Kirithika , Pilling Rachel , Petrushkin Harry , Tadic Valerija 
Published: April 2024

AbstractWe aimed to develop and assess age-appropriate child and young person, self and proxy report tools to capture and characterise eye symptoms in childhood ocular inflammatory disease.Children and young people aged under 18 years diagnosed with inflammatory eye disease (uveitis), and their families, were recruited to a multiphase study, involving: text and pictogram items generation through focus groups and interviews (Phase 1), pre-testing face validity analysis including and discussion amongst a multidisciplinary professional panel (Phase 2), and pre-piloting (Phase 3) and piloting (Phase 4) of the instrument amongst a representative sample of the target population.A total of 170 participants, comprising 113 children/young people and 57 parents/carers, were recruited. Phase 1 resulted in the generation of 60 items. Following phases 2 to 3, these items were developed into self-completion, and assisted self-completion tools for children aged 9 years and older, and those aged under 9 years respectively, and a proxy score, for completion by parents and carers. Correlations scores between individual item and whole domain scoring were above 0.58 for the self-completion tools and above 0.39 for the proxy completion tool. Initial Cronbach’s alpha for the tool overall was good at 0.84, with within-domain alphas of 0.81 – 0.87.In conclusion, these instruments demonstrate the feasibility of capturing ocular sensations in children and young people, with a patient centred development approach resulting in tools with high rates of completion, and acceptable internal instrument consistency.
Influence of Anemia on Prevalence of Gestational Diabetes among Pregnant Women in Tripoli, Libya
Authors: Atia Ahmed , Elmahmoudi Hosam 
Published: April 2024

AbstractGestational diabetes mellitus (GDM) is raised globally leading to substantial maternal and foetal morbidity. This study aimed to determine the prevalence of GDM among pregnant women delivering in different private polyclinics in Tripoli, Libya. A cross-sectional study was conducted among pregnant women who were admitted to gynecology department of in different medical polyclinics, Tripoli, Libya from Jan to Dec 2022. The prevalence of GDM in pregnant women increased with increase of the gestational age to reach maximum (86%) at the third trimester of gestation. About 31% (96 patients) anemic pregnant women were observed in 312 GDM. Careful surveillance is required for these pregnancies in high-risk units for early detection and treatment of possible complications, in order to try to reduce maternal and neonatal morbidities.
Phosphate starvation stops bacteria digesting algal fucan that sequesters carbon
Authors: Xu Yi , Schultz-Johansen Mikkel , Yao Huiying , Wilkie Isabella , Klau Leesa Jane , Chen Yuerong , Orellana Luis H. , Aachmann Finn Lillelund , Farhan Mahum , Gu Bowei , Reintjes Greta , Vidal-Melgosa Silvia , Qiao Dairong , Cao Yi , Hehemann Jan-Hendrik 
Published: April 2024

AbstractAlgae provide a solar powered pathway to capture and sequester carbon by injecting stable fucan made from carbon dioxide into the ocean1–4. Stability of the pathway is at odds with the presence of marine bacteria with genes of enzymes that can digest fucan and release the carbon dioxide5. Biochemical explanations for stable fucan remain hypothetical6. We assembled a biological carbon cycle model and found phosphate limitation enhanced fucan synthesis by algae, stopped digestion by bacteria and thereby stabilized the fucan carbon sequestration pathway. Marine microalgaeGlossomastixsp. PLY432 increased synthesis of fucan, a part of its extracellular matrix, under nutrient-growth limiting conditions. Rate and extent of fucan digestion by a marine, isolated bacterium of theAkkermansiaceaefamily decreased with decreasing phosphate concentration. Phosphate starvation restricted bacterial growth rate, biomass yield and in turn increased the amount of stable fucan. Phosphate is universally required for growth but rare relative to glycan carbon in photosynthesis-derived ecosystems. The fact that phosphate is required for replication, transcription and translation explains why bacteria can digest gigatons of laminarin with a few enzymes, but not fucan during nutrient limited algal blooms. We conclude phosphate starvation constrains the ability of bacteria to digest fucan, which evolves to maintain stability around algal cells and consequentially also to keep carbon dioxide in the ocean.
A health systems analysis of non-compliance to the maternity referral system by health facilities in Uganda: Findings from a mixed-methods study
Authors: Zakumumpa Henry , Kyozira Caroline , Bulamu Martin , Buhuguru Remmy 
Published: April 2024

ABSTRACTIntroductionA fully functional referral system is central to achieving quality maternal and newborn care. In 2018, Uganda established Kawempe National Referral hospital (KRNH) as the highest level of care for maternity services. There is a dearth of data examining if the referral function for which it was established has been met. The objectives of this study were two fold; i) to assess the appropriateness of in-coming referrals at KRNH ii) to examine factors underpinning referral decisions at lower referring facilities across Uganda.MethodsThis was a two-phased, mixed-methods study involving 76 health facilities across Uganda. In Phase One, we conducted a cross-sectional study examining incoming referrals at KNRH between July 2019 and August 2020 based on routinely collected data in the Health Information System (HMIS) in-patient registers. In Phase Two, we qualitatively explored factors underpinning maternity referrals at 75 purposively selected facilities. Descriptive statistics were managed in STATA (v14) while qualitative data were analyzed by thematic approach.ResultsA total of 461,226 referrals were made to KNRH during the period under review. The three most common indications for referral at KNRH were; previous caesarian scar, premature rupture of membranes and obstructed labour. Facilities mandated to offer comprehensive emergency obstetric care such as general hospitals (84%) and sub-district hospitals or Health Centre IVs (18%) were the two leading sources of referrals at KNRH. Shortage of basic commodities, poorly equipped theatres, deficiencies in skills for labour, study leaves for maternity workforce at lower facilities contributed to unnecessary referrals.ConclusionSeveral of the indications of referrals at KNRH are ideally manageable at lower referring facilities such as district and sub-district hospitals levels suggesting deficiencies in the national obstetric referral system. Interventions for strengthening basic clinical skills in the management of labour at lower referring facilities and addressing underpinning health system constraints is recommended.
Role of Blood Lipids in the Shared Genetic Etiology Between Major Depressive Disorder and Myocardial Infarction: A Large-scale Multi-trait Association Analysis
Authors: Zhu Yanchen , Wu Zhengbo , Wang Yahui , Cui Zhaorui , Liu Fani , Hu Jiqiang 
Published: April 2024

BackgroundThe genetic role of blood lipids (BL) in the shared genetic etiology between major depressive disorder (MDD) and myocardial infarction (MI) has not been fully characterized.MethodsWe first evaluated genetic associations and causal inferences between MDD, MI and the quantitative traits of BL. To further unravel the underlying genetic mechanisms, we performed multi-trait association analysis to identify novel or pleiotropic genomic risk loci, and shared causal variants for diseases involving BL. Using multiple post-GWAS methods, we explored potential genes, pathways, tissues, cells, and therapeutic targets associated with diseases from different perspectives.FindingsWe found extensive global and local genetic correlations between MDD, MI and the traits of BL. Mendelian randomization (MR) analyses showed that lipid metabolism mediated 26.5% of the mediating effect of MDD leading to MI. Multi-trait association analysis successfully identified 13 MDD- and 36 MI- novel risk loci which have never been reported before. Notably, many pleiotropic loci and shared causal variants were identified across risk loci for both diseases, such as 11q23.3 (rs117937125) and 12q13.3 (rs188571756), which also colocalized for traits of BL. Pathway enrichment analysis further highlighted shared biological pathways primarily involving synaptic function, arterial development, and lipid metabolism. Lastly, gene-mapping, gene-based, transcriptome-wide and proteome-wide association, and MR-proteomic analyses revealed candidate pathogenic genes and therapeutic targets (such as ANGPTL4 and TMEM106B).InterpretationThese findings not only provide novel insights into the role of BL in the comorbidity between MDD and MI, but also benefit the development of preventive or therapeutic drugs for diseases.
Activating an invertebrate bistable opsin with the all-trans 6.11 retinal analogue
Authors: Rodrigues Matthew J. , Tejero Oliver , Mühle Jonas , Pamula Filip K. , Das Ishita , Tsai Ching-Ju , Terakita Akihisa , Sheves Mordechai , Schertler Gebhard F.X. 
Published: April 2024

AbstractAnimal vision depends on opsins, a category of G protein-coupled receptor (GPCR) that achieves light sensitivity by covalent attachment to retinal. Typically binding as an inverse agonist in the 11-cis form, retinal photoisomerizes to the all-trans isomer and activates the receptor, initiating downstream signaling cascades. Retinal bound to bistable opsins isomerizes back to the 11-cis state after absorption of a second photon, inactivating the receptor. Bistable opsins are essential for invertebrate vision and non-visual light perception across the animal kingdom. While crystal structures are available for bistable opsins in the inactive state, it has proven difficult to form homogeneous populations of activated bistable opsins either via illumination or reconstitution with all-trans retinal. Here we show that a non-natural retinal analogue, all-trans retinal 6.11 (ATR6.11), can be reconstituted with the invertebrate bistable opsin, Jumping Spider Rhodopsin-1 (JSR1). Biochemical activity assays demonstrate that ATR6.11 functions as an agonist of JSR1. ATR6.11 binding also enables complex formation between JSR1 and downstream signaling partners. Our findings demonstrate the utility of retinal analogues for biophysical characterization of bistable opsins, which will deepen our understanding of light perception in animals.
Dissecting translation elongation dynamics through ultra-long tracking of single ribosomes
Authors: Madern Maximilian F. , Yang Sora , Witteveen Olivier , Bauer Marianne , Tanenbaum Marvin E. 
Published: April 2024

AbstractmRNA translation by ribosomes is a highly dynamic and heterogeneous process. However, current approaches cannot readily resolve individual ribosomes during translation, limiting our understanding of translation dynamics. Here, we develop an imaging approach based on Stopless-ORF circular RNAs (socRNAs) to monitor individual translating ribosomes for hours. Using the socRNA imaging technology we obtained accurate measurements of ribosome pausing on various problematic RNA sequences or induced by ribosome-targeting drugs. In addition, we identified a novel translation factor involved in translation elongation, and revealed that translocation rates of ribosomes vary, indicative of intracellular ribosomal heterogeneity. Finally, socRNAs allow very sensitive measurements of translation elongation fidelity, revealing widespread frameshifting during translation. In summary, our single-ribosome imaging approach provides a detailed view of ribosome translocation kinetics and a powerful new tool to study the translation elongation phase.
ER-associated degradation by Doa10 restrains mitophagy in yeast
Authors: Eiyama Akinori , Onishi Mashun , Omi Yukiko , Nagumo Sachiyo , Nakatsukasa Kunio , Okamoto Koji 
Published: April 2024

ABSTRACTDegradation of defective or superfluous mitochondria via mitophagy, a specialized form of selective autophagy, is important for maintaining mitochondrial quality and quantity. In yeast, the pro-mitophagic factor Atg32 is transcriptionally upregulated upon oxidative stress and anchored to the mitochondrial surface, where it acts as a molecular signal to initiate efficient degradation of mitochondria. However, how the protein levels of Atg32 are regulated post-translationally remains enigmatic. Here we show that the endoplasmic reticulum (ER) serves as a hub to govern Atg32 protein turnover. We found that the ER-associated degradation (ERAD) E3 ligase Doa10 interacts with Atg32, leading to its degradation by the proteasome. Furthermore, we show that Atg32 is destined for the ER in a manner dependent on the GET (guided entry of tail-anchored proteins) pathway, which mediates the delivery of tail-anchored (TA) proteins to the ER where Atg32 is potentially recognized by Doa10. Notably, Doa10 deficiency increased Atg32 levels and enhanced mitophagy under respiratory conditions, thus determining that ERAD serves as a brake on mitophagy.