bluuebunny/crossref_metadata_2025_split huggingface dataset:
Integrated multi-omics for rapid rare disease diagnosis on a national scale
Authors: Lunke Sebastian , Bouffler Sophie E. , Patel Chirag V. , Sandaradura Sarah A. , Wilson Meredith , Pinner Jason , Hunter Matthew F. , Barnett Christopher P. , Wallis Mathew , Kamien Benjamin , Tan Tiong Y. , Freckmann Mary-Louise , Chong Belinda , Phelan Dean , Francis David , Kassahn Karin S. , Ha Thuong , Gao Song , Arts Peer , Jackson Matilda R. , Scott Hamish S. , Eggers Stefanie , Rowley Simone , Boggs Kirsten , Rakonjac Ana , Brett Gemma R. , de Silva Michelle G. , Springer Amanda , Ward Michelle , Stallard Kirsty , Simons Cas , Conway Thomas , Halman Andreas , Van Bergen Nicole J. , Sikora Tim , Semcesen Liana N. , Stroud David A. , Compton Alison G. , Thorburn David R. , Bell Katrina M. , Sadedin Simon , North Kathryn N. , Christodoulou John , Stark Zornitza 
Published: June 2023

AbstractCritically ill infants and children with rare diseases need equitable access to rapid and accurate diagnosis to direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing to 290 families whose critically ill infants and children were admitted to hospitals throughout Australia with suspected genetic conditions. The average time to result was 2.9 d and diagnostic yield was 47%. We performed additional bioinformatic analyses and transcriptome sequencing in all patients who remained undiagnosed. Long-read sequencing and functional assays, ranging from clinically accredited enzyme analysis to bespoke quantitative proteomics, were deployed in selected cases. This resulted in an additional 19 diagnoses and an overall diagnostic yield of 54%. Diagnostic variants ranged from structural chromosomal abnormalities through to an intronic retrotransposon, disrupting splicing. Critical care management changed in 120 diagnosed patients (77%). This included major impacts, such as informing precision treatments, surgical and transplant decisions and palliation, in 94 patients (60%). Our results provide preliminary evidence of the clinical utility of integrating multi-omic approaches into mainstream diagnostic practice to fully realize the potential of rare disease genomic testing in a timely manner.
Structure of nascent 5S RNPs at the crossroad between ribosome assembly and MDM2–p53 pathways
Authors: Castillo Duque de Estrada Nestor Miguel , Thoms Matthias , Flemming Dirk , Hammaren Henrik M. , Buschauer Robert , Ameismeier Michael , Baßler Jochen , Beck Martin , Beckmann Roland , Hurt Ed 
Published: June 2023

AbstractThe 5S ribonucleoprotein (RNP) is assembled from its three components (5S rRNA, Rpl5/uL18 and Rpl11/uL5) before being incorporated into the pre-60S subunit. However, when ribosome synthesis is disturbed, a free 5S RNP can enter the MDM2–p53 pathway to regulate cell cycle and apoptotic signaling. Here we reconstitute and determine the cryo-electron microscopy structure of the conserved hexameric 5S RNP with fungal or human factors. This reveals how the nascent 5S rRNA associates with the initial nuclear import complex Syo1–uL18–uL5 and, upon further recruitment of the nucleolar factors Rpf2 and Rrs1, develops into the 5S RNP precursor that can assemble into the pre-ribosome. In addition, we elucidate the structure of another 5S RNP intermediate, carrying the human ubiquitin ligase Mdm2, which unravels how this enzyme can be sequestered from its target substrate p53. Our data provide molecular insight into how the 5S RNP can mediate between ribosome biogenesis and cell proliferation.
Home monitoring with connected mobile devices for asthma attack prediction with machine learning
Authors: Tsang Kevin C. H. , Pinnock Hilary , Wilson Andrew M. , Salvi Dario , Shah Syed Ahmar 
Published: June 2023

AbstractMonitoring asthma is essential for self-management. However, traditional monitoring methods require high levels of active engagement, and some patients may find this tedious. Passive monitoring with mobile-health devices, especially when combined with machine-learning, provides an avenue to reduce management burden. Data for developing machine-learning algorithms are scarce, and gathering new data is expensive. A few datasets, such as the Asthma Mobile Health Study, are publicly available, but they only consist of self-reported diaries and lack any objective and passively collected data. To fill this gap, we carried out a 2-phase, 7-month AAMOS-00 observational study to monitor asthma using three smart-monitoring devices (smart-peak-flow-meter/smart-inhaler/smartwatch), and daily symptom questionnaires. Combined with localised weather, pollen, and air-quality reports, we collected a rich longitudinal dataset to explore the feasibility of passive monitoring and asthma attack prediction. This valuable anonymised dataset for phase-2 of the study (device monitoring) has been made publicly available. Between June-2021 and June-2022, in the midst of UK’s COVID-19 lockdowns, 22 participants across the UK provided 2,054 unique patient-days of data.
Genome-resolved carbon processing potential of tropical peat microbiomes from an oil palm plantation
Authors: Bandla Aditya , Mukhopadhyay Sourav , Mishra Shailendra , Sudarshan Ashwin Sridhar , Swarup Sanjay 
Published: June 2023

AbstractTropical peatlands in South-East Asia are some of the most carbon-dense ecosystems in the world. Extensive repurposing of such peatlands for forestry and agriculture has resulted in substantial microbially-driven carbon emissions. However, we lack an understanding of the microorganisms and their metabolic pathways involved in carbon turnover. Here, we address this gap by reconstructing 764 sub-species-level genomes from peat microbiomes sampled from an oil palm plantation located on a peatland in Indonesia. The 764 genomes cluster into 333 microbial species (245 bacterial and 88 archaeal), of which, 47 are near-complete (completeness ≥90%, redundancy ≤5%, number of unique tRNAs ≥18) and 170 are substantially complete (completeness ≥70%, redundancy ≤10%). The capacity to respire amino acids, fatty acids, and polysaccharides was widespread in both bacterial and archaeal genomes. In contrast, the ability to sequester carbon was detected only in a few bacterial genomes. We expect our collection of reference genomes to help fill some of the existing knowledge gaps about microbial diversity and carbon metabolism in tropical peatlands.
Comparison of Oxford Nanopore Technologies and Illumina MiSeq sequencing with mock communities and agricultural soil
Authors: Stevens Bo Maxwell , Creed Tim B. , Reardon Catherine L. , Manter Daniel K. 
Published: June 2023

AbstractIllumina MiSeq is the current standard for characterizing microbial communities in soil. The newer alternative, Oxford Nanopore Technologies MinION sequencer, is quickly gaining popularity because of the low initial cost and longer sequence reads. However, the accuracy of MinION, per base, is much lower than MiSeq (95% versus 99.9%). The effects of this difference in base-calling accuracy on taxonomic and diversity estimates remains unclear. We compared the effects of platform, primers, and bioinformatics on mock community and agricultural soil samples using short MiSeq, and short and full-length MinION 16S rRNA amplicon sequencing. For all three methods, we found that taxonomic assignments of the mock community at both the genus and species level matched expectations with minimal deviation (genus: 80.9–90.5%; species: 70.9–85.2% Bray–Curtis similarity); however, the short MiSeq with error correction (DADA2) resulted in the correct estimate of mock community species richness and much lower alpha diversity for soils. Several filtering strategies were tested to improve these estimates with varying results. The sequencing platform also had a significant influence on the relative abundances of taxa with MiSeq resulting in significantly higher abundances Actinobacteria, Chloroflexi, and Gemmatimonadetes and lower abundances of Acidobacteria, Bacteroides, Firmicutes, Proteobacteria, and Verrucomicrobia compared to the MinION platform. When comparing agricultural soils from two different sites (Fort Collins, CO and Pendleton, OR), methods varied in the taxa identified as significantly different between sites. At all taxonomic levels, the full-length MinION method had the highest similarity to the short MiSeq method with DADA2 correction with 73.2%, 69.3%, 74.1%, 79.3%, 79.4%, and 82.28% of the taxa at the phyla, class, order, family, genus, and species levels, respectively, showing similar patterns in differences between the sites. In summary, although both platforms appear suitable for 16S rRNA microbial community composition, biases for different taxa may make the comparison between studies problematic; and even with a single study (i.e., comparing sites or treatments), the sequencing platform can influence the differentially abundant taxa identified.
A pilot study investigating affective forecasting biases with a novel virtual reality-based paradigm
Authors: Loisel-Fleuriot Louise , Fovet Thomas , Bugnet Arnaud , Creupelandt Coralie , Wathelet Marielle , Szaffarczyk Sébastien , Duhem Stéphane , Vaiva Guillaume , Horn Mathilde , D’Hondt Fabien 
Published: June 2023

AbstractA body of research indicates that people are prone to overestimate the affective impact of future events. Here, we developed a novel experimental paradigm to study these affective forecasting biases under laboratory conditions using subjective (arousal and valence) and autonomic measures (skin conductance responses, SCRs, and heart rate). Thirty participants predicted their emotional responses to 15 unpleasant, 15 neutral, and 15 pleasant scenarios (affective forecasting phase) to which they were then exposed in virtual reality (emotional experience phase). Results showed that participants anticipated more extreme arousal and valence scores than they actually experienced for unpleasant and pleasant scenarios. The emotional experience phase was characterized by classic autonomic patterns, i.e., higher SCRs for emotionally arousing scenarios and greater peak cardiac acceleration for pleasant scenarios. During the affective forecasting phase, we found only a moderate association between arousal scores and SCRs and no valence-dependent modulation of cardiac activity. This paradigm opens up new perspectives for investigating affective forecasting abilities under lab-controlled conditions, notably in psychiatric disorders with anxious anticipations.
Upgradation of methane in the biogas by hydrogenation of CO2 in a prototype reactor with double pass operation over optimized Ni-Ce/Al-MCM-41 catalyst
Authors: Aieamsam-Aung Pichawee , Srifa Atthapon , Koo-Amornpattana Wanida , Assabumrungrat Suttichai , Reubroycharoen Prasert , Suchamalawong Phorndranrat , Fukuhara Choji , Ratchahat Sakhon 
Published: June 2023

AbstractThe upgradation of methane in biogas by hydrogenation of CO2 has been currently recognized as a promising route for efficient full utilization of renewable biogas with potential benefits for storage of renewable hydrogen energy and abatement of greenhouse gas emission. As a main constituent of biogas, CO2 can act as a backbone for the formation of additional CH4 by hydrogenation, then producing higher amounts of biomethane. In this work, the upgradation process was investigated in a prototype reactor of double pass operation with vertical alignment using an optimized Ni-Ce/Al-MCM-41 catalyst. The experimental results show that the double pass operation that removes water vapor during the run can significantly increase CO2 conversion, resulting in higher CH4 production yield. As a result, the purity of biomethane increased by 15% higher than a single pass operation. In addition, search for optimum condition of the process was carried out within an investigated range of conditions including flowrate (77–1108 ml min−1), pressure (1 atm–20 bar), and temperature (200–500 °C). The durability test for 458 h was performed using the obtained optimum condition, and it shows that the optimized catalyst can perform excellent stability with negligible influence by the observed change in catalyst properties. The comprehensive characterization on physicochemical properties of fresh and spent catalysts was performed, and the results were discussed.
High expression of GPR176 predicts poor prognosis of gastric cancer patients and promotes the proliferation, migration, and invasion of gastric cancer cells
Authors: Zhang Yu , Gu Xinliang , Zhu Feilong , Li Yang , Huang Yuejiao , Ju Shaoqing 
Published: June 2023

AbstractG-protein-coupled receptors (GPCRs) are the most prominent family of cell surface receptors, which can regulate various biological functions and play an essential role in many diseases. GPR176 is a member of the GPCRs family and has been rarely studied in cancer. We aim to investigate the diagnostic and prognostic value of GPR176 in gastric cancer (GC) and explore its potential mechanism. Through the TCGA database and real-time quantitative PCR, we found that the expression level of GPR176 was significantly increased in GC and had good value in the diagnosis and prognosis of GC. Vitro experiments revealed that GPR176 could promote the proliferation, migration, and invasion of GC cells and may be involved in regulating multiple tumors and immune-related signaling pathways. In addition, we found that GPR176 is associated with GC immune infiltration and may affect the immune efficacy of GC patients. In summary, the high GPR176 expression level was associated with poor prognosis, more robust immune infiltration, and worse immunotherapy efficacy in GC patients, suggesting that GPR176 may be an immune-related biomarker for GC that can promote the proliferation, migration, and invasion of GC cells.
The impact of Atlantic Multidecadal Variability on Baltic Sea temperatures limited to winter
Authors: Börgel Florian , Gröger Matthias , Meier H. E. Markus , Dutheil Cyril , Radtke Hagen , Borchert Leonard 
Published: June 2023

AbstractWe analyze multidecadal temperature fluctuations of the Atlantic Ocean and their influence on Northern Europe, focusing on the Baltic Sea, without a priori assuming a linear relationship of this teleconnection. Instead, we use the method of low-frequency component analysis to identify modes of multidecadal variability in the Baltic Sea temperature signal and relate this signal to the Atlantic climate variability. Disentangling the seasonal impact reveals that a large fraction of the variability in Baltic Sea winter temperatures is related to multidecadal temperature fluctuations in the North Atlantic, known as Atlantic Multidecadal Variability (AMV). The strong winter response can be linked to the interaction between the North Atlantic Oscillation and the AMV and is maintained by oceanic inertia. In contrast, the AMV does not influence the Baltic Sea’s summer and spring water temperatures.
AI for climate impacts: applications in flood risk
Authors: Jones Anne , Kuehnert Julian , Fraccaro Paolo , Meuriot Ophélie , Ishikawa Tatsuya , Edwards Blair , Stoyanov Nikola , Remy Sekou L. , Weldemariam Kommy , Assefa Solomon 
Published: June 2023

AbstractIn recent years there has been a surge of interest in the potential of Artificial Intelligence (AI) to address the global threat of climate change. Here, we consider climate change applications, and review the ability of AI technologies to better quantify climate change-induced hazards, impacts and risks, and address key challenges in this domain. We focus on three application areas: data-driven modeling, enabling uncertainty quantification, and leveraging geospatial big data. For these, we provide examples from flood-related applications to illustrate the advantages of AI, in comparison to alternative methods, whilst also considering its limitations. We conclude that by streamlining the process of translating weather and climate data into actionable information, facilitated by a suitable technology framework, AI can play a key role in building climate change resilience.
The functional anatomy of elephant trunk whiskers
Authors: Deiringer Nora , Schneeweiß Undine , Kaufmann Lena V. , Eigen Lennart , Speissegger Celina , Gerhardt Ben , Holtze Susanne , Fritsch Guido , Göritz Frank , Becker Rolf , Ochs Andreas , Hildebrandt Thomas , Brecht Michael 
Published: June 2023

AbstractBehavior and innervation suggest a high tactile sensitivity of elephant trunks. To clarify the tactile trunk periphery we studied whiskers with the following findings. Whisker density is high at the trunk tip and African savanna elephants have more trunk tip whiskers than Asian elephants. Adult elephants show striking lateralized whisker abrasion caused by lateralized trunk behavior. Elephant whiskers are thick and show little tapering. Whisker follicles are large, lack a ring sinus and their organization varies across the trunk. Follicles are innervated by ~90 axons from multiple nerves. Because elephants don’t whisk, trunk movements determine whisker contacts. Whisker-arrays on the ventral trunk-ridge contact objects balanced on the ventral trunk. Trunk whiskers differ from the mobile, thin and tapered facial whiskers that sample peri-rostrum space symmetrically in many mammals. We suggest their distinctive features—being thick, non-tapered, lateralized and arranged in specific high-density arrays—evolved along with the manipulative capacities of the trunk.
Carnitine palmitoyltransferase 1A promotes mitochondrial fission by enhancing MFF succinylation in ovarian cancer
Authors: Zhu Yaqin , Wang Yue , Li Ying , Li Zhongqi , Kong Wenhui , Zhao Xiaoxuan , Chen Shuting , Yan Liting , Wang Lenan , Tong Yunli , Shao Huanjie 
Published: June 2023

AbstractMitochondria are dynamic organelles that are important for cell growth and proliferation. Dysregulated mitochondrial dynamics are highly associated with the initiation and progression of various cancers, including ovarian cancer. However, the regulatory mechanism underlying mitochondrial dynamics is still not fully understood. Previously, our study showed that carnitine palmitoyltransferase 1A (CPT1A) is highly expressed in ovarian cancer cells and promotes the development of ovarian cancer. Here, we find that CPT1A regulates mitochondrial dynamics and promotes mitochondrial fission in ovarian cancer cells. Our study futher shows that CPT1A regulates mitochondrial fission and function through mitochondrial fission factor (MFF) to promote the growth and proliferation of ovarian cancer cells. Mechanistically, we show that CPT1A promotes succinylation of MFF at lysine 302 (K302), which protects against Parkin-mediated ubiquitin-proteasomal degradation of MFF. Finally, the study shows that MFF is highly expressed in ovarian cancer cells and that high MFF expression is associated with poor prognosis in patients with ovarian cancer. MFF inhibition significantly inhibits the progression of ovarian cancer in vivo. Overall, CPT1A regulates mitochondrial dynamics through MFF succinylation to promote the development of ovarian cancer. Moreover, our findings suggest that MFF is a potential therapeutic target for ovarian cancer.
Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique
Authors: da Silva Clemente , Boene Simone , Datta Debayan , Rovira-Vallbona Eduard , Aranda-Díaz Andrés , Cisteró Pau , Hathaway Nicholas , Tessema Sofonias , Chidimatembue Arlindo , Matambisso Glória , Nhama Abel , Macete Eusebio , Pujol Arnau , Nhamussua Lidia , Galatas Beatriz , Guinovart Caterina , Enosse Sónia , De Carvalho Eva , Rogier Eric , Plucinski Mateusz M. , Colborn James , Zulliger Rose , Saifodine Abuchahama , Alonso Pedro L. , Candrinho Baltazar , Greenhouse Bryan , Aide Pedro , Saute Francisco , Mayor Alfredo 
Published: June 2023

AbstractMozambique is one of the four African countries which account for over half of all malaria deaths worldwide, yet little is known about the parasite genetic structure in that country. We performed P. falciparum amplicon and whole genome sequencing on 2251 malaria-infected blood samples collected in 2015 and 2018 in seven provinces of Mozambique to genotype antimalarial resistance markers and interrogate parasite population structure using genome-wide microhaplotyes. Here we show that the only resistance-associated markers observed at frequencies above 5% were pfmdr1-184F (59%), pfdhfr-51I/59 R/108 N (99%) and pfdhps-437G/540E (89%). The frequency of pfdhfr/pfdhps quintuple mutants associated with sulfadoxine-pyrimethamine resistance increased from 80% in 2015 to 89% in 2018 (p < 0.001), with a lower expected heterozygosity and higher relatedness of microhaplotypes surrounding pfdhps mutants than wild-type parasites suggestive of recent selection. pfdhfr/pfdhps quintuple mutants also increased from 72% in the north to 95% in the south (2018; p < 0.001). This resistance gradient was accompanied by a concentration of mutations at pfdhps-436 (17%) in the north, a south-to-north increase in the genetic complexity of P. falciparum infections (p = 0.001) and a microhaplotype signature of regional differentiation. The parasite population structure identified here offers insights to guide antimalarial interventions and epidemiological surveys.
Translational regulation and protein-coding capacity of the 5′ untranslated region of human TREM2
Authors: Yanaizu Motoaki , Adachi Haruka , Araki Makoto , Kontani Kenji , Kino Yoshihiro 
Published: June 2023

AbstractTREM2 is a transmembrane receptor expressed in microglia and macrophages. Elevated TREM2 levels in these cells are associated with age-related pathological conditions, including Alzheimer’s disease. However, the regulatory mechanism underlying the protein expression of TREM2 remains unclear. In this study, we uncover the role of the 5′ untranslated region (5′-UTR) of human TREM2 in translation. An upstream start codon (uAUG) in the 5′-UTR of TREM2 is specific to some primates, including humans. The expression of the conventional TREM2 protein, starting from the downstream AUG (dTREM2), is repressed by the 5′-UTR in a uAUG-mediated manner. We also detect a TREM2 protein isoform starting from uAUG (uTREM2) that is largely degraded by proteasomes. Finally, the 5′-UTR is essential for the downregulation of dTREM2 expression in response to amino acid starvation. Collectively, our study identifies a species-specific regulatory role of the 5′-UTR in TREM2 translation.
Deglacial perspectives of future sea level for Singapore
Authors: Shaw Timothy A. , Li Tanghua , Ng Trina , Cahill Niamh , Chua Stephen , Majewski Jedrzej M. , Nathan Yudhishthra , Garner Gregory G. , Kopp Robert E. , Hanebuth Till J. J. , Switzer Adam D. , Horton Benjamin P. 
Published: June 2023

AbstractLow elevation equatorial and tropical coastal regions are highly vulnerable to sea level rise. Here we provide probability perspectives of future sea level for Singapore using regional geological reconstructions and instrumental records since the last glacial maximum ~21.5 thousand years ago. We quantify magnitudes and rates of sea-level change showing deglacial sea level rose from ~121 m below present level and increased at averaged rates up to ~15 mm/yr, which reduced the paleogeographic landscape by ~2.3 million km2. Projections under a moderate emissions scenario show sea level rising 0.95 m at a rate of 7.3 mm/yr by 2150 which has only been exceeded (at least 99% probability) during rapid ice mass loss events ~14.5 and ~9 thousand years ago. Projections under a high emissions scenario incorporating low confidence ice-sheet processes, however, have no precedent during the last deglaciation.