bluuebunny/crossref_metadata_2025_split huggingface dataset:
The HCN1 p.Ser399Pro variant causes epileptic encephalopathy with super-refractory status epilepticus
Authors: Kobayashi Yu , Tohyama Jun , Akasaka Noriyuki , Yamada Kei , Hojo Moemi , Seki Eijun , Miura Masaki , Soma Noriko , Ono Takeshi , Kato Mitsuhiro , Nakashima Mitsuko , Saitsu Hirotomo , Matsumoto Naomichi 
Published: June 2023

AbstractHCN1 is one of four genes encoding hyperpolarization-activated cyclic nucleotide-gated channels. The phenotypic spectrum associated with HCN1 variants ranges from neonatal developmental and epileptic encephalopathy to idiopathic generalized epilepsy. We report a Japanese patient with repetitive focal seizures and super-refractory status epilepticus since early infancy caused by a de novo HCN1 variant, NM_021072.4, c.1195T>C, p.(Ser399Pro). This variant might have a dominant-negative effect on channel function, leading to severe epileptic encephalopathy.
Mechanistic insights into the aggregation pathway of the patient-derived immunoglobulin light chain variable domain protein FOR005
Authors: Pradhan Tejaswini , Sarkar Riddhiman , Meighen-Berger Kevin M. , Feige Matthias J. , Zacharias Martin , Reif Bernd 
Published: June 2023

AbstractSystemic antibody light chain (AL) amyloidosis is characterized by deposition of amyloid fibrils. Prior to fibril formation, soluble oligomeric AL protein has a direct cytotoxic effect on cardiomyocytes. We focus on the patient derived λ-III AL variable domain FOR005 which is mutated at five positions with respect to the closest germline protein. Using solution-state NMR spectroscopy, we follow the individual steps involved in protein misfolding from the native to the amyloid fibril state. Unfavorable mutations in the complementary determining regions introduce a strain in the native protein structure which yields partial unfolding. Driven by electrostatic interactions, the protein converts into a high molecular weight, oligomeric, molten globule. The high local concentration of aggregation prone regions in the oligomer finally catalyzes the conversion into fibrils. The topology is determined by balanced electrostatic interactions in the fibril core implying a 180° rotational switch of the beta-sheets around the conserved disulfide bond.
A joint proteomic and genomic investigation provides insights into the mechanism of calcification in coccolithophores
Authors: Skeffington Alastair , Fischer Axel , Sviben Sanja , Brzezinka Magdalena , Górka Michał , Bertinetti Luca , Woehle Christian , Huettel Bruno , Graf Alexander , Scheffel André 
Published: June 2023

AbstractCoccolithophores are globally abundant, calcifying microalgae that have profound effects on marine biogeochemical cycles, the climate, and life in the oceans. They are characterized by a cell wall of CaCO3 scales called coccoliths, which may contribute to their ecological success. The intricate morphologies of coccoliths are of interest for biomimetic materials synthesis. Despite the global impact of coccolithophore calcification, we know little about the molecular machinery underpinning coccolithophore biology. Working on the model Emiliania huxleyi, a globally distributed bloom-former, we deploy a range of proteomic strategies to identify coccolithogenesis-related proteins. These analyses are supported by a new genome, with gene models derived from long-read transcriptome sequencing, which revealed many novel proteins specific to the calcifying haptophytes. Our experiments provide insights into proteins involved in various aspects of coccolithogenesis. Our improved genome, complemented with transcriptomic and proteomic data, constitutes a new resource for investigating fundamental aspects of coccolithophore biology.
Summer atmospheric circulation over Greenland in response to Arctic amplification and diminished spring snow cover
Authors: Preece Jonathon R. , Mote Thomas L. , Cohen Judah , Wachowicz Lori J. , Knox John A. , Tedesco Marco , Kooperman Gabriel J. 
Published: June 2023

AbstractThe exceptional atmospheric conditions that have accelerated Greenland Ice Sheet mass loss in recent decades have been repeatedly recognized as a possible dynamical response to Arctic amplification. Here, we present evidence of two potentially synergistic mechanisms linking high-latitude warming to the observed increase in Greenland blocking. Consistent with a prominent hypothesis associating Arctic amplification and persistent weather extremes, we show that the summer atmospheric circulation over the North Atlantic has become wavier and link this wavier flow to more prevalent Greenland blocking. While a concomitant decline in terrestrial snow cover has likely contributed to this mechanism by further amplifying warming at high latitudes, we also show that there is a direct stationary Rossby wave response to low spring North American snow cover that enforces an anomalous anticyclone over Greenland, thus helping to anchor the ridge over Greenland in this wavier atmospheric state.
DOCU-CLIM: A global documentary climate dataset for climate reconstructions
Authors: Burgdorf Angela-Maria , Brönnimann Stefan , Adamson George , Amano Tatsuya , Aono Yasuyuki , Barriopedro David , Bullón Teresa , Camenisch Chantal , Camuffo Dario , Daux Valérie , del Rosario Prieto María , Dobrovolný Petr , Gallego David , García-Herrera Ricardo , Gergis Joelle , Grab Stefan , Hannaford Matthew J. , Holopainen Jari , Kelso Clare , Kern Zoltán , Kiss Andrea , Kuan-Hui Lin Elaine , Loader Neil J. , Možný Martin , Nash David , Nicholson Sharon E. , Pfister Christian , Rodrigo Fernando S. , Rutishauser This , Sharma Sapna , Takács Katalin , Vargas Ernesto T. , Vega Inmaculada 
Published: June 2023

AbstractDocumentary climate data describe evidence of past climate arising from predominantly written historical documents such as diaries, chronicles, newspapers, or logbooks. Over the past decades, historians and climatologists have generated numerous document-based time series of local and regional climates. However, a global dataset of documentary climate time series has never been compiled, and documentary data are rarely used in large-scale climate reconstructions. Here, we present the first global multi-variable collection of documentary climate records. The dataset DOCU-CLIM comprises 621 time series (both published and hitherto unpublished) providing information on historical variations in temperature, precipitation, and wind regime. The series are evaluated by formulating proxy forward models (i.e., predicting the documentary observations from climate fields) in an overlapping period. Results show strong correlations, particularly for the temperature-sensitive series. Correlations are somewhat lower for precipitation-sensitive series. Overall, we ascribe considerable potential to documentary records as climate data, especially in regions and seasons not well represented by early instrumental data and palaeoclimate proxies.
Sea ice drift tracks from autonomous buoys in the MOSAiC Distributed Network
Authors: Bliss Angela C. , Hutchings Jennifer K. , Watkins Daniel M. 
Published: June 2023

AbstractA network of autonomous, ice-tethered buoys was deployed around the Multidisciplinary drifting Observatory for the Study of Arctic Climate (MOSAiC) experiment in late September 2019 for a year-long drift in the Arctic Transpolar Drift Stream. The buoys were deployed as part of the MOSAiC distributed network (DN) which included 12 multi-instrumented ice stations and an additional 116 GPS buoys distributed primarily within a 40 km radius of the MOSAiC Central Observatory. Buoy coverage within the DN was maintained with additional deployments throughout the year-long drift allowing for collection of data over a full sea ice growth and melt cycle. All GPS position data from buoys deployed within the DN have been assembled and processed into the collection of 216 quality-controlled buoy drift tracks presented in this dataset covering the period 26 September 2019 – 23 May 2021. The drift tracks in this collection are ideal for studies of dynamic sea ice motion around the MOSAiC experiment at cascading spatial scales ranging from 100s of meters to 100s of km.
An automated framework for evaluation of deep learning models for splice site predictions
Authors: Zabardast Amin , Tamer Elif Güney , Son Yeşim Aydın , Yılmaz Arif 
Published: June 2023

AbstractA novel framework for the automated evaluation of various deep learning-based splice site detectors is presented. The framework eliminates time-consuming development and experimenting activities for different codebases, architectures, and configurations to obtain the best models for a given RNA splice site dataset. RNA splicing is a cellular process in which pre-mRNAs are processed into mature mRNAs and used to produce multiple mRNA transcripts from a single gene sequence. Since the advancement of sequencing technologies, many splice site variants have been identified and associated with the diseases. So, RNA splice site prediction is essential for gene finding, genome annotation, disease-causing variants, and identification of potential biomarkers. Recently, deep learning models performed highly accurately for classifying genomic signals. Convolutional Neural Network (CNN), Long Short-Term Memory (LSTM) and its bidirectional version (BLSTM), Gated Recurrent Unit (GRU), and its bidirectional version (BGRU) are promising models. During genomic data analysis, CNN’s locality feature helps where each nucleotide correlates with other bases in its vicinity. In contrast, BLSTM can be trained bidirectionally, allowing sequential data to be processed from forward and reverse directions. Therefore, it can process 1-D encoded genomic data effectively. Even though both methods have been used in the literature, a performance comparison was missing. To compare selected models under similar conditions, we have created a blueprint for a series of networks with five different levels. As a case study, we compared CNN and BLSTM models’ learning capabilities as building blocks for RNA splice site prediction in two different datasets. Overall, CNN performed better with$$92\%$$92%accuracy ($$6\%$$6%improvement),$$89\%$$89%F1 score ($$8\%$$8%improvement), and$$96\%$$96%AUC-PR ($$4\%$$4%improvement) in human splice site prediction. Likewise, an outperforming performance with$$96\%$$96%accuracy ($$11\%$$11%improvement),$$94\%$$94%F1 score ($$16\%$$16%improvement), and$$99\%$$99%AUC-PR ($$7\%$$7%improvement) is achieved inC. eleganssplice site prediction. Overall, our results showed that CNN learns faster than BLSTM and BGRU. Moreover, CNN performs better at extracting sequence patterns than BLSTM and BGRU. To our knowledge, no other framework is developed explicitly for evaluating splice detection models to decide the best possible model in an automated manner. So, the proposed framework and the blueprint would help selecting different deep learning models, such as CNN vs. BLSTM and BGRU, for splice site analysis or similar classification tasks and in different problems.
Impact of community-based interventions on out-of-hospital cardiac arrest outcomes: a systematic review and meta-analysis
Authors: Simmons Kayla M. , McIsaac Sarah M. , Ohle Robert 
Published: June 2023

AbstractSurvival following out-of-hospital cardiac arrest (OHCA) remains low, typically less than 10%. Bystander cardiopulmonary resuscitation (CPR) and bystander-AED use have been shown to improve survival by up to fourfold in individual studies. Numerous community-based interventions have been implemented worldwide in an effort to enhance rates of bystander-CPR, bystander-AED use, and improve OHCA survival. This systematic review and meta-analysis aims to evaluate the effect of such interventions on OHCA outcomes. Medline and Embase were systematically searched from inception through July 2021 for studies describing the implementation and effect of one or more community-based interventions targeting OHCA outcomes. Two reviewers screened articles, extracted data, and evaluated study quality using the Newcastle–Ottawa Scale. For each outcome, data were pooled using random-effects meta-analysis. Of the 2481 studies identified, 16 met inclusion criteria. All included studies were observational. They reported a total of 1,081,040 OHCAs across 11 countries. The most common interventions included community-based CPR training (n = 12), community-based AED training (n = 9), and dispatcher-assisted CPR (n = 8). Health system interventions (hospital or paramedical services) were also described in 11 of the included studies. Evidence certainty among all outcomes was low or very low according to GRADE criteria. On meta-analysis, community-based interventions with and without health system interventions were consistently associated with improved OCHA outcomes: rates of bystander-CPR, bystander-AED use, survival, and survival with a favorable neurological outcome. Bystander CPR—14 studies showed a significant increase in post-intervention bystander-CPR rates (n = 285 752; OR 2.26 [1.74, 2.94]; I2 = 99%, and bystander AED use (n = 37 882; OR 2.08 [1.44, 3.01]; I2 = 54%) and durvival—10 studies, pooling survival to hospital discharge and survival to 30 days (n = 79 206; OR 1.59 [1.20, 2.10]; I2 = 95%. The results provide foundational support for the efficacy of community-based interventions in enhancing OHCA outcomes. These findings inform our recommendation that communities, regions, and countries should implement community-based interventions in their pre-hospital strategy for OHCA. Further research is needed to identify which specific intervention types are most effective.
Longitudinal investigation of changes in resting-state co-activation patterns and their predictive ability in the zQ175 DN mouse model of Huntington’s disease
Authors: Adhikari Mohit H. , Vasilkovska Tamara , Cachope Roger , Tang Haiying , Liu Longbin , Keliris Georgios A. , Munoz-Sanjuan Ignacio , Pustina Dorian , Van der Linden Annemie , Verhoye Marleen 
Published: June 2023

AbstractHuntington’s disease (HD) is a neurodegenerative disorder caused by expanded (≥ 40) glutamine-encoding CAG repeats in the huntingtin gene, which leads to dysfunction and death of predominantly striatal and cortical neurons. While the genetic profile and clinical signs and symptoms of the disease are better known, changes in the functional architecture of the brain, especially before the clinical expression becomes apparent, are not fully and consistently characterized. In this study, we sought to uncover functional changes in the brain in the heterozygous (HET) zQ175 delta-neo (DN) mouse model at 3, 6, and 10 months of age, using resting-state functional magnetic resonance imaging (RS-fMRI). This mouse model shows molecular, cellular and circuitry alterations that worsen through age. Motor function disturbances are manifested in this model at 6 and 10 months of age. Specifically, we investigated, longitudinally, changes in co-activation patterns (CAPs) that are the transient states of brain activity constituting the resting-state networks (RSNs). Most robust changes in the temporal properties of CAPs occurred at the 10-months time point; the durations of two anti-correlated CAPs, characterized by simultaneous co-activation of default-mode like network (DMLN) and co-deactivation of lateral-cortical network (LCN) and vice-versa, were reduced in the zQ175 DN HET animals compared to the wild-type mice. Changes in the spatial properties, measured in terms of activation levels of different brain regions, during CAPs were found at all three ages and became progressively more pronounced at 6-, and 10 months of age. We then assessed the cross-validated predictive power of CAP metrics to distinguish HET animals from controls. Spatial properties of CAPs performed significantly better than the chance level at all three ages with 80% classification accuracy at 6 and 10 months of age.
GATS tag system is compatible with biotin labelling methods for protein analysis
Authors: Yamada Kohdai , Soga Fumiya , Tokunaga Soh , Nagaoka Hikaru , Ozawa Tatsuhiko , Kishi Hiroyuki , Takashima Eizo , Sawasaki Tatsuya 
Published: June 2023

AbstractPolypeptide tags and biotin labelling technologies are widely used for protein analyses in biochemistry and cell biology. However, many peptide tag epitopes contain lysine residues (or amino acids) that are masked after biotinylation. Here, we propose the GATS tag system without a lysine residue and with high sensitivity and low non-specific binding using a rabbit monoclonal antibody against Plasmodium falciparum glycosylphosphatidylinositol (GPI)-anchored micronemal antigen (PfGAMA). From 14 monoclonal clones, an Ra3 clone was selected as it recognized an epitope—TLSVGVQNTF—without a lysine residue; this antibody and epitope tag set was called the GATS tag system. Surface plasmon resonance analysis showed that the tag system had a high affinity of 8.71 × 10–9 M. GATS tag indicated a very low background with remarkably high sensitivity and specificity in immunoblotting using the lysates of mammalian cells. It also showed a high sensitivity for immunoprecipitation and immunostaining of cultured human cells. The tag system was highly sensitive in both biotin labelling methods for proteins using NHS-Sulfo-biotin and BioID (proximity-dependent biotin identification) in the human cells, as opposed to a commercially available tag system having lysine residues, which showed reduced sensitivity. These results showed that the GATS tag system is suitable for methods such as BioID involving labelling lysine residues.
Elastic, optoelectronic and photocatalytic properties of semiconducting CsNbO3: first principles insights
Authors: Monira M. , Helal M. A. , Liton M. N. H. , Kamruzzaman M. , Kojima S. 
Published: June 2023

AbstractThe cubic phase of CsNbO3 (CNO) perovskite has been hypothesized to investigate the elastic, electronic, photocatalytic, and optical properties for various technological applications using first-principles method. The pressure dependent structural stability has been confirmed from computed elastic constants. Relatively high value of elastic moduli, large hardness and toughness suggested that CNO would be applicable to design industrial machineries. The ductile to brittle transition is noticed at 20 GPa. The indirect bandgap of CNO proclaims its suitability for photovoltaic and IR photodetector applications. The total and partial density of states are calculated to show in evidence the contribution of individual atomic orbitals in the formation of bands. The pressure changes orbitals hybridization which can be substantiated by the change in the bandgap. Strong covalency of the Nb–O bond and antibonding character of Cs–O have been anticipated by the Mulliken population analysis and by the contour maps of electron charge density. The low carrier effective mass and high mobility carriers predict the good electrical conductivity of the material. The calculated values of conduction and valance band edge potential illustrate the excellent water-splitting and environmental pollutants degradation properties of CNO.
A newly identified small tRNA fragment reveals the regulation of different wool types and oxidative stress in lambs
Authors: Wang Jiankui , Hua Guoying , Yang Xue , Zhang Letian , Ma Yuhao , Ma Qing , Li Rui , Wu Keliang , Zhao Yaofeng , Deng Xuemei 
Published: June 2023

AbstractNovel small RNAs derived from tRNAs are continuously identified, however, their biological functions are rarely reported. Here, we accidentally found the reads peak at 32nt during statistical analysis on the miRNA-seq data of lamb skin tissue, and found that it was related to the wool type of lambs. This 32nt peak was composed of small tRNA fragments. The main component sequence of this peak was a novel small tRNA derived from Glycyl tRNA (tRNAGly), the expression level of tRNAGly-derived tRNA fragments (tRFGly) was 5.77 folds higher in the coarse wool lambs than that in the fine wool lambs. However, in contrast, the expression of tRNAGly in the skin of fine wool lambs is 6.28 folds more than that in coarse wool lambs. tRNAGly promoted the synthesis of high glycine protein including KAP6 in fine wool lamb skin. These proteins were reported as the major genes for fine curly wool. Integrative analysis of target gene prediction, proteomics and metabolomics results revealed that tRFGly reduced the level of reactive oxygen species (ROS) in the skin of coarse wool lambs by targeted inhibition of the Metabolic signal and the corresponding Glutathione metabolic pathway, on the contrary, the level of oxidative stress in the skin of fine wool lambs was significantly higher. This study revealed for the first time the relationship between tRNAGly and its derived tRFGly and animal traits. tRFGly has the function of targeting and regulating protein synthesis. At the same time, tRFGly can reduce the expression of its resource complete tRNA, thereby reducing its ability to transport specific amino acid and affecting the expression of corresponding proteins.
Spatial distribution of elements during osteoarthritis disease progression using synchrotron X-ray fluorescence microscopy
Authors: Fan Xiwei , Lee Kah Meng , Jones Michael W. M. , Howard Daryl , Sun Antonia Rujia , Crawford Ross , Prasadam Indira 
Published: June 2023

AbstractThe osteochondral interface is a thin layer that connects hyaline cartilage to subchondral bone. Subcellular elemental distribution can be visualised using synchrotron X-ray fluorescence microscopy (SR-XFM) (1 μm). This study aims to determine the relationship between elemental distribution and osteoarthritis (OA) progression based on disease severity. Using modified Mankin scores, we collected tibia plates from 9 knee OA patients who underwent knee replacement surgery and graded them as intact cartilage (non-OA) or degraded cartilage (OA). We used a tape-assisted system with a silicon nitride sandwich structure to collect fresh-frozen osteochondral sections, and changes in the osteochondral unit were defined using quantified SR-XFM elemental mapping at the Australian synchrotron's XFM beamline. Non-OA osteochondral samples were found to have significantly different zinc (Zn) and calcium (Ca) compositions than OA samples. The tidemark separating noncalcified and calcified cartilage was rich in zinc. Zn levels in OA samples were lower than in non-OA samples (P = 0.0072). In OA samples, the tidemark had less Ca than the calcified cartilage zone and subchondral bone plate (P < 0.0001). The Zn–strontium (Sr) colocalisation index was higher in OA samples than in non-OA samples. The lead, potassium, phosphate, sulphur, and chloride distributions were not significantly different (P > 0.05). In conclusion, SR-XFM analysis revealed spatial elemental distribution at the subcellular level during OA development.
A comparative study of femtosecond pulsed laser ablation of meloxicam in distilled water and in air
Authors: Nagy Eszter , Kopniczky Judit , Smausz Tamás , Náfrádi Máté , Alapi Tünde , Bohus János , Pajer Viktor , Szabó-Révész Piroska , Ambrus Rita , Hopp Béla 
Published: June 2023

AbstractThe increasing prevalence of water insoluble or poorly soluble drugs calls for the development of new formulation methods. Common approaches include the reduction of particle size and degree of crystallinity. Pulsed laser ablation is a clean technique for producing sub-micrometre sized drug particles and has the potential to induce amorphization. We studied the effect of femtosecond pulsed laser ablation (ELI ALPS THz pump laser system: λc = 781 nm, τ = 135 fs) on meloxicam in distilled water and in air. The ablated particles were characterized chemically, morphologically and in terms of crystallinity. We demonstrated that femtosecond laser ablation can induce partial amorphization of the particles in addition to a reduction in particle size. In the case of femtosecond pulsed laser ablation in air, the formation of pure meloxicam spheres showed that this technique can produce amorphous meloxicam without the use of excipients, which is a unique result. We also aimed to describe the ablation processes in both investigated media.