bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunogenicity and efficacy of vaccine boosters against SARS-CoV-2 Omicron subvariant BA.5 in male Syrian hamsters
Authors: Machado Rafael R. G. , Walker Jordyn L. , Scharton Dionna , Rafael Grace H. , Mitchell Brooke M. , Reyna Rachel A. , de Souza William M. , Liu Jianying , Walker David H. , Plante Jessica A. , Plante Kenneth S. , Weaver Scott C. 
Published: July 2023

AbstractThe SARS-CoV-2 Omicron subvariant BA.5 rapidly spread worldwide and replaced BA.1/BA.2 in many countries, becoming globally dominant. BA.5 has unique amino acid substitutions in the spike protein that both mediate immune escape from neutralizing antibodies produced by immunizations and increase ACE2 receptor binding affinity. In a comprehensive, long-term (up to 9 months post primary vaccination), experimental vaccination study using male Syrian hamsters, we evaluate neutralizing antibody responses and efficacy against BA.5 challenge after primary vaccination with Ad26.COV2.S (Janssen) or BNT162b2 (Pfizer/BioNTech) followed by a homologous or heterologous booster with mRNA-1273 (Moderna) or NVX-CoV2373 (Novavax). Notably, one high or low dose of Ad26.COV2.S provides more durable immunity than two primary doses of BNT162b2, and the NVX-CoV2373 booster provides the strongest augmentation of immunity, reduction in BA.5 viral replication, and disease. Our data demonstrate the immunogenicity and efficacy of different prime/boost vaccine regimens against BA.5 infection in an immune-competent model and provide new insights regarding COVID-19 vaccine strategies.
Structural basis of sequence-specific cytosine deamination by double-stranded DNA deaminase toxin DddA
Authors: Yin Lulu , Shi Ke , Aihara Hideki 
Published: July 2023

AbstractThe interbacterial deaminase toxin DddA catalyzes cytosine-to-uracil conversion in double-stranded (ds) DNA and enables CRISPR-free mitochondrial base editing, but the molecular mechanisms underlying its unique substrate selectivity have remained elusive. Here, we report crystal structures of DddA bound to a dsDNA substrate containing the 5′-TC target motif. These structures show that DddA binds to the minor groove of a sharply bent dsDNA and engages the target cytosine extruded from the double helix. DddA Phe1375 intercalates in dsDNA and displaces the 5′ (−1) thymine, which in turn replaces the target (0) cytosine and forms a noncanonical T–G base pair with the juxtaposed guanine. This tandem displacement mechanism allows DddA to locate a target cytosine without flipping it into the active site. Biochemical experiments demonstrate that DNA base mismatches enhance the DddA deaminase activity and relax its sequence selectivity. On the basis of the structural information, we further identified DddA mutants that exhibit attenuated activity or altered substrate preference. Our studies may help design new tools useful in genome editing or other applications.
Mechanistic and evolutionary insights into a type V-M CRISPR–Cas effector enzyme
Authors: Omura Satoshi N. , Nakagawa Ryoya , Südfeld Christian , Villegas Warren Ricardo , Wu Wen Y. , Hirano Hisato , Laffeber Charlie , Kusakizako Tsukasa , Kise Yoshiaki , Lebbink Joyce H. G. , Itoh Yuzuru , van der Oost John , Nureki Osamu 
Published: July 2023

AbstractRNA-guided type V CRISPR–Cas12 effectors provide adaptive immunity against mobile genetic elements (MGEs) in bacteria and archaea. Among diverse Cas12 enzymes, the recently identified Cas12m2 (CRISPR–Cas type V-M) is highly compact and has a unique RuvC active site. Although the non-canonical RuvC triad does not permit dsDNA cleavage, Cas12m2 still protects against invading MGEs through transcriptional silencing by strong DNA binding. However, the molecular mechanism of RNA-guided genome inactivation by Cas12m2 remains unknown. Here we report cryo-electron microscopy structures of two states of Cas12m2–CRISPR RNA (crRNA)–target DNA ternary complexes and the Cas12m2–crRNA binary complex, revealing structural dynamics during crRNA–target DNA heteroduplex formation. The structures indicate that the non-target DNA strand is tightly bound to a unique arginine-rich cluster in the recognition (REC) domains and the non-canonical active site in the RuvC domain, ensuring strong DNA-binding affinity of Cas12m2. Furthermore, a structural comparison of Cas12m2 with TnpB, a putative ancestor of Cas12 enzymes, suggests that the interaction of the characteristic coiled-coil REC2 insertion with the protospacer-adjacent motif-distal region of the heteroduplex is crucial for Cas12m2 to engage in adaptive immunity. Collectively, our findings improve mechanistic understanding of diverse type V CRISPR–Cas effectors and provide insights into the evolution of TnpB to Cas12 enzymes.
Impact of cigarette smoking on fluorescence lifetime of ocular fundus
Authors: Sonntag Svenja Rebecca , Kreikenbohm Marie , Böhmerle Giulia , Stagge Jessica , Grisanti Salvatore , Miura Yoko 
Published: July 2023

AbstractCigarette smoking is known to adversely affect cellular metabolism and is a risk factor for various retinal diseases. Fluorescence lifetime imaging ophthalmoscopy (FLIO) has the potential to detect metabolic changes in the ocular fundus. Aim of this study was to analyze the influence of cigarette smoking on fluorescence lifetime (FLT) of healthy eyes using FLIO. Twenty-six non-smokers and 28 smokers aged between 20 and 37 years without systemic and ocular diseases were investigated by FLIO (excitation: 473 nm, emission: short spectral channel (SSC) 498–560 nm, long spectral channel (LSC) 560–720 nm). The FLT at the ETDRS grid regions were analyzed and compared. In SSC, the mean FLT (τm) of smokers was significantly longer in the ETDRS inner ring region, whereas the τm in LSC was significantly shorter in the outer ring. For the long component (τ2), smokers with pack year < 7.11 showed significantly shorter τ2 in SSC than non-smokers and the smokers with pack year ≥ 7.11. There were no significant differences in retinal thickness. The lack of obvious structural differences implies that the observed FLT changes are likely related to smoking-induced metabolic changes. These results suggest that FLIO may be useful in assessing retinal conditions related to lifestyle and systemic metabolic status.
Numerical simulation for impact of implement of reflector and turbulator within the solar system in existence of nanomaterial
Authors: Sheikholeslami M. , Jafaryar M. 
Published: July 2023

AbstractTurbulent flow of oil based hybrid nanofluid within an absorber tube of concentrated solar system has been evaluated in this article. To concentrate the solar irradiation, the parabolic plate has been located below the tube and variable heat flux was considered as the boundary condition of the tube. The presence of a turbulator within the circular tube causes secondary flow to increase. Both thermal (Sgen,th) and frictional (Sgen,f) components of irreversibility were reported in outputs. As Re increases, the residence time decreases and lower outlet temperature has been achieved. Sgen,th decreases about 57.36% with growth of Re while Sgen,f increases about 17.44 times. As the number of rows of tapes increases, the value of Sgen,f enhances about 69.23% while the value of Sgen,th decreases around 3.67%. Increase of pitch ratio causes Sgen,th to decrease about 11.25% while frictional component increases around 76.7%.
A comparison of synthetic data generation and federated analysis for enabling international evaluations of cardiovascular health
Authors: Azizi Zahra , Lindner Simon , Shiba Yumika , Raparelli Valeria , Norris Colleen M. , Kublickiene Karolina , Herrero Maria Trinidad , Kautzky-Willer Alexandra , Klimek Peter , Gisinger Teresa , Pilote Louise , El Emam Khaled 
Published: July 2023

AbstractSharing health data for research purposes across international jurisdictions has been a challenge due to privacy concerns. Two privacy enhancing technologies that can enable such sharing are synthetic data generation (SDG) and federated analysis, but their relative strengths and weaknesses have not been evaluated thus far. In this study we compared SDG with federated analysis to enable such international comparative studies. The objective of the analysis was to assess country-level differences in the role of sex on cardiovascular health (CVH) using a pooled dataset of Canadian and Austrian individuals. The Canadian data was synthesized and sent to the Austrian team for analysis. The utility of the pooled (synthetic Canadian + real Austrian) dataset was evaluated by comparing the regression results from the two approaches. The privacy of the Canadian synthetic data was assessed using a membership disclosure test which showed an F1 score of 0.001, indicating low privacy risk. The outcome variable of interest was CVH, calculated through a modified CANHEART index. The main and interaction effect parameter estimates of the federated and pooled analyses were consistent and directionally the same. It took approximately one month to set up the synthetic data generation platform and generate the synthetic data, whereas it took over 1.5 years to set up the federated analysis system. Synthetic data generation can be an efficient and effective tool for enabling multi-jurisdictional studies while addressing privacy concerns.
Investigation on mechanical properties and corrosion resistance of Ti-modified AA5083 aluminum alloy for aerospace and automotive applications
Authors: Alghannam Abdullah A. , Soliman Mahmoud S. , Seikh Asiful H. , Alnaser Ibrahim A. , Fouly Ahmed , Mohammed Jabair A. , Ragab Sameh A. , Abdo Hany S. 
Published: July 2023

AbstractCasting of aluminum with different concentration of alloying elements such as Mg, Mn (similar to that in AA5083) with additional percentages of 0.1, 0.2 and 0.3% Ti, are carried out using graphite crucible. The as-cast microstructure is modified by hot rolling to a thickness of ~ 2 mm. Mechanical and metallurgical and characterization of heat-treated thin sheets are carried out using tensile testing, hardness measurement, metallography, image analysis and optical microscope. By increasing the Ti content, the results show grain refinement and increase in the formation of Al3Ti which reflected positively on the mechanical properties. Specifically, Ultimate tensile strength is increased from 260 MPa (0 wt% Ti) to 345 MPa (0.3 wt% Ti) when using water quenching, 32.6% improvement for air cooling, and 23.3% for furnace cooling. Electrochemical corrosion behavior of heat-treated water quenched, air cooled and furnace cooled samples were tested in 3.5% NaCl solution. The results show that the heat-treated alloys have very good resistance against corrosion, while by increasing the Ti content, the corrosion rate increases due to the grain refinement phenomena.
Enabling X-ray fluorescence imaging for in vivo immune cell tracking
Authors: Staufer Theresa , Körnig Christian , Liu Beibei , Liu Yang , Lanzloth Clarissa , Schmutzler Oliver , Bedke Tanja , Machicote Andres , Parak Wolfgang J. , Feliu Neus , Bosurgi Lidia , Huber Samuel , Grüner Florian 
Published: July 2023

AbstractThe infiltration of immune cells into sites of inflammation is one key feature of immune mediated inflammatory diseases. A detailed assessment of the in vivo dynamics of relevant cell subtypes could booster the understanding of this disease and the development of novel therapies. We show in detail how advanced X-ray fluorescence imaging enables such quantitative in vivo cell tracking, offering solutions that could pave the way beyond what other imaging modalities provide today. The key for this achievement is a detailed study of the spectral background contribution from multiple Compton scattering in a mouse-scaled object when this is scanned with a monochromatic pencil X-ray beam from a synchrotron. Under optimal conditions, the detection sensitivity is sufficient for detecting local accumulations of the labelled immune cells, hence providing experimental demonstration of in vivo immune cell tracking in mice.
A new role for concentrated solar radiation (CSR) as a renewable heat source for the catalyst-solvent free synthesis of tetrahydrobenzo[b]pyran scaffolds
Authors: Mohamadpour Farzaneh 
Published: July 2023

AbstractIncreased energy consumption as a result of population growth and industrialization necessitates the use of renewable energy sources in the field of chemistry. Nonrenewable energy sources release not only greenhouse gases but also other hazardous pollutants that are damaging to all living things. This plainly mandates the researchers' use of a renewable energy source that is both environmentally friendly and cost-effective. This study shows that a renewable energy source (sunlight) can be used to synthesize tetrahydrobenzo[b]pyran scaffolds using the Knoevenagel–Michael cyclocondensation of aldehyde derivatives, malononitrile, and dimedone via a three-condensation domino reaction. This research establishes a new role for solar energy as a renewable energy source for the synthesis of tetrahydrobenzo[b]pyran scaffolds under catalyst-solvent-free conditions, with outstanding yields, shorter reaction time, and great atom economy. This cyclization may also be done on a gram scale with free, safe, and clean energy from concentrated solar radiation (CSR), indicating the reaction's potential for industrial applications.
An assessment of whether long-term global changes in waves and storm surges have impacted global coastlines
Authors: Ghanavati Mandana , Young Ian , Kirezci Ebru , Ranasinghe Roshanka , Duong Trang Minh , Luijendijk Arjen P. 
Published: July 2023

AbstractA common inference in research studies of observed and projected changes in global ocean wave height and storm surge, is that such changes are potentially important for long-term coastal management. Despite numerous studies of the impacts of anthropogenic climate change on trends in global wind and waves, a clear link to impacts on sandy coastlines, at global scale, is yet to be demonstrated. This study presents a first-pass assessment of the potential link between historical trends in global wave and storm surge values and recession/progradation rates of sandy coastlines since the 1980s. Global datasets of waves, surge and shoreline change rate are used for this purpose. Over the past 30 + years, we show that there have been clear changes in waves and storm surge at global scale. The data, however, does not show an unequivocal linkage between trends in wave and storm surge climate and sandy shoreline recession/progradation. We conclude that these long-term changes in oceanographic parameters may still be too small to have a measurable impact on shoreline recession/progradation and that primary drivers such as ambient imbalances in the coastal sediment budget may be masking any such linkages.
Microbe-metabolite interaction networks, antibiotic resistance, and in vitro reconstitution of the penile prosthesis biofilm support a paradigm shift from infection to colonization
Authors: Werneburg Glenn T. , Lundy Scott D. , Hettel Daniel , Bajic Petar , Gill Bradley C. , Adler Ava , Mukherjee Sromona D. , Wood Hadley M. , Angermeier Kenneth W. , Shoskes Daniel A. , Miller Aaron W. 
Published: July 2023

AbstractTo understand differences between asymptomatic colonized and infected states of indwelling medical devices, we sought to determine penile prosthesis biofilm composition, microbe-metabolite interaction networks, and association with clinical factors. Patients scheduled for penile prosthesis removal/revision were included. Samples from swabbed devices and controls underwent next-generation sequencing, metabolomics, and culture-based assessments. Biofilm formation from device isolates was reconstituted in a continuous-flow stir tank bioreactor. 93% of 27 analyzed devices harbored demonstrable biofilm. Seven genera including Faecalibaculum and Jeotgalicoccus were more abundant in infected than uninfected device biofilms (p < 0.001). Smokers and those with diabetes mellitus or cardiac disease had lower total normalized microbial counts than those without the conditions (p < 0.001). We identified microbe-metabolite interaction networks enriched in devices explanted for infection and pain. Biofilm formation was recapitulated on medical device materials including silicone, PTFE, polyurethane, and titanium in vitro to facilitate further mechanistic studies. Nearly all penile prosthesis devices harbor biofilms. Staphylococcus and Escherichia, the most common causative organisms of prosthesis infection, had similar abundance irrespective of infection status. A series of other uncommon genera and metabolites were differentially abundant, suggesting a complex microbe-metabolite pattern–rather than a single organism–is responsible for the transition from asymptomatic to infected or painful states.
Machine learning-based prediction of in-ICU mortality in pneumonia patients
Authors: Jeon Eun-Tae , Lee Hyo Jin , Park Tae Yun , Jin Kwang Nam , Ryu Borim , Lee Hyun Woo , Kim Dong Hyun 
Published: July 2023

AbstractConventional severity-of-illness scoring systems have shown suboptimal performance for predicting in-intensive care unit (ICU) mortality in patients with severe pneumonia. This study aimed to develop and validate machine learning (ML) models for mortality prediction in patients with severe pneumonia. This retrospective study evaluated patients admitted to the ICU for severe pneumonia between January 2016 and December 2021. The predictive performance was analyzed by comparing the area under the receiver operating characteristic curve (AU-ROC) of ML models to that of conventional severity-of-illness scoring systems. Three ML models were evaluated: (1) logistic regression with L2 regularization, (2) gradient-boosted decision tree (LightGBM), and (3) multilayer perceptron (MLP). Among the 816 pneumonia patients included, 223 (27.3%) patients died. All ML models significantly outperformed the Simplified Acute Physiology Score II (AU-ROC: 0.650 [0.584–0.716] vs 0.820 [0.771–0.869] for logistic regression vs 0.827 [0.777–0.876] for LightGBM 0.838 [0.791–0.884] for MLP; P < 0.001). In the analysis for NRI, the LightGBM and MLP models showed superior reclassification compared with the logistic regression model in predicting in-ICU mortality in all length of stay in the ICU subgroups; all age subgroups; all subgroups with any APACHE II score, PaO2/FiO2 ratio < 200; all subgroups with or without history of respiratory disease; with or without history of CVA or dementia; treatment with mechanical ventilation, and use of inotropic agents. In conclusion, the ML models have excellent performance in predicting in-ICU mortality in patients with severe pneumonia. Moreover, this study highlights the potential advantages of selecting individual ML models for predicting in-ICU mortality in different subgroups.
A multi-parameter tunable plasmon modulator
Authors: Hu Xuefang , Lu Changgui , Zhao Xiangyue , Gu Yinwei , Lu Mengjia , Sun Dechao 
Published: July 2023

AbstractMulti-parameter control of light is a key functionality to modulate optical signals in photonic integrated circuits for various applications. However, the traditional optical modulators can only control one or two properties of light at the same time. Herein, we propose a hybrid structure which can modulate the amplitude, wavelength and phase of surface plasmon polaritons (SPPs) simultaneously to overcome these limitations. The numerical results show that when the Fermi level of graphene changes from 0.3 to 0.9 eV, the variation of optical transmission, wavelength and phase are 32.7 dB, 428 nm and 306°, respectively. The demonstrated structure triggers an approach for the realization of ultracompact modulation and has potential applications in the fields of optical switches, communications and photo-detection.
Fatty acid oxidation organizes mitochondrial supercomplexes to sustain astrocytic ROS and cognition
Authors: Morant-Ferrando Brenda , Jimenez-Blasco Daniel , Alonso-Batan Paula , Agulla Jesús , Lapresa Rebeca , Garcia-Rodriguez Dario , Yunta-Sanchez Sara , Lopez-Fabuel Irene , Fernandez Emilio , Carmeliet Peter , Almeida Angeles , Garcia-Macia Marina , Bolaños Juan P. 
Published: July 2023

AbstractHaving direct access to brain vasculature, astrocytes can take up available blood nutrients and metabolize them to fulfil their own energy needs and deliver metabolic intermediates to local synapses1,2. These glial cells should be, therefore, metabolically adaptable to swap different substrates. However, in vitro and in vivo studies consistently show that astrocytes are primarily glycolytic3–7, suggesting glucose is their main metabolic precursor. Notably, transcriptomic data8,9 and in vitro10 studies reveal that mouse astrocytes are capable of mitochondrially oxidizing fatty acids and that they can detoxify excess neuronal-derived fatty acids in disease models11,12. Still, the factual metabolic advantage of fatty acid use by astrocytes and its physiological impact on higher-order cerebral functions remain unknown. Here, we show that knockout of carnitine-palmitoyl transferase-1A (CPT1A)—a key enzyme of mitochondrial fatty acid oxidation—in adult mouse astrocytes causes cognitive impairment. Mechanistically, decreased fatty acid oxidation rewired astrocytic pyruvate metabolism to facilitate electron flux through a super-assembled mitochondrial respiratory chain, resulting in attenuation of reactive oxygen species formation. Thus, astrocytes naturally metabolize fatty acids to preserve the mitochondrial respiratory chain in an energetically inefficient disassembled conformation that secures signalling reactive oxygen species and sustains cognitive performance.
Hypergraph factorization for multi-tissue gene expression imputation
Authors: Viñas Ramon , Joshi Chaitanya K. , Georgiev Dobrik , Lin Phillip , Dumitrascu Bianca , Gamazon Eric R. , Liò Pietro 
Published: July 2023

AbstractIntegrating gene expression across tissues and cell types is crucial for understanding the coordinated biological mechanisms that drive disease and characterize homoeostasis. However, traditional multi-tissue integration methods either cannot handle uncollected tissues or rely on genotype information, which is often unavailable and subject to privacy concerns. Here we present HYFA (hypergraph factorization), a parameter-efficient graph representation learning approach for joint imputation of multi-tissue and cell-type gene expression. HYFA is genotype agnostic, supports a variable number of collected tissues per individual, and imposes strong inductive biases to leverage the shared regulatory architecture of tissues and genes. In performance comparison on Genotype–Tissue Expression project data, HYFA achieves superior performance over existing methods, especially when multiple reference tissues are available. The HYFA-imputed dataset can be used to identify replicable regulatory genetic variations (expression quantitative trait loci), with substantial gains over the original incomplete dataset. HYFA can accelerate the effective and scalable integration of tissue and cell-type transcriptome biorepositories.