bluuebunny/crossref_metadata_2025_split huggingface dataset:
Affinity-matured homotypic interactions induce spectrum of PfCSP structures that influence protection from malaria infection
Authors: Martin Gregory M. , Torres Jonathan L. , Pholcharee Tossapol , Oyen David , Flores-Garcia Yevel , Gibson Grace , Moskovitz Re’em , Beutler Nathan , Jung Diana D. , Copps Jeffrey , Lee Wen-Hsin , Gonzalez-Paez Gonzalo , Emerling Daniel , MacGill Randall S. , Locke Emily , King C. Richter , Zavala Fidel , Wilson Ian A. , Ward Andrew B. 
Published: July 2023

AbstractThe generation of high-quality antibody responses to Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP), the primary surface antigen of Pf sporozoites, is paramount to the development of an effective malaria vaccine. Here we present an in-depth structural and functional analysis of a panel of potent antibodies encoded by the immunoglobulin heavy chain variable (IGHV) gene IGHV3-33, which is among the most prevalent and potent antibody families induced in the anti-PfCSP immune response and targets the Asn-Ala-Asn-Pro (NANP) repeat region. Cryo-electron microscopy (cryo-EM) reveals a remarkable spectrum of helical antibody-PfCSP structures stabilized by homotypic interactions between tightly packed fragments antigen binding (Fabs), many of which correlate with somatic hypermutation. We demonstrate a key role of these mutated homotypic contacts for high avidity binding to PfCSP and in protection from Pf malaria infection. Together, these data emphasize the importance of anti-homotypic affinity maturation in the frequent selection of IGHV3–33 antibodies and highlight key features underlying the potent protection of this antibody family.
Elucidating electrochemical nitrate and nitrite reduction over atomically-dispersed transition metal sites
Authors: Murphy Eamonn , Liu Yuanchao , Matanovic Ivana , Rüscher Martina , Huang Ying , Ly Alvin , Guo Shengyuan , Zang Wenjie , Yan Xingxu , Martini Andrea , Timoshenko Janis , Cuenya Beatriz Roldán , Zenyuk Iryna V. , Pan Xiaoqing , Spoerke Erik D. , Atanassov Plamen 
Published: July 2023

AbstractElectrocatalytic reduction of waste nitrates (NO3−) enables the synthesis of ammonia (NH3) in a carbon neutral and decentralized manner. Atomically dispersed metal-nitrogen-carbon (M-N-C) catalysts demonstrate a high catalytic activity and uniquely favor mono-nitrogen products. However, the reaction fundamentals remain largely underexplored. Herein, we report a set of 14; 3d-, 4d-, 5d- and f-block M-N-C catalysts. The selectivity and activity of NO3− reduction to NH3 in neutral media, with a specific focus on deciphering the role of the NO2− intermediate in the reaction cascade, reveals strong correlations (R=0.9) between the NO2− reduction activity and NO3− reduction selectivity for NH3. Moreover, theoretical computations reveal the associative/dissociative adsorption pathways for NO2− evolution, over the normal M-N4 sites and their oxo-form (O-M-N4) for oxyphilic metals. This work provides a platform for designing multi-element NO3RR cascades with single-atom sites or their hybridization with extended catalytic surfaces.
Trimannose-coupled antimiR-21 for macrophage-targeted inhalation treatment of acute inflammatory lung damage
Authors: Beck Christina , Ramanujam Deepak , Vaccarello Paula , Widenmeyer Florenc , Feuerherd Martin , Cheng Cho-Chin , Bomhard Anton , Abikeeva Tatiana , Schädler Julia , Sperhake Jan-Peter , Graw Matthias , Safi Seyer , Hoffmann Hans , Staab-Weijnitz Claudia A. , Rad Roland , Protzer Ulrike , Frischmuth Thomas , Engelhardt Stefan 
Published: July 2023

AbstractRecent studies of severe acute inflammatory lung disease including COVID-19 identify macrophages to drive pulmonary hyperinflammation and long-term damage such as fibrosis. Here, we report on the development of a first-in-class, carbohydrate-coupled inhibitor of microRNA-21 (RCS-21), as a therapeutic means against pulmonary hyperinflammation and fibrosis. MicroRNA-21 is among the strongest upregulated microRNAs in human COVID-19 and in mice with acute inflammatory lung damage, and it is the strongest expressed microRNA in pulmonary macrophages. Chemical linkage of a microRNA-21 inhibitor to trimannose achieves rapid and specific delivery to macrophages upon inhalation in mice. RCS-21 reverses pathological activation of macrophages and prevents pulmonary dysfunction and fibrosis after acute lung damage in mice. In human lung tissue infected with SARS-CoV-2 ex vivo, RCS-21 effectively prevents the exaggerated inflammatory response. Our data imply trimannose-coupling for effective and selective delivery of inhaled oligonucleotides to pulmonary macrophages and report on a first mannose-coupled candidate therapeutic for COVID-19.
Monoclonal antibody levels and protection from COVID-19
Authors: Stadler Eva , Burgess Martin T. , Schlub Timothy E. , Khan Shanchita R. , Chai Khai Li , McQuilten Zoe K. , Wood Erica M. , Polizzotto Mark N. , Kent Stephen J. , Cromer Deborah , Davenport Miles P. , Khoury David S. 
Published: July 2023

AbstractMultiple monoclonal antibodies have been shown to be effective for both prophylaxis and therapy for SARS-CoV-2 infection. Here we aggregate data from randomized controlled trials assessing the use of monoclonal antibodies (mAb) in preventing symptomatic SARS-CoV-2 infection. We use data on the in vivo concentration of mAb and the associated protection from COVID-19 over time to model the dose-response relationship of mAb for prophylaxis. We estimate that 50% protection from COVID-19 is achieved with a mAb concentration of 96-fold of the in vitro IC50 (95% CI: 32—285). This relationship provides a tool for predicting the prophylactic efficacy of new mAb and against SARS-CoV-2 variants. Finally, we compare the relationship between neutralization titer and protection from COVID-19 after either mAb treatment or vaccination. We find no significant difference between the 50% protective titer for mAb and vaccination, although sample sizes limited the power to detect a difference.
Discovery and rational engineering of PET hydrolase with both mesophilic and thermophilic PET hydrolase properties
Authors: Hong Hwaseok , Ki Dongwoo , Seo Hogyun , Park Jiyoung , Jang Jaewon , Kim Kyung-Jin 
Published: July 2023

AbstractExcessive polyethylene terephthalate (PET) waste causes a variety of problems. Extensive research focused on the development of superior PET hydrolases for PET biorecycling has been conducted. However, template enzymes employed in enzyme engineering mainly focused onIsPETase and leaf-branch compost cutinase, which exhibit mesophilic and thermophilic hydrolytic properties, respectively. Herein, we report a PET hydrolase fromCryptosporangium aurantiacum(CaPETase) that exhibits high thermostability and remarkable PET degradation activity at ambient temperatures. We uncover the crystal structure ofCaPETase, which displays a distinct backbone conformation at the active site and residues forming the substrate binding cleft, compared with other PET hydrolases. We further develop aCaPETaseM9variant that exhibits robust thermostability with aTmof 83.2 °C and 41.7-fold enhanced PET hydrolytic activity at 60 °C compared withCaPETaseWT.CaPETaseM9almost completely decompose both transparent and colored post-consumer PET powder at 55 °C within half a day in a pH-stat bioreactor.
A small area model to assess temporal trends and sub-national disparities in healthcare quality
Authors: Allorant Adrien , Fullman Nancy , Leslie Hannah H. , Sarr Moussa , Gueye Daouda , Eliakimu Eliudi , Wakefield Jon , Dieleman Joseph L. , Pigott David , Puttkammer Nancy , Reiner Robert C. 
Published: July 2023

AbstractMonitoring subnational healthcare quality is important for identifying and addressing geographic inequities. Yet, health facility surveys are rarely powered to support the generation of estimates at more local levels. With this study, we propose an analytical approach for estimating both temporal and subnational patterns of healthcare quality indicators from health facility survey data. This method uses random effects to account for differences between survey instruments; space-time processes to leverage correlations in space and time; and covariates to incorporate auxiliary information. We applied this method for three countries in which at least four health facility surveys had been conducted since 1999 – Kenya, Senegal, and Tanzania – and estimated measures of sick-child care quality per WHO Service Availability and Readiness Assessment (SARA) guidelines at programmatic subnational level, between 1999 and 2020. Model performance metrics indicated good out-of-sample predictive validity, illustrating the potential utility of geospatial statistical models for health facility data. This method offers a way to jointly estimate indicators of healthcare quality over space and time, which could then provide insights to decision-makers and health service program managers.
Electrochemical synthesis of biaryls by reductive extrusion from N,N’-diarylureas
Authors: Stammers Ellie , Parsons Chris D. , Clayden Jonathan , Lennox Alastair J. J. 
Published: July 2023

AbstractThe synthesis of biaryl compounds by the transition-metal free coupling of arenes is an important contemporary challenge, aiming to avoid the toxicity and cost profiles associated with the metal catalysts commonly used in the synthesis of these pharmaceutically relevant motifs. In this paper, we describe an electrochemical approach to the synthesis of biaryls in which aniline derivatives are coupled through the formation and reduction of a temporary urea linkage. The conformational alignment of the arenes in theN,N’-diaryl urea intermediates promotes C-C bond formation following single-electron reduction. Our optimized conditions are suitable for the synthesis of a variety of biaryls, including sterically hindered examples carrying ortho-substituents, representing complementary reactivity to most metal catalysed methods.
Knowledge-enhanced visual-language pre-training on chest radiology images
Authors: Zhang Xiaoman , Wu Chaoyi , Zhang Ya , Xie Weidi , Wang Yanfeng 
Published: July 2023

AbstractWhile multi-modal foundation models pre-trained on large-scale data have been successful in natural language understanding and vision recognition, their use in medical domains is still limited due to the fine-grained nature of medical tasks and the high demand for domain knowledge. To address this challenge, we propose an approach called Knowledge-enhanced Auto Diagnosis (KAD) which leverages existing medical domain knowledge to guide vision-language pre-training using paired chest X-rays and radiology reports. We evaluate KAD on four external X-ray datasets and demonstrate that its zero-shot performance is not only comparable to that of fully supervised models but also superior to the average of three expert radiologists for three (out of five) pathologies with statistical significance. Moreover, when few-shot annotation is available, KAD outperforms all existing approaches in fine-tuning settings, demonstrating its potential for application in different clinical scenarios.
Cancer cell-mitochondria hybrid membrane coated Gboxin loaded nanomedicines for glioblastoma treatment
Authors: Zou Yan , Sun Yajing , Wang Yibin , Zhang Dongya , Yang Huiqing , Wang Xin , Zheng Meng , Shi Bingyang 
Published: July 2023

AbstractGlioblastoma (GBM) remains the most lethal malignant tumours. Gboxin, an oxidative phosphorylation inhibitor, specifically restrains GBM growth by inhibiting the activity of F0F1 ATPase complex V. However, its anti-GBM effect is seriously limited by poor blood circulation, the blood brain barrier (BBB) and non-specific GBM tissue/cell uptake, leading to insufficient Gboxin accumulation at GBM sites, which limits its further clinical application. Here we present a biomimetic nanomedicine (HM-NPs@G) by coating cancer cell-mitochondria hybrid membrane (HM) on the surface of Gboxin-loaded nanoparticles. An additional design element uses a reactive oxygen species responsive polymer to facilitate at-site Gboxin release. The HM camouflaging endows HM-NPs@G with unique features including good biocompatibility, improved pharmacokinetic profile, efficient BBB permeability and homotypic dual tumour cell and mitochondria targeting. The results suggest that HM-NPs@G achieve improved blood circulation (4.90 h versus 0.47 h of free Gboxin) and tumour accumulation (7.73% ID/g versus 1.06% ID/g shown by free Gboxin). Effective tumour inhibition in orthotopic U87MG GBM and patient derived X01 GBM stem cell xenografts in female mice with extended survival time and negligible side effects are also noted. We believe that the biomimetic Gboxin nanomedicine represents a promising treatment for brain tumours with clinical potential.
Wastewater-based epidemiology predicts COVID-19-induced weekly new hospital admissions in over 150 USA counties
Authors: Li Xuan , Liu Huan , Gao Li , Sherchan Samendra P. , Zhou Ting , Khan Stuart J. , van Loosdrecht Mark C. M. , Wang Qilin 
Published: July 2023

AbstractAlthough the coronavirus disease (COVID-19) emergency status is easing, the COVID-19 pandemic continues to affect healthcare systems globally. It is crucial to have a reliable and population-wide prediction tool for estimating COVID-19-induced hospital admissions. We evaluated the feasibility of using wastewater-based epidemiology (WBE) to predict COVID-19-induced weekly new hospitalizations in 159 counties across 45 states in the United States of America (USA), covering a population of nearly 100 million. Using county-level weekly wastewater surveillance data (over 20 months), WBE-based models were established through the random forest algorithm. WBE-based models accurately predicted the county-level weekly new admissions, allowing a preparation window of 1-4 weeks. In real applications, periodically updated WBE-based models showed good accuracy and transferability, with mean absolute error within 4-6 patients/100k population for upcoming weekly new hospitalization numbers. Our study demonstrated the potential of using WBE as an effective method to provide early warnings for healthcare systems.
Intra-gastric phytoliths provide evidence for folivory in basal avialans of the Early Cretaceous Jehol Biota
Authors: Wu Yan , Ge Yong , Hu Han , Stidham Thomas A. , Li Zhiheng , Bailleul Alida M. , Zhou Zhonghe 
Published: July 2023

AbstractAngiosperms became the dominant plant group in early to middle Cretaceous terrestrial ecosystems, coincident with the timing of the earliest pulse of bird diversification. While living birds and angiosperms exhibit strong interactions across pollination/nectivory, seed dispersal/frugivory, and folivory, documentation of the evolutionary origins and construction of that ecological complexity remains scarce in the Mesozoic. Through the first study of preserved in situ dietary derived phytoliths in a nearly complete skeleton of the early diverging avialan clade Jeholornithidae, we provide direct dietary evidence that Jeholornis consumed leaves likely from the magnoliid angiosperm clade, and these results lend further support for early ecological connections among the earliest birds and angiosperms. The broad diet of the early diverging avialan Jeholornis including at least fruits and leaves marks a clear transition in the early evolution of birds in the establishment of an arboreal (angiosperm) herbivore niche in the Early Cretaceous occupied largely by birds today. Morphometric reanalysis of the lower jaw of Jeholornis further supports a generalized morphology shared with other herbivorous birds, including an extant avian folivore, the hoatzin.
Modulating p38 MAPK signaling by proteostasis mechanisms supports tissue integrity during growth and aging
Authors: Yuan Wang , Weaver Yi M. , Earnest Svetlana , Taylor Clinton A. , Cobb Melanie H. , Weaver Benjamin P. 
Published: July 2023

AbstractThe conserved p38 MAPK family is activated by phosphorylation during stress responses and inactivated by phosphatases. C. elegans PMK-1 p38 MAPK initiates innate immune responses and blocks development when hyperactivated. Here we show that PMK-1 signaling is enhanced during early aging by modulating the stoichiometry of non-phospho-PMK-1 to promote tissue integrity and longevity. Loss of pmk-1 function accelerates progressive declines in neuronal integrity and lysosome function compromising longevity which has both cell autonomous and cell non-autonomous contributions. CED-3 caspase cleavage limits phosphorylated PMK-1. Enhancing p38 signaling with caspase cleavage-resistant PMK-1 protects lysosomal and neuronal integrity extending a youthful phase. PMK-1 works through a complex transcriptional program to regulate lysosome formation. During early aging, the absolute phospho-p38 amount is maintained but the reservoir of non-phospho-p38 diminishes to enhance signaling without hyperactivation. Our findings show that modulating the stoichiometry of non-phospho-p38 dynamically supports tissue-homeostasis during aging without hyper-activation of stress response.
Spin selection in atomic-level chiral metal oxide for photocatalysis
Authors: Ai Minhua , Pan Lun , Shi Chengxiang , Huang Zhen-Feng , Zhang Xiangwen , Mi Wenbo , Zou Ji-Jun 
Published: July 2023

AbstractThe spin degree of freedom is an important and intrinsic parameter in boosting carrier dynamics and surface reaction kinetics of photocatalysis. Here we show that chiral structure in ZnO can induce spin selectivity effect to promote photocatalytic performance. The ZnO crystals synthesized using chiral methionine molecules as symmetry-breaking agents show hierarchical chirality. Magnetic circular dichroism spectroscopic and magnetic conductive-probe atomic force microscopic measurements demonstrate that chiral structure acts as spin filters and induces spin polarization in photoinduced carriers. The polarized carriers not only possess the prolonged carrier lifetime, but also increase the triplet species instead of singlet byproducts during reaction. Accordingly, the left- and right-hand chiral ZnO exhibit 2.0- and 1.9-times higher activity in photocatalytic O2 production and 2.5- and 2.0-times higher activities in contaminant photodegradation, respectively, compared with achiral ZnO. This work provides a feasible strategy to manipulate the spin properties in metal oxides for electron spin-related redox catalysis.
Genome assembly of the Korean intertidal mud-creeper Batillaria attramentaria
Authors: Patra Ajit Kumar , Ho Phuong-Thao , Jun Siyeong , Lee Seung Jae , Kim Yuseob , Won Yong-Jin 
Published: July 2023

AbstractBatillaridae is a common gastropod family that occurs abundantly in the shallow coastal zone of the intertidal mudflats of the northwest Pacific Ocean, Australasia, and North America. In this family, Batillaria attramentaria is known for its biological invasion and colonization in estuarine and intertidal zones. It can endure and adapt the harsh intertidal conditions such as frequent temperature alteration, salinity, and air exposure. Therefore, we sequenced and assembled this Korean batillariid genome to get insight into its intertidal adaptive features. Approximately 53 Gb of DNA sequences were generated, and 863 scaffolds were assembled into a draft genome of 0.715 Gb with 97.1% BUSCO completeness value. A total of 40,596 genes were predicted. We estimated that B. attramentaria and Conus consors diverged about 230 million years ago (MYA) based on the phylogenetic analysis of closely related gastropod species. This genome study sets the footstep for genomics studies among native and introduced Batillaria populations and the Batillaridae family members.
Relationship between biomechanics and energy cost in graded treadmill running
Authors: Lemire Marcel , Faricier Robin , Dieterlen Alain , Meyer Frédéric , Millet Grégoire P. 
Published: July 2023

AbstractThe objective of this study was to determine whether the relationships between energy cost of running (Cr) and running mechanics during downhill (DR), level (LR) and uphill (UR) running could be related to fitness level. Nineteen athletes performed four experimental tests on an instrumented treadmill: one maximal incremental test in LR, and three randomized running bouts at constant speed (10 km h−1) in LR, UR and DR (± 10% slope). Gas exchange, heart rate and ground reaction forces were collected during steady-state. Subjects were split into two groups using the median Cr for all participants. Contact time, duty factor, and positive external work correlated with Cr during UR (all, p < 0.05), while none of the mechanical variables correlated with Cr during LR and DR. Mechanical differences between the two groups were observed in UR only: contact time and step length were higher in the economical than in the non-economical group (both p < 0.031). This study shows that longer stance duration during UR contributes to lower energy expenditure and Cr (i.e., running economy improvement), which opens the way to optimize specific running training programs.
Techniques to produce and evaluate realistic multivariate synthetic data
Authors: Heine John , Fowler Erin E. E. , Berglund Anders , Schell Michael J. , Eschrich Steven 
Published: July 2023

AbstractData modeling requires a sufficient sample size for reproducibility. A small sample size can inhibit model evaluation. A synthetic data generation technique addressing this small sample size problem is evaluated: from the space of arbitrarily distributed samples, a subgroup (class) has a latent multivariate normal characteristic; synthetic data can be generated from this class with univariate kernel density estimation (KDE); and synthetic samples are statistically like their respective samples. Three samples (n = 667) were investigated with 10 input variables (X). KDE was used to augment the sample size in X. Maps produced univariate normal variables in Y. Principal component analysis in Y produced uncorrelated variables in T, where the probability density functions were approximated as normal and characterized; synthetic data was generated with normally distributed univariate random variables in T. Reversing each step produced synthetic data in Y and X. All samples were approximately multivariate normal in Y, permitting the generation of synthetic data. Probability density function and covariance comparisons showed similarity between samples and synthetic samples. A class of samples has a latent normal characteristic. For such samples, this approach offers a solution to the small sample size problem. Further studies are required to understand this latent class.