bluuebunny/crossref_metadata_2025_split huggingface dataset:
Modular stimuli-responsive hydrogel sealants for early gastrointestinal leak detection and containment
Authors: Anthis Alexandre H. C. , Abundo Maria Paulene , Neuer Anna L. , Tsolaki Elena , Rosendorf Jachym , Rduch Thomas , Starsich Fabian H. L. , Weisse Bernhard , Liska Vaclav , Schlegel Andrea A. , Shapiro Mikhail G. , Herrmann Inge K. 
Published: November 2022

AbstractMillions of patients every year undergo gastrointestinal surgery. While often lifesaving, sutured and stapled reconnections leak in around 10% of cases. Currently, surgeons rely on the monitoring of surrogate markers and clinical symptoms, which often lack sensitivity and specificity, hence only offering late-stage detection of fully developed leaks. Here, we present a holistic solution in the form of a modular, intelligent suture support sealant patch capable of containing and detecting leaks early. The pH and/or enzyme-responsive triggerable sensing elements can be read out by point-of-need ultrasound imaging. We demonstrate reliable detection of the breaching of sutures, in as little as 3 hours in intestinal leak scenarios and 15 minutes in gastric leak conditions. This technology paves the way for next-generation suture support materials that seal and offer disambiguation in cases of anastomotic leaks based on point-of-need monitoring, without reliance on complex electronics or bulky (bio)electronic implantables.
Geometrical congruence, greedy navigability and myopic transfer in complex networks and brain connectomes
Authors: Cannistraci Carlo Vittorio , Muscoloni Alessandro 
Published: November 2022

AbstractWe introduce in network geometry a measure of geometrical congruence (GC) to evaluate the extent a network topology follows an underlying geometry. This requires finding all topological shortest-paths for each nonadjacent node pair in the network: a nontrivial computational task. Hence, we propose an optimized algorithm that reduces 26 years of worst scenario computation to one week parallel computing. Analysing artificial networks with patent geometry we discover that, different from current belief, hyperbolic networks do not show in general high GC and efficient greedy navigability (GN) with respect to the geodesics. The myopic transfer which rules GN works best only when degree-distribution power-law exponent is strictly close to two. Analysing real networks—whose geometry is often latent—GC overcomes GN as marker to differentiate phenotypical states in macroscale structural-MRI brain connectomes, suggesting connectomes might have a latent neurobiological geometry accounting for more information than the visible tridimensional Euclidean.
Predicting protein function and orientation on a gold nanoparticle surface using a residue-based affinity scale
Authors: Xu Joanna Xiuzhu , Alom Md. Siddik , Yadav Rahul , Fitzkee Nicholas C. 
Published: November 2022

AbstractThe orientation adopted by proteins on nanoparticle surfaces determines the nanoparticle’s bioactivity and its interactions with living systems. Here, we present a residue-based affinity scale for predicting protein orientation on citrate-gold nanoparticles (AuNPs). Competitive binding between protein variants accounts for thermodynamic and kinetic aspects of adsorption in this scale. For hydrophobic residues, the steric considerations dominate, whereas electrostatic interactions are critical for hydrophilic residues. The scale rationalizes the well-defined binding orientation of the small GB3 protein, and it subsequently predicts the orientation and active site accessibility of two enzymes on AuNPs. Additionally, our approach accounts for the AuNP-bound activity of five out of six additional enzymes from the literature. The model developed here enables high-throughput predictions of protein behavior on nanoparticles, and it enhances our understanding of protein orientation in the biomolecular corona, which should greatly enhance the performance and safety of nanomedicines used in vivo.
Improved bounds on Lorentz violation from composite pulse Ramsey spectroscopy in a trapped ion
Authors: Dreissen Laura S. , Yeh Chih-Han , Fürst Henning A. , Grensemann Kai C. , Mehlstäubler Tanja E. 
Published: November 2022

AbstractIn attempts to unify the four known fundamental forces in a single quantum-consistent theory, it is suggested that Lorentz symmetry may be broken at the Planck scale. Here we search for Lorentz violation at the low-energy limit by comparing orthogonally oriented atomic orbitals in a Michelson-Morley-type experiment. We apply a robust radiofrequency composite pulse sequence in the 2F7/2 manifold of an Yb+ ion, extending the coherence time from 200 μs to more than 1 s. In this manner, we fully exploit the high intrinsic susceptibility of the 2F7/2 state and take advantage of its exceptionally long lifetime. We match the stability of the previous best Lorentz symmetry test nearly an order of magnitude faster and improve the constraints on the symmetry breaking coefficients to the 10−21 level. These results represent the most stringent test of this type of Lorentz violation. The demonstrated method can be further extended to ion Coulomb crystals.
Chern Fermi pocket, topological pair density wave, and charge-4e and charge-6e superconductivity in kagomé superconductors
Authors: Zhou Sen , Wang Ziqiang 
Published: November 2022

AbstractThe recent discovery of novel charge density wave (CDW) and pair density wave (PDW) in kagomé lattice superconductorsAV3Sb5(A = K, Rb, Cs) hints at unexpected time-reversal symmetry breaking correlated and topological states whose physical origin and broader implications are not understood. Here, we make conceptual advances toward a mechanism behind the striking observations and new predictions for novel macroscopic phase coherent quantum states. We show that the metallic CDW state with circulating loop currents is a doped orbital Chern insulator near van Hove filling. The emergent Chern Fermi pockets (CFPs) carry concentrated Berry curvature and orbital magnetic moment. We find that the pairing of electrons on the CFPs leads to a superconducting state with an emergent vortex-antivortex lattice and the formation of a complex triple-QPDW. A plethora of correlated and topological states emerge, including a never-before-encountered chiral topological PDW superconductor, a loop-current pseudogap phase, and vestigial charge-4eand charge-6esuperconductivity in staged melting of the vortex-antivortex lattice and hexatic liquid crystal. Our findings reveal previously unknown nature of the superconducting state of a current-carrying Chern metal, with broad implications for correlated and topological materials.
How mono- and diphosphine ligands alter regioselectivity of the Rh-catalyzed annulative cleavage of bicyclo[1.1.0]butanes
Authors: Chen Pan-Pan , Wipf Peter , Houk K. N. 
Published: November 2022

AbstractRh(I)-catalyzed cycloisomerizations of bicyclo[1.1.0]butanes provide a fruitful approach to cyclopropane-fused heterocycles. Products and stereochemical outcome are highly dependent on catalyst. The triphenylphosphine (PPh3) ligand provides pyrrolidines, placing substituents anti to the cyclopropyl group. The 1,2-bis(diphenylphosphino)ethane (dppe) ligand yields azepanes with substituents syn to the cyclopropyl group. In this work, quantum mechanical DFT calculations pinpoint a reversal of regio- and diastereoselectivity, suggesting a concerted (double) C−C bond cleavage and rhodium carbenoid formation, driven by strain-release. The ligand-influenced cleavage step determines the regioselectivity of carbometalation and product formation, and suggests new applications of bicyclobutanes.
Characterisation of SARS-CoV-2 genomic variation in response to molnupiravir treatment in the AGILE Phase IIa clinical trial
Authors: Donovan-Banfield I’ah , Penrice-Randal Rebekah , Goldswain Hannah , Rzeszutek Aleksandra M. , Pilgrim Jack , Bullock Katie , Saunders Geoffrey , Northey Josh , Dong Xiaofeng , Ryan Yan , Reynolds Helen , Tetlow Michelle , Walker Lauren E. , FitzGerald Richard , Hale Colin , Lyon Rebecca , Woods Christie , Ahmad Shazaad , Hadjiyiannakis Dennis , Periselneris Jimstan , Knox Emma , Middleton Calley , Lavelle-Langham Lara , Shaw Victoria , Greenhalf William , Edwards Thomas , Lalloo David G. , Edwards Christopher J. , Darby Alistair C. , Carroll Miles W. , Griffiths Gareth , Khoo Saye H. , Hiscox Julian A. , Fletcher Thomas 
Published: November 2022

AbstractMolnupiravir is an antiviral, currently approved by the UK Medicines and Healthcare products Regulatory Agency (MHRA) for treating at-risk COVID-19 patients, that induces lethal error catastrophe in SARS-CoV-2. How this drug-induced mechanism of action might impact the emergence of resistance mutations is unclear. To investigate this, we used samples from the AGILE Candidate Specific Trial (CST)−2 (clinical trial number NCT04746183). The primary outcomes of AGILE CST-2 were to measure the drug safety and antiviral efficacy of molnupiravir in humans (180 participants randomised 1:1 with placebo). Here, we describe the pre-specified exploratory virological endpoint of CST-2, which was to determine the possible genomic changes in SARS-CoV-2 induced by molnupiravir treatment. We use high-throughput amplicon sequencing and minor variant analysis to characterise viral genomics in each participant whose longitudinal samples (days 1, 3 and 5 post-randomisation) pass the viral genomic quality criteria (n = 59 for molnupiravir and n = 65 for placebo). Over the course of treatment, no specific mutations were associated with molnupiravir treatment. We find that molnupiravir significantly increased the transition:transversion mutation ratio in SARS-CoV-2, consistent with the model of lethal error catastrophe. This study highlights the utility of examining intra-host virus populations to strengthen the prediction, and surveillance, of potential treatment-emergent adaptations.
Shape morphing of plastic films
Authors: Zhang Feilong , Li Dong , Wang Changxian , Liu Zhihua , Yang Man , Cui Zequn , Yi Junqi , Wang Ming , Jiang Ying , Lv Zhisheng , Wang Shutao , Gao Huajian , Chen Xiaodong 
Published: November 2022

AbstractThree-dimensional (3D) architectures have qualitatively expanded the functions of materials and flexible electronics. However, current fabrication techniques for devices constrain their substrates to 2D geometries and current post-shape transformation strategies are limited to heterogenous or responsive materials and are not amenable to free-standing inert plastic films such as polyethylene terephthalate (PET) and polyimide (PI), which are vital substrates for flexible electronics. Here, we realize the shape morphing of homogeneous plastic films for various free-standing 3D frameworks from their 2D precursors by introducing a general strategy based on programming the plastic strain in films under peeling. By modulating the peeling parameters, previously inaccessible free-standing 3D geometries ranging from millimeter to micrometer were predicted theoretically and obtained experimentally. This strategy is applicable to most materials capable of plastic deformation, including polymers, metals, and composite materials, and can even enable 4D transformation with responsive plastic films. Enhanced performance of 3D circuits and piezoelectric systems demonstrates the enormous potential of peeling-induced shape morphing for 3D devices.
ARID1A loss induces polymorphonuclear myeloid-derived suppressor cell chemotaxis and promotes prostate cancer progression
Authors: Li Ni , Liu Qiuli , Han Ying , Pei Siyu , Cheng Bisheng , Xu Junyu , Miao Xiang , Pan Qiang , Wang Hanling , Guo Jiacheng , Wang Xuege , Zhang Guoying , Lian Yannan , Zhang Wei , Zang Yi , Tan Minjia , Li Qintong , Wang Xiaoming , Xiao Yichuan , Hu Guohong , Jiang Jun , Huang Hai , Qin Jun 
Published: November 2022

AbstractChronic inflammation and an immunosuppressive microenvironment promote prostate cancer (PCa) progression and diminish the response to immune checkpoint blockade (ICB) therapies. However, it remains unclear how and to what extent these two events are coordinated. Here, we show that ARID1A, a subunit of the SWI/SNF chromatin remodeling complex, functions downstream of inflammation-induced IKKβ activation to shape the immunosuppressive tumor microenvironment (TME). Prostate-specific deletion ofArid1acooperates withPtenloss to accelerate prostate tumorigenesis. We identify polymorphonuclear myeloid-derived suppressor cells (PMN-MDSCs) as the major infiltrating immune cell type that causes immune evasion and reveal that neutralization of PMN-MDSCs restricts the progression ofArid1a-deficient tumors. Mechanistically, inflammatory cues activate IKKβ to phosphorylate ARID1A, leading to its degradation via β-TRCP. ARID1A downregulation in turn silences the enhancer ofA20deubiquitinase, a critical negative regulator of NF-κB signaling, and thereby unleashes CXCR2 ligand-mediated MDSC chemotaxis. Importantly, our results support the therapeutic strategy of anti-NF-κB antibody or targeting CXCR2 combined with ICB for advanced PCa. Together, our findings highlight that the IKKβ/ARID1A/NF-κB feedback axis integrates inflammation and immunosuppression to promote PCa progression.
Decoding molecular programs in melanoma brain metastases
Authors: Radke Josefine , Schumann Elisa , Onken Julia , Koll Randi , Acker Güliz , Bodnar Bohdan , Senger Carolin , Tierling Sascha , Möbs Markus , Vajkoczy Peter , Vidal Anna , Högler Sandra , Kodajova Petra , Westphal Dana , Meier Friedegund , Heppner Frank , Kreuzer-Redmer Susanne , Grebien Florian , Jürchott Karsten , Redmer Torben 
Published: November 2022

AbstractMelanoma brain metastases (MBM) variably respond to therapeutic interventions; thus determining patient’s prognosis. However, the mechanisms that govern therapy response are poorly understood. Here, we use a multi-OMICS approach and targeted sequencing (TargetSeq) to unravel the programs that potentially control the development of progressive intracranial disease. Molecularly, the expression of E-cadherin (Ecad) or NGFR, the BRAF mutation state and level of immune cell infiltration subdivides tumors into proliferative/pigmented and invasive/stem-like/therapy-resistant irrespective of the intracranial location. The analysis of MAPK inhibitor-naive and refractory MBM reveals switching from Ecad-associated into NGFR-associated programs during progression. NGFR-associated programs control cell migration and proliferation via downstream transcription factors such as SOX4. Moreover, global methylome profiling uncovers 46 differentially methylated regions that discriminate BRAFmut and wildtype MBM. In summary, we propose that the expression of Ecad and NGFR sub- classifies MBM and suggest that the Ecad-to-NGFR phenotype switch is a rate-limiting process which potentially indicates drug-response and intracranial progression states in melanoma patients.
Structural basis for lipid and copper regulation of the ABC transporter MsbA
Authors: Lyu Jixing , Liu Chang , Zhang Tianqi , Schrecke Samantha , Elam Nicklaus P. , Packianathan Charles , Hochberg Georg K. A. , Russell David , Zhao Minglei , Laganowsky Arthur 
Published: November 2022

AbstractA critical step in lipopolysaccharide (LPS) biogenesis involves flipping lipooligosaccharide, an LPS precursor, from the cytoplasmic to the periplasmic leaflet of the inner membrane, an operation carried out by the ATP-binding cassette transporter MsbA. Although LPS binding to the inner cavity of MsbA is well established, the selectivity of MsbA-lipid interactions at other site(s) remains poorly understood. Here we use native mass spectrometry (MS) to characterize MsbA-lipid interactions and guide structural studies. We show the transporter co-purifies with copper(II) and metal binding modulates protein-lipid interactions. A 2.15 Å resolution structure of an N-terminal region of MsbA in complex with copper(II) is presented, revealing a structure reminiscent of the GHK peptide, a high-affinity copper(II) chelator. Our results demonstrate conformation-dependent lipid binding affinities, particularly for the LPS-precursor, 3-deoxy-D-manno-oct-2-ulosonic acid (Kdo)2-lipid A (KDL). We report a 3.6 Å-resolution structure of MsbA trapped in an open, outward-facing conformation with adenosine 5’-diphosphate and vanadate, revealing a distinct KDL binding site, wherein the lipid forms extensive interactions with the transporter. Additional studies provide evidence that the exterior KDL binding site is conserved and a positive allosteric modulator of ATPase activity, serving as a feedforward activation mechanism to couple transporter activity with LPS biosynthesis.
Structural characterization of protective non-neutralizing antibodies targeting Crimean-Congo hemorrhagic fever virus
Authors: Durie Ian A. , Tehrani Zahra R. , Karaaslan Elif , Sorvillo Teresa E. , McGuire Jack , Golden Joseph W. , Welch Stephen R. , Kainulainen Markus H. , Harmon Jessica R. , Mousa Jarrod J. , Gonzalez David , Enos Suzanne , Koksal Iftihar , Yilmaz Gurdal , Karakoc Hanife Nur , Hamidi Sanaz , Albay Cansu , Spengler Jessica R. , Spiropoulou Christina F. , Garrison Aura R. , Sajadi Mohammad M. , Bergeron Éric , Pegan Scott D. 
Published: November 2022

AbstractCrimean-Congo Hemorrhagic Fever Virus (CCHFV) causes a life-threatening disease with up to a 40% mortality rate. With no approved medical countermeasures, CCHFV is considered a public health priority agent. The non-neutralizing mouse monoclonal antibody (mAb) 13G8 targets CCHFV glycoprotein GP38 and protects mice from lethal CCHFV challenge when administered prophylactically or therapeutically. Here, we reveal the structures of GP38 bound with a human chimeric 13G8 mAb and a newly isolated CC5-17 mAb from a human survivor. These mAbs bind overlapping epitopes with a shifted angle. The broad-spectrum potential of c13G8 and CC5-17 and the practicality of using them against Aigai virus, a closely related nairovirus were examined. Binding studies demonstrate that the presence of non-conserved amino acids in Aigai virus corresponding region prevent CCHFV mAbs from binding Aigai virus GP38. This information, coupled with in vivo efficacy, paves the way for future mAb therapeutics effective against a wide swath of CCHFV strains.
Kinetochore- and chromosome-driven transition of microtubules into bundles promotes spindle assembly
Authors: Matković Jurica , Ghosh Subhadip , Ćosić Mateja , Eibes Susana , Barišić Marin , Pavin Nenad , Tolić Iva M. 
Published: November 2022

AbstractMitotic spindle assembly is crucial for chromosome segregation and relies on bundles of microtubules that extend from the poles and overlap in the middle. However, how these structures form remains poorly understood. Here we show that overlap bundles arise through a network-to-bundles transition driven by kinetochores and chromosomes. STED super-resolution microscopy reveals that PRC1-crosslinked microtubules initially form loose arrays, which become rearranged into bundles. Kinetochores promote microtubule bundling by lateral binding via CENP-E/kinesin-7 in an Aurora B-regulated manner. Steric interactions between the bundle-associated chromosomes at the spindle midplane drive bundle separation and spindle widening. In agreement with experiments, theoretical modeling suggests that bundles arise through competing attractive and repulsive mechanisms. Finally, perturbation of overlap bundles leads to inefficient correction of erroneous kinetochore-microtubule attachments. Thus, kinetochores and chromosomes drive coarsening of a uniform microtubule array into overlap bundles, which promote not only spindle formation but also chromosome segregation fidelity.
Epigenetic regulation of white adipose tissue plasticity and energy metabolism by nucleosome binding HMGN proteins
Authors: Nanduri Ravikanth , Furusawa Takashi , Lobanov Alexei , He Bing , Xie Carol , Dadkhah Kimia , Kelly Michael C. , Gavrilova Oksana , Gonzalez Frank J. , Bustin Michael 
Published: November 2022

AbstractWhite adipose tissue browning is a key metabolic process controlled by epigenetic factors that facilitate changes in gene expression leading to altered cell identity. We find that male mice lacking the nucleosome binding proteins HMGN1 and HMGN2 (DKO mice), show decreased body weight and inguinal WAT mass, but elevated food intake, WAT browning and energy expenditure. DKO white preadipocytes show reduced chromatin accessibility and lower FRA2 and JUN binding at Pparγ and Pparα promoters. White preadipocytes and mouse embryonic fibroblasts from DKO mice show enhanced rate of differentiation into brown-like adipocytes. Differentiating DKO adipocytes show reduced H3K27ac levels at white adipocyte-specific enhancers but elevated H3K27ac levels at brown adipocyte-specific enhancers, suggesting a faster rate of change in cell identity, from white to brown-like adipocytes. Thus, HMGN proteins function as epigenetic factors that stabilize white adipocyte cell identity, thereby modulating the rate of white adipose tissue browning and affecting energy metabolism in mice.
Observation of a transient intermediate in the ultrafast relaxation dynamics of the excess electron in strong-field-ionized liquid water
Authors: Low Pei Jiang , Chu Weibin , Nie Zhaogang , Bin Mohd Yusof Muhammad Shafiq , Prezhdo Oleg V. , Loh Zhi-Heng 
Published: November 2022

AbstractA unified picture of the electronic relaxation dynamics of ionized liquid water has remained elusive despite decades of study. Here, we employ sub-two-cycle visible to short-wave infrared pump-probe spectroscopy and ab initio nonadiabatic molecular dynamics simulations to reveal that the excess electron injected into the conduction band (CB) of ionized liquid water undergoes sequential relaxation to the hydrated electron s ground state via an intermediate state, identified as the elusive p excited state. The measured CB and p-electron lifetimes are 0.26 ± 0.02 ps and 62 ± 10 fs, respectively. Ab initio quantum dynamics yield similar lifetimes and furthermore reveal vibrational modes that participate in the different stages of electronic relaxation, with initial relaxation within the dense CB manifold coupled to hindered translational motions whereas subsequent p-to-s relaxation facilitated by librational and even intramolecular bending modes of water. Finally, energetic considerations suggest that a hitherto unobserved trap state resides ~0.3-eV below the CB edge of liquid water. Our results provide a detailed atomistic picture of the electronic relaxation dynamics of ionized liquid water with unprecedented time resolution.
Seroepidemiology of enterovirus A71 infection in prospective cohort studies of children in southern China, 2013-2018
Authors: Yang Juan , Liao Qiaohong , Luo Kaiwei , Liu Fengfeng , Zhou Yonghong , Zou Gang , Huang Wei , Yu Shuanbao , Wei Xianglin , Zhou Jiaxin , Dai Bingbing , Qiu Qi , Altmeyer Ralf , Hu Hongan , Paireau Juliette , Luo Li , Gao Lidong , Nikolay Birgit , Hu Shixiong , Xing Weijia , Wu Peng , van Doorn H. Rogier , Horby Peter W. , Simmonds Peter , Leung Gabriel M. , Cowling Benjamin J. , Cauchemez Simon , Yu Hongjie 
Published: November 2022

AbstractEnterovirus A71 (EV-A71)–related hand, foot, and mouth disease (HFMD) imposes a substantial clinical burden in the Asia Pacific region. To inform policy on the introduction of the EV-A71 vaccine into the National Immunization Programme, we investigated the seroepidemiological characteristics of EV-A71 in two prospective cohorts of children in southern China conducted between 2013 and 2018. Our results show that maternal antibody titres declined rapidly in neonates, with over half becoming susceptible to EV-A71 at 1 month of age. Between 6 months and 2 years of age, over 80% of study participants were susceptible, while one third remained susceptible at 5 years old. The highest incidence of EV-A71 infections was observed in children aged 5-6 months. Our findings support EV-A71 vaccination before 6 months for birth cohorts in southern China, potentially with a one-time catch-up vaccination for children 6 months-5 years old. More regionally representative longitudinal seroepidemiological studies are needed to further validate these findings.