bluuebunny/crossref_metadata_2025_split huggingface dataset:
Technical Considerations in Surgical Fixation of Jefferson Fracture
Authors: Gurjar Hitesh Kumar , Rai Hitesh Inder Singh , Mishra Shashwat , Garg Kanwaljeet 
Published: December 2022

AbstractJefferson fracture is defined as the simultaneous disruption of the continuity of the anterior and posterior arches of the atlas vertebra. It generally results from an axial impact to the head. Most of these fractures are amenable to nonoperative management. Significant disruption of the transverse atlantal ligament that is the main stabilizing ligament of the atlantoaxial articulation and contiguous spinal injuries often form the indications for operative intervention in these fractures. The outward and caudal displacement of the C1 lateral masses observed in these fractures often requires significant deviation from the standard operative technique of atlantoaxial fixation when the osseous elements are intact. Accordingly, we have described the surgical nuances relevant to the exposure and instrumentation of the atlantoaxial region in the setting of Jefferson fracture, through our experience in two cases.
Management of Acute Complications during Endovascular Procedures in Peripheral Arterial Disease: A Review
Authors: Kumar Ajay Pawan , Valakkada Jineesh , Ayappan Anoop , Kannath Santhosh 
Published: December 2022

AbstractEndovascular therapy, as opposed to surgical bypass, has become the mainstay for peripheral arterial disease even in long segment occlusions. Complications can occur during the arterial access, catheter manipulation, balloon dilation, and/or stent placement. Given the high prevalence of comorbidities such as diabetes, hypertension, renal dysfunction, and coronary artery disease in these patients, early identification of procedural complications and initiation of treatment are of paramount importance. This review aims to provide comprehensive data on the identification and management of commonly encountered endovascular complications during endovascular interventions in peripheral arterial disease.
A quantitative model of charge injection by ruthenium chromophores connecting femtosecond to continuous irradiance conditions
Authors: Cheshire Thomas P. , Boodry Jéa , Kober Erin A. , Brennaman M. Kyle , Giokas Paul G. , Zigler David F. , Moran Andrew M. , Papanikolas John M. , Meyer Gerald J. , Meyer Thomas J. , Houle Frances A. 
Published: December 2022

A kinetic framework for the ultrafast photophysics of tris(2,2-bipyridine)ruthenium(II) phosphonated and methyl-phosphonated derivatives is used as a basis for modeling charge injection by ruthenium dyes into a semiconductor substrate. By including the effects of light scattering, dye diffusion, and adsorption kinetics during sample preparation and the optical response of oxidized dyes, quantitative agreement with multiple transient absorption datasets is achieved on timescales spanning femtoseconds to nanoseconds. In particular, quantitative agreement with important spectroscopic handles—the decay of an excited state absorption signal component associated with charge injection in the UV region of the spectrum and the dynamical redshift of a ∼500 nm isosbestic point—validates our kinetic model. Pseudo-first-order rate coefficients for charge injection are estimated in this work, with an order of magnitude ranging from 1011 to 1012 s−1. The model makes the minimalist assumption that all excited states of a particular dye have the same charge injection coefficient, an assumption that would benefit from additional theoretical and experimental exploration. We have adapted this kinetic model to predict charge injection under continuous solar irradiation and find that as many as 68 electron transfer events per dye per second take place, significantly more than prior estimates in the literature.
A specific MNDO parameterization for water
Authors: Hennemann Matthias , Clark Timothy 
Published: December 2022

A modified neglect of differential overlap has been parameterized specifically for water and its oligomers with the addition of polarization functions on both hydrogen and oxygen, Feynman dispersion, and a slight modification of the treatment of the hydrogen nucleus. The results show that it is possible to easily obtain good geometries and energies for hydrogen-bonded water aggregates. Data from the Benchmark Energy and Geometry Database water-cluster database were used to parameterize the new Hamiltonian for water clusters from the dimer to the decamer using MP2/aug-cc-pVDZ optimized geometries and CCSD(T)/CBS oligomerization energies. Seventy five oligomerization and rearrangement energies derived from the parameterization data are reproduced with a root mean-square error (RMSE) of 0.79 kcal mol−1 and the geometries of 38 oligomers with an RMSE of 0.17 Å. Interestingly, the Feynman dispersion term adopts a role different from that intended and tunes the atomic polarizability. The implications of these results in terms of future dedicated neglect of diatomic differential overlap Hamiltonians and those that use force-field-like atom types are discussed.
Does twist angle affect the properties of water confined inside twisted bilayer graphene?
Authors: Majumdar Jeet , Dasgupta Subhadeep , Mandal Soham , Moid Mohd , Jain Manish , Maiti Prabal K. 
Published: December 2022

Graphene nanoslit pores are used for nanofluidic devices, such as, in water desalination, ion-selective channels, ionic transistors, sensing, molecular sieving, blue energy harvesting, and protein sequencing. It is a strenuous task to prepare nanofluidic devices, because a small misalignment leads to a significant alteration in various properties of the devices. Here, we focus on the rotational misalignment between two parallel graphene sheets. Using molecular dynamics simulation, we probe the structure and dynamics of monolayer water confined inside graphene nanochannels for a range of commensurate twist angles. With SPC/E and TIP4P/2005 water models, our simulations reveal the independence of the equilibrium number density— n ∼ 13 nm−2 for SPC/E and n ∼ 11.5 nm−2 for TIP4P/2005— across twists. Based on the respective densities of the water models, the structure and dielectric constant are invariant of twist angles. The confined water structure at this density shows square ice ordering for SPC/E water only. TIP4P/2005 shows ordering at the vicinity of a critical density (n ∼ 12.5 nm−2). The average perpendicular dielectric constant of the confined water remains anomalously low (∼2 for SPC/E and ∼6 for TIP4P/2005) for the studied twist angles. We find that the friction coefficient of confined water molecules varies for small twist angles, while becoming independent for twists greater than 5.1°. Our results indicate that a small, angular misalignment will not impair the dielectric properties of monolayer water within a graphene slit-pore, but can significantly influence its dynamics.
Genetic dissection of intercellular interactions in vivo by membrane-permeable protein
Authors: Zhang Shaohua , Zhang Qianyu , Liu Zixin , Liu Kuo , He Lingjuan , Lui Kathy O. , Wang Lixin , Zhou Bin 
Published: December 2022

Unraveling cell–cell interaction is fundamental to understanding many biological processes. To date, genetic tools for labeling neighboring cells in mammals are not available. Here, we developed a labeling strategy based on the Cre-induced intercellular labeling protein (CILP). Cre-expressing donor cells release a lipid-soluble and membrane-permeable fluorescent protein that is then taken up by recipient cells, enabling fluorescent labeling of neighboring cells. Using CILP, we specifically labeled endothelial cells surrounding a special population of hepatocytes in adult mice and revealed their distinct gene signatures. Our results highlight the potential of CILP as a platform to reveal cell–cell interactions and communications in vivo.
Natural selection of immune and metabolic genes associated with health in two lowland Bolivian populations
Authors: Lea Amanda J. , Garcia Angela , Arevalo Jesusa , Ayroles Julien F. , Buetow Kenneth , Cole Steve W. , Eid Rodriguez Daniel , Gutierrez Maguin , Highland Heather M. , Hooper Paul L. , Justice Anne , Kraft Thomas , North Kari E. , Stieglitz Jonathan , Kaplan Hillard , Trumble Benjamin C. , Gurven Michael D. 
Published: December 2022

A growing body of work has addressed human adaptations to diverse environments using genomic data, but few studies have connected putatively selected alleles to phenotypes, much less among underrepresented populations such as Amerindians. Studies of natural selection and genotype–phenotype relationships in underrepresented populations hold potential to uncover previously undescribed loci underlying evolutionarily and biomedically relevant traits. Here, we worked with the Tsimane and the Moseten, two Amerindian populations inhabiting the Bolivian lowlands. We focused most intensively on the Tsimane, because long-term anthropological work with this group has shown that they have a high burden of both macro and microparasites, as well as minimal cardiometabolic disease or dementia. We therefore generated genome-wide genotype data for Tsimane individuals to study natural selection, and paired this with blood mRNA-seq as well as cardiometabolic and immune biomarker data generated from a larger sample that included both populations. In the Tsimane, we identified 21 regions that are candidates for selective sweeps, as well as 5 immune traits that show evidence for polygenic selection (e.g., C-reactive protein levels and the response to coronaviruses). Genes overlapping candidate regions were strongly enriched for known involvement in immune-related traits, such as abundance of lymphocytes and eosinophils. Importantly, we were also able to draw on extensive phenotype information for the Tsimane and Moseten and link five regions (containingPSD4,MUC21andMUC22,TOX2,ANXA6, andABCA1) with biomarkers of immune and metabolic function. Together, our work highlights the utility of pairing evolutionary analyses with anthropological and biomedical data to gain insight into the genetic basis of health-related traits.
SARS-CoV-2 accessory proteins ORF7a and ORF3a use distinct mechanisms to down-regulate MHC-I surface expression
Authors: Arshad Najla , Laurent-Rolle Maudry , Ahmed Wesam S. , Hsu Jack Chun-Chieh , Mitchell Susan M. , Pawlak Joanna , Sengupta Debrup , Biswas Kabir H. , Cresswell Peter 
Published: December 2022

Major histocompatibility complex class I (MHC-I) molecules, which are dimers of a glycosylated polymorphic transmembrane heavy chain and the small-protein β
2
-microglobulin (β
2
m), bind peptides in the endoplasmic reticulum that are generated by the cytosolic turnover of cellular proteins. In virus-infected cells, these peptides may include those derived from viral proteins. Peptide-MHC-I complexes then traffic through the secretory pathway and are displayed at the cell surface where those containing viral peptides can be detected by CD8
+
T lymphocytes that kill infected cells. Many viruses enhance their in vivo survival by encoding genes that down-regulate MHC-I expression to avoid CD8
+
T cell recognition. Here, we report that two accessory proteins encoded by SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, down-regulate MHC-I expression using distinct mechanisms. First, ORF3a, a viroporin, reduces the global trafficking of proteins, including MHC-I, through the secretory pathway. The second, ORF7a, interacts specifically with the MHC-I heavy chain, acting as a molecular mimic of β
2
m to inhibit its association. This slows the exit of properly assembled MHC-I molecules from the endoplasmic reticulum. We demonstrate that ORF7a reduces antigen presentation by the human MHC-I allele HLA-A*02:01. Thus, both ORF3a and ORF7a act post-translationally in the secretory pathway to lower surface MHC-I expression, with ORF7a exhibiting a specific mechanism that allows immune evasion by SARS-CoV-2.
Extracellular matrix physical properties govern the diffusion of nanoparticles in tumor microenvironment
Authors: He Xiaocong , Yang Yuanyuan , Han Yulong , Cao Chunyu , Zhang Zhongbin , Li Lingxiao , Xiao Cailan , Guo Hui , Wang Lin , Han Lichun , Qu Zhiguo , Liu Na , Han Shuang , Xu Feng 
Published: December 2022

Nanoparticles (NPs) are confronted with limited and disappointing delivery efficiency in tumors clinically. The tumor extracellular matrix (ECM), whose physical traits have recently been recognized as new hallmarks of cancer, forms a main steric obstacle for NP diffusion, yet the role of tumor ECM physical traits in NP diffusion remains largely unexplored. Here, we characterized the physical properties of clinical gastric tumor samples and observed limited distribution of NPs in decellularized tumor tissues. We also performed molecular dynamics simulations and in vitro hydrogel experiments through single-particle tracking to investigate the diffusion mechanism of NPs and understand the influence of tumor ECM physical properties on NP diffusion both individually and collectively. Furthermore, we developed an estimation matrix model with evaluation scores of NP diffusion efficiency through comprehensive analyses of the data. Thus, beyond finding that loose and soft ECM with aligned structure contribute to efficient diffusion, we now have a systemic model to predict NP diffusion efficiency based on ECM physical traits and provide critical guidance for personalized tumor diagnosis and treatment.
Beta-endoproteolysis of the cellular prion protein by dipeptidyl peptidase-4 and fibroblast activation protein
Authors: Castle Andrew R. , Kang Sang-Gyun , Eskandari-Sedighi Ghazaleh , Wohlgemuth Serene , Nguyen My-Anh , Drucker Daniel J. , Mulvihill Erin E. , Westaway David 
Published: December 2022

The cellular prion protein (PrPC) converts to alternatively folded pathogenic conformations (PrPSc) in prion infections and binds neurotoxic oligomers formed by amyloid-β α-synuclein, and tau. β-Endoproteolysis, which splits PrPCinto N- and C-terminal fragments (N2 and C2, respectively), is of interest because a protease-resistant, C2-sized fragment (C2Sc) accumulates in the brain during prion infections, seemingly comprising the majority of PrPScat disease endpoint in mice. However, candidates for the underlying proteolytic mechanism(s) remain unconfirmed in vivo. Here, a cell-based screen of protease inhibitors unexpectedly linked type II membrane proteins of the S9B serine peptidase subfamily to PrPCβ-cleavage. Overexpression experiments in cells and assays with recombinant proteins confirmed that fibroblast activation protein (FAP) and its paralog, dipeptidyl peptidase-4 (DPP4), cleave directly at multiple sites within PrPC’s N-terminal domain. For wild-type mouse and human PrPCsubstrates expressed in cells, the rank orders of activity were human FAP ~ mouse FAP > mouse DPP4 > human DPP4 and human FAP > mouse FAP > mouse DPP4 >> human DPP4, respectively. C2 levels relative to total PrPCwere reduced in several tissues from FAP-null mice, and, while knockout of DPP4 lacked an analogous effect, the combined DPP4/FAP inhibitor linagliptin, but not the FAP-specific inhibitor SP-13786, reduced C2Scand total PrPSclevels in two murine cell-based models of prion infections. Thus, the net activity of the S9B peptidases FAP and DPP4 and their cognate inhibitors/modulators affect the physiology and pathogenic potential of PrPC.
Obesity triggers tumoral senescence and renders poorly immunogenic malignancies amenable to senolysis
Authors: Fournier Frédérik , Diaz-Marin Roberto , Pilon Frédérique , Neault Mathieu , Juneau Rachel , Girouard Gabrielle , Wilson Ariel M. , Larrivée Bruno , Mallette Frédérick A. , Crespo-Garcia Sergio , Sapieha Przemyslaw 
Published: December 2022

Obesity is a major risk factor for cancer. Conventional thought suggests that elevated adiposity predisposes to heightened inflammatory stress and potentiates tumor growth, yet underlying mechanisms remain ill-defined. Here, we show that tumors from patients with a body mass index >35 carry a high burden of senescent cells. In mouse syngeneic tumor models, we correlated a pronounced accretion of senescent cancer cells with poorly immunogenic tumors when mice were subjected to diet-induced obesity (DIO). Highly immunogenic tumors showed lesser senescence burden suggesting immune-mediated elimination of senescent cancer cells, likely targeted as a consequence of their senescence-associated secretory phenotype. Treatment with the senolytic BH3 mimetic small molecule inhibitor ABT-263 selectively stalled tumor growth in mice with DIO to rates comparable to regular diet-fed mice. Thus, consideration of body adiposity in the selection of cancer therapy may be a critical determinant for disease outcome in poorly immunogenic malignancies.
Non–B-form DNA tends to form in centromeric regions and has undergone changes in polyploid oat subgenomes
Authors: Liu Qian , Yi Congyang , Zhang Zeyan , Su Handong , Liu Chang , Huang Yuhong , Li Wei , Hu Xiaojun , Liu Cheng , Birchler James A. , Liu Yang , Han Fangpu 
Published: December 2022

Centromeres are the specialized regions of the chromosomes that direct faithful chromosome segregation during cell division. Despite their functional conservation, centromeres display features of rapidly evolving DNA and wide evolutionary diversity in size and organization. Previous work found that the noncanonical B-form DNA structures are abundant in the centromeres of several eukaryotic species with a possible implication for centromere specification. Thus far, systematic studies into the organization and function of non–B-form DNA in plants remain scarce. Here, we applied the oat system to investigate the role of non–B-form DNA in centromeres. We conducted chromatin immunoprecipitation sequencing using an antibody to the centromere-specific histone H3 variant (CENH3); this accurately positioned oat centromeres with different ploidy levels and identified a series of centromere-specific sequences including minisatellites and retrotransposons. To define genetic characteristics of oat centromeres, we surveyed the repeat sequences and found that dyad symmetries were abundant in oat centromeres and were predicted to form non–B-DNA structures in vivo. These structures including bent DNA, slipped DNA, Z-DNA, G-quadruplexes, and R-loops were prone to form within CENH3-binding regions. Dynamic conformational changes of predicted non–B-DNA occurred during the evolution from diploid to tetraploid to hexaploid oat. Furthermore, we applied the single-molecule technique of AFM and DNA:RNA immunoprecipitation with deep sequencing to validate R-loop enrichment in oat centromeres. Centromeric retrotransposons exhibited strong associations with R-loop formation. Taken together, our study elucidates the fundamental character of non–B-form DNA in the oat genome and reveals its potential role in centromeres.
ERK and c-Myc signaling in host-derived tumor endothelial cells is essential for solid tumor growth
Authors: Zuo Zehua , Liu Jie , Sun Zhihao , Cheng Yu-Wei , Ewing Michael , Bugge Thomas H. , Finkel Toren , Leppla Stephen H. , Liu Shihui 
Published: December 2022

The limited efficacy of the current antitumor microenvironment strategies is due in part to the poor understanding of the roles and relative contributions of the various tumor stromal cells to tumor development. Here, we describe a versatile in vivo anthrax toxin protein delivery system allowing for the unambiguous genetic evaluation of individual tumor stromal elements in cancer. Our reengineered tumor-selective anthrax toxin exhibits potent antiproliferative activity by disrupting ERK signaling in sensitive cells. Since this activity requires the surface expression of the capillary morphogenesis protein-2 (CMG2) toxin receptor, genetic manipulation of CMG2 expression using our cell-type–specific CMG2 transgenic mice allows us to specifically define the role of individual tumor stromal cell types in tumor development. Here, we established mice with CMG2 only expressed in tumor endothelial cells (ECs) and determined the specific contribution of tumor stromal ECs to the toxin’s antitumor activity. Our results demonstrate that disruption of ERK signaling only within tumor ECs is sufficient to halt tumor growth. We discovered that c-Myc is a downstream effector of ERK signaling and that the MEK–ERK–c-Myc central metabolic axis in tumor ECs is essential for tumor progression. As such, disruption of ERK–c-Myc signaling in host-derived tumor ECs by our tumor-selective anthrax toxins explains their high efficacy in solid tumor therapy.
Granular crystals as strong and fully dense architectured materials
Authors: Karuriya Ashta Navdeep , Barthelat Francois 
Published: December 2022

Dense topologically interlocked panels are made of well-ordered, stiff building blocks interacting mainly by frictional contact. Under mechanical loads, the deformation of the individual blocks is small, but they can slide and rotate collectively, generating high strength, toughness, impact resistance, and damage tolerance. Here, we expand this construction strategy to fully dense, 3D architectured materials made of space filling building blocks or “grains.” We used mechanical vibrations to assemble 3D printed rhombic dodecahedral and truncated octahedral grains into fully dense face-centered cubic and body-centered cubic “granular crystals.” Triaxial compression tests revealed that these granular crystals are up to 25 times stronger than randomly packed spheres and that after testing, the grains can be recycled into new samples with no loss of strength. They also displayed a rich set of mechanisms: nonlinear deformations, crystal plasticity reminiscent of atomistic mechanisms, geometrical hardening, cross-slip, shear-induced dilatancy, and microbuckling. A most intriguing mechanism involved a pressure-dependent “granular crystal plasticity” with interlocked slip planes that completely forbid slip along certain loading directions. We captured these phenomena using a three-length scale theoretical model which agreed well with the experiments. Once fully understood and harnessed, we envision that these mechanisms will lead to 3D architectured materials with unusual and attractive combinations of mechanical performances as well as capabilities for repair, reshaping, on-site alterations, and recycling of the building blocks. In addition, these granular crystals could serve as “model materials” to explore unusual atomic scale deformation mechanisms, for example, non-Schmid plasticity.
Bioprosthetic heart valve structural degeneration associated with metabolic syndrome: Mitigation with polyoxazoline modification
Authors: Abramov Alexey , Xue Yingfei , Zakharchenko Andrey , Kurade Mangesh , Soni Rajesh K. , Levy Robert J. , Ferrari Giovanni 
Published: December 2022

Bioprosthetic heart valves (BHV), made from glutaraldehyde-fixed xenografts, are widely used for surgical and transcatheter valve interventions but suffer from limited durability due to structural valve degeneration (SVD). We focused on metabolic syndrome (MetS), a risk factor for SVD and a highly prevalent phenotype in patients affected by valvular heart disease with a well-recognized cluster of comorbidities. Multicenter patient data (N = 251) revealed that patients with MetS were at significantly higher risk of accelerated SVD and required BHV replacement sooner. Using a next-generation proteomics approach, we identified significantly differential proteomes from leaflets of explanted BHV from MetS and non-MetS patients (N = 24). Given the significance of protein infiltration in MetS-induced SVD, we then demonstrated the protective effects of polyoxazoline modification of BHV leaflets to mitigate MetS-induced BHV biomaterial degeneration (calcification, tissue cross-linking, and microstructural changes) in an ex vivo serum model and an in vivo with MetS rat subcutaneous implants.