bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2+ breast cancer in the adaptively randomized I-SPY2 trial
Authors: Clark Amy S. , Yau Christina , Wolf Denise M. , Petricoin Emanuel F. , van ‘t Veer Laura J. , Yee Douglas , Moulder Stacy L. , Wallace Anne M. , Chien A. Jo , Isaacs Claudine , Boughey Judy C. , Albain Kathy S. , Kemmer Kathleen , Haley Barbara B. , Han Hyo S. , Forero-Torres Andres , Elias Anthony , Lang Julie E. , Ellis Erin D. , Yung Rachel , Tripathy Debu , Nanda Rita , Wulfkuhle Julia D. , Brown-Swigart Lamorna , Gallagher Rosa I. , Helsten Teresa , Roesch Erin , Ewing Cheryl A. , Alvarado Michael , Crane Erin P. , Buxton Meredith , Clennell Julia L. , Paoloni Melissa , Asare Smita M. , Wilson Amy , Hirst Gillian L. , Singhrao Ruby , Steeg Katherine , Asare Adam , Matthews Jeffrey B. , Berry Scott , Sanil Ashish , Melisko Michelle , Perlmutter Jane , Rugo Hope S. , Schwab Richard B. , Symmans W. Fraser , Hylton Nola M. , Berry Donald A. , Esserman Laura J. , DeMichele Angela M. 
Published: November 2021

AbstractHER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.5 cm clinical stage II/III HER2+breast cancer, adaptively randomized to T-DM1/P, THP, or a common control arm of paclitaxel/trastuzumab (TH), followed by doxorubicin/cyclophosphamide, then surgery. Both T-DM1/P and THP arms ‘graduate’ in all subtypes: predicted pCR rates are 63%, 72% and 33% for T-DM1/P (n = 52), THP (n = 45) and TH (n = 31) respectively. Toxicity burden is similar between arms. Degree of HER2 pathway signaling and phosphorylation in pretreatment biopsy specimens are associated with response to both T-DM1/P and THP and can further identify highly responsive HER2+tumors to HER2-directed therapy. This may help identify patients who can safely de-escalate cytotoxic chemotherapy without compromising excellent outcome.
Stability and molecular pathways to the formation of spin defects in silicon carbide
Authors: Lee Elizabeth M. Y. , Yu Alvin , de Pablo Juan J. , Galli Giulia 
Published: November 2021

AbstractSpin defects in wide-bandgap semiconductors provide a promising platform to create qubits for quantum technologies. Their synthesis, however, presents considerable challenges, and the mechanisms responsible for their generation or annihilation are poorly understood. Here, we elucidate spin defect formation processes in a binary crystal for a key qubit candidate—the divacancy complex (VV) in silicon carbide (SiC). Using atomistic models, enhanced sampling simulations, and density functional theory calculations, we find that VV formation is a thermally activated process that competes with the conversion of silicon (VSi) to carbon monovacancies (VC), and that VV reorientation can occur without dissociation. We also find that increasing the concentration of VSi relative to VC favors the formation of divacancies. Moreover, we identify pathways to create spin defects consisting of antisite-double vacancy complexes and determine their electronic properties. The detailed view of the mechanisms that underpin the formation and dynamics of spin defects presented here may facilitate the realization of qubits in an industrially relevant material.
NRG1/ErbB signalling controls the dialogue between macrophages and neural crest-derived cells during zebrafish fin regeneration
Authors: Laplace-Builhé Béryl , Barthelaix Audrey , Assou Said , Bohaud Candice , Pratlong Marine , Severac Dany , Tejedor Gautier , Luz-Crawford Patricia , Nguyen-Chi Mai , Mathieu Marc , Jorgensen Christian , Djouad Farida 
Published: November 2021

AbstractFish species, such as zebrafish (Danio rerio), can regenerate their appendages after amputation through the formation of a heterogeneous cellular structure named blastema. Here, by combining live imaging of triple transgenic zebrafish embryos and single-cell RNA sequencing we established a detailed cell atlas of the regenerating caudal fin in zebrafish larvae. We confirmed the presence of macrophage subsets that govern zebrafish fin regeneration, and identified afoxd3-positive cell population within the regenerating fin. Genetic depletion of thesefoxd3-positive neural crest-derived cells (NCdC) showed that they are involved in blastema formation and caudal fin regeneration. Finally, chemical inhibition and transcriptomic analysis demonstrated that thesefoxd3-positive cells regulate macrophage recruitment and polarization through the NRG1/ErbB pathway. Here, we show the diversity of the cells required for blastema formation, identify a discretefoxd3-positive NCdC population, and reveal the critical function of the NRG1/ErbB pathway in controlling the dialogue between macrophages and NCdC.
Estimating disease prevalence in large datasets using genetic risk scores
Authors: Evans Benjamin D. , Słowiński Piotr , Hattersley Andrew T. , Jones Samuel E. , Sharp Seth , Kimmitt Robert A. , Weedon Michael N. , Oram Richard A. , Tsaneva-Atanasova Krasimira , Thomas Nicholas J. 
Published: November 2021

AbstractClinical classification is essential for estimating disease prevalence but is difficult, often requiring complex investigations. The widespread availability of population level genetic data makes novel genetic stratification techniques a highly attractive alternative. We propose a generalizable mathematical framework for determining disease prevalence within a cohort using genetic risk scores. We compare and evaluate methods based on the means of genetic risk scores’ distributions; the Earth Mover’s Distance between distributions; a linear combination of kernel density estimates of distributions; and an Excess method. We demonstrate the performance of genetic stratification to produce robust prevalence estimates. Specifically, we show that robust estimates of prevalence are still possible even with rarer diseases, smaller cohort sizes and less discriminative genetic risk scores, highlighting the general utility of these approaches. Genetic stratification techniques offer exciting new research tools, enabling unbiased insights into disease prevalence and clinical characteristics unhampered by clinical classification criteria.
A Fe3N/carbon composite electrocatalyst for effective polysulfides regulation in room-temperature Na-S batteries
Authors: Qi Yuruo , Li Qing-Jie , Wu Yuanke , Bao Shu-juan , Li Changming , Chen Yuming , Wang Guoxiu , Xu Maowen 
Published: November 2021

AbstractThe practical application of room-temperature Na-S batteries is hindered by the low sulfur utilization, inadequate rate capability and poor cycling performance. To circumvent these issues, here, we propose an electrocatalyst composite material comprising of N-doped nanocarbon and Fe3N. The multilayered porous network of the carbon accommodates large amounts of sulfur, decreases the detrimental effect of volume expansion, and stabilizes the electrodes structure during cycling. Experimental and theoretical results testify the Fe3N affinity to sodium polysulfides via Na-N and Fe-S bonds, leading to strong adsorption and fast dissociation of sodium polysulfides. With a sulfur content of 85 wt.%, the positive electrode tested at room-temperature in non-aqueous Na metal coin cell configuration delivers a reversible capacity of about 1165 mA h g−1 at 167.5 mA g−1, satisfactory rate capability and stable capacity of about 696 mA h g−1 for 2800 cycles at 8375 mA g−1.
Association between serum retinol and overall and cause-specific mortality in a 30-year prospective cohort study
Authors: Huang Jiaqi , Weinstein Stephanie J. , Yu Kai , Männistö Satu , Albanes Demetrius 
Published: November 2021

AbstractHow retinol as a clinical indicator of vitamin A status is related to long-term mortality is unknown. Here we report the results of a prospective analysis examining associations between serum retinol and risk of overall and cause-specific mortality. During a 30-year cohort follow-up, 23,797 deaths were identified among 29,104 men. Participants with higher serum retinol experienced significantly lower overall, CVD, heart disease, and respiratory disease mortality compared to men with the lowest retinol concentrations, reflecting 17–32% lower mortality risk (Ptrend < 0.0001). The retinol-overall mortality association is similar across subgroups of smoking intensity, alcohol consumption, body mass index, trial supplementation, serum alpha-tocopherol and beta-carotene concentrations, and follow-up time. Mediation analysis indicated that <3% of the effects of smoking duration and diabetes mellitus on mortality were mediated through retinol concentration. These findings indicate higher serum retinol is associated with lower overall mortality, including death from cardiovascular, heart, and respiratory diseases.
A sandcastle worm-inspired strategy to functionalize wet hydrogels
Authors: Zhang Donghui , Liu Jingjing , Chen Qi , Jiang Weinan , Wang Yibing , Xie Jiayang , Ma Kaiqian , Shi Chao , Zhang Haodong , Chen Minzhang , Wan Jianglin , Ma Pengcheng , Zou Jingcheng , Zhang Wenjing , Zhou Feng , Liu Runhui 
Published: November 2021

AbstractHydrogels have been extensively used in many fields. Current synthesis of functional hydrogels requires incorporation of functional molecules either before or during gelation via the pre-organized reactive site along the polymer chains within hydrogels, which is tedious for polymer synthesis and not flexible for different types of hydrogels. Inspired by sandcastle worm, we develop a simple one-step strategy to functionalize wet hydrogels using molecules bearing an adhesive dibutylamine-DOPA-lysine-DOPA tripeptide. This tripeptide can be easily modified with various functional groups to initiate diverse types of polymerizations and provide functional polymers with a terminal adhesive tripeptide. Such functional molecules enable direct modification of wet hydrogels to acquire biological functions such as antimicrobial, cell adhesion and wound repair. The strategy has a tunable functionalization degree and a stable attachment of functional molecules, which provides a tool for direct and convenient modification of wet hydrogels to provide them with diverse functions and applications.
Massively parallel interrogation of protein fragment secretability using SECRiFY reveals features influencing secretory system transit
Authors: Boone Morgane , Ramasamy Pathmanaban , Zuallaert Jasper , Bouwmeester Robbin , Van Moer Berre , Maddelein Davy , Turan Demet , Hulstaert Niels , Eeckhaut Hannah , Vandermarliere Elien , Martens Lennart , Degroeve Sven , De Neve Wesley , Vranken Wim , Callewaert Nico 
Published: November 2021

AbstractWhile transcriptome- and proteome-wide technologies to assess processes in protein biogenesis are now widely available, we still lack global approaches to assay post-ribosomal biogenesis events, in particular those occurring in the eukaryotic secretory system. We here develop a method, SECRiFY, to simultaneously assess the secretability of >105 protein fragments by two yeast species, S. cerevisiae and P. pastoris, using custom fragment libraries, surface display and a sequencing-based readout. Screening human proteome fragments with a median size of 50–100 amino acids, we generate datasets that enable datamining into protein features underlying secretability, revealing a striking role for intrinsic disorder and chain flexibility. The SECRiFY methodology generates sufficient amounts of annotated data for advanced machine learning methods to deduce secretability patterns. The finding that secretability is indeed a learnable feature of protein sequences provides a solid base for application-focused studies.
A sensory memory to preserve visual representations across eye movements
Authors: Akbarian Amir , Clark Kelsey , Noudoost Behrad , Nategh Neda 
Published: November 2021

AbstractSaccadic eye movements (saccades) disrupt the continuous flow of visual information, yet our perception of the visual world remains uninterrupted. Here we assess the representation of the visual scene across saccades from single-trial spike trains of extrastriate visual areas, using a combined electrophysiology and statistical modeling approach. Using a model-based decoder we generate a high temporal resolution readout of visual information, and identify the specific changes in neurons’ spatiotemporal sensitivity that underly an integrated perisaccadic representation of visual space. Our results show that by maintaining a memory of the visual scene, extrastriate neurons produce an uninterrupted representation of the visual world. Extrastriate neurons exhibit a late response enhancement close to the time of saccade onset, which preserves the latest pre-saccadic information until the post-saccadic flow of retinal information resumes. These results show how our brain exploits available information to maintain a representation of the scene while visual inputs are disrupted.
Structure and activation mechanism of the hexameric plasma membrane H+-ATPase
Authors: Zhao Peng , Zhao Chaoran , Chen Dandan , Yun Caihong , Li Huilin , Bai Lin 
Published: November 2021

AbstractThe S. cerevisiae plasma membrane H+-ATPase, Pma1, is a P3A-type ATPase and the primary protein component of the membrane compartment of Pma1 (MCP). Like other plasma membrane H+-ATPases, Pma1 assembles and functions as a hexamer, a property unique to this subfamily among the larger family of P-type ATPases. It has been unclear how Pma1 organizes the yeast membrane into MCP microdomains, or why it is that Pma1 needs to assemble into a hexamer to establish the membrane electrochemical proton gradient. Here we report a high-resolution cryo-EM study of native Pma1 hexamers embedded in endogenous lipids. Remarkably, we found that the Pma1 hexamer encircles a liquid-crystalline membrane domain composed of 57 ordered lipid molecules. The Pma1-encircled lipid patch structure likely serves as the building block of the MCP. At pH 7.4, the carboxyl-terminal regulatory α-helix binds to the phosphorylation domains of two neighboring Pma1 subunits, locking the hexamer in the autoinhibited state. The regulatory helix becomes disordered at lower pH, leading to activation of the Pma1 hexamer. The activation process is accompanied by a 6.7 Å downward shift and a 40° rotation of transmembrane helices 1 and 2 that line the proton translocation path. The conformational changes have enabled us to propose a detailed mechanism for ATP-hydrolysis-driven proton pumping across the plasma membrane. Our structures will facilitate the development of antifungal drugs that target this essential protein.
MMAB promotes negative feedback control of cholesterol homeostasis
Authors: Goedeke Leigh , Canfrán-Duque Alberto , Rotllan Noemi , Chaube Balkrishna , Thompson Bonne M. , Lee Richard G. , Cline Gary W. , McDonald Jeffrey G. , Shulman Gerald I. , Lasunción Miguel A. , Suárez Yajaira , Fernández-Hernando Carlos 
Published: November 2021

AbstractIntricate regulatory networks govern the net balance of cholesterol biosynthesis, uptake and efflux; however, the mechanisms surrounding cholesterol homeostasis remain incompletely understood. Here, we develop an integrative genomic strategy to detect regulators of LDLR activity and identify 250 genes whose knockdown affects LDL-cholesterol uptake and whose expression is modulated by intracellular cholesterol levels in human hepatic cells. From these hits, we focus on MMAB, an enzyme which catalyzes the conversion of vitamin B12 to adenosylcobalamin, and whose expression has previously been linked with altered levels of circulating cholesterol in humans. We demonstrate that hepatic levels of MMAB are modulated by dietary and cellular cholesterol levels through SREBP2, the master transcriptional regulator of cholesterol homeostasis. Knockdown of MMAB decreases intracellular cholesterol levels and augments SREBP2-mediated gene expression and LDL-cholesterol uptake in human and mouse hepatic cell lines. Reductions in total sterol content were attributed to increased intracellular levels of propionic and methylmalonic acid and subsequent inhibition of HMGCR activity and cholesterol biosynthesis. Moreover, mice treated with antisense inhibitors of MMAB display a significant reduction in hepatic HMGCR activity, hepatic sterol content and increased expression of SREBP2-mediated genes. Collectively, these findings reveal an unexpected role for the adenosylcobalamin pathway in regulating LDLR expression and identify MMAB as an additional control point by which cholesterol biosynthesis is regulated by its end product.
Mass of Abrikosov vortex in high-temperature superconductor YBa$$_2$$Cu$$_3$$O$$_{7-\delta }$$
Authors: Tesař Roman , Šindler Michal , Kadlec Christelle , Lipavský Pavel , Skrbek Ladislav , Koláček Jan 
Published: November 2021

AbstractFor more than four decades, mass of Abrikosov vortices defied experimental observations. We demonstrate a method of its detection in high-temperature superconductors. Similarly to electrons, fluxons circulate in the direction given by the magnetic field, causing circular dichroism. We report the magneto-transmittance of a nearly optimally doped thin YBa$$_2$$

2

Cu$$_3$$

3

O$$_{7-\delta }$$

7
-
δ

film, measured using circularly polarized submillimeter waves. The circular dichroism emerges in the superconducting state and increases with dropping temperature. Our results confirm the dominant role of quasiparticle states in the vortex core and yield the diagonal fluxon mass of $$2.2 \times 10^8$$

2.2
×

10
8

electron masses per centimeter at 45 K and zero-frequency limit, and even larger off-diagonal mass of $$4.9 \times 10^8 m_e$$

4.9
×

10
8

m
e

/cm.
Tissue, age, sex, and disease patterns of matrisome expression in GTEx transcriptome data
Authors: Nieuwenhuis Tim O. , Rosenberg Avi Z. , McCall Matthew N. , Halushka Marc K. 
Published: November 2021

AbstractThe extracellular matrix (ECM) has historically been explored through proteomic methods. Whether or not global transcriptomics can yield meaningful information on the human matrisome is unknown. Gene expression data from 17,382 samples across 52 tissues, were obtained from the Genotype-Tissue Expression (GTEx) project. Additional datasets were obtained from The Cancer Genome Atlas (TCGA) program and the Gene Expression Omnibus for comparisons. Gene expression levels generally matched proteome-derived matrisome expression patterns. Further, matrisome gene expression properly clustered tissue types, with some matrisome genes including SERPIN family members having tissue-restricted expression patterns. Deeper analyses revealed 382 gene transcripts varied by age and 315 varied by sex in at least one tissue, with expression correlating with digitally imaged histologic tissue features. A comparison of TCGA tumor, TCGA adjacent normal and GTEx normal tissues demonstrated robustness of the GTEx samples as a generalized matrix control, while also determining a common primary tumor matrisome. Additionally, GTEx tissues served as a useful non-diseased control in a separate study of idiopathic pulmonary fibrosis (IPF) matrix changes, while identifying 22 matrix genes upregulated in IPF. Altogether, these findings indicate that the transcriptome, in general, and GTEx in particular, has value in understanding the state of organ ECM.
A machine learning framework for rapid forecasting and history matching in unconventional reservoirs
Authors: Srinivasan Shriram , O’Malley Daniel , Mudunuru Maruti K. , Sweeney Matthew R. , Hyman Jeffrey D. , Karra Satish , Frash Luke , Carey J. William , Gross Michael R. , Guthrie George D. , Carr Timothy , Li Liwei , Viswanathan Hari S. 
Published: November 2021

AbstractWe present a novel workflow for forecasting production in unconventional reservoirs using reduced-order models and machine-learning. Our physics-informed machine-learning workflow addresses the challenges to real-time reservoir management in unconventionals, namely the lack of data (i.e., the time-frame for which the wells have been producing), and the significant computational expense of high-fidelity modeling. We do this by applying the machine-learning paradigm of transfer learning, where we combine fast, but less accurate reduced-order models with slow, but accurate high-fidelity models. We use the Patzek model (Proc Natl Acad Sci 11:19731–19736, https://doi.org/10.1073/pnas.1313380110, 2013) as the reduced-order model to generate synthetic production data and supplement this data with synthetic production data obtained from high-fidelity discrete fracture network simulations of the site of interest. Our results demonstrate that training with low-fidelity models is not sufficient for accurate forecasting, but transfer learning is able to augment the knowledge and perform well once trained with the small set of results from the high-fidelity model. Such a physics-informed machine-learning (PIML) workflow, grounded in physics, is a viable candidate for real-time history matching and production forecasting in a fractured shale gas reservoir.
Fibromine is a multi-omics database and mining tool for target discovery in pulmonary fibrosis
Authors: Fanidis Dionysios , Moulos Panagiotis , Aidinis Vassilis 
Published: November 2021

AbstractIdiopathic pulmonary fibrosis is a lethal lung fibroproliferative disease with limited therapeutic options. Differential expression profiling of affected sites has been instrumental for involved pathogenetic mechanisms dissection and therapeutic targets discovery. However, there have been limited efforts to comparatively analyse/mine the numerous related publicly available datasets, to fully exploit their potential on the validation/creation of novel research hypotheses. In this context and towards that goal, we present Fibromine, an integrated database and exploration environment comprising of consistently re-analysed, manually curated transcriptomic and proteomic pulmonary fibrosis datasets covering a wide range of experimental designs in both patients and animal models. Fibromine can be accessed via an R Shiny application (http://www.fibromine.com/Fibromine) which offers dynamic data exploration and real-time integration functionalities. Moreover, we introduce a novel benchmarking system based on transcriptomic datasets underlying characteristics, resulting to dataset accreditation aiming to aid the user on dataset selection. Cell specificity of gene expression can be visualised and/or explored in several scRNA-seq datasets, in an effort to link legacy data with this cutting-edge methodology and paving the way to their integration. Several use case examples are presented, that, importantly, can be reproduced on-the-fly by a non-specialist user, the primary target and potential user of this endeavour.