bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autophagy-related circRNA evaluation reveals hsa_circ_0001747 as a potential favorable prognostic factor for biochemical recurrence in patients with prostate cancer
Authors: Zhong Chuanfan , Wu Kaihui , Wang Shuo , Long Zining , Yang Taowei , Zhong Weibo , Tan Xiao , Wang Zixian , Li Chuanyin , Lu Jianming , Mao Xiangming 
Published: July 2021

AbstractProstate cancer (PCa) is a common high-incidence malignancy in men, some of whom develop biochemical recurrence (BCR) in the advanced stage. However, there are currently no accurate prognostic indicators of BCR in PCa. The aim of our study was to identify an autophagy-related circular RNA prognostic factor of BCR for patients with PCa. In this study, immunochemistry revealed that the classic autophagy marker MAP1LC3B was positively correlated with Gleason score. Least absolute shrinkage and selector operator regression were conducted to develop a novel prognostic model with tenfold cross-validation and an L1 penalty. Five autophagy-related circRNA signatures were included in the prognostic model. Patients with PCa were ultimately divided into high- and low-risk groups, based on the median risk score. Patients with PCa, who had a high risk score, were more likely to develop BCR in a shorter period of time. Univariate and multivariate Cox regression analyses demonstrated that the risk score was an independent variable for predicting BCR in PCa. In addition, a prognostic nomogram integrated with the risk score and numerous clinicopathological parameters was developed to accurately predict 3- and 5-year BCR of patients with PCa. Finally, the hsa_circ_0001747 signature was selected for further experimental verification in vitro and in vivo, which showed that downregulated hsa_circ_0001747 might facilitate PCa via augmenting autophagy. Our findings indicate that the autophagy-related circRNA signature hsa_circ_0001747 may serve as a promising indicator for BCR prediction in patients with PCa.
Quantifying the contribution of Neanderthal introgression to the heritability of complex traits
Authors: McArthur Evonne , Rinker David C. , Capra John A. 
Published: July 2021

AbstractEurasians have ~2% Neanderthal ancestry, but we lack a comprehensive understanding of the genome-wide influence of Neanderthal introgression on modern human diseases and traits. Here, we quantify the contribution of introgressed alleles to the heritability of more than 400 diverse traits. We show that genomic regions in which detectable Neanderthal ancestry remains are depleted of heritability for all traits considered, except those related to skin and hair. Introgressed variants themselves are also depleted for contributions to the heritability of most traits. However, introgressed variants shared across multiple Neanderthal populations are enriched for heritability and have consistent directions of effect on several traits with potential relevance to human adaptation to non-African environments, including hair and skin traits, autoimmunity, chronotype, bone density, lung capacity, and menopause age. Integrating our results, we propose a model in which selection against introgressed functional variation was the dominant trend (especially for cognitive traits); however, for a few traits, introgressed variants provided beneficial variation via uni-directional (e.g., lightening skin color) or bi-directional (e.g., modulating immune response) effects.
Structural and mechanistic basis for translation inhibition by macrolide and ketolide antibiotics
Authors: Beckert Bertrand , Leroy Elodie C. , Sothiselvam Shanmugapriya , Bock Lars V. , Svetlov Maxim S. , Graf Michael , Arenz Stefan , Abdelshahid Maha , Seip Britta , Grubmüller Helmut , Mankin Alexander S. , Innis C. Axel , Vázquez-Laslop Nora , Wilson Daniel N. 
Published: July 2021

AbstractMacrolides and ketolides comprise a family of clinically important antibiotics that inhibit protein synthesis by binding within the exit tunnel of the bacterial ribosome. While these antibiotics are known to interrupt translation at specific sequence motifs, with ketolides predominantly stalling at Arg/Lys-X-Arg/Lys motifs and macrolides displaying a broader specificity, a structural basis for their context-specific action has been lacking. Here, we present structures of ribosomes arrested during the synthesis of an Arg-Leu-Arg sequence by the macrolide erythromycin (ERY) and the ketolide telithromycin (TEL). Together with deep mutagenesis and molecular dynamics simulations, the structures reveal how ERY and TEL interplay with the Arg-Leu-Arg motif to induce translational arrest and illuminate the basis for the less stringent sequence-specific action of ERY over TEL. Because programmed stalling at the Arg/Lys-X-Arg/Lys motifs is used to activate expression of antibiotic resistance genes, our study also provides important insights for future development of improved macrolide antibiotics.
Structure of the mini-RNA-guided endonuclease CRISPR-Cas12j3
Authors: Carabias Arturo , Fuglsang Anders , Temperini Piero , Pape Tillmann , Sofos Nicholas , Stella Stefano , Erlendsson Simon , Montoya Guillermo 
Published: July 2021

AbstractCRISPR-Cas12j is a recently identified family of miniaturized RNA-guided endonucleases from phages. These ribonucleoproteins provide a compact scaffold gathering all key activities of a genome editing tool. We provide the first structural insight into the Cas12j family by determining the cryoEM structure of Cas12j3/R-loop complex after DNA cleavage. The structure reveals the machinery for PAM recognition, hybrid assembly and DNA cleavage. The crRNA-DNA hybrid is directed to the stop domain that splits the hybrid, guiding the T-strand towards the catalytic site. The conserved RuvC insertion is anchored in the stop domain and interacts along the phosphate backbone of the crRNA in the hybrid. The assembly of a hybrid longer than 12-nt activates catalysis through key functional residues in the RuvC insertion. Our findings suggest why Cas12j unleashes unspecific ssDNA degradation after activation. A site-directed mutagenesis analysis supports the DNA cutting mechanism, providing new avenues to redesign CRISPR-Cas12j nucleases for genome editing.
A machine learning approach to brain epigenetic analysis reveals kinases associated with Alzheimer’s disease
Authors: Huang Yanting , Sun Xiaobo , Jiang Huige , Yu Shaojun , Robins Chloe , Armstrong Matthew J. , Li Ronghua , Mei Zhen , Shi Xiaochuan , Gerasimov Ekaterina Sergeevna , De Jager Philip L. , Bennett David A. , Wingo Aliza P. , Jin Peng , Wingo Thomas S. , Qin Zhaohui S. 
Published: July 2021

AbstractAlzheimer’s disease (AD) is influenced by both genetic and environmental factors; thus, brain epigenomic alterations may provide insights into AD pathogenesis. Multiple array-based Epigenome-Wide Association Studies (EWASs) have identified robust brain methylation changes in AD; however, array-based assays only test about 2% of all CpG sites in the genome. Here, we develop EWASplus, a computational method that uses a supervised machine learning strategy to extend EWAS coverage to the entire genome. Application to six AD-related traits predicts hundreds of new significant brain CpGs associated with AD, some of which are further validated experimentally. EWASplus also performs well on data collected from independent cohorts and different brain regions. Genes found near top EWASplus loci are enriched for kinases and for genes with evidence for physical interactions with known AD genes. In this work, we show that EWASplus implicates additional epigenetic loci for AD that are not found using array-based AD EWASs.
Spin defects in hBN as promising temperature, pressure and magnetic field quantum sensors
Authors: Gottscholl Andreas , Diez Matthias , Soltamov Victor , Kasper Christian , Krauße Dominik , Sperlich Andreas , Kianinia Mehran , Bradac Carlo , Aharonovich Igor , Dyakonov Vladimir 
Published: July 2021

AbstractSpin defects in solid-state materials are strong candidate systems for quantum information technology and sensing applications. Here we explore in details the recently discovered negatively charged boron vacancies (VB−) in hexagonal boron nitride (hBN) and demonstrate their use as atomic scale sensors for temperature, magnetic fields and externally applied pressure. These applications are possible due to the high-spin triplet ground state and bright spin-dependent photoluminescence of the VB−. Specifically, we find that the frequency shift in optically detected magnetic resonance measurements is not only sensitive to static magnetic fields, but also to temperature and pressure changes which we relate to crystal lattice parameters. We show that spin-rich hBN films are potentially applicable as intrinsic sensors in heterostructures made of functionalized 2D materials.
CD8+ tissue-resident memory T cells promote liver fibrosis resolution by inducing apoptosis of hepatic stellate cells
Authors: Koda Yuzo , Teratani Toshiaki , Chu Po-Sung , Hagihara Yuya , Mikami Yohei , Harada Yosuke , Tsujikawa Hanako , Miyamoto Kentaro , Suzuki Takahiro , Taniki Nobuhito , Sujino Tomohisa , Sakamoto Michiie , Kanai Takanori , Nakamoto Nobuhiro 
Published: July 2021

AbstractNon-alcoholic steatohepatitis (NASH) is a leading cause of chronic liver disease that can progress to liver fibrosis. Recent clinical advance suggests a reversibility of liver fibrosis, but the cellular and molecular mechanisms underlying NASH resolution remain unclarified. Here, using a murine diet-induced NASH and the subsequent resolution model, we demonstrate direct roles of CD8+ tissue-resident memory CD8+ T (CD8+ Trm) cells in resolving liver fibrosis. Single-cell transcriptome analysis and FACS analysis revealed CD69+CD103−CD8+ Trm cell enrichment in NASH resolution livers. The reduction of liver CD8+ Trm cells, maintained by tissue IL-15, significantly delayed fibrosis resolution, while adoptive transfer of these cells protected mice from fibrosis progression. During resolution, CD8+ Trm cells attracted hepatic stellate cells (HSCs) in a CCR5-dependent manner, and predisposed activated HSCs to FasL-Fas-mediated apoptosis. Histological assessment of patients with NASH revealed CD69+CD8+ Trm abundance in fibrotic areas, further supporting their roles in humans. These results highlight the undefined role of liver CD8+ Trm in fibrosis resolution.
Harmful R-loops are prevented via different cell cycle-specific mechanisms
Authors: San Martin-Alonso Marta , Soler-Oliva María E. , García-Rubio María , García-Muse Tatiana , Aguilera Andrés 
Published: July 2021

AbstractIdentifying how R-loops are generated is crucial to know how transcription compromises genome integrity. We show by genome-wide analysis of conditional yeast mutants that the THO transcription complex, prevents R-loop formation in G1 and S-phase, whereas the Sen1 DNA-RNA helicase prevents them only in S-phase. Interestingly, damage accumulates asymmetrically downstream of the replication fork in sen1 cells but symmetrically in the hpr1 THO mutant. Our results indicate that: R-loops form co-transcriptionally independently of DNA replication; that THO is a general and cell-cycle independent safeguard against R-loops, and that Sen1, in contrast to previously believed, is an S-phase-specific R-loop resolvase. These conclusions have important implications for the mechanism of R-loop formation and the role of other factors reported to affect on R-loop homeostasis.
Tailored growth of single-crystalline InP tetrapods
Authors: Kim Youngsik , Choi Hyekyoung , Lee Yeunhee , Koh Weon-kyu , Cho Eunhye , Kim Taewan , Kim Hamin , Kim Yong-Hyun , Jeong Hu Young , Jeong Sohee 
Published: July 2021

AbstractDespite the technological importance of colloidal covalent III-V nanocrystals with unique optoelectronic properties, their synthetic process still has challenges originating from the complex energy landscape of the reaction. Here, we present InP tetrapod nanocrystals as a crystalline late intermediate in the synthetic pathway that warrants controlled growth. We isolate tetrapod intermediate species with well-defined surfaces of (110) and ($$\bar{1}\bar{1}\bar{1}$$

1

¯

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¯

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¯

) via the suppression of further growth. An additional precursor supply at low temperature induces $$[\bar{1}\bar{1}\bar{1}]$$

[

1

¯

1

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]

-specific growth, whereas the [110]-directional growth occurs over the activation barrier of 65.7 kJ/mol at a higher temperature, thus finalizes into the (111)-faceted tetrahedron nanocrystals. We address the use of late intermediates with well-defined facets at the sub-10 nm scale for the tailored growth of covalent III-V nanocrystals and highlight the potential for the directed approach of nanocrystal synthesis.
Pancreatic Ppy-expressing γ-cells display mixed phenotypic traits and the adaptive plasticity to engage insulin production
Authors: Perez-Frances Marta , van Gurp Léon , Abate Maria Valentina , Cigliola Valentina , Furuyama Kenichiro , Bru-Tari Eva , Oropeza Daniel , Carreaux Taïna , Fujitani Yoshio , Thorel Fabrizio , Herrera Pedro L. 
Published: July 2021

AbstractThe cellular identity of pancreatic polypeptide (Ppy)-expressing γ-cells, one of the rarest pancreatic islet cell-type, remains elusive. Within islets, glucagon and somatostatin, released respectively from α- and δ-cells, modulate the secretion of insulin by β-cells. Dysregulation of insulin production raises blood glucose levels, leading to diabetes onset. Here, we present the genetic signature of human and mouse γ-cells. Using different approaches, we identified a set of genes and pathways defining their functional identity. We found that the γ-cell population is heterogeneous, with subsets of cells producing another hormone in addition to Ppy. These bihormonal cells share identity markers typical of the other islet cell-types. In mice, Ppy gene inactivation or conditional γ-cell ablation did not alter glycemia nor body weight. Interestingly, upon β-cell injury induction, γ-cells exhibited gene expression changes and some of them engaged insulin production, like α- and δ-cells. In conclusion, we provide a comprehensive characterization of γ-cells and highlight their plasticity and therapeutic potential.
Crown-like structures in breast adipose tissue of breast cancer patients: associations with CD68 expression, obesity, metabolic factors and prognosis
Authors: Chang Martin C. , Eslami Zohreh , Ennis Marguerite , Goodwin Pamela J. 
Published: July 2021

AbstractCrown-like structures of the breast (CLS-B), defined by the clustering of macrophages (identified using CD68 immunohistochemical staining) to surround a dying adipocyte, are a sign of adipose-tissue inflammation. In human cohorts, CLS-B positively correlates with older age, obesity, dyslipidemia and higher levels of glucose, insulin, C-reactive protein and IL-6. In an existing cohort of early-stage breast cancer patients, CLS-B were identified using H&E stained histologic sections (hCLS-B), and by CD68 immunohistochemistry (CD68 + CLS-B). We examined associations of H&E and CD68-detected CLS-B with clinicopathologic features using χ2 tests, with metabolic factors using Wilcoxon rank sum tests and with disease free and overall survival using Cox regression models. hCLS-B were detected in 59 of 163 patients with slides (36.2%) and CD68 + CLS-B in 37 of 119 patients with paraffin blocks (31.1%). hCLS-B were positively correlated with higher weight (p = 0.003), BMI (p = 0.0008) and C-reactive protein (p = 0.045). CD68 + CLS-B were positively correlated with higher weight (p = 0.006), BMI p = 0.001), leptin (p = 0.034), insulin (p = 0.008) and Homeostasis Model Assessment (p = 0.027). CD68 + CLS-B were associated with poor distant disease-free with a hazard ratio (HR) of 2.81, 95% confidence interval (CI) 1.20–6.57, and overall survival with HR 3.97 (1.66–9.48), while hCLS-B were not associated with either: HR for distant recurrence 0.59 (0.26–1.30); HR for death 1.04 (0.50–2.16). The presence of hCLS-B and of CD68 + CLS-B were associated with obesity; CD68 + CLS-B were associated with insulin resistance and adverse prognosis. Similar patterns were not seen for hCLS-B. Research is needed to understand the biologic basis for these differences.
The critical role of hot carrier cooling in optically excited structural transitions
Authors: Liu Wen-Hao , Luo Jun-Wei , Li Shu-Shen , Wang Lin-Wang 
Published: July 2021

AbstractThe hot carrier cooling occurs in most photoexcitation-induced phase transitions (PIPTs), but its role has often been neglected in many theoretical simulations as well as in proposed mechanisms. Here, by including the previously ignored hot carrier cooling in real-time time-dependent density functional theory (rt-TDDFT) simulations, we investigated the role of hot carrier cooling in PIPTs. Taking IrTe2 as an example, we reveal that the cooling of hot electrons from the higher energy levels of spatially extended states to the lower energy levels of the localized Ir–Ir dimer antibonding states strengthens remarkably the atomic driving forces and enhances atomic kinetic energy. These two factors combine to dissolute the Ir–Ir dimers on a timescale near the limit of atomic motions, thus initiating a deterministic kinetic phase transition. We further demonstrate that the subsequent cooling induces nonradiative recombination of photoexcited electrons and holes, leading to the ultrafast recovery of the Ir–Ir dimers observed experimentally. These findings provide a complete picture of the atomic dynamics in optically excited structural phase transitions.
Lateralized effects of deep brain stimulation in Parkinson’s disease: evidence and controversies
Authors: Lin Zhengyu , Zhang Chencheng , Li Dianyou , Sun Bomin 
Published: July 2021

AbstractThe bilateral effects of deep brain stimulation (DBS) on motor and non-motor symptoms of Parkinson’s disease (PD) have been extensively studied and reviewed. However, the unilateral effects—in particular, the potential lateralized effects of left- versus right-sided DBS—have not been adequately recognized or studied. Here we summarized the current evidence and controversies in the literature regarding the lateralized effects of DBS on motor and non-motor outcomes in PD patients. Publications in English language before February 2021 were obtained from the PubMed database and included if they directly compared the effects of unilateral versus contralateral side DBS on motor or non-motor outcomes in PD. The current literature is overall of low-quality and is biased by various confounders. Researchers have investigated mainly PD patients receiving subthalamic nucleus (STN) DBS while the potential lateralized effects of globus pallidus interna (GPi) DBS have not been adequately studied. Evidence suggests potential lateralized effects of STN DBS on axial motor symptoms and deleterious effects of left-sided DBS on language-related functions, in particular, the verbal fluency, in PD. The lateralized DBS effects on appendicular motor symptoms as well as other neurocognitive and neuropsychiatric domains remain inconclusive. Future studies should control for varying methodological approaches as well as clinical and DBS management heterogeneities, including symptom laterality, stimulation parameters, location of active contacts, and lead trajectories. This would contribute to improved treatment strategies such as personalized target selection, surgical planning, and postoperative management that ultimately benefit patients.
Demonstrating the power of quantum computers, certification of highly entangled measurements and scalable quantum nonlocality
Authors: Bäumer Elisa , Gisin Nicolas , Tavakoli Armin 
Published: July 2021

AbstractIncreasingly sophisticated quantum computers motivate the exploration of their abilities in certifying genuine quantum phenomena. Here, we demonstrate the power of state-of-the-art IBM quantum computers in correlation experiments inspired by quantum networks. Our experiments feature up to 12 qubits and require the implementation of paradigmatic Bell-State Measurements for scalable entanglement-swapping. First, we demonstrate quantum correlations that defy classical models in up to nine-qubit systems while only assuming that the quantum computer operates on qubits. Harvesting these quantum advantages, we are able to certify 82 basis elements as entangled in a 512-outcome measurement. Then, we relax the qubit assumption and consider quantum nonlocality in a scenario with multiple independent entangled states arranged in a star configuration. We report quantum violations of source-independent Bell inequalities for up to ten qubits. Our results demonstrate the ability of quantum computers to outperform classical limitations and certify scalable entangled measurements.
Variational quantum algorithm with information sharing
Authors: Self Chris N. , Khosla Kiran E. , Smith Alistair W. R. , Sauvage Frédéric , Haynes Peter D. , Knolle Johannes , Mintert Florian , Kim M. S. 
Published: July 2021

AbstractWe introduce an optimisation method for variational quantum algorithms and experimentally demonstrate a 100-fold improvement in efficiency compared to naive implementations. The effectiveness of our approach is shown by obtaining multi-dimensional energy surfaces for small molecules and a spin model. Our method solves related variational problems in parallel by exploiting the global nature of Bayesian optimisation and sharing information between different optimisers. Parallelisation makes our method ideally suited to the next generation of variational problems with many physical degrees of freedom. This addresses a key challenge in scaling-up quantum algorithms towards demonstrating quantum advantage for problems of real-world interest.
Hemodynamic performance of tissue-engineered vascular grafts in Fontan patients
Authors: Schwarz Erica L. , Kelly John M. , Blum Kevin M. , Hor Kan N. , Yates Andrew R. , Zbinden Jacob C. , Verma Aekaansh , Lindsey Stephanie E. , Ramachandra Abhay B. , Szafron Jason M. , Humphrey Jay D. , Shin’oka Toshiharu , Marsden Alison L. , Breuer Christopher K. 
Published: July 2021

AbstractIn the field of congenital heart surgery, tissue-engineered vascular grafts (TEVGs) are a promising alternative to traditionally used synthetic grafts. Our group has pioneered the use of TEVGs as a conduit between the inferior vena cava and the pulmonary arteries in the Fontan operation. The natural history of graft remodeling and its effect on hemodynamic performance has not been well characterized. In this study, we provide a detailed analysis of the first U.S. clinical trial evaluating TEVGs in the treatment of congenital heart disease. We show two distinct phases of graft remodeling: an early phase distinguished by rapid changes in graft geometry and a second phase of sustained growth and decreased graft stiffness. Using clinically informed and patient-specific computational fluid dynamics (CFD) simulations, we demonstrate how changes to TEVG geometry, thickness, and stiffness affect patient hemodynamics. We show that metrics of patient hemodynamics remain within normal ranges despite clinically observed levels of graft narrowing. These insights strengthen the continued clinical evaluation of this technology while supporting recent indications that reversible graft narrowing can be well tolerated, thus suggesting caution before intervening clinically.