bluuebunny/crossref_metadata_2025_split huggingface dataset:
A comparative study of PCS and PAM50 prostate cancer classification schemes
Authors: Yoon Junhee , Kim Minhyung , Posadas Edwin M. , Freedland Stephen J. , Liu Yang , Davicioni Elai , Den Robert B. , Trock Bruce J. , Karnes R. Jeffrey , Klein Eric A. , Freeman Michael R. , You Sungyong 
Published: February 2021

Abstract
Background
Two prostate cancer (PC) classification methods based on transcriptome profiles, a de novo method referred to as the “Prostate Cancer Classification System” (PCS) and a variation of the established PAM50 breast cancer algorithm, were recently proposed. Both studies concluded that most human PC can be assigned to one of three tumor subtypes, two categorized as luminal and one as basal, suggesting the two methods reflect consistency in underlying biology. Despite the similarity, differences and commonalities between the two classification methods have not yet been reported.

Methods
Here, we describe a comparison of the PCS and PAM50 classification systems. PCS and PAM50 signatures consisting of 37 (PCS37) and 50 genes, respectively, were used to categorize 9,947 PC patients into PCS and PAM50 classes. Enrichment of hallmark gene sets and luminal and basal marker gene expression were assessed in the same datasets. Finally, survival analysis was performed to compare PCS and PAM50 subtypes in terms of clinical outcomes.

Results
PCS and PAM50 subtypes show clear differential expression of PCS37 and PAM50 genes. While only three genes are shared in common between the two systems, there is some consensus between three subtype pairs (PCS1 versus Luminal B, PCS2 versus Luminal A, and PCS3 versus Basal) with respect to gene expression, cellular processes, and clinical outcomes. PCS categories displayed better separation of cellular processes and luminal and basal marker gene expression compared to PAM50. Although both PCS1 and Luminal B tumors exhibited the worst clinical outcomes, outcomes between aggressive and less aggressive subtypes were better defined in the PCS system, based on larger hazard ratios observed.

Conclusion
The PCS and PAM50 classification systems are similar in terms of molecular profiles and clinical outcomes. However, the PCS system exhibits greater separation in multiple clinical outcomes and provides better separation of prostate luminal and basal characteristics.
Immunological surrogate endpoints of COVID-2019 vaccines: the evidence we have versus the evidence we need
Authors: Jin Pengfei , Li Jingxin , Pan Hongxing , Wu Yanfei , Zhu Fengcai 
Published: February 2021

AbstractIn response to the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) pandemic, over 200 vaccine candidates against coronavirus disease 2019 (COVID-2019) are under development and currently moving forward at an unparalleled speed. The availability of surrogate endpoints would help to avoid large-scale filed efficacy trials and facilitate the approval of vaccine candidates, which is crucial to control COVID-19 pandemic. Several phase 3 efficacy trials of COVID-19 vaccine candidates are under way, which provide opportunities for the determination of COVID-19 correlates of protection. In this paper, we review current knowledge for existence of COVID-19 correlates of protection, methods for assessment of immune correlates of protection and issues related to COVID-19 correlates of protection.
Chronic d-ribose and d-mannose overload induce depressive/anxiety-like behavior and spatial memory impairment in mice
Authors: Xu Ke , Wang Mingyang , Zhou Wei , Pu Juncai , Wang Haiyang , Xie Peng 
Published: February 2021

AbstractThe effects of different forms of monosaccharides on the brain remain unclear, though neuropsychiatric disorders undergo changes in glucose metabolism. This study assessed cell viability responses to five commonly consumed monosaccharides—D-ribose (RIB), D-glucose, D-mannose (MAN), D-xylose and L-arabinose—in cultured neuro-2a cells. Markedly decreased cell viability was observed in cells treated with RIB and MAN. We then showed that high-dose administration of RIB induced depressive- and anxiety-like behavior as well as spatial memory impairment in mice, while high-dose administration of MAN induced anxiety-like behavior and spatial memory impairment only. Moreover, significant pathological changes were observed in the hippocampus of high-dose RIB-treated mice by hematoxylin-eosin staining. Association analysis of the metabolome and transcriptome suggested that the anxiety-like behavior and spatial memory impairment induced by RIB and MAN may be attributed to the changes in four metabolites and 81 genes in the hippocampus, which is involved in amino acid metabolism and serotonin transport. In addition, combined with previous genome-wide association studies on depression, a correlation was found between the levels of Tnni3k and Tbx1 in the hippocampus and RIB induced depressive-like behavior. Finally, metabolite–gene network, qRT-PCR and western blot analysis showed that the insulin-POMC-MEK-TCF7L2 and MAPK-CREB-GRIN2A-CaMKII signaling pathways were respectively associated with RIB and MAN induced depressive/anxiety-like behavior and spatial memory impairment. Our findings clarified our understanding of the biological mechanisms underlying RIB and MAN induced depressive/anxiety-like behavior and spatial memory impairment in mice and highlighted the deleterious effects of high-dose RIB and MAN as long-term energy sources.
Control of replication stress and mitosis in colorectal cancer stem cells through the interplay of PARP1, MRE11 and RAD51
Authors: Manic Gwenola , Musella Martina , Corradi Francesca , Sistigu Antonella , Vitale Sara , Soliman Abdel Rehim Sara , Mattiello Luca , Malacaria Eva , Galassi Claudia , Signore Michele , Pallocca Matteo , Scalera Stefano , Goeman Frauke , De Nicola Francesca , Guarracino Andrea , Pennisi Rosa , Antonangeli Fabrizio , Sperati Francesca , Baiocchi Marta , Biffoni Mauro , Fanciulli Maurizio , Maugeri-Saccà Marcello , Franchitto Annapaola , Pichierri Pietro , De Maria Ruggero , Vitale Ilio 
Published: February 2021

AbstractCancer stem cells (CSCs) are tumor subpopulations driving disease development, progression, relapse and therapy resistance, and their targeting ensures tumor eradication. CSCs display heterogeneous replication stress (RS), but the functionality/relevance of the RS response (RSR) centered on the ATR-CHK1 axis is debated. Here, we show that the RSR is efficient in primary CSCs from colorectal cancer (CRC-SCs), and describe unique roles for PARP1 and MRE11/RAD51. First, we demonstrated that PARP1 is upregulated in CRC-SCs resistant to several replication poisons and RSR inhibitors (RSRi). In these cells, PARP1 modulates replication fork speed resulting in low constitutive RS. Second, we showed that MRE11 and RAD51 cooperate in the genoprotection and mitosis execution of PARP1-upregulated CRC-SCs. These roles represent therapeutic vulnerabilities for CSCs. Indeed, PARP1i sensitized CRC-SCs to ATRi/CHK1i, inducing replication catastrophe, and prevented the development of resistance to CHK1i. Also, MRE11i + RAD51i selectively killed PARP1-upregulated CRC-SCs via mitotic catastrophe. These results provide the rationale for biomarker-driven clinical trials in CRC using distinct RSRi combinations.
Human MiniPromoters for ocular-rAAV expression in ON bipolar, cone, corneal, endothelial, Müller glial, and PAX6 cells
Authors: Korecki Andrea J. , Cueva-Vargas Jorge L. , Fornes Oriol , Agostinone Jessica , Farkas Rachelle A. , Hickmott Jack W. , Lam Siu Ling , Mathelier Anthony , Zhou Michelle , Wasserman Wyeth W. , Di Polo Adriana , Simpson Elizabeth M. 
Published: February 2021

AbstractSmall and cell-type restricted promoters are important tools for basic and preclinical research, and clinical delivery of gene therapies. In clinical gene therapy, ophthalmic trials have been leading the field, with over 50% of ocular clinical trials using promoters that restrict expression based on cell type. Here, 19 human DNA MiniPromoters were bioinformatically designed for rAAV, tested by neonatal intravenous delivery in mouse, and successful MiniPromoters went on to be tested by intravitreal, subretinal, intrastromal, and/or intravenous delivery in adult mouse. We present promoter development as an overview for each cell type, but only show results in detail for the recommended MiniPromoters: Ple265 and Ple341 (PCP2) ON bipolar, Ple349 (PDE6H) cone, Ple253 (PITX3) corneal stroma, Ple32 (CLDN5) endothelial cells of the blood–retina barrier, Ple316 (NR2E1) Müller glia, and Ple331 (PAX6) PAX6 positive. Overall, we present a resource of new, redesigned, and improved MiniPromoters for ocular gene therapy that range in size from 784 to 2484 bp, and from weaker, equal, or stronger in strength relative to the ubiquitous control promoter smCBA. All MiniPromoters will be useful for therapies involving small regulatory RNA and DNA, and proteins ranging from 517 to 1084 amino acids, representing 62.9–90.2% of human proteins.
A combinatory ferroelectric compound bridging simple ABO3 and A-site-ordered quadruple perovskite
Authors: Zhao Jianfa , Gao Jiacheng , Li Wenmin , Qian Yuting , Shen Xudong , Wang Xiao , Shen Xi , Hu Zhiwei , Dong Cheng , Huang Qingzhen , Cao Lipeng , Li Zhi , Zhang Jun , Ren Chongwen , Duan Lei , Liu Qingqing , Yu Richeng , Ren Yang , Weng Shih-Chang , Lin Hong-Ji , Chen Chien-Te , Tjeng Liu-Hao , Long Youwen , Deng Zheng , Zhu Jinlong , Wang Xiancheng , Weng Hongming , Yu Runze , Greenblatt Martha , Jin Changqing 
Published: February 2021

AbstractThe simple ABO3 and A-site-ordered AA′3B4O12 perovskites represent two types of classical perovskite functional materials. There are well-known simple perovskites with ferroelectric properties, while there is still no report of ferroelectricity due to symmetry breaking transition in A-site-ordered quadruple perovskites. Here we report the high pressure synthesis of an A-site-ordered perovskite PbHg3Ti4O12, the only known quadruple perovskite that transforms from high-temperature centrosymmetric paraelectric phase to low-temperature non-centrosymmetric ferroelectric phase. The coordination chemistry of Hg2+ is changed from square planar as in typical A-site-ordered quadruple perovskite to a rare stereo type with 8 ligands in PbHg3Ti4O12. Thus PbHg3Ti4O12 appears to be a combinatory link from simple ABO3 perovskites to A-site-ordered AA′3Ti4O12 perovskites, sharing both displacive ferroelectricity with former and structure coordination with latter. This is the only example so far showing ferroelectricity due to symmetry breaking phase transition in AA′3B4O12-type A-site-ordered perovskites, and opens a direction to search for ferroelectric materials.
A safety cap protects hydrogenase from oxygen attack
Authors: Winkler Martin , Duan Jifu , Rutz Andreas , Felbek Christina , Scholtysek Lisa , Lampret Oliver , Jaenecke Jan , Apfel Ulf-Peter , Gilardi Gianfranco , Valetti Francesca , Fourmond Vincent , Hofmann Eckhard , Léger Christophe , Happe Thomas 
Published: February 2021

Abstract[FeFe]-hydrogenases are efficient H2-catalysts, yet upon contact with dioxygen their catalytic cofactor (H-cluster) is irreversibly inactivated. Here, we combine X-ray crystallography, rational protein design, direct electrochemistry, and Fourier-transform infrared spectroscopy to describe a protein morphing mechanism that controls the reversible transition between the catalytic Hox-state and the inactive but oxygen-resistant Hinact-state in [FeFe]-hydrogenase CbA5H of Clostridium beijerinckii. The X-ray structure of air-exposed CbA5H reveals that a conserved cysteine residue in the local environment of the active site (H-cluster) directly coordinates the substrate-binding site, providing a safety cap that prevents O2-binding and consequently, cofactor degradation. This protection mechanism depends on three non-conserved amino acids situated approximately 13 Å away from the H-cluster, demonstrating that the 1st coordination sphere chemistry of the H-cluster can be remote-controlled by distant residues.
Under-reporting of greenhouse gas emissions in U.S. cities
Authors: Gurney Kevin Robert , Liang Jianming , Roest Geoffrey , Song Yang , Mueller Kimberly , Lauvaux Thomas 
Published: February 2021

AbstractCities dominate greenhouse gas emissions. Many have generated self-reported emission inventories, but their value to emissions mitigation depends on their accuracy, which remains untested. Here, we compare self-reported inventories from 48 US cities to independent estimates from the Vulcan carbon dioxide emissions data product, which is consistent with atmospheric measurements. We found that cities under-report their own greenhouse gas emissions, on average, by 18.3% (range: −145.5% to +63.5%) – a difference which if extrapolated to all U.S. cities, exceeds California’s total emissions by 23.5%. Differences arise because city inventories omit particular fuels and source types and estimate transportation emissions differently. These results raise concerns about self-reported inventories in planning or assessing emissions, and warrant consideration of the new urban greenhouse gas information system recently developed by the scientific community.
Surface-bound reactive oxygen species generating nanozymes for selective antibacterial action
Authors: Gao Feng , Shao Tianyi , Yu Yunpeng , Xiong Yujie , Yang Lihua 
Published: February 2021

AbstractActing by producing reactive oxygen species (ROS) in situ, nanozymes are promising as antimicrobials. ROS’ intrinsic inability to distinguish bacteria from mammalian cells, however, deprives nanozymes of the selectivity necessary for an ideal antimicrobial. Here we report that nanozymes that generate surface-bound ROS selectively kill bacteria over mammalian cells. This result is robust across three distinct nanozymes that universally generate surface-bound ROS, with an oxidase-like silver-palladium bimetallic alloy nanocage, AgPd0.38, being the lead model. The selectivity is attributable to both the surface-bound nature of ROS these nanozymes generate and an unexpected antidote role of endocytosis. Though surface-bound, the ROS on AgPd0.38 efficiently eliminated antibiotic-resistant bacteria and effectively delayed the onset of bacterial resistance emergence. When used as coating additives, AgPd0.38 enabled an inert substrate to inhibit biofilm formation and suppress infection-related immune responses in mouse models. This work opens an avenue toward biocompatible nanozymes and may have implication in our fight against antimicrobial resistance.
Histone Parylation factor 1 contributes to the inhibition of PARP1 by cancer drugs
Authors: Rudolph Johannes , Roberts Genevieve , Luger Karolin 
Published: February 2021

AbstractPoly-(ADP-ribose) polymerase 1 and 2 (PARP1 and PARP2) are key enzymes in the DNA damage response. Four different inhibitors (PARPi) are currently in the clinic for treatment of ovarian and breast cancer. Recently, histone PARylation Factor 1 (HPF1) has been shown to play an essential role in the PARP1- and PARP2-dependent poly-(ADP-ribosylation) (PARylation) of histones, by forming a complex with both enzymes and altering their catalytic properties. Given the proximity of HPF1 to the inhibitor binding site both PARPs, we hypothesized that HPF1 may modulate the affinity of inhibitors toward PARP1 and/or PARP2. Here we demonstrate that HPF1 significantly increases the affinity for a PARP1 – DNA complex of some PARPi (i.e., olaparib), but not others (i.e., veliparib). This effect of HPF1 on the binding affinity of Olaparib also holds true for the more physiologically relevant PARP1 – nucleosome complex but does not extend to PARP2. Our results have important implications for the interpretation of PARP inhibition by current PARPi as well as for the design and analysis of the next generation of clinically relevant PARP inhibitors.
3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels
Authors: Daly Andrew C. , Davidson Matthew D. , Burdick Jason A. 
Published: February 2021

AbstractCellular models are needed to study human development and disease in vitro, and to screen drugs for toxicity and efficacy. Current approaches are limited in the engineering of functional tissue models with requisite cell densities and heterogeneity to appropriately model cell and tissue behaviors. Here, we develop a bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization. As an example application, we bioprint induced pluripotent stem cell-derived cardiac microtissue models with spatially controlled cardiomyocyte and fibroblast cell ratios to replicate the structural and functional features of scarred cardiac tissue that arise following myocardial infarction, including reduced contractility and irregular electrical activity. The bioprinted in vitro model is combined with functional readouts to probe how various pro-regenerative microRNA treatment regimes influence tissue regeneration and recovery of function as a result of cardiomyocyte proliferation. This method is useful for a range of biomedical applications, including the development of precision models to mimic diseases and the screening of drugs, particularly where high cell densities and heterogeneity are important.
Non-linear Terahertz driving of plasma waves in layered cuprates
Authors: Gabriele Francesco , Udina Mattia , Benfatto Lara 
Published: February 2021

AbstractThe hallmark of superconductivity is the rigidity of the quantum-mechanical phase of electrons, responsible for superfluid behavior and Meissner effect. The strength of the phase stiffness is set by the Josephson coupling, which is strongly anisotropic in layered cuprates. So far, THz light pulses have been used to achieve non-linear control of the out-of-plane Josephson plasma mode, whose frequency lies in the THz range. However, the high-energy in-plane plasma mode has been considered insensitive to THz pumping. Here, we show that THz driving of both low-frequency and high-frequency plasma waves is possible via a general two-plasmon excitation mechanism. The anisotropy of the Josephson couplings leads to markedly different thermal effects for the out-of-plane and in-plane response, linking in both cases the emergence of non-linear photonics across Tc to the superfluid stiffness. Our results show that THz light pulses represent a preferential knob to selectively drive phase excitations in unconventional superconductors.
Molecular mechanism for vitamin C-derived C5-glyceryl-methylcytosine DNA modification catalyzed by algal TET homologue CMD1
Authors: Li Wenjing , Zhang Tianlong , Sun Mingliang , Shi Yu , Zhang Xiao-Jie , Xu Guo-Liang , Ding Jianping 
Published: February 2021

AbstractC5-glyceryl-methylcytosine (5gmC) is a novel DNA modification catalyzed by algal TET homologue CMD1 using vitamin C (VC) as co-substrate. Here, we report the structures of CMD1 in apo form and in complexes with VC or/and dsDNA. CMD1 exhibits comparable binding affinities for DNAs of different lengths, structures, and 5mC levels, and displays a moderate substrate preference for 5mCpG-containing DNA. CMD1 adopts the typical DSBH fold of Fe2+/2-OG-dependent dioxygenases. The lactone form of VC binds to the active site and mono-coordinates the Fe2+ in a manner different from 2-OG. The dsDNA binds to a positively charged cleft of CMD1 and the 5mC/C is inserted into the active site and recognized by CMD1 in a similar manner as the TET proteins. The functions of key residues are validated by mutagenesis and activity assay. Our structural and biochemical data together reveal the molecular mechanism for the VC-derived 5gmC DNA modification by CMD1.
A multi-center cross-platform single-cell RNA sequencing reference dataset
Authors: Chen Xin , Yang Zhaowei , Chen Wanqiu , Zhao Yongmei , Farmer Andrew , Tran Bao , Furtak Vyacheslav , Moos Malcolm , Xiao Wenming , Wang Charles 
Published: February 2021

AbstractSingle-cell RNA sequencing (scRNA-seq) is developing rapidly, and investigators seeking to use this technology are left with a variety of options for both experimental platform and bioinformatics methods. There is an urgent need for scRNA-seq reference datasets for benchmarking of different scRNA-seq platforms and bioinformatics methods. To be broadly applicable, these should be generated from renewable, well characterized reference samples and processed in multiple centers across different platforms. Here we present a benchmark scRNA-seq dataset that includes 20 scRNA-seq datasets acquired either as mixtures or as individual samples from two biologically distinct cell lines for which a large amount of multi-platform whole genome sequencing data are also available. These scRNA-seq datasets were generated from multiple popular platforms across four sequencing centers. We believe the datasets we describe here will provide a resource that meets this need by allowing evaluation of various bioinformatics methods for scRNA-seq analyses, including but not limited to data preprocessing, imputation, normalization, clustering, batch correction, and differential analysis.
The 10-m crop type maps in Northeast China during 2017–2019
Authors: You Nanshan , Dong Jinwei , Huang Jianxi , Du Guoming , Zhang Geli , He Yingli , Yang Tong , Di Yuanyuan , Xiao Xiangming 
Published: February 2021

AbstractNortheast China is the leading grain production region in China where one-fifth of the national grain is produced; however, consistent and reliable crop maps are still unavailable, impeding crop management decisions for regional and national food security. Here, we produced annual 10-m crop maps of the major crops (maize, soybean, and rice) in Northeast China from 2017 to 2019, by using (1) a hierarchical mapping strategy (cropland mapping followed by crop classification), (2) agro-climate zone-specific random forest classifiers, (3) interpolated and smoothed 10-day Sentinel-2 time series data, and (4) optimized features from spectral, temporal, and texture characteristics of the land surface. The resultant maps have high overall accuracies (OA) spanning from 0.81 to 0.86 based on abundant ground truth data. The satellite estimates agreed well with the statistical data for most of the municipalities (R2 ≥ 0.83, p < 0.01). This is the first effort on regional annual crop mapping in China at the 10-m resolution, which permits assessing the performance of the soybean rejuvenation plan and crop rotation practice in China.
Social network structure and composition in former NFL football players
Authors: Dhand Amar , McCafferty Liam , Grashow Rachel , Corbin Ian M. , Cohan Sarah , Whittington Alicia J. , Connor Ann , Baggish Aaron , Weisskopf Mark , Zafonte Ross , Pascual-Leone Alvaro , Barabási Albert-László 
Published: February 2021

AbstractSocial networks have broad effects on health and quality of life. Biopsychosocial factors may also modify the effects of brain trauma on clinical and pathological outcomes. However, social network characterization is missing in studies of contact sports athletes. Here, we characterized the personal social networks of former National Football League players compared to non-football US males. In 303 former football players and 269 US males, we found that network structure (e.g., network size) did not differ, but network composition (e.g., proportion of family versus friends) did differ. Football players had more men than women, and more friends than family in their networks compared to US males. Black players had more racially diverse networks than White players and US males. These results are unexpected because brain trauma and chronic illnesses typically cause diminished social relationships. We anticipate our study will inform more multi-dimensional study of, and treatment options for, contact sports athletes. For example, the strong allegiances of former athletes may be harnessed in the form of social network interventions after brain trauma. Because preserving health of contact sports athletes is a major goal, the study of social networks is critical to the design of future research and treatment trials.