bluuebunny/crossref_metadata_2025_split huggingface dataset:
From Crystals to Crustal‐Scale Seismic Anisotropy: Bridging the Gap Between Rocks and Seismic Studies With Digital Geologic Map Data in Colorado
Authors: Frothingham Michael G. , Mahan Kevin H. , Schulte‐Pelkum Vera , Caine Jonathan Saul , Vollmer Frederick W. 
Published: January 2022

AbstractDeep continental crustal structures are enigmatic due to lack of direct exposures and limited tools to investigate them remotely. Seismic waves can sample these rocks, but most seismic methods focus on coarse crustal structures while laboratory measurements concentrate on crystal‐scale rock properties, and little work has been conducted to bridge this interpretation gap. In some places, geologic maps of crystalline basement provide samples of the intermediate‐scale fabrics and structures that may represent in situ deep crust. However, previous research has not considered natural geometric variations from map data, nor is this heterogeneity typically included in map‐scale seismic property calculations. Here, we test how map‐scale fabrics influence crustal seismic anisotropy in Colorado by analyzing structural data from geologic maps, combining those data with bulk rock elastic tensors to calculate map‐scale seismic properties, and evaluating the resulting comparisons with observed receiver function A1 (360° periodic) arrivals. Crystalline fabrics, predicted seismic properties, and tectonic structures positively correlate with shallow and deep crustal A1 arrivals. Additionally, widespread correlations occur between mapped fault traces and regional foliations, implying that preexisting mechanical heterogeneity may have strongly influenced subsequent reactivation. We interpret that various mapped geologic contact types (e.g., lithologic and structural) generate A1 arrivals and that multiple parallel features (e.g., faults, foliations, and intrusions) contribute to a seismically visible tectonic grain. Therefore, Colorado's exhumed basement, as expressed in outcrops and maps, offers insight into modern deep crustal geological and geophysical structure.
Water Footprints, Intra‐National Virtual Water Flows, and Associated Sustainability Related to Pork Production and Consumption: A Case for China
Authors: Ji Xiangxiang , Xie Dong , Zhuo La , Liu Yilin , Feng Bianbian , Wu Pute 
Published: January 2022

AbstractGrowth in water consumption with intensified virtual water (VW) flows from increased production and consumption of both meat and feed crops threatens the sustainability of water resources in water‐scarce countries and export regions. However, a sustainability assessment of both water footprints (WFs) and VW flows related to animal products at a subnational scale is lacking. Here we estimate direct and indirect WFs as well as the inter‐provincial VW flows associated with pork production and consumption in China for the years 2008 and 2017. The contributions of feed crop production and consumption were identified. Both life cycle assessment and WF network frameworks were applied to evaluate the sustainability of blue WF and VW flows. Results show that the national annual consumptive (green‐blue) WF and degradative (gray) WF of pork production increased by 8.7% and 15.8%, respectively. More than 80% of the blue WF in pork production was unsustainable. By 2017, 62% of the unsustainable blue WF and 64% of the water scarcity footprints of pork production in the south resulted from consuming the feed crops from the north. This analysis highlights the importance and provides feasible approaches to uncover remote geographical effects on regional water scarcities from different steps in the value chains of livestock products.
Phase Diversity Electro-optic Sampling: A new approach to single-shot terahertz waveform recording
Authors: Roussel Eléonore , Szwaj Christophe , Evain Clément , Steffen Bernd , Gerth Christopher , Jalali Bahram , Bielawski Serge 
Published: January 2022

AbstractRecording electric field evolution in single-shot with THz bandwidth is needed in science including spectroscopy, plasmas, biology, chemistry, Free-Electron Lasers, accelerators, and material inspection. However, the potential application range depends on the possibility to achieve sub-picosecond resolution over a long time window, which is a largely open problem for single-shot techniques. To solve this problem, we present a new conceptual approach for the so-called spectral decoding technique, where a chirped laser pulse interacts with a THz signal in a Pockels crystal, and is analyzed using a grating optical spectrum analyzer. By borrowing mathematical concepts from photonic time stretch theory and radio-frequency communication, we deduce a novel dual-output electro-optic sampling system, for which the input THz signal can be numerically retrieved—with unprecedented resolution—using the so-called phase diversity technique. We show numerically and experimentally that this approach enables the recording of THz waveforms in single-shot over much longer durations and/or higher bandwidth than previous spectral decoding techniques. We present and test the proposed DEOS (Diversity Electro-Optic Sampling) design for recording 1.5 THz bandwidth THz pulses, over 20 ps duration, in single-shot. Then we demonstrate the potential of DEOS in accelerator physics by recording, in two successive shots, the shape of 200 fs RMS relativistic electron bunches at European X-FEL, over 10 ps recording windows. The designs presented here can be used directly for accelerator diagnostics, characterization of THz sources, and single-shot Time-Domain Spectroscopy.
Delivering on the promise of early detection with liquid biopsies
Authors: Crosby David 
Published: January 2022

AbstractLiquid biopsy approaches are relatively well developed for cancer therapy monitoring and disease relapse, but they also have incredible potential in the cancer early detection and screening field. There are, however, several challenges to overcome before this potential can be met. Research in this area needs to be cohesive and, as a driver of research, Cancer Research UK is in an ideal position to enable this.
MicroRNA-149 suppresses osteogenic differentiation of mesenchymal stem cells via inhibition of AKT1-dependent Twist1 phosphorylation
Authors: Fan Jingzhang , Li Shiming , Wang Dawei 
Published: January 2022

AbstractOsteogenic differentiation is a vital process for growth, repair, and remodeling of bones. Accumulating evidence have suggested that microRNAs (miRNAs or miRs) play a crucial role in osteogenic differentiation of mesenchymal stem cells (MSCs). Hence, the current study set out to elucidate the role of miR-149 in osteogenic differentiation of MSCs and the underlying mechanism. First, rat models of bone differentiation were established using the Masquelet-induced membrane technique, and MSCs were isolated. The expression of miR-149 and AKT1 in the rats and cells was detected with RT-qPCR and western blot analysis. The relationships among miR-149, AKT1, and Twist1 were further predicted by online bioinformatics prediction and verified using dual luciferase reporter gene assay. Alteration of miR-149, AKT1, or Twist1 was performed to further explore their effect on osteogenic differentiation of MSCs. miR-149 was poorly expressed in the process of osteogenic differentiation of MSCs, while AKT1 was highly expressed. miR-149 negatively regulated the expression of AKT1, which in turn diminished the protein levels of Twist1 and promoted the phosphorylation levels of Twist1. Lastly, miR-149 acted as an inhibitor of osteogenic differentiation of MSCs, which could be reversed by AKT1. To sum up, miR-149 silencing promoted osteogenic differentiation of MSCs by enhancing Twist1 degradation through AKT1 upregulation, representing a new method for bone repair treatment.
Knockdown of NRMT enhances sensitivity of retinoblastoma cells to cisplatin through upregulation of the CENPA/Myc/Bcl2 axis
Authors: Li Zhongrui , Zhang Lan , Liu Dongrui , Yang Zhanghui , Xuan Di , Zhang Yi 
Published: January 2022

AbstractChemotherapy resistance of tumor cells causes failure in anti-tumor therapies. Recently, N-terminal regulator of chromatin condensation 1 methyltransferase (NRMT) is abnormally expressed in different cancers. Hence, we speculate that NRMT may pay a crucial role in the development of chemosensitivity in retinoblastoma. We characterized the upregulation of NRMT in the developed cisplatin (CDDP)-resistant retinoblastoma cell line relative to parental cells. Loss-of-function experiments demonstrated that NRMT silencing enhanced chemosensitivity of retinoblastoma cells to CDDP. Next, NRMT was identified to enrich histone-H3 lysine 4 trimethylation in the promoter of centromere protein A (CENPA) by chromatin immunoprecipitation assay. Rescue experiments suggested that CENPA reduced chemosensitivity by increasing the viability and proliferation and reducing apoptosis of CDDP-resistant retinoblastoma cells, which was reversed by NRMT. Subsequently, CENPA was witnessed to induce the transcription of Myc and to elevate the expression of B cell lymphoma-2. At last, in vivo experiments confirmed the promotive effect of NRMT knockdown on chemosensitivity of retinoblastoma cells to CDDP in tumor-bearing mice. Taken together, NRMT is an inhibitor of chemosensitivity in retinoblastoma. Those findings shed new light on NRMT-targeted therapies for retinoblastoma.
The involvement of the circFOXM1–miR–432–Gα12 axis in glioma cell proliferation and aggressiveness
Authors: Gong Yong , Zhang Shuai , Wang HongXin , Huang Yunfeng , Fu Xing , Xiang Peng , Fan Tianyu 
Published: January 2022

AbstractAccumulating evidence indicates that circFOXM1 (Hsa_circ_0025033) is highly expressed in several cancers; however, the function of circFOXM1 in glioma and the molecular mechanism have not been well explored. In the present study, we found that expression of circFOXM1 was upregulated in both glioma tissues and cell lines. In addition, circFOXM1 knockdown suppressed glioma-cell proliferation, activated apoptosis in vitro, and repressed tumour growth in vivo. Moreover, we clarified that circFOXM1 binds with miR-432, which was downregulated in glioma cells. Furthermore, we indicated that Gα12, a direct target of miR-432, was highly expressed in glioma cells, and Gα12 silencing might limit the progression of glioma. Rescue assays indicated that Gα12 reversed the inhibitory effect of circFOXM1 silencing on glioma-cell tumorigenesis. In conclusion, circFOXM1 acts as a sponge of miR-432 to promote the proliferation and aggressiveness of glioma cells through the Gα12 signalling pathway.
Transcription Factor Activation Profiles (TFAP) identify compounds promoting differentiation of Acute Myeloid Leukemia cell lines
Authors: Riccio Federica , Micarelli Elisa , Secci Riccardo , Giuliani Giulio , Vumbaca Simone , Massacci Giorgia , Castagnoli Luisa , Fuoco Claudia , Cesareni Gianni 
Published: January 2022

AbstractRepurposing of drugs for new therapeutic use has received considerable attention for its potential to limit time and cost of drug development. Here we present a new strategy to identify chemicals that are likely to promote a desired phenotype. We used data from the Connectivity Map (CMap) to produce a ranked list of drugs according to their potential to activate transcription factors that mediate myeloid differentiation of leukemic progenitor cells. To validate our strategy, we tested the in vitro differentiation potential of candidate compounds using the HL-60 human cell line as a myeloid differentiation model. Ten out of 22 compounds, which were ranked high in the inferred list, were confirmed to promote significant differentiation of HL-60. These compounds may be considered candidate for differentiation therapy. The method that we have developed is versatile and it can be adapted to different drug repurposing projects.
Penile surgery for patients with Peyronie’s disease initially treated with collagenase clostridium histolyticum or surgery: a claims database analysis
Authors: Trost Landon , Huang Huan , Han Xu , Burudpakdee Chakkarin , Hu Yiqun 
Published: January 2022

AbstractCollagenase clostridium histolyticum (CCH) is an injectable therapy targeting collagen present in penile plaques in Peyronie’s disease (PD). Data comparing CCH to penile surgery are limited, and long-term therapeutic outcomes are unknown. This retrospective analysis used a US claims database (January 2014–June 2017) to determine the percentage of men with subsequent penile surgery among those who initially received CCH (n = 1227) or surgery (index treatment; n = 620) for PD. Eligible patients were aged ≥18 years with continuous enrollment ≥6 months before and ≥12 months after index treatment date. During 12 months of post-index treatment follow-up, fewer patients with PD initially treated with CCH (4.6% [56/1227]) had subsequent penile surgery versus those initially treated with penile surgery (10.3% [64/620]; p < 0.0001). Mean ± SD time to first subsequent surgery after initial PD treatment was longer in the CCH versus surgery cohort (7.7 ± 3.0 vs 1.7 ± 3.2 months). The likelihood of subsequent surgery varied by initial surgery type: 18.2% after plaque incision or excision with grafting; 11.6% after penile implant; and 8.2% after tunical plication. Patients with PD who received CCH first were less likely to undergo subsequent surgery compared with those who received surgery first within a 12-month post-treatment follow-up.
Effects of neoadjuvant trastuzumab, pertuzumab and palbociclib on Ki67 in HER2 and ER-positive breast cancer
Authors: Gianni Luca , Colleoni Marco , Bisagni Giancarlo , Mansutti Mauro , Zamagni Claudio , Del Mastro Lucia , Zambelli Stefania , Bianchini Giampaolo , Frassoldati Antonio , Maffeis Ilaria , Valagussa Pinuccia , Viale Giuseppe 
Published: January 2022

AbstractThe crosstalk between estrogen and HER2 receptors and cell-cycle regulation sustains resistance to endocrine therapy of HER2- and hormone receptor-positive breast cancer. We earlier reported that women with HER2 and ER-positive breast cancer receiving neoadjuvant dual HER2-block and palbociclib in the NA-PHER2 trial had Ki67 decrease and 27% pathological complete responses (pCR). We extended NA-PHER2 to Cohort B using dual HER2-block and palbociclib without fulvestrant and report here Ki67 drops at week-2 (mean change −25.7), at surgery (after 16 weeks, mean change −9.5), high objective response (88.5%) and pCR (19.2%). In Cohort C [Ki67 > 20% and HER2low (IHC 1+/2+ without gene amplification)], women also received fulvestrant, had dramatic Ki67 drop at week 2 (−29.5) persisting at surgery (−19.3), and objective responses in 78.3%. In view of the favorable tolerability and of the efficacy-predictive value of Ki67 drop at week-2, the chemotherapy-free approach of NA-PHER2 deserves further investigation in HER2 and ER-positive breast cancer. The trial is registered with ClinicalTrials.gov, number NCT02530424.
First-principles search of hot superconductivity in La-X-H ternary hydrides
Authors: Di Cataldo Simone , von der Linden Wolfgang , Boeri Lilia 
Published: January 2022

AbstractMotivated by the recent claim of hot superconductivity with critical temperatures up to 550 K in La + x hydrides, we investigate the high-pressure phase diagram of compounds that may have formed in the experiment, using first-principles calculations for evolutionary crystal structure prediction and superconductivity. Starting from the hypothesis that the observed Tc may be realized by successive heating upon a pre-formed LaH10 phase, we examine plausible ternaries of lanthanum, hydrogen and other elements present in the diamond anvil cell: boron, nitrogen, carbon, platinum, gallium, gold. We find that only boron and, to a lesser extent, gallium form metastable superhydride-like structures that can host high-Tc superconductivity, but the predicted Tc’s are incompatible with the experimental reports. Our results indicate that, while the claims of hot superconductivity should be reconsidered, it is very likely that unknown H-rich ternary or multinary phases containing lanthanum, hydrogen, and possibly boron or gallium may have formed under the reported experimental conditions, and that these may exhibit superconducting properties comparable, or even superior, to those of currently known hydrides.
Cofilin 1 promotes the pathogenicity and transmission of pathological α-synuclein in mouse models of Parkinson’s disease
Authors: Yan Mingmin , Xiong Min , Dai Lijun , Zhang Xingyu , Zha Yunhong , Deng Xiaorong , Yu Zhui , Zhang Zhentao 
Published: January 2022

AbstractThe pathological hallmark of Parkinson’s disease (PD) is the presence of Lewy bodies (LBs) with aggregated α-synuclein being the major component. The abnormal α-synuclein aggregates transfer between cells, recruit endogenous α-synuclein into toxic LBs, and finally trigger neuronal injury. However, the molecular mechanisms mediating the aggregation and transmission of pathological α-synuclein remain unknown. Previously we found that cofilin 1, a member of the actin-binding protein, promotes the aggregation and pathogenicity of α-synuclein in vitro. Here we further investigated the effect of cofilin 1 in mouse models of PD. We found that the mixed fibrils composed of cofilin 1 and α-synuclein are more pathogenic to mice and more prone to propagation than pure α-synuclein fibrils. Overexpression of cofilin 1 enhances the seeding and spreading of α-synuclein aggregates, and induces PD-like behavioral impairments in mice. Together, these results illustrate the important role of cofilin 1 in the pathogenicity and transmission of α-synuclein during the onset and progression of PD.
Lewy body disease or diseases with Lewy bodies?
Authors: Menšíková Kateřina , Matěj Radoslav , Colosimo Carlo , Rosales Raymond , Tučková Lucie , Ehrmann Jiří , Hraboš Dominik , Kolaříková Kristýna , Vodička Radek , Vrtěl Radek , Procházka Martin , Nevrlý Martin , Kaiserová Michaela , Kurčová Sandra , Otruba Pavel , Kaňovský Petr 
Published: January 2022

AbstractThe current nosological concept of α-synucleinopathies characterized by the presence of Lewy bodies (LBs) includes Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), and dementia with Lewy bodies (DLB), for which the term “Lewy body disease” (LBD) has recently been proposed due to their considerable clinical and pathological overlap. However, even this term does not seem to describe the true nature of this group of diseases. The subsequent discoveries of α-synuclein (αSyn), SNCA gene, and the introduction of new immunohistochemical methods have started intensive research into the molecular-biological aspects of these diseases. In light of today’s knowledge, the role of LBs in the pathogenesis and classification of these nosological entities remains somewhat uncertain. An increasingly more important role is attributed to other factors as the presence of various LBs precursors, post-translational αSyn modifications, various αSyn strains, the deposition of other pathological proteins (particularly β-amyloid), and the discovery of selective vulnerability of specific cells due to anatomical configuration or synaptic dysfunction. Resulting genetic inputs can undoubtedly be considered as the main essence of these factors. Molecular–genetic data indicate that not only in PD but also in DLB, a unique genetic architecture can be ascertained, predisposing to the development of specific disease phenotypes. The presence of LBs thus remains only a kind of link between these disorders, and the term “diseases with Lewy bodies” therefore results somewhat more accurate.
Parameter estimation in quantum sensing based on deep reinforcement learning
Authors: Xiao Tailong , Fan Jianping , Zeng Guihua 
Published: January 2022

AbstractParameter estimation is a pivotal task, where quantum technologies can enhance precision greatly. We investigate the time-dependent parameter estimation based on deep reinforcement learning, where the noise-free and noisy bounds of parameter estimation are derived from a geometrical perspective. We propose a physical-inspired linear time-correlated control ansatz and a general well-defined reward function integrated with the derived bounds to accelerate the network training for fast generating quantum control signals. In the light of the proposed scheme, we validate the performance of time-dependent and time-independent parameter estimation under noise-free and noisy dynamics. In particular, we evaluate the transferability of the scheme when the parameter has a shift from the true parameter. The simulation showcases the robustness and sample efficiency of the scheme and achieves the state-of-the-art performance. Our work highlights the universality and global optimality of deep reinforcement learning over conventional methods in practical parameter estimation of quantum sensing.
Efficacy and immunogenicity of MultiTEP-based DNA vaccines targeting human α-synuclein: prelude for IND enabling studies
Authors: Kim Changyoun , Hovakimyan Armine , Zagorski Karen , Antonyan Tatevik , Petrushina Irina , Davtyan Hayk , Chailyan Gor , Hasselmann Jonathan , Iba Michiyo , Adame Anthony , Rockenstein Edward , Szabo Marcell , Blurton-Jones Mathew , Cribbs David H. , Ghochikyan Anahit , Masliah Eliezer , Agadjanyan Michael G. 
Published: January 2022

AbstractAccumulation of misfolded proteins such as amyloid-β (Aβ), tau, and α-synuclein (α-Syn) in the brain leads to synaptic dysfunction, neuronal damage, and the onset of relevant neurodegenerative disorder/s. Dementia with Lewy bodies (DLB) and Parkinson’s disease (PD) are characterized by the aberrant accumulation of α-Syn intracytoplasmic Lewy body inclusions and dystrophic Lewy neurites resulting in neurodegeneration associated with inflammation. Cell to cell propagation of α-Syn aggregates is implicated in the progression of PD/DLB, and high concentrations of anti-α-Syn antibodies could inhibit/reduce the spreading of this pathological molecule in the brain. To ensure sufficient therapeutic concentrations of anti-α-Syn antibodies in the periphery and CNS, we developed four α-Syn DNA vaccines based on the universal MultiTEP platform technology designed especially for the elderly with immunosenescence. Here, we are reporting on the efficacy and immunogenicity of these vaccines targeting three B-cell epitopes of hα-Syn aa85–99 (PV-1947D), aa109–126 (PV-1948D), aa126–140 (PV-1949D) separately or simultaneously (PV-1950D) in a mouse model of synucleinopathies mimicking PD/DLB. All vaccines induced high titers of antibodies specific to hα-Syn that significantly reduced PD/DLB-like pathology in hα-Syn D line mice. The most significant reduction of the total and protein kinase resistant hα-Syn, as well as neurodegeneration, were observed in various brain regions of mice vaccinated with PV-1949D and PV-1950D in a sex-dependent manner. Based on these preclinical data, we selected the PV-1950D vaccine for future IND enabling preclinical studies and clinical development.