bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimizing Spatial Allocation of COVID‐19 Vaccine by Agent‐Based Spatiotemporal Simulations
Authors: Zhou Shuli , Zhou Suhong , Zheng Zhong , Lu Junwen 
Published: May 2021

AbstractOptimizing allocation of vaccine, a highly scarce resource, is an urgent and critical issue during fighting against on‐going COVID‐19 epidemic. Prior studies suggested that vaccine should be prioritized by age and risk groups, but few of them have considered the spatial prioritization strategy. This study aims to examine the spatial heterogeneity of COVID‐19 transmission in the city naturally, and optimize vaccine distribution strategies considering spatial prioritization. We proposed an integrated spatial model of agent‐based model and SEIR (susceptible‐exposed‐infected‐recovered). It simulated spatiotemporal process of COVID‐19 transmission in a realistic urban context. Individual movements were represented by trajectories of 8,146 randomly sampled mobile phone users on December 28, 2016 in Guangzhou, China, 90% of whom aged 18–60. Simulations were conducted under seven scenarios. Scenarios 1 and 2 examined natural spreading process of COVID‐19 and its final state of herd immunity. Scenarios 3–6 applied four vaccination strategies (random strategy, age strategy, space strategy, and space & age strategy), and identified the optimal vaccine strategy. Scenario 7 assessed the most appropriate vaccine coverage. The results demonstrates herd immunity is heterogeneously distributed in space, thus, vaccine intervention strategies should be spatialized. Among four strategies, space & age strategy is substantially most efficient, with 7.7% fewer in attack rate and 44 days longer than random strategy under 20% vaccine uptake. Space & age strategy requires 30%–40% vaccine coverage to control the epidemic, while the coverage for a random strategy is 60%–70% as a comparison. The application of our research would greatly improves the effectiveness of the vaccine usability.
Corals Reveal an Unprecedented Decrease of Arabian Sea Upwelling During the Current Warming Era
Authors: Watanabe Takaaki K. , Watanabe Tsuyoshi , Pfeiffer Miriam , Hu Hsun‐Ming , Shen Chuan‐Chou , Yamazaki Atsuko 
Published: May 2021

AbstractUpwelling in the Arabian Sea driven by the Indian summer monsoon pumps deep, cold, and eutrophic seawater to the sea surface every summer. The Indian summer monsoon and the Arabian Sea upwelling were expected to intensify with global warming, following the hypothesis that the Eurasian landmass would warm faster than the Indian Ocean. Contrary to expectations, the northern Indian Ocean currently warms faster than the Indian subcontinent. A weakening of the Indian summer monsoon circulation is reported, which possibly weakens the Arabian Sea upwelling. However, a lack of observations limits understanding of current and historical changes of the Arabian Sea upwelling. Here, we reconstruct the Arabian Sea upwelling over the past millennium using modern and fossil corals. Our coral records show that the Arabian Sea upwelling intensity was very stable over the last millennium and unprecedentedly declines at present. Our finding implies anthropogenic forcing likely weakens the Arabian Sea upwelling.
Localized Anisotropy in the Mantle Transition Zone Due to Flow Through Slab Gaps
Authors: Zhang Han , Schmandt Brandon , Zhang Jin S. 
Published: May 2021

AbstractMeasurement of anisotropy advances our understanding of mantle dynamics by linking remote seismic observations to local deformation state through constraints from mineral physics. The Pacific Northwest records the largest depth‐integrated anisotropic signals across the western United States but the depths contributing to the total signal are unclear. We used the amplitudes of orthogonally polarized P‐to‐S converted phases from the mantle transition zone boundaries to identify anisotropy within the ∼400–700 km deep layer. Significant anisotropy is found near slab gaps imaged by prior tomography. Focusing of mantle flow through slab gaps may lead to locally elevated stress that enhances lattice preferred orientation of anisotropic minerals within the transition zone, such as wadsleyite.
Heterogeneous Reaction of CaCO3 With NO2 at Different Relative Humidities: Kinetics, Mechanisms, and Impacts on Aerosol Hygroscopicity
Authors: Jia Xiaohong , Gu Wenjun , Peng Chao , Li Rui , Chen Lanxiadi , Wang Hongli , Wang Haichao , Wang Xinming , Tang Mingjin 
Published: May 2021

AbstractHeterogeneous reaction of NO2 with CaCO3, an abundant and reactive component in mineral dust aerosol, was investigated in this work at different relative humidifies (RH, up to 80%), using a fixed‐bed reactor. Ion chromatograph and a vapor sorption analyzer were employed to measure changes in particulate nitrate and water with reaction time (up to 24 h). When NO2 concentration was ∼10 ppmv (∼2.5 × 1014 molecule cm−3), CaCO3 showed very low reactivity toward NO2 at <1% RH, and γ(NO2) was estimated to be <2 × 10−8; consequently, no significant change in hygroscopicity of CaCO3 particles was observed after reaction with NO2 for 24 h at <1% RH, as the amount of nitrate formed was very limited. Heterogeneous reactivity was significantly enhanced at elevated RH (20%–80%), and during the reaction CaCO3 was covered with a deliquesced layer resulting from water uptake by formed nitrate; in addition, the average γ(NO2) was determined to be (1.21 ± 0.45) × 10−7, independent of RH (20%–80%) and reaction time (3–24 h). After reaction with 10 ppmv NO2 for 24 h at elevated RH (20%–80%), the mass of particulate water associated with reacted CaCO3 at 90% RH was equal to ∼45% of the mass of unreacted CaCO3, suggesting that heterogeneous reaction of CaCO3 with NO2 at 20%–80% RH could substantially increase its hygroscopicity. Overall, our laboratory study suggested that heterogeneous reaction with NO2 may significantly impact composition and hygroscopicity of CaCO3 particles.
FLT3 tyrosine kinase inhibitors synergize with BCL-2 inhibition to eliminate FLT3/ITD acute leukemia cells through BIM activation
Authors: Zhu Ruiqi , Li Li , Nguyen Bao , Seo Jaesung , Wu Min , Seale Tessa , Levis Mark , Duffield Amy , Hu Yu , Small Donald 
Published: May 2021

AbstractTyrosine kinase inhibitors (TKIs) targeting FLT3 have shown activity but when used alone have achieved limited success in clinical trials, suggesting the need for combination with other drugs. We investigated the combination of FLT3 TKIs (Gilteritinib or Sorafenib), with Venetoclax, a BCL-2 selective inhibitor (BCL-2i), on FLT3/ITD leukemia cells. The combination of a FLT3 TKI and a BCL-2i synergistically reduced cell proliferation and enhanced apoptosis/cell death in FLT3/ITD cell lines and primary AML samples. Venetoclax also re-sensitized FLT3 TKI-resistant cells to Gilteritinib or Sorafenib treatment, mediated through MAPK pathway inhibition. Gilteritinib treatment alone dissociated BIM from MCL-1 but increased the binding of BIM to BCL-2. Venetoclax treatment enhanced the binding of BIM to MCL-1 but dissociated BIM from BCL-2. Treatment with the drugs together resulted in dissociation of BIM from both BCL-2 and MCL-1, with an increased binding of BIM to the cell death mediator BAX, leading to increased apoptosis. These findings suggest that Venetoclax mitigates the unintended pro-survival effects of FLT3 TKI mainly through the dissociation of BIM and BCL-2 and also decreased BIM expression. This study provides evidence that the addition of BCL-2i enhances the effect of FLT3 TKI therapy in FLT3/ITD AML treatment.
Multimodal prognosis of negative symptom severity in individuals at increased risk of developing psychosis
Authors: Hauke Daniel J. , Schmidt André , Studerus Erich , Andreou Christina , Riecher-Rössler Anita , Radua Joaquim , Kambeitz Joseph , Ruef Anne , Dwyer Dominic B. , Kambeitz-Ilankovic Lana , Lichtenstein Theresa , Sanfelici Rachele , Penzel Nora , Haas Shalaila S. , Antonucci Linda A. , Lalousis Paris Alexandros , Chisholm Katharine , Schultze-Lutter Frauke , Ruhrmann Stephan , Hietala Jarmo , Brambilla Paolo , Koutsouleris Nikolaos , Meisenzahl Eva , Pantelis Christos , Rosen Marlene , Salokangas Raimo K. R. , Upthegrove Rachel , Wood Stephen J. , Borgwardt Stefan ,   and the PRONIA Group
Published: May 2021

AbstractNegative symptoms occur frequently in individuals at clinical high risk (CHR) for psychosis and contribute to functional impairments. The aim of this study was to predict negative symptom severity in CHR after 9 months. Predictive models either included baseline negative symptoms measured with the Structured Interview for Psychosis-Risk Syndromes (SIPS-N), whole-brain gyrification, or both to forecast negative symptoms of at least moderate severity in 94 CHR. We also conducted sequential risk stratification to stratify CHR into different risk groups based on the SIPS-N and gyrification model. Additionally, we assessed the models’ ability to predict functional outcomes in CHR and their transdiagnostic generalizability to predict negative symptoms in 96 patients with recent-onset psychosis (ROP) and 97 patients with recent-onset depression (ROD). Baseline SIPS-N and gyrification predicted moderate/severe negative symptoms with significant balanced accuracies of 68 and 62%, while the combined model achieved 73% accuracy. Sequential risk stratification stratified CHR into a high (83%), medium (40–64%), and low (19%) risk group regarding their risk of having moderate/severe negative symptoms at 9 months follow-up. The baseline SIPS-N model was also able to predict social (61%), but not role functioning (59%) at above-chance accuracies, whereas the gyrification model achieved significant accuracies in predicting both social (76%) and role (74%) functioning in CHR. Finally, only the baseline SIPS-N model showed transdiagnostic generalization to ROP (63%). This study delivers a multimodal prognostic model to identify those CHR with a clinically relevant negative symptom severity and functional impairments, potentially requiring further therapeutic consideration.
Parsing variability in borderline personality disorder: a meta-analysis of neuroimaging studies
Authors: Degasperi Giorgia , Cristea Ioana Alina , Di Rosa Elisa , Costa Cristiano , Gentili Claudio 
Published: May 2021

AbstractThough a plethora of functional magnetic resonance imaging (fMRI) studies explored the neurobiological underpinnings of borderline personality disorder (BPD), findings across different tasks were divergent. We conducted a systematic review and activation likelihood estimation (ALE) meta-analysis on the fMRI studies conducted in BPD patients compared to healthy controls (HC). We systematically searched PubMed and PsychINFO from inception until July 9th 2020 using combinations of database-specific terms like ‘fMRI’, ‘Neuroimaging’, ‘borderline’. Eligible studies employed task-based fMRI of the brain in participants of any age diagnosed with BPD compared to HC, during any behavioral task and providing a direct contrast between the groups. From 762 entries, we inspected 92 reports full-texts and included 52 studies (describing 54 experiments). Across all experiments, the HC > BPD and BPD > HC meta-analyses did not yield any cluster of significant convergence of differences. Analyses restricted to studies of emotion processing revealed two significant clusters of activation in the bilateral hippocampal/amygdala complex and anterior cingulate for the BPD > HC meta-analysis. Fail-safe N and single study sensitivity analysis suggested significant findings were not robust. For the subgroup of emotional processing experiments, on a restricted number of experiments providing results for each group separately, another meta-analysis method (difference of convergence) showed a significant cluster in the insula/inferior frontal gyrus for the HC > BPD contrast. No consistent pattern of alteration in brain activity for BPD was evidenced suggesting substantial heterogeneity of processes and populations studied. A pattern of amygdala dysfunction emerged across emotion processing tasks, indicating a potential pathophysiological mechanism that could be transdiagnostic.
Epigenetic regulation of intestinal peptide transporter PEPT1 as a potential strategy for colorectal cancer sensitization
Authors: Wang Yanhong , Wang Jiaqi , Yang Lingrong , Qiu Liqing , Hua Yuhui , Wu Shixiu , Zeng Su , Yu Lushan , Zheng Xiaoli 
Published: May 2021

AbstractHuman intestinal peptide transporter PEPT1 is commonly repressed in human colorectal cancer (CRC), yet its relationship with sensitivity to the common CRC treatment ubenimex has not previously been elucidated. In this study, we confirmed PEPT1 suppression in CRC using real-time quantitative polymerase chain reaction and western blotting and then investigated the underlying epigenetic pathways involved using bisulfite sequencing, chromatin immunoprecipitation, siRNA knockdown, and reporter gene assays. We found that PEPT1 transcriptional repression was due to both DNMT1-mediated DNA methylation of the proximal promoter region and HDAC1-mediated histone deacetylation, which blocked P300-mediated H3K18/27Ac at the PEPT1 distal promoter. Finally, the effects of the epigenetic activation of PEPT1 on the CRC response to ubenimex were evaluated using sequential combination therapy of decitabine and ubenimex both in vitro and in xenografts. In conclusion, epigenetic silencing of PEPT1 due to increased DNMT1 and HDAC1 expression plays a vital role in the poor response of CRC to ubenimex.
Cerebrovascular diseases in two patients with entire NSD1 deletion
Authors: Itai Toshiyuki , Miyatake Satoko , Hatano Taku , Hattori Nobutaka , Ohno Atsuko , Aoki Yusuke , Itomi Kazuya , Mori Harushi , Saitsu Hirotomo , Matsumoto Naomichi 
Published: May 2021

AbstractWe describe two patients with NSD1 deletion, who presented with early-onset, or recurrent cerebrovascular diseases (CVDs). A 39-year-old female showed developmental delay and abnormal gait in infancy, and developed slowly-progressive intellectual disability and movement disorders. Brain imaging suggested recurrent parenchymal hemorrhages. A 6-year-old male had tremor as a neonate and brain imaging revealed subdural hematoma and brain contusion. This report suggests possible involvement of CVDs associated with NSD1 deletion.
Mining mutation contexts across the cancer genome to map tumor site of origin
Authors: Chakraborty Saptarshi , Martin Axel , Guan Zoe , Begg Colin B. , Shen Ronglai 
Published: May 2021

AbstractThe vast preponderance of somatic mutations in a typical cancer are either extremely rare or have never been previously recorded in available databases that track somatic mutations. These constitute a hidden genome that contrasts the relatively small number of mutations that occur frequently, the properties of which have been studied in depth. Here we demonstrate that this hidden genome contains much more accurate information than common mutations for the purpose of identifying the site of origin of primary cancers in settings where this is unknown. We accomplish this using a projection-based statistical method that achieves a highly effective signal condensation, by leveraging DNA sequence and epigenetic contexts using a set of meta-features that embody the mutation contexts of rare variants throughout the genome.
Versatile non-luminescent color palette based on guest exchange dynamics in paramagnetic cavitands
Authors: Goren Elad , Avram Liat , Bar-Shir Amnon 
Published: May 2021

AbstractMulticolor luminescent portrayal of complexed arrays is indispensable for many aspects of science and technology. Nevertheless, challenges such as inaccessible readouts from opaque objects, a limited visible-light spectrum and restricted spectral resolution call for alternative approaches for multicolor representation. Here, we present a strategy for spatial COlor Display by Exploiting Host-guest Dynamics (CODE-HD), comprising a paramagnetic cavitand library and various guests. First, a set of lanthanide-cradled α-cyclodextrins (Ln-CDs) is designed to induce pseudo-contact shifts in the19F-NMR spectrum ofLn-CD-bound guest. Then, capitalizing on reversible host-guest binding dynamics and using magnetization-transfer19F-MRI, pseudo-colored maps of complexed arrays are acquired and applied in molecular-steganography scenarios, showing CODE-HD’s ability to generate versatile outputs for information encoding. By exploiting the widely shifted resonances induced byLn-CDs, the guest versatility and supramolecular systems' reversibility, CODE-HD provides a switchable, polychromatic palette, as an advanced strategy for light-free, multicolor-mapping.
Identifying molecules as biosignatures with assembly theory and mass spectrometry
Authors: Marshall Stuart M. , Mathis Cole , Carrick Emma , Keenan Graham , Cooper Geoffrey J. T. , Graham Heather , Craven Matthew , Gromski Piotr S. , Moore Douglas G. , Walker Sara. I. , Cronin Leroy 
Published: May 2021

AbstractThe search for alien life is hard because we do not know what signatures are unique to life. We show why complex molecules found in high abundance are universal biosignatures and demonstrate the first intrinsic experimentally tractable measure of molecular complexity, called the molecular assembly index (MA). To do this we calculate the complexity of several million molecules and validate that their complexity can be experimentally determined by mass spectrometry. This approach allows us to identify molecular biosignatures from a set of diverse samples from around the world, outer space, and the laboratory, demonstrating it is possible to build a life detection experiment based on MA that could be deployed to extraterrestrial locations, and used as a complexity scale to quantify constraints needed to direct prebiotically plausible processes in the laboratory. Such an approach is vital for finding life elsewhere in the universe or creating de-novo life in the lab.
MPP8 is essential for sustaining self-renewal of ground-state pluripotent stem cells
Authors: Müller Iris , Moroni Ann Sophie , Shlyueva Daria , Sahadevan Sudeep , Schoof Erwin M. , Radzisheuskaya Aliaksandra , Højfeldt Jonas W. , Tatar Tülin , Koche Richard P. , Huang Chang , Helin Kristian 
Published: May 2021

AbstractDeciphering the mechanisms that control the pluripotent ground state is key for understanding embryonic development. Nonetheless, the epigenetic regulation of ground-state mouse embryonic stem cells (mESCs) is not fully understood. Here, we identify the epigenetic protein MPP8 as being essential for ground-state pluripotency. Its depletion leads to cell cycle arrest and spontaneous differentiation. MPP8 has been suggested to repress LINE1 elements by recruiting the human silencing hub (HUSH) complex to H3K9me3-rich regions. Unexpectedly, we find that LINE1 elements are efficiently repressed by MPP8 lacking the chromodomain, while the unannotated C-terminus is essential for its function. Moreover, we show that SETDB1 recruits MPP8 to its genomic target loci, whereas transcriptional repression of LINE1 elements is maintained without retaining H3K9me3 levels. Taken together, our findings demonstrate that MPP8 protects the DNA-hypomethylated pluripotent ground state through its association with the HUSH core complex, however, independently of detectable chromatin binding and maintenance of H3K9me3.
Dynamic fingerprint of fractionalized excitations in single-crystalline Cu3Zn(OH)6FBr
Authors: Fu Ying , Lin Miao-Ling , Wang Le , Liu Qiye , Huang Lianglong , Jiang Wenrui , Hao Zhanyang , Liu Cai , Zhang Hu , Shi Xingqiang , Zhang Jun , Dai Junfeng , Yu Dapeng , Ye Fei , Lee Patrick A. , Tan Ping-Heng , Mei Jia-Wei 
Published: May 2021

AbstractBeyond the absence of long-range magnetic orders, the most prominent feature of the elusive quantum spin liquid (QSL) state is the existence of fractionalized spin excitations, i.e., spinons. When the system orders, the spin-wave excitation appears as the bound state of the spinon-antispinon pair. Although scarcely reported, a direct comparison between similar compounds illustrates the evolution from spinon to magnon. Here, we perform the Raman scattering on single crystals of two quantum kagome antiferromagnets, of which one is the kagome QSL candidate Cu3Zn(OH)6FBr, and another is an antiferromagnetically ordered compound EuCu3(OH)6Cl3. In Cu3Zn(OH)6FBr, we identify a unique one spinon-antispinon pair component in the E2g magnetic Raman continuum, providing strong evidence for deconfined spinon excitations. In contrast, a sharp magnon peak emerges from the one-pair spinon continuum in the Eg magnetic Raman response once EuCu3(OH)6Cl3 undergoes the antiferromagnetic order transition. From the comparative Raman studies, we can regard the magnon mode as the spinon-antispinon bound state, and the spinon confinement drives the magnetic ordering.
Global health effects of future atmospheric mercury emissions
Authors: Zhang Yanxu , Song Zhengcheng , Huang Shaojian , Zhang Peng , Peng Yiming , Wu Peipei , Gu Jing , Dutkiewicz Stephanie , Zhang Huanxin , Wu Shiliang , Wang Feiyue , Chen Long , Wang Shuxiao , Li Ping 
Published: May 2021

AbstractMercury is a potent neurotoxin that poses health risks to the global population. Anthropogenic mercury emissions to the atmosphere are projected to decrease in the future due to enhanced policy efforts such as the Minamata Convention, a legally-binding international treaty entered into force in 2017. Here, we report the development of a comprehensive climate-atmosphere-land-ocean-ecosystem and exposure-risk model framework for mercury and its application to project the health effects of future atmospheric emissions. Our results show that the accumulated health effects associated with mercury exposure during 2010–2050 are $19 (95% confidence interval: 4.7–54) trillion (2020 USD) realized to 2050 (3% discount rate) for the current policy scenario. Our results suggest a substantial increase in global human health cost if emission reduction actions are delayed. This comprehensive modeling approach provides a much-needed tool to help parties to evaluate the effectiveness of Hg emission controls as required by the Minamata Convention.
Electrochemical C−C bond cleavage of cyclopropanes towards the synthesis of 1,3-difunctionalized molecules
Authors: Peng Pan , Yan Xingxiu , Zhang Ke , Liu Zhao , Zeng Li , Chen Yixuan , Zhang Heng , Lei Aiwen 
Published: May 2021

AbstractElectrochemistry has a lot of inherent advantages in organic synthesis and many redox reactions have been achieved under electrochemical condition. However, the electrochemical C−C bond cleavage and functionalization reactions are less studied. Here we develop electrochemical C−C bond cleavage and 1,3-difuntionalization of arylcyclopropanes under catalyst-free and external-oxidant-free conditions. 1,3-difluorination, 1,3-oxyfluorination and 1,3-dioxygenation of arylcyclopropanes are achieved with a high chemo- and regioselectivity by the strategic choice of nucleophiles. This protocol has good functional groups tolerance and can be scaled up. Mechanistic studies demonstrate that arylcyclopropane radical cation obtained from the anode oxidation and the subsequently generated benzyl carbonium are the key intermediates in this transformation. This development provides a scenario for constructing 1,3-difunctionalized molecules.