bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induced Polarization and Magnetic Responses of Serpentinized Ultramafic Rocks From Mid‐Ocean Ridges
Authors: Chen H. , Tao C. , Revil A. , Zhu Z. , Zhou J. , Wu T. , Deng X. 
Published: December 2021

AbstractThe outcrops of ultramafic rock along mid‐ocean ridges experience variable extents of serpentinization related to tectonic and hydrothermal processes. It involves the water‐assisted alteration of primary ferromagnesian minerals (e.g., olivine and pyroxenes) to produce secondary minerals including serpentine, magnetite and brucite. This hydration process induces profound changes in both the rheological and petrophysical properties of the ocean lithosphere. That said, the evolution of the low‐frequency electrical polarization properties of these rocks along the serpentinization path remains poorly explored. A total of 47 core samples were collected at the seafloor along the Southwest Indian Ridge (SWIR) in order to investigate the process of serpentinization in terms of combined magnetization and polarization signatures. We found a linear relationship connecting chargeability and magnetic susceptibility for both fresh basalts and ultramafic rocks. A unique trend between these two properties is associated with the production of magnetite during serpentinization of peridotites. Magnetite acts indeed as a semi‐conductor responsible for a high chargeability in a low‐frequency (<10 kHertz) electrical field and because of its magnetic properties, it increases the magnetic susceptibility of the ultramafic rocks during serpentinization. In addition, both the chargeability and the magnetic susceptibility change with the grain density of the core samples, which depends on the degree of serpentinization.
Insulin and glucose metabolism with olanzapine and a combination of olanzapine and samidorphan: exploratory phase 1 results in healthy volunteers
Authors: Toledo Frederico G. S. , Martin William F. , Morrow Linda , Beysen Carine , Bajorunas Daiva , Jiang Ying , Silverman Bernard L. , McDonnell David , Namchuk Mark N. , Newcomer John W. , Graham Christine 
Published: December 2021

AbstractA combination of olanzapine and samidorphan (OLZ/SAM) received US Food and Drug Administration approval in May 2021 for the treatment of adults with schizophrenia or bipolar I disorder. OLZ/SAM provides the efficacy of olanzapine, while mitigating olanzapine-associated weight gain. This exploratory study characterized the metabolic profile of OLZ/SAM in healthy volunteers to gain mechanistic insights. Volunteers received once-daily oral 10 mg/10 mg OLZ/SAM, 10 mg olanzapine, or placebo for 21 days. Assessments included insulin sensitivity during an oral glucose tolerance test (OGTT), hyperinsulinemic-euglycemic clamp, other measures of glucose/lipid metabolism, and adverse event (AE) monitoring. Treatment effects were estimated with analysis of covariance. In total, 60 subjects were randomized (double-blind; placebo, n = 12; olanzapine, n = 24; OLZ/SAM, n = 24). Olanzapine resulted in hyperinsulinemia and reduced insulin sensitivity during an OGTT at day 19, changes not observed with OLZ/SAM or placebo. Insulin sensitivity, measured by hyperinsulinemic-euglycemic clamp, was decreased in all treatment groups relative to baseline, but this effect was greatest with olanzapine and OLZ/SAM. Although postprandial (OGTT) glucose and fasting cholesterol concentrations were similarly increased with olanzapine or OLZ/SAM, other early metabolic effects were distinct, including post-OGTT C-peptide concentrations and aspects of energy metabolism. Forty-nine subjects (81.7%) experienced at least 1 AE, most mild or moderate in severity. OLZ/SAM appeared to mitigate some of olanzapine’s unfavorable postprandial metabolic effects (e.g., hyperinsulinemia, elevated C-peptide) in this exploratory study. These findings supplement the body of evidence from completed or ongoing OLZ/SAM clinical trials supporting its role in the treatment of schizophrenia and bipolar I disorder.
Current landscape of tumor-derived exosomal ncRNAs in glioma progression, detection, and drug resistance
Authors: He Xiao , Qi Yiwei , Zhang Xian , Liu Xiaojin , Li Xingbo , Li Sihan , Wu Yiping , Zhang Qi 
Published: December 2021

AbstractGlioma is the most common and fatal tumor of the central nervous system in humans. Despite advances in surgery, radiotherapy, and chemotherapeutic agents, glioma still has a poor prognosis. The tumor microenvironment (TME) of glioma is of highly complex heterogeneity, which relies on a network-based communication between glioma cells and other stromal cell types. Exosomes are the most common type of naturally occurring extracellular vesicles, ranging in size from 40 to 160 nm, and can serve as carriers for proteins, RNAs, and other biologically active molecules. Recent evidence has shown that glioma-derived exosomes (GDEs) can be integrally detected in the local tissue and circulatory blood samples, and also can be transferred to recipient cells to mediate transmission of genetic information. Non-coding RNAs (ncRNAs) mainly including microRNA, long non-coding RNA, and circular RNA, account for a large portion of the human transcriptome. A broad range of ncRNAs encapsulated in GDEs is reported to exert regulatory functions in various pathophysiological processes of glioma. Herein, this review summarizes the latest findings on the fundamental roles of GDE ncRNAs that have been implicated in glioma behaviors, immunological regulation, diagnosis potential, and treatment resistance, as well as the current limitations and perspectives. Undoubtedly, a thorough understanding of this area will provide comprehensive insights into GDE-based clinical applications for combating gliomas.
Massive image-based single-cell profiling reveals high levels of circulating platelet aggregates in patients with COVID-19
Authors: Nishikawa Masako , Kanno Hiroshi , Zhou Yuqi , Xiao Ting-Hui , Suzuki Takuma , Ibayashi Yuma , Harmon Jeffrey , Takizawa Shigekazu , Hiramatsu Kotaro , Nitta Nao , Kameyama Risako , Peterson Walker , Takiguchi Jun , Shifat-E-Rabbi Mohammad , Zhuang Yan , Yin Xuwang , Rubaiyat Abu Hasnat Mohammad , Deng Yunjie , Zhang Hongqian , Miyata Shigeki , Rohde Gustavo K. , Iwasaki Wataru , Yatomi Yutaka , Goda Keisuke 
Published: December 2021

AbstractA characteristic clinical feature of COVID-19 is the frequent incidence of microvascular thrombosis. In fact, COVID-19 autopsy reports have shown widespread thrombotic microangiopathy characterized by extensive diffuse microthrombi within peripheral capillaries and arterioles in lungs, hearts, and other organs, resulting in multiorgan failure. However, the underlying process of COVID-19-associated microvascular thrombosis remains elusive due to the lack of tools to statistically examine platelet aggregation (i.e., the initiation of microthrombus formation) in detail. Here we report the landscape of circulating platelet aggregates in COVID-19 obtained by massive single-cell image-based profiling and temporal monitoring of the blood of COVID-19 patients (n = 110). Surprisingly, our analysis of the big image data shows the anomalous presence of excessive platelet aggregates in nearly 90% of all COVID-19 patients. Furthermore, results indicate strong links between the concentration of platelet aggregates and the severity, mortality, respiratory condition, and vascular endothelial dysfunction level of COVID-19 patients.
CRIg on liver macrophages clears pathobionts and protects against alcoholic liver disease
Authors: Duan Yi , Chu Huikuan , Brandl Katharina , Jiang Lu , Zeng Suling , Meshgin Nairika , Papachristoforou Eleni , Argemi Josepmaria , Mendes Beatriz G. , Wang Yanhan , Su Hua , Sun Weizhong , Llorente Cristina , Hendrikx Tim , Liu Xiao , Hosseini Mojgan , Kisseleva Tatiana , Brenner David A. , Bataller Ramon , Ramachandran Prakash , Karin Michael , Fu Wenxian , Schnabl Bernd 
Published: December 2021

AbstractComplement receptor of immunoglobulin superfamily (CRIg) is expressed on liver macrophages and directly binds complement component C3b or Gram-positive bacteria to mediate phagocytosis. CRIg plays important roles in several immune-mediated diseases, but it is not clear how its pathogen recognition and phagocytic functions maintain homeostasis and prevent disease. We previously associated cytolysin-positive Enterococcus faecalis with severity of alcohol-related liver disease. Here, we demonstrate that CRIg is reduced in liver tissues from patients with alcohol-related liver disease. CRIg-deficient mice developed more severe ethanol-induced liver disease than wild-type mice; disease severity was reduced with loss of toll-like receptor 2. CRIg-deficient mice were less efficient than wild-type mice at clearing Gram-positive bacteria such as Enterococcus faecalis that had translocated from gut to liver. Administration of the soluble extracellular domain CRIg–Ig protein protected mice from ethanol-induced steatohepatitis. Our findings indicate that ethanol impairs hepatic clearance of translocated pathobionts, via decreased hepatic CRIg, which facilitates progression of liver disease.
Istaroxime treatment ameliorates calcium dysregulation in a zebrafish model of phospholamban R14del cardiomyopathy
Authors: Kamel S. M. , van Opbergen C. J. M. , Koopman C. D. , Verkerk A. O. , Boukens B. J. D. , de Jonge B. , Onderwater Y. L. , van Alebeek E. , Chocron S. , Polidoro Pontalti C. , Weuring W. J. , Vos M. A. , de Boer T. P. , van Veen T. A. B. , Bakkers J. 
Published: December 2021

AbstractThe heterozygous Phospholamban p.Arg14del mutation is found in patients with dilated or arrhythmogenic cardiomyopathy. This mutation triggers cardiac contractile dysfunction and arrhythmogenesis by affecting intracellular Ca2+ dynamics. Little is known about the physiological processes preceding induced cardiomyopathy, which is characterized by sub-epicardial accumulation of fibrofatty tissue, and a specific drug treatment is currently lacking. Here, we address these issues using a knock-in Phospholamban p.Arg14del zebrafish model. Hearts from adult zebrafish with this mutation display age-related remodeling with sub-epicardial inflammation and fibrosis. Echocardiography reveals contractile variations before overt structural changes occur, which correlates at the cellular level with action potential duration alternans. These functional alterations are preceded by diminished Ca2+ transient amplitudes in embryonic hearts as well as an increase in diastolic Ca2+ level, slower Ca2+ transient decay and longer Ca2+ transients in cells of adult hearts. We find that istaroxime treatment ameliorates the in vivo Ca2+ dysregulation, rescues the cellular action potential duration alternans, while it improves cardiac relaxation. Thus, we present insight into the pathophysiology of Phospholamban p.Arg14del cardiomyopathy.
Vanishing weekly hydropeaking cycles in American and Canadian rivers
Authors: Déry Stephen J. , Hernández-Henríquez Marco A. , Stadnyk Tricia A. , Troy Tara J. 
Published: December 2021

AbstractSub-daily and weekly flow cycles termed ‘hydropeaking’ are common features in regulated rivers worldwide. Weekly flow periodicity arises from fluctuating electricity demand and production tied to socioeconomic activity, typically with higher consumption during weekdays followed by reductions on weekends. Here, we propose a weekly hydropeaking index to quantify the 1920–2019 intensity and prevalence of weekly hydropeaking cycles at 500 sites across the United States of America and Canada. A robust weekly hydropeaking signal exists at 1.8% of sites starting in 1920, peaking at 18.9% in 1963, and diminishing to 3.1% in 2019, marking a 21st century decline in weekly hydropeaking intensity. We propose this decline may be tied to recent, above-average precipitation, socioeconomic shifts, alternative energy production, and legislative and policy changes impacting water management in regulated systems. Vanishing weekly hydropeaking cycles may offset some of the prior deleterious ecohydrological impacts from hydropeaking in highly regulated rivers.
Population analysis of Legionella pneumophila reveals a basis for resistance to complement-mediated killing
Authors: Wee Bryan A. , Alves Joana , Lindsay Diane S. J. , Klatt Ann-Brit , Sargison Fiona A. , Cameron Ross L. , Pickering Amy , Gorzynski Jamie , Corander Jukka , Marttinen Pekka , Opitz Bastian , Smith Andrew J. , Fitzgerald J. Ross 
Published: December 2021

AbstractLegionella pneumophila is the most common cause of the severe respiratory infection known as Legionnaires’ disease. However, the microorganism is typically a symbiont of free-living amoeba, and our understanding of the bacterial factors that determine human pathogenicity is limited. Here we carried out a population genomic study of 902 L. pneumophila isolates from human clinical and environmental samples to examine their genetic diversity, global distribution and the basis for human pathogenicity. We find that the capacity for human disease is representative of the breadth of species diversity although some clones are more commonly associated with clinical infections. We identified a single gene (lag-1) to be most strongly associated with clinical isolates. lag-1, which encodes an O-acetyltransferase for lipopolysaccharide modification, has been distributed horizontally across all major phylogenetic clades of L. pneumophila by frequent recent recombination events. The gene confers resistance to complement-mediated killing in human serum by inhibiting deposition of classical pathway molecules on the bacterial surface. Furthermore, acquisition of lag-1 inhibits complement-dependent phagocytosis by human neutrophils, and promoted survival in a mouse model of pulmonary legionellosis. Thus, our results reveal L. pneumophila genetic traits linked to disease and provide a molecular basis for resistance to complement-mediated killing.
Theranostic near-infrared-IIb emitting nanoprobes for promoting immunogenic radiotherapy and abscopal effects against cancer metastasis
Authors: Li Hao , Wang Meng , Huang Biao , Zhu Su-Wen , Zhou Jun-Jie , Chen De-Run , Cui Ran , Zhang Mingxi , Sun Zhi-Jun 
Published: December 2021

AbstractRadiotherapy is an important therapeutic strategy for cancer treatment through direct damage to cancer cells and augmentation of antitumor immune responses. However, the efficacy of radiotherapy is limited by hypoxia-mediated radioresistance and immunosuppression in tumor microenvironment. Here, we construct a stabilized theranostic nanoprobe based on quantum dots emitting in the near-infrared IIb (NIR-IIb, 1,500–1,700 nm) window modified by catalase, arginine–glycine–aspartate peptides and poly(ethylene glycol). We demonstrate that the nanoprobes effectively aggregate in the tumor site to locate the tumor region, thereby realizing precision radiotherapy with few side-effects. In addition, nanoprobes relieve intratumoral hypoxia and reduce the tumor infiltration of immunosuppressive cells. Moreover, the nanoprobes promote the immunogenic cell death of cancer cells to trigger the activation of dendritic cells and enhance T cell-mediated antitumor immunity to inhibit tumor metastasis. Collectively, the nanoprobe-mediated immunogenic radiotherapy can boost the abscopal effect to inhibit tumor metastasis and prolong survival.
NuMA regulates mitotic spindle assembly, structural dynamics and function via phase separation
Authors: Sun Mengjie , Jia Mingkang , Ren He , Yang Biying , Chi Wangfei , Xin Guangwei , Jiang Qing , Zhang Chuanmao 
Published: December 2021

AbstractA functional mitotic spindle is essential for accurate chromosome congression and segregation during cell proliferation; however, the underlying mechanisms of its assembly remain unclear. Here we show that NuMA regulates this assembly process via phase separation regulated by Aurora A. NuMA undergoes liquid-liquid phase separation during mitotic entry and KifC1 facilitates NuMA condensates concentrating on spindle poles. Phase separation of NuMA is mediated by its C-terminus, whereas its dynein-dynactin binding motif also facilitates this process. Phase-separated NuMA droplets concentrate tubulins, bind microtubules, and enrich crucial regulators, including Kif2A, at the spindle poles, which then depolymerizes spindle microtubules and promotes poleward spindle microtubule flux for spindle assembly and structural dynamics. In this work, we show that NuMA orchestrates mitotic spindle assembly, structural dynamics and function via liquid-liquid phase separation regulated by Aurora A phosphorylation.
Valley-filling instability and critical magnetic field for interaction-enhanced Zeeman response in doped WSe2 monolayers
Authors: Xuan Fengyuan , Quek Su Ying 
Published: December 2021

AbstractCarrier-doped transition metal dichalcogenide (TMD) monolayers are of great interest in valleytronics due to the large Zeeman response (g-factors) in these spin-valley-locked materials, arising from many-body interactions. We develop an ab initio approach based on many-body perturbation theory to compute the interaction-enhanced g-factors in carrier-doped materials. We show that the g-factors of doped WSe2 monolayers are enhanced by screened-exchange interactions resulting from magnetic-field-induced changes in band occupancies. Our interaction-enhanced g-factors g* agree well with experiment. Unlike traditional valleytronic materials such as silicon, the enhancement in g-factor vanishes beyond a critical magnetic field Bc achievable in standard laboratories. We identify ranges of g* for which this change in g-factor at Bc leads to a valley-filling instability and Landau level alignment, which is important for the study of quantum phase transitions in doped TMDs. We further demonstrate how to tune the g-factors and optimize the valley-polarization for the valley Hall effect.
COPEX: co-evolutionary crystal structure prediction algorithm for complex systems
Authors: Liu Xiangyang , Niu Haiyang , Oganov Artem R. 
Published: December 2021

AbstractCrystal structure prediction has been widely used to accelerate the discovery of new materials in recent years. Up to this day, it remains a challenge to predict the stable stoichiometries and structures of ternary or more complex systems due to the explosive increase of the size of the chemical and configurational space. Numerous novel materials with a series of unique characteristics are expected to be found in this virgin territory while new algorithms to predict crystal structures in complex systems are urgently called for. Inspired by co-evolution in biology, here we propose a co-evolutionary algorithm, which we name COPEX, and which is based on the well-known evolutionary algorithm USPEX. Within this proposed algorithm, a few USPEX calculations for ternary systems and multiple for energetically-favored pseudobinary or fixed-composition systems are carried out in parallel, and co-evolution is achieved by sharing structural information on the fittest individuals among different USPEX sub-processes during the joint evolution. We have applied the algorithm to W–Cr–B, Mg–Si–O, and Hf–Ta–C, three very different systems, and many ternary compounds have been identified. Our results clearly demonstrate that the COPEX algorithm combines efficiency and reliability even for complex systems.
Dynamic synthesis of Heisenberg-limited spin squeezing
Authors: Huang Long-Gang , Chen Feng , Li Xinwei , Li Yaohua , Lü Rong , Liu Yong-Chun 
Published: December 2021

AbstractSpin squeezing is a key resource in quantum metrology, allowing improvements of measurement signal-to-noise ratio. Its generation is a challenging task because the experimental realization of the required squeezing interaction remains difficult. Here, we propose a generic scheme to synthesize spin squeezing in non-squeezing systems. By using periodical rotation pulses, the original non-squeezing interaction can be transformed into squeezing interaction, with significantly enhanced interaction strength. The sign of the interaction coefficient is also flippable, facilitating time-reversal readout protocol for nonlinear interferometers. The generated spin squeezing is capable of achieving the Heisenberg limit with measurement precision ∝ 1/N for N particles and its robustness to noises of pulse areas and separations has been verified as well. This work offers a path to extending the scope of Heisenberg-limited quantum precision measurements in non-squeezing systems.
A phase 1/2 trial of an immune-modulatory vaccine against IDO/PD-L1 in combination with nivolumab in metastatic melanoma
Authors: Kjeldsen Julie Westerlin , Lorentzen Cathrine Lund , Martinenaite Evelina , Ellebaek Eva , Donia Marco , Holmstroem Rikke Boedker , Klausen Tobias Wirenfeldt , Madsen Cecilie Oelvang , Ahmed Shamaila Munir , Weis-Banke Stine Emilie , Holmström Morten Orebo , Hendel Helle Westergren , Ehrnrooth Eva , Zocca Mai-Britt , Pedersen Ayako Wakatsuki , Andersen Mads Hald , Svane Inge Marie 
Published: December 2021

AbstractAnti-programmed death (PD)-1 (aPD1) therapy is an effective treatment for metastatic melanoma (MM); however, over 50% of patients progress due to resistance. We tested a first-in-class immune-modulatory vaccine (IO102/IO103) against indoleamine 2,3-dioxygenase (IDO) and PD ligand 1 (PD-L1), targeting immunosuppressive cells and tumor cells expressing IDO and/or PD-L1 (IDO/PD-L1), combined with nivolumab. Thirty aPD1 therapy-naive patients with MM were treated in a phase 1/2 study (https://clinicaltrials.gov/, NCT03047928). The primary endpoint was feasibility and safety; the systemic toxicity profile was comparable to that of nivolumab monotherapy. Secondary endpoints were efficacy and immunogenicity; an objective response rate (ORR) of 80% (confidence interval (CI), 62.7–90.5%) was reached, with 43% (CI, 27.4–60.8%) complete responses. After a median follow-up of 22.9 months, the median progression-free survival (PFS) was 26 months (CI, 15.4–69 months). Median overall survival (OS) was not reached. Vaccine-specific responses assessed in vitro were detected in the blood of >93% of patients during vaccination. Vaccine-reactive T cells comprised CD4+ and CD8+ T cells with activity against IDO- and PD-L1-expressing cancer and immune cells. T cell influx of peripherally expanded T cells into tumor sites was observed in responding patients, and general enrichment of IDO- and PD-L1-specific clones after treatment was documented. These clinical efficacy and favorable safety data support further validation in a larger randomized trial to confirm the clinical potential of this immunomodulating approach.