bluuebunny/crossref_metadata_2025_split huggingface dataset:
FORTIS: a live-cell assay to monitor AMPA receptors using pH-sensitive fluorescence tags
Authors: Calleja-Felipe María , Wojtas Magdalena Natalia , Diaz-González Marta , Ciceri Dalila , Escribano Raúl , Ouro Alberto , Morales Miguel , Knafo Shira 
Published: May 2021

AbstractThe real-time live fluorescent monitoring of surface AMPA receptors (AMPARs) could open new opportunities for drug discovery and phenotypic screening concerning neuropsychiatric disorders. We have developed FORTIS, a tool based on pH sensitivity capable of detecting subtle changes in surface AMPARs at a neuronal population level. The expression of SEP-GluA1 or pHuji-GluA1 recombinant AMPAR subunits in mammalian neurons cultured in 96-well plates enables surface AMPARs to be monitored with a microplate reader. Thus, FORTIS can register rapid changes in surface AMPARs induced by drugs or genetic modifications without having to rely on conventional electrophysiology or imaging. By combining FORTIS with pharmacological manipulations, basal surface AMPARs, and plasticity-like changes can be monitored. We expect that employing FORTIS to screen for changes in surface AMPARs will accelerate both neuroscience research and drug discovery.
FLT3 mutated acute myeloid leukemia: 2021 treatment algorithm
Authors: Daver Naval , Venugopal Sangeetha , Ravandi Farhad 
Published: May 2021

AbstractApproximately 30% of patients with newly diagnosed acute myeloid leukemia (AML) harbor mutations in the fms-like tyrosine kinase 3 (FLT3) gene. While the adverse prognostic impact of FLT3-ITDmut in AML has been clearly proven, the prognostic significance of FLT3-TKDmut remains speculative. Current guidelines recommend rapid molecular testing for FLT3mut at diagnosis and earlier incorporation of targeted agents to achieve deeper remissions and early consideration for allogeneic stem cell transplant (ASCT). Mounting evidence suggests that FLT3mut can emerge at any timepoint in the disease spectrum emphasizing the need for repetitive mutational testing not only at diagnosis but also at each relapse. The approval of multi-kinase FLT3 inhibitor (FLT3i) midostaurin with induction therapy for newly diagnosed FLT3mut AML, and a more specific, potent FLT3i, gilteritinib as monotherapy for relapsed/refractory (R/R) FLT3mut AML have improved outcomes in patients with FLT3mut AML. Nevertheless, the short duration of remission with single-agent FLT3i’s in R/R FLT3mut AML in the absence of ASCT, limited options in patients refractory to gilteritinib therapy, and diverse primary and secondary mechanisms of resistance to different FLT3i’s remain ongoing challenges that compel the development and rapid implementation of multi-agent combinatorial or sequential therapies for FLT3mut AML.
Human stem cells harboring a suicide gene improve the safety and standardisation of neural transplants in Parkinsonian rats
Authors: de Luzy Isabelle R. , Law Kevin C. L. , Moriarty Niamh , Hunt Cameron P. J. , Durnall Jennifer C. , Thompson Lachlan H. , Nagy Andras , Parish Clare L. 
Published: May 2021

AbstractDespite advancements in human pluripotent stem cells (hPSCs) differentiation protocols to generate appropriate neuronal progenitors suitable for transplantation in Parkinson’s disease, resultant grafts contain low proportions of dopamine neurons. Added to this is the tumorigenic risk associated with the potential presence of incompletely patterned, proliferative cells within grafts. Here, we utilised a hPSC line carrying a FailSafeTM suicide gene (thymidine kinase linked to cyclinD1) to selectively ablate proliferative cells in order to improve safety and purity of neural transplantation in a Parkinsonian model. The engineered FailSafeTM hPSCs demonstrated robust ventral midbrain specification in vitro, capable of forming neural grafts upon transplantation. Activation of the suicide gene within weeks after transplantation, by ganciclovir administration, resulted in significantly smaller grafts without affecting the total yield of dopamine neurons, their capacity to innervate the host brain or reverse motor deficits at six months in a rat Parkinsonian model. Within ganciclovir-treated grafts, other neuronal, glial and non-neural populations (including proliferative cells), were significantly reduced—cell types that may pose adverse or unknown influences on graft and host function. These findings demonstrate the capacity of a suicide gene-based system to improve both the standardisation and safety of hPSC-derived grafts in a rat model of Parkinsonism.
Quantized spin Hall conductance in a magnetically doped two dimensional topological insulator
Authors: Shamim Saquib , Beugeling Wouter , Shekhar Pragya , Bendias Kalle , Lunczer Lukas , Kleinlein Johannes , Buhmann Hartmut , Molenkamp Laurens W. 
Published: May 2021

AbstractSoon after the discovery of the quantum spin Hall effect, it has been predicted that a magnetic impurity in the presence of strong Coulomb interactions will destroy the quantum spin Hall effect. However, the fate of the quantum spin Hall effect in the presence of magnetic impurities has not yet been experimentally investigated. Here, we report the successful experimental demonstration of a quantized spin Hall resistance in HgTe quantum wells dilutely alloyed with magnetic Mn atoms. These quantum wells exhibit an inverted band structure that is very similar to that of the undoped material. Micron sized devices of (Hg,Mn)Te quantum well (in the topological phase) show a quantized spin Hall resistance of h/2e2 at low temperatures and zero magnetic field. At finite temperatures, we observe signatures of the Kondo effect due to interaction between the helical edge channels and magnetic impurities. Our work lays the foundation for future investigations of magnetically doped quantum spin Hall materials towards the realization of chiral Majorana fermions.
Salting-out effect promoting highly efficient ambient ammonia synthesis
Authors: Wang Mengfan , Liu Sisi , Ji Haoqing , Yang Tingzhou , Qian Tao , Yan Chenglin 
Published: May 2021

AbstractThe electroreduction of nitrogen to ammonia offers a promising alternative to the energy-intensive Haber–Bosch process. Unfortunately, the reaction suffers from low activity and selectivity, owing to competing hydrogen evolution and the poor accessibility of nitrogen to the electrocatalyst. Here, we report that deliberately triggering a salting-out effect in a highly concentrated electrolyte can simultaneously tackle the above challenges and achieve highly efficient ammonia synthesis. The solute ions exhibit strong affinity for the surrounding H2O molecules, forming a hydration shell and limiting their efficacy as both proton sources and solvents. This not only effectively suppresses hydrogen evolution but also ensures considerable nitrogen flux at the reaction interface via heterogeneous nucleation of the precipitate, thus facilitating the subsequent reduction process in terms of both selectivity and activity. As expected, even when assembled with a metal-free electrocatalyst, a high Faradaic efficiency of 71 ± 1.9% is achieved with this proof-of-concept system.
Modularity and composite diversity affect the collective gathering of information online
Authors: Pescetelli Niccolò , Rutherford Alex , Rahwan Iyad 
Published: May 2021

AbstractMany modern interactions happen in a digital space, where automated recommendations and homophily can shape the composition of groups interacting together and the knowledge that groups are able to tap into when operating online. Digital interactions are also characterized by different scales, from small interest groups to large online communities. Here, we manipulate the composition of groups based on a large multi-trait profiling space (including demographic, professional, psychological and relational variables) to explore the causal link between group composition and performance as a function of group size. We asked volunteers to search news online under time pressure and measured individual and group performance in forecasting real geo-political events. Our manipulation affected the correlation of forecasts made by people after online searches. Group composition interacted with group size so that composite diversity benefited individual and group performance proportionally to group size. Aggregating opinions of modular crowds composed of small independent groups achieved better forecasts than aggregating a similar number of forecasts from non-modular ones. Finally, we show differences existing among groups in terms of disagreement, speed of convergence to consensus forecasts and within-group variability in performance. The present work sheds light on the mechanisms underlying effective online information gathering in digital environments.
Systemic metastasis-targeted nanotherapeutic reinforces tumor surgical resection and chemotherapy
Authors: Xu Minjun , Hu Kaili , Liu Yipu , Huang Yukun , Liu Shanshan , Chen Yu , Wang Dayuan , Zhou Songlei , Zhang Qian , Mei Ni , Lu Huiping , Li Fengan , Gao Xiaoling , Chen Jun 
Published: May 2021

AbstractFailure of conventional clinical therapies such as tumor resection and chemotherapy are mainly due to the ineffective control of tumor metastasis. Metastasis consists of three steps: (i) tumor cells extravasate from the primary sites into the circulation system via epithelial-mesenchymal transition (EMT), (ii) the circulating tumor cells (CTCs) form “micro-thrombi” with platelets to evade the immune surveillance in circulation, and (iii) the CTCs colonize in the pre-metastatic niche. Here, we design a systemic metastasis-targeted nanotherapeutic (H@CaPP) composed of an anti-inflammatory agent, piceatannol, and an anti-thrombotic agent, low molecular weight heparin, to hinder the multiple steps of tumor metastasis. H@CaPP is found efficiently impeded EMT, inhibited the formation of “micro-thrombi”, and prevented the development of pre-metastatic niche. When combined with surgical resection or chemotherapy, H@CaPP efficiently inhibits tumor metastasis and prolonged overall survival of tumor-bearing mice. Collectively, we provide a simple and effective systemic metastasis-targeted nanotherapeutic for combating tumor metastasis.
Neratinib plus trastuzumab is superior to pertuzumab plus trastuzumab in HER2-positive breast cancer xenograft models
Authors: Veeraraghavan Jamunarani , Gutierrez Carolina , Sethunath Vidyalakshmi , Mehravaran Sepideh , Giuliano Mario , Shea Martin J. , Mitchell Tamika , Wang Tao , Nanda Sarmistha , Pereira Resel , Davis Robert , Goutsouliak Kristina , Qin Lanfang , De Angelis Carmine , Diala Irmina , Lalani Alshad S. , Nagi Chandandeep , Hilsenbeck Susan G. , Rimawi Mothaffar F. , Osborne C. Kent , Schiff Rachel 
Published: May 2021

AbstractLapatinib (L) plus trastuzumab (T), with endocrine therapy for estrogen receptor (ER)+ tumors, but without chemotherapy, yielded meaningful response in HER2+ breast cancer (BC) neoadjuvant trials. The irreversible/pan-HER inhibitor neratinib (N) has proven more potent than L. However, the efficacy of N+T in comparison to pertuzumab (P) + T or L + T (without chemotherapy) remains less studied. To address this, mice bearing HER2+ BT474-AZ (ER+) cell and BCM-3963 patient-derived BC xenografts were randomized to vehicle, N, T, P, N+T, or P+T, with simultaneous estrogen deprivation for BT474-AZ. Time to tumor regression/progression and incidence/time to complete response (CR) were determined. Changes in key HER pathway and proliferative markers were assessed by immunohistochemistry and western blot of short-term-treated tumors. In the BT474-AZ model, while all N, P, T, N + T, and P + T treated tumors regressed, N + T-treated tumors regressed faster than P, T, and P + T. Further, N + T was superior to N and T alone in accelerating CR. In the BCM-3963 model, which was refractory to T, P, and P + T, while N and N + T yielded 100% CR, N + T accelerated the CR compared to N. Ki67, phosphorylated (p) AKT, pS6, and pERK levels were largely inhibited by N and N + T, but not by T, P, or P + T. Phosphorylated HER receptor levels were also markedly inhibited by N and N + T, but not by P + T or L + T. Our findings establish the efficacy of combining N with T and support clinical testing to investigate the efficacy of N + T with or without chemotherapy in the neoadjuvant setting for HER2+ BC.
Dataset of low global warming potential refrigerant refrigeration system for fault detection and diagnostics
Authors: Sun Jian , Im Piljae , Bae Yeonjin , Munk Jeff , Kuruganti Teja , Fricke Brian 
Published: May 2021

AbstractHVAC and refrigeration system fault detection and diagnostics (FDD) has attracted extensive studies for decades; however, FDD of supermarket refrigeration systems has not gained significant attention. Supermarkets consume around 50 kWh/ft2 of electricity annually. The biggest consumer of energy in a supermarket is its refrigeration system, which accounts for 40%–60% of its total electricity usage and is equivalent to about 2%–3% of the total energy consumed by commercial buildings in the United States. Also, the supermarket refrigeration system is one of the biggest consumers of refrigerants. Reducing refrigerant usage or using environmentally friendly alternatives can result in significant climate benefits. A challenge is the lack of publicly available data sets to benchmark the system performance and record the faulted performance. This paper identifies common faults of supermarket refrigeration systems and conducts an experimental study to collect the faulted performance data and analyze these faults. This work provides a foundation for future research on the development of FDD methods and field automated FDD implementation.
New insights on interpersonal violence in the Late Pleistocene based on the Nile valley cemetery of Jebel Sahaba
Authors: Crevecoeur Isabelle , Dias-Meirinho Marie-Hélène , Zazzo Antoine , Antoine Daniel , Bon François 
Published: May 2021

AbstractThe remains of 61 individuals buried in the cemetery of Jebel Sahaba (site 117) offer unique and substantial evidence to the emergence of violence in the Nile Valley at the end of the Late Pleistocene. Excavated and assessed in the 1960s, some of the original findings and interpretations are disputed. A full reanalysis of the timing, nature and extent of the violence was conducted through the microscopic characterization of the nature of each osseous lesion, and the reassessment of the archaeological data. Over 100 previously undocumented healed and unhealed lesions were identified on both new and/or previously identified victims, including several embedded lithic artefacts. Most trauma appears to be the result of projectile weapons and new analyses confirm for the first time the repetitive nature of the interpersonal acts of violence. Indeed, a quarter of the skeletons with lesions exhibit both healed and unhealed trauma. We dismiss the hypothesis that Jebel Sahaba reflects a single warfare event, with the new data supporting sporadic and recurrent episodes of inter-personal violence, probably triggered by major climatic and environmental changes. At least 13.4 ka old, Jebel Sahaba is one of the earliest sites displaying interpersonal violence in the world.
Investigating the relationship between women’s experience of intimate partner violence and utilization of maternal healthcare services in India
Authors: Paul Pintu , Mondal Dinabandhu 
Published: May 2021

AbstractThe utilization of maternal healthcare services is a key measure to reduce the incidence of maternal mortality. This study aims to examine the relationship between women’s exposure to intimate partner violence (IPV) and the utilization of maternal healthcare services, using a large-scale nationally representative data among Indian women. Data for this study were drawn from the fourth round of the National Family Health Survey (NFHS-4), which is collected during 2015–2016. In order to analyze, we utilized 24,882 currently married women aged 15–49 years who had at least one living child in the past five years preceding the survey. Women’s experience of IPV, which is manifested in various forms of physical, emotional, and/or sexual violence perpetrated by the partner, was considered as the key explanatory variable. Adequate antenatal care (ANC) [four or more ANC visits], delivery assistance by the skilled health provider, and postnatal care (PNC) within two days of delivery were used as outcome variables for assessing the utilization of maternal healthcare services. Descriptive statistics, cross-tabulation, Pearson’s chi-square test, and bivariate and multivariate logistic regression models were used in this study. Approximately 26% of the sample women (currently married) experienced any form of IPV in the past year. Bivariate analyses show that the utilization of all three components of maternal healthcare services was lower among women who experienced physical, sexual, or emotional violence, as compared to those who did not face any violence perpetrated by the partner. Multivariate analysis indicates that women’s exposure to IPV was significantly associated with a lower likelihood of adequate ANC utilization (Adjusted Odds Ratio [OR]: 0.90, 95% CI 0.84–0.97), even after controlling for socio-demographic characteristics. However, IPV had no significant relationship with skilled delivery assistance and unexpectedly a positive association with PNC usage (Adjusted OR: 1.09, 95% CI 1.02–1.16) in the adjusted analysis. Our study suggests formulating strategies toward the prevention of husband-perpetrated violence against women and targeting women who experienced spousal violence to improve their utilization of maternal healthcare services.
A heterogeneous subcontinental mantle under the African–Arabian Plate boundary revealed by boron and radiogenic isotopes
Authors: Agostini Samuele , Di Giuseppe Paolo , Manetti Piero , Doglioni Carlo , Conticelli Sandro 
Published: May 2021

AbstractThe northern and northwestern margins of the Arabian Plate are a locus of a diffuse and long-lasting (early Miocene to Pleistocene) Na-alkali basaltic volcanism, sourced in the asthenosphere mantle. The upwelling asthenosphere at the Africa–Arabia margin produces very limited magma volumes in the axial zone. Therefore, portions of hot, fertile mantle continue their eastward migration and are stored at shallower depths under the 100-km thick Arabian lithosphere, which is much thinner than the African one (≈175 km): this causes the occurrence and 20-Ma persistence of magma supply under the study area. Erupted basalts sampled a continuous variation of the mantle source, with a striking correlation among temperature, pressure and isotopic composition shifting between two end members: a 100 km-deep, more depleted source, and a 60 km-deep, more enriched one. In particular, we observed an unusual variation in boron isotopes, which in the oceanic domain does not vary between more depleted and more enriched mantle sources. This study shows that, at least in the considered region, subcontinental mantle is more heterogeneous than the suboceanic one, and able to record for very long times recycling of shallow material.
Evolution of opposing regulatory interactions underlies the emergence of eukaryotic cell cycle checkpoints
Authors: Hernansaiz-Ballesteros Rosa D. , Földi Csenge , Cardelli Luca , Nagy László G. , Csikász-Nagy Attila 
Published: May 2021

AbstractIn eukaryotes the entry into mitosis is initiated by activation of cyclin-dependent kinases (CDKs), which in turn activate a large number of protein kinases to induce all mitotic processes. The general view is that kinases are active in mitosis and phosphatases turn them off in interphase. Kinases activate each other by cross- and self-phosphorylation, while phosphatases remove these phosphate groups to inactivate kinases. Crucial exceptions to this general rule are the interphase kinase Wee1 and the mitotic phosphatase Cdc25. Together they directly control CDK in an opposite way of the general rule of mitotic phosphorylation and interphase dephosphorylation. Here we investigate why this opposite system emerged and got fixed in almost all eukaryotes. Our results show that this reversed action of a kinase-phosphatase pair, Wee1 and Cdc25, on CDK is particularly suited to establish a stable G2 phase and to add checkpoints to the cell cycle. We show that all these regulators appeared together in LECA (Last Eukaryote Common Ancestor) and co-evolved in eukaryotes, suggesting that this twist in kinase-phosphatase regulation was a crucial step happening at the emergence of eukaryotes.
Complex network model indicates a positive effect of inspiratory muscles pre-activation on performance parameters in a judo match
Authors: Cirino Carolina , Gobatto Claudio A. , Pinto Allan S. , Torres Ricardo S. , Hartz Charlini S. , Azevedo Paulo H. S. M. , Moreno Marlene A. , Manchado-Gobatto Fúlvia B. 
Published: May 2021

AbstractThis study investigated the effects of inspiratory muscle pre-activation (IMPA) on the interactions among the technical-tactical, physical, physiological, and psychophysiological parameters in a simulated judo match, based on the centrality metrics by complex network model. Ten male athletes performed 4 experimental sessions. Firstly, anthropometric measurements, maximal inspiratory pressure (MIP) and global strenght of the inspiratory muscles were determined. In the following days, all athletes performed four-minute video-recorded judo matches, under three conditions: without IMPA(CON), after IMPAat 15% (IMPA15), and at 40% (IMPA40) of MIP using an exerciser device. Blood lactate, heart rate and rating of perceived exertion were monitored, and the technical-tactical parameters during the match were related to offensive actions and the time-motion. Based on the complex network, graphs were constructed for each scenario (CON, IMPA15, and IMPA40) to investigate the Degree and Pagerank centrality metrics. IMPA40 increased the connectivity of the physical and technical-tactical parameters in complex network and highlighted the combat frequency and average combat time in top-five ranked nodes. IMPA15 also favoured the interactions among the psychophysiological, physical, and physiological parameters. Our results suggest the positive effects of the IMPA, indicating this strategy to prepare the organism (IMPA15) and to improve performance (IMPA40) in judo match.
Activity in the brain’s valuation and mentalizing networks is associated with propagation of online recommendations
Authors: Baek Elisa C. , O’Donnell Matthew Brook , Scholz Christin , Pei Rui , Garcia Javier O. , Vettel Jean M. , Falk Emily B. 
Published: May 2021

AbstractWord of mouth recommendations influence a wide range of choices and behaviors. What takes place in the mind of recommendation receivers that determines whether they will be successfully influenced? Prior work suggests that brain systems implicated in assessing the value of stimuli (i.e., subjective valuation) and understanding others’ mental states (i.e., mentalizing) play key roles. The current study used neuroimaging and natural language classifiers to extend these findings in a naturalistic context and tested the extent to which the two systems work together or independently in responding to social influence. First, we show that in response to text-based social media recommendations, activity in both the brain’s valuation system and mentalizing system was associated with greater likelihood of opinion change. Second, participants were more likely to update their opinions in response to negative, compared to positive, recommendations, with activity in the mentalizing system scaling with the negativity of the recommendations. Third, decreased functional connectivity between valuation and mentalizing systems was associated with opinion change. Results highlight the role of brain regions involved in mentalizing and positive valuation in recommendation propagation, and further show that mentalizing may be particularly key in processing negative recommendations, whereas the valuation system is relevant in evaluating both positive and negative recommendations.