bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing the influence of climate on wintertime SARS-CoV-2 outbreaks
Authors: Baker Rachel E. , Yang Wenchang , Vecchi Gabriel A. , Metcalf C. Jessica E. , Grenfell Bryan T. 
Published: February 2021

AbstractHigh susceptibility has limited the role of climate in the SARS-CoV-2 pandemic to date. However, understanding a possible future effect of climate, as susceptibility declines and the northern-hemisphere winter approaches, is an important open question. Here we use an epidemiological model, constrained by observations, to assess the sensitivity of future SARS-CoV-2 disease trajectories to local climate conditions. We find this sensitivity depends on both the susceptibility of the population and the efficacy of non-pharmaceutical interventions (NPIs) in reducing transmission. Assuming high susceptibility, more stringent NPIs may be required to minimize outbreak risk in the winter months. Our results suggest that the strength of NPIs remain the greatest determinant of future pre-vaccination outbreak size. While we find a small role for meteorological forecasts in projecting outbreak severity, reducing uncertainty in epidemiological parameters will likely have a more substantial impact on generating accurate predictions.
Genome-wide fine-mapping identifies pleiotropic and functional variants that predict many traits across global cattle populations
Authors: Xiang Ruidong , MacLeod Iona M. , Daetwyler Hans D. , de Jong Gerben , O’Connor Erin , Schrooten Chris , Chamberlain Amanda J. , Goddard Michael E. 
Published: February 2021

AbstractThe difficulty in finding causative mutations has hampered their use in genomic prediction. Here, we present a methodology to fine-map potentially causal variants genome-wide by integrating the functional, evolutionary and pleiotropic information of variants using GWAS, variant clustering and Bayesian mixture models. Our analysis of 17 million sequence variants in 44,000+ Australian dairy cattle for 34 traits suggests, on average, one pleiotropic QTL existing in each 50 kb chromosome-segment. We selected a set of 80k variants representing potentially causal variants within each chromosome segment to develop a bovine XT-50K genotyping array. The custom array contains many pleiotropic variants with biological functions, including splicing QTLs and variants at conserved sites across 100 vertebrate species. This biology-informed custom array outperformed the standard array in predicting genetic value of multiple traits across populations in independent datasets of 90,000+ dairy cattle from the USA, Australia and New Zealand.
Host interneurons mediate plasticity reactivated by embryonic inhibitory cell transplantation in mouse visual cortex
Authors: Zheng XiaoTing , Salinas Kirstie J. , Velez Dario X. Figueroa , Nakayama Taylor , Lin Xiaoxiao , Banerjee Dhruba , Xu Xiangmin , Gandhi Sunil P. 
Published: February 2021

AbstractThe adult brain lacks sensitivity to changes in the sensory environment found in the juvenile brain. The transplantation of embryonic interneurons has been shown to restore juvenile plasticity to the adult host visual cortex. It is unclear whether transplanted interneurons directly mediate the renewed cortical plasticity or whether these cells act indirectly by modifying the host interneuron circuitry. Here we find that the transplant-induced reorganization of mouse host circuits is specifically mediated by Neuregulin (NRG1)/ErbB4 signaling in host parvalbumin (PV) interneurons. Brief visual deprivation reduces the visual activity of host PV interneurons but has negligible effects on the responses of transplanted PV interneurons. Exogenous NRG1 both prevents the deprivation-induced reduction in the visual responses of host PV interneurons and blocks the transplant-induced reorganization of the host circuit. While deletion of ErbB4 receptors from host PV interneurons blocks cortical plasticity in the transplant recipients, deletion of the receptors from the donor PV interneurons does not. Altogether, our results indicate that transplanted embryonic interneurons reactivate cortical plasticity by rejuvenating the function of host PV interneurons.
SARS-CoV-2 D614G spike mutation increases entry efficiency with enhanced ACE2-binding affinity
Authors: Ozono Seiya , Zhang Yanzhao , Ode Hirotaka , Sano Kaori , Tan Toong Seng , Imai Kazuo , Miyoshi Kazuyasu , Kishigami Satoshi , Ueno Takamasa , Iwatani Yasumasa , Suzuki Tadaki , Tokunaga Kenzo 
Published: February 2021

AbstractThe causative agent of the COVID-19 pandemic, SARS-CoV-2, is steadily mutating during continuous transmission among humans. Such mutations can occur in the spike (S) protein that binds to the ACE2 receptor and is cleaved by TMPRSS2. However, whether S mutations affect SARS-CoV-2 cell entry remains unknown. Here, we show that naturally occurring S mutations can reduce or enhance cell entry via ACE2 and TMPRSS2. A SARS-CoV-2 S-pseudotyped lentivirus exhibits substantially lower entry than that of SARS-CoV S. Among S variants, the D614G mutant shows the highest cell entry, as supported by structural and binding analyses. Nevertheless, the D614G mutation does not affect neutralization by antisera against prototypic viruses. Taken together, we conclude that the D614G mutation increases cell entry by acquiring higher affinity to ACE2 while maintaining neutralization susceptibility. Based on these findings, further worldwide surveillance is required to understand SARS-CoV-2 transmissibility among humans.
Experimental demonstration of quantum advantage for NP verification with limited information
Authors: Centrone Federico , Kumar Niraj , Diamanti Eleni , Kerenidis Iordanis 
Published: February 2021

AbstractIn recent years, many computational tasks have been proposed as candidates for showing a quantum computational advantage, that is an advantage in the time needed to perform the task using a quantum instead of a classical machine. Nevertheless, practical demonstrations of such an advantage remain particularly challenging because of the difficulty in bringing together all necessary theoretical and experimental ingredients. Here, we show an experimental demonstration of a quantum computational advantage in a prover-verifier interactive setting, where the computational task consists in the verification of an NP-complete problem by a verifier who only gets limited information about the proof sent by an untrusted prover in the form of a series of unentangled quantum states. We provide a simple linear optical implementation that can perform this verification task efficiently (within a few seconds), while we also provide strong evidence that, fixing the size of the proof, a classical computer would take much longer time (assuming only that it takes exponential time to solve an NP-complete problem). While our computational advantage concerns a specific task in a scenario of mostly theoretical interest, it brings us a step closer to potential useful applications, such as server-client quantum computing.
Giant optical anisotropy in transition metal dichalcogenides for next-generation photonics
Authors: Ermolaev G. A. , Grudinin D. V. , Stebunov Y. V. , Voronin K. V. , Kravets V. G. , Duan J. , Mazitov A. B. , Tselikov G. I. , Bylinkin A. , Yakubovsky D. I. , Novikov S. M. , Baranov D. G. , Nikitin A. Y. , Kruglov I. A. , Shegai T. , Alonso-González P. , Grigorenko A. N. , Arsenin A. V. , Novoselov K. S. , Volkov V. S. 
Published: February 2021

AbstractLarge optical anisotropy observed in a broad spectral range is of paramount importance for efficient light manipulation in countless devices. Although a giant anisotropy has been recently observed in the mid-infrared wavelength range, for visible and near-infrared spectral intervals, the problem remains acute with the highest reported birefringence values of 0.8 in BaTiS3 and h-BN crystals. This issue inspired an intensive search for giant optical anisotropy among natural and artificial materials. Here, we demonstrate that layered transition metal dichalcogenides (TMDCs) provide an answer to this quest owing to their fundamental differences between intralayer strong covalent bonding and weak interlayer van der Waals interaction. To do this, we made correlative far- and near-field characterizations validated by first-principle calculations that reveal a huge birefringence of 1.5 in the infrared and 3 in the visible light for MoS2. Our findings demonstrate that this remarkable anisotropy allows for tackling the diffraction limit enabling an avenue for on-chip next-generation photonics.
Intrinsic donor-bound excitons in ultraclean monolayer semiconductors
Authors: Rivera Pasqual , He Minhao , Kim Bumho , Liu Song , Rubio-Verdú Carmen , Moon Hyowon , Mennel Lukas , Rhodes Daniel A. , Yu Hongyi , Taniguchi Takashi , Watanabe Kenji , Yan Jiaqiang , Mandrus David G. , Dery Hanan , Pasupathy Abhay , Englund Dirk , Hone James , Yao Wang , Xu Xiaodong 
Published: February 2021

AbstractThe monolayer transition metal dichalcogenides are an emergent semiconductor platform exhibiting rich excitonic physics with coupled spin-valley degree of freedom and optical addressability. Here, we report a new series of low energy excitonic emission lines in the photoluminescence spectrum of ultraclean monolayer WSe2. These excitonic satellites are composed of three major peaks with energy separations matching known phonons, and appear only with electron doping. They possess homogenous spatial and spectral distribution, strong power saturation, and anomalously long population (>6 µs) and polarization lifetimes (>100 ns). Resonant excitation of the free inter- and intravalley bright trions leads to opposite optical orientation of the satellites, while excitation of the free dark trion resonance suppresses the satellitesʼ photoluminescence. Defect-controlled crystal synthesis and scanning tunneling microscopy measurements provide corroboration that these features are dark excitons bound to dilute donors, along with associated phonon replicas. Our work opens opportunities to engineer homogenous single emitters and explore collective quantum optical phenomena using intrinsic donor-bound excitons in ultraclean 2D semiconductors.
Malignant subclone drives metastasis of genetically and phenotypically heterogenous cell clusters through fibrotic niche generation
Authors: Kok Sau Yee , Oshima Hiroko , Takahashi Kei , Nakayama Mizuho , Murakami Kazuhiro , Ueda Hiroki R. , Miyazono Kohei , Oshima Masanobu 
Published: February 2021

AbstractA concept of polyclonal metastasis has recently been proposed, wherein tumor cell clusters break off from the primary site and are disseminated. However, the involvement of driver mutations in such polyclonal mechanism is not fully understood. Here, we show that non-metastatic AP cells metastasize to the liver with metastatic AKTP cells after co-transplantation to the spleen. Furthermore, AKTP cell depletion after the development of metastases results in the continuous proliferation of the remaining AP cells, indicating a role of AKTP cells in the early step of polyclonal metastasis. Importantly, AKTP cells, but not AP cells, induce fibrotic niche generation when arrested in the sinusoid, and such fibrotic microenvironment promotes the colonization of AP cells. These results indicate that non-metastatic cells can metastasize via the polyclonal metastasis mechanism using the fibrotic niche induced by malignant cells. Thus, targeting the fibrotic niche is an effective strategy for halting polyclonal metastasis.
Ancestry-associated transcriptomic profiles of breast cancer in patients of African, Arab, and European ancestry
Authors: Roelands Jessica , Mall Raghvendra , Almeer Hossam , Thomas Remy , Mohamed Mahmoud G. , Bedri Shahinaz , Al-Bader Salha Bujassoum , Junejo Kulsoom , Ziv Elad , Sayaman Rosalyn W. , Kuppen Peter J. K. , Bedognetti Davide , Hendrickx Wouter , Decock Julie 
Published: February 2021

AbstractBreast cancer largely dominates the global cancer burden statistics; however, there are striking disparities in mortality rates across countries. While socioeconomic factors contribute to population-based differences in mortality, they do not fully explain disparity among women of African ancestry (AA) and Arab ancestry (ArA) compared to women of European ancestry (EA). In this study, we sought to identify molecular differences that could provide insight into the biology of ancestry-associated disparities in clinical outcomes. We applied a unique approach that combines the use of curated survival data from The Cancer Genome Atlas (TCGA) Pan-Cancer clinical data resource, improved single-nucleotide polymorphism-based inferred ancestry assignment, and a novel breast cancer subtype classification to interrogate the TCGA and a local Arab breast cancer dataset. We observed an enrichment of BasalMyo tumors in AA patients (38 vs 16.5% in EA, p = 1.30E − 10), associated with a significant worse overall (hazard ratio (HR) = 2.39, p = 0.02) and disease-specific survival (HR = 2.57, p = 0.03). Gene set enrichment analysis of BasalMyo AA and EA samples revealed differences in the abundance of T-regulatory and T-helper type 2 cells, and enrichment of cancer-related pathways with prognostic implications (AA: PI3K-Akt-mTOR and ErbB signaling; EA: EGF, estrogen-dependent and DNA repair signaling). Strikingly, AMPK signaling was associated with opposing prognostic connotation (AA: 10-year HR = 2.79, EA: 10-year HR = 0.34). Analysis of ArA patients suggests enrichment of BasalMyo tumors with a trend for differential enrichment of T-regulatory cells and AMPK signaling. Together, our findings suggest that the disparity in the clinical outcome of AA breast cancer patients is likely related to differences in cancer-related and microenvironmental features.
Label-free characterization of single extracellular vesicles using two-photon fluorescence lifetime imaging microscopy of NAD(P)H
Authors: Sorrells Janet E. , Martin Elisabeth M. , Aksamitiene Edita , Mukherjee Prabuddha , Alex Aneesh , Chaney Eric J. , Marjanovic Marina , Boppart Stephen A. 
Published: February 2021

AbstractThe heterogeneous nature of extracellular vesicles (EVs) creates the need for single EV characterization techniques. However, many common biochemical and functional EV analysis techniques lack single EV resolution. Two-photon fluorescence lifetime imaging microscopy (FLIM) is widely used to functionally characterize the reduced form of nicotinamide adenine dinucleotide and nicotinamide adenine dinucleotide phosphate (NAD(P)H) in cells and tissues. Here, we demonstrate that FLIM can also be used to image and characterize NAD(P)H in single isolated EVs. EVs were isolated using standard differential ultracentrifugation techniques from multiple cell lines and imaged using a custom two-photon FLIM system. The presented data show that the NAD(P)H fluorescence lifetimes in isolated cell-derived EVs follow a wide Gaussian distribution, indicating the presence of a range of different protein-bound and free NAD(P)H species. EV NAD(P)H fluorescence lifetime distribution has a larger standard deviation than that of cells and a significantly different fluorescence lifetime distribution than the nuclei, mitochondria, and cytosol of cells. Additionally, changes in the metabolic conditions of cells were reflected in changes in the mean fluorescence lifetime of NAD(P)H in the produced EVs. These data suggest that FLIM of NAD(P)H could be a valuable tool for EV research.
Systemic nicotine enhances opioid self-administration and modulates the formation of opioid-associated memories partly through actions within the insular cortex
Authors: Loney Gregory C. , King Christopher P. , Meyer Paul J. 
Published: February 2021

AbstractHabitual use of nicotine containing products increases propensity to misuse prescription opioids and its prevalence is substantially increased in individuals currently involved in opioid-treatment programs. Nicotine enhances self-administration of many classes of drugs in rodents, though evidence for direct effects on opioids is lacking. We sought to measure the effects of nicotine pretreatment on the reinforcing efficacy of opioids in both self-administration and contextual conditioning paradigms. First, we measured the effect of systemic nicotine pretreatment on self-administration of two opioids. Additionally, we measured the degree to which systemic nicotine pretreatment impacts the formation of morphine-associated contextual memories in conditioned taste avoidance and place preference paradigms. Given the involvement of the insula in the maintenance of substance abuse, its importance in nicotine addiction, and findings that insular inactivation impairs contextual drug conditioning, we examined whether nicotine administered directly to the insula could recapitulate the effects of systemic nicotine. We demonstrate that systemic nicotine pretreatment significantly enhances opioid self-administration and alters contextual conditioning. Furthermore, intra-insula nicotine similarly altered morphine contextual conditioning by blocking the formation of taste avoidance at all three morphine doses tested (5.0, 10, and 20 mg/kg), while shifting the dose–response curve of morphine in the place preference paradigm rightward. In conclusion, these data demonstrate that nicotine facilitates opioid intake and is partly acting within the insular cortex to obfuscate aversive opiate memories while potentiating approach to morphine-associated stimuli at higher doses.
Meta-analysis of the effect of the pringle maneuver on long-term oncological outcomes following liver resection
Authors: Khajeh Elias , Shafiei Saeed , Al-Saegh Sadeq Ali-Hasan , Ramouz Ali , Hammad Ahmed , Ghamarnejad Omid , Al-Saeedi Mohammed , Rahbari Nuh , Reissfelder Christoph , Mehrabi Arianeb , Probst Pascal , Oweira Hani 
Published: February 2021

AbstractHepatic pedicle clamping reduces intraoperative blood loss and the need for transfusion, but its long-term effect on survival and recurrence remains controversial. The aim of this meta-analysis was to evaluate the effect of the Pringle maneuver (PM) on long-term oncological outcomes in patients with primary or metastatic liver malignancies who underwent liver resection. Literature was searched in the Cochrane Central Register of Controlled Trials (CENTRAL), Medline (via PubMed), and Web of Science databases. Survival was measured as the survival rate or as a continuous endpoint. Pooled estimates were represented as odds ratios (ORs) using the Mantel–Haenszel test with a random-effects model. The literature search retrieved 435 studies. One RCT and 18 NRS, including 7480 patients who underwent liver resection with the PM (4309 cases) or without the PM (3171 cases) were included. The PM did not decrease the 1-year overall survival rate (OR 0.86; 95% CI 0.67–1.09; P = 0.22) or the 3- and 5-year overall survival rates. The PM did not decrease the 1-year recurrence-free survival rate (OR 1.06; 95% CI 0.75–1.50; P = 0.75) or the 3- and 5-year recurrence-free survival rates. There is no evidence that the Pringle maneuver has a negative effect on recurrence-free or overall survival rates.
Deep action learning enables robust 3D segmentation of body organs in various CT and MRI images
Authors: Zhong Xia , Amrehn Mario , Ravikumar Nishant , Chen Shuqing , Strobel Norbert , Birkhold Annette , Kowarschik Markus , Fahrig Rebecca , Maier Andreas 
Published: February 2021

AbstractIn this study, we propose a novel point cloud based 3D registration and segmentation framework using reinforcement learning. An artificial agent, implemented as a distinct actor based on value networks, is trained to predict the optimal piece-wise linear transformation of a point cloud for the joint tasks of registration and segmentation. The actor network estimates a set of plausible actions and the value network aims to select the optimal action for the current observation. Point-wise features that comprise spatial positions (and surface normal vectors in the case of structured meshes), and their corresponding image features, are used to encode the observation and represent the underlying 3D volume. The actor and value networks are applied iteratively to estimate a sequence of transformations that enable accurate delineation of object boundaries. The proposed approach was extensively evaluated in both segmentation and registration tasks using a variety of challenging clinical datasets. Our method has fewer trainable parameters and lower computational complexity compared to the 3D U-Net, and it is independent of the volume resolution. We show that the proposed method is applicable to mono- and multi-modal segmentation tasks, achieving significant improvements over the state-of-the-art for the latter. The flexibility of the proposed framework is further demonstrated for a multi-modal registration application. As we learn to predict actions rather than a target, the proposed method is more robust compared to the 3D U-Net when dealing with previously unseen datasets, acquired using different protocols or modalities. As a result, the proposed method provides a promising multi-purpose segmentation and registration framework, particular in the context of image-guided interventions.
Species traits affect phenological responses to climate change in a butterfly community
Authors: Zografou Konstantina , Swartz Mark T. , Adamidis George C. , Tilden Virginia P. , McKinney Erika N. , Sewall Brent J. 
Published: February 2021

AbstractDiverse taxa have undergone phenological shifts in response to anthropogenic climate change. While such shifts generally follow predicted patterns, they are not uniform, and interspecific variation may have important ecological consequences. We evaluated relationships among species’ phenological shifts (mean flight date, duration of flight period), ecological traits (larval trophic specialization, larval diet composition, voltinism), and population trends in a butterfly community in Pennsylvania, USA, where the summer growing season has become warmer, wetter, and longer. Data were collected over 7–19 years from 18 species or species groups, including the extremely rare eastern regal fritillary Speyeria idalia idalia. Both the direction and magnitude of phenological change over time was linked to species traits. Polyphagous species advanced and prolonged the duration of their flight period while oligophagous species delayed and shortened theirs. Herb feeders advanced their flight periods while woody feeders delayed theirs. Multivoltine species consistently prolonged flight periods in response to warmer temperatures, while univoltine species were less consistent. Butterflies that shifted to longer flight durations, and those that had polyphagous diets and multivoltine reproductive strategies tended to decline in population. Our results suggest species’ traits shape butterfly phenological responses to climate change, and are linked to important community impacts.