bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimating global economic well-being with unlit settlements
Authors: McCallum Ian , Kyba Christopher Conrad Maximillian , Bayas Juan Carlos Laso , Moltchanova Elena , Cooper Matt , Cuaresma Jesus Crespo , Pachauri Shonali , See Linda , Danylo Olga , Moorthy Inian , Lesiv Myroslava , Baugh Kimberly , Elvidge Christopher D. , Hofer Martin , Fritz Steffen 
Published: May 2022

AbstractIt is well established that nighttime radiance, measured from satellites, correlates with economic prosperity across the globe. In developing countries, areas with low levels of detected radiance generally indicate limited development – with unlit areas typically being disregarded. Here we combine satellite nighttime lights and the world settlement footprint for the year 2015 to show that 19% of the total settlement footprint of the planet had no detectable artificial radiance associated with it. The majority of unlit settlement footprints are found in Africa (39%), rising to 65% if we consider only rural settlement areas, along with numerous countries in the Middle East and Asia. Significant areas of unlit settlements are also located in some developed countries. For 49 countries spread across Africa, Asia and the Americas we are able to predict and map the wealth class obtained from ~2,400,000 geo-located households based upon the percent of unlit settlements, with an overall accuracy of 87%.
Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS
Authors: Shi Xiaojian , Reinstadler Bryn , Shah Hardik , To Tsz-Leung , Byrne Katie , Summer Luanna , Calvo Sarah E. , Goldberger Olga , Doench John G. , Mootha Vamsi K. , Shen Hongying 
Published: May 2022

AbstractThe SLC25 carrier family consists of 53 transporters that shuttle nutrients and co-factors across mitochondrial membranes. The family is highly redundant and their transport activities coupled to metabolic state. Here, we use a pooled, dual CRISPR screening strategy that knocks out pairs of transporters in four metabolic states — glucose, galactose, OXPHOS inhibition, and absence of pyruvate — designed to unmask the inter-dependence of these genes. In total, we screen 63 genes in four metabolic states, corresponding to 2016 single and pair-wise genetic perturbations. We recover 19 gene-by-environment (GxE) interactions and 9 gene-by-gene (GxG) interactions. One GxE interaction hit illustrates that the fitness defect in the mitochondrial folate carrier (SLC25A32) KO cells is genetically buffered in galactose due to a lack of substrate in de novo purine biosynthesis. GxG analysis highlights a buffering interaction between the iron transporter SLC25A37 (A37) and the poorly characterized SLC25A39 (A39). Mitochondrial metabolite profiling, organelle transport assays, and structure-guided mutagenesis identify A39 as critical for mitochondrial glutathione (GSH) import. Functional studies reveal that A39-mediated glutathione homeostasis and A37-mediated mitochondrial iron uptake operate jointly to support mitochondrial OXPHOS. Our work underscores the value of studying family-wide genetic interactions across different metabolic environments.
A multiplex platform for small RNA sequencing elucidates multifaceted tRNA stress response and translational regulation
Authors: Watkins Christopher P. , Zhang Wen , Wylder Adam C. , Katanski Christopher D. , Pan Tao 
Published: May 2022

AbstractSmall RNAs include tRNA, snRNA, micro-RNA, tRNA fragments and others that constitute > 90% of RNA copy numbers in a human cell and perform many essential functions. Popular small RNA-seq strategies limit the insights into coordinated small RNA response to cellular stress. Small RNA-seq also lacks multiplexing capabilities. Here, we report a multiplex small RNA-seq library preparation method (MSR-seq) to investigate cellular small RNA and mRNA response to heat shock, hydrogen peroxide, and arsenite stress. Comparing stress-induced changes of total cellular RNA and polysome-associated RNA, we identify a coordinated tRNA response that involves polysome-specific tRNA abundance and synergistic N3-methylcytosine (m3C) tRNA modification. Combining tRNA and mRNA response to stress we reveal a mechanism of stress-induced down-regulation in translational elongation. We also find that native tRNA molecules lacking several modifications are biased reservoirs for the biogenesis of tRNA fragments. Our results demonstrate the importance of simultaneous investigation of small RNAs and their modifications in response to varying biological conditions.
Detecting positive quantum capacities of quantum channels
Authors: Singh Satvik , Datta Nilanjana 
Published: May 2022

AbstractDetermining whether a noisy quantum channel can be used to reliably transmit quantum information is a challenging problem in quantum information theory. This is because it requires computation of the channel’s coherent information for an unbounded number of copies of the channel. In this paper, we devise an elementary perturbative technique to solve this problem in a wide variety of circumstances. Our analysis reveals that a channel’s ability to transmit information is intimately connected to the relative sizes of its input, output, and environment spaces. We exploit this link to develop easy tests which can be used to detect positivity of quantum channel capacities simply by comparing the channels’ input, output, and environment dimensions. Several noteworthy examples, such as the depolarizing and transpose-depolarizing channels (including the Werner-Holevo channel), dephasing channels, generalized Pauli channels, multi-level amplitude damping channels, and (conjugate) diagonal unitary covariant channels, serve to aptly exhibit the utility of our method. Notably, in all these examples, the coherent information of a single copy of the channel turns out to be positive.
Development of functionally relevant potency assays for monovalent and multivalent vaccines delivered by evolving technologies
Authors: Sanyal Gautam 
Published: May 2022

AbstractA potency or potency-indicating assay is a regulatory requirement for the release of every lot of a vaccine. Potency is a critical quality attribute that is also monitored as a stability indicator of a vaccine product. In essence, a potency measurement is a test of the functional integrity of the antigen and is intended to ensure that the antigen retains immunocompetence, i.e., the ability to stimulate the desired immune response, in its final formulation. Despite its central importance, there is incomplete clarity about the definition and expectation of a potency assay. This article provides a perspective on the purpose, value, and challenges associated with potency testing for vaccines produced by new technologies. The focus is on messenger RNA vaccines in the light of experience gained with recombinant protein-based vaccines, which offer the opportunity to directly correlate in vitro antigenicity with in vivo immunogenicity. The challenges with developing immunologically relevant in vitro assays are discussed especially for multivalent vaccine products, the importance of which has been reinforced by the ongoing emergence of SARS-CoV-2 variants of concern. Immunoassay-based release of multivalent vaccine products, such as those containing multiple antigens from different variants or serotypes of the same virus, require antibodies that are selective for each antigen and do not significantly cross-react with the others. In the absence of such exclusively specific antibodies, alternative functional assays with demonstrable correlation to immunogenicity may be acceptable. Initiatives for geographically distributed vaccine technology facilities should include establishing these assay capabilities to enable rapid delivery of vaccines globally.
Fault-tolerant operation of a logical qubit in a diamond quantum processor
Authors: Abobeih M. H. , Wang Y. , Randall J. , Loenen S. J. H. , Bradley C. E. , Markham M. , Twitchen D. J. , Terhal B. M. , Taminiau T. H. 
Published: May 2022

AbstractSolid-state spin qubits is a promising platform for quantum computation and quantum networks1,2. Recent experiments have demonstrated high-quality control over multi-qubit systems3–8, elementary quantum algorithms8–11 and non-fault-tolerant error correction12–14. Large-scale systems will require using error-corrected logical qubits that are operated fault tolerantly, so that reliable computation becomes possible despite noisy operations15–18. Overcoming imperfections in this way remains an important outstanding challenge for quantum science15,19–27. Here, we demonstrate fault-tolerant operations on a logical qubit using spin qubits in diamond. Our approach is based on the five-qubit code with a recently discovered flag protocol that enables fault tolerance using a total of seven qubits28–30. We encode the logical qubit using a new protocol based on repeated multi-qubit measurements and show that it outperforms non-fault-tolerant encoding schemes. We then fault-tolerantly manipulate the logical qubit through a complete set of single-qubit Clifford gates. Finally, we demonstrate flagged stabilizer measurements with real-time processing of the outcomes. Such measurements are a primitive for fault-tolerant quantum error correction. Although future improvements in fidelity and the number of qubits will be required to suppress logical error rates below the physical error rates, our realization of fault-tolerant protocols on the logical-qubit level is a key step towards quantum information processing based on solid-state spins.
Single-cell genomic profiling of human dopamine neurons identifies a population that selectively degenerates in Parkinson’s disease
Authors: Kamath Tushar , Abdulraouf Abdulraouf , Burris S. J. , Langlieb Jonah , Gazestani Vahid , Nadaf Naeem M. , Balderrama Karol , Vanderburg Charles , Macosko Evan Z. 
Published: May 2022

AbstractThe loss of dopamine (DA) neurons within the substantia nigra pars compacta (SNpc) is a defining pathological hallmark of Parkinson’s disease (PD). Nevertheless, the molecular features associated with DA neuron vulnerability have not yet been fully identified. Here, we developed a protocol to enrich and transcriptionally profile DA neurons from patients with PD and matched controls, sampling a total of 387,483 nuclei, including 22,048 DA neuron profiles. We identified ten populations and spatially localized each within the SNpc using Slide-seq. A single subtype, marked by the expression of the geneAGTR1and spatially confined to the ventral tier of SNpc, was highly susceptible to loss in PD and showed the strongest upregulation of targets ofTP53andNR2F2, nominating molecular processes associated with degeneration. This same vulnerable population was specifically enriched for the heritable risk associated with PD, highlighting the importance of cell-intrinsic processes in determining the differential vulnerability of DA neurons to PD-associated degeneration.
Hyperexcitability in young iPSC-derived C9ORF72 mutant motor neurons is associated with increased intracellular calcium release
Authors: Burley Sarah , Beccano-Kelly Dayne A. , Talbot Kevin , Llana Oscar Cordero , Wade-Martins Richard 
Published: May 2022

AbstractA large hexanucleotide repeat expansion in the C9ORF72 gene is the most prevalent cause of amyotrophic lateral sclerosis (ALS). To better understand neuronal dysfunction during ALS progression, we studied motor neuron (MN) cultures derived from iPSC lines generated from C9ORF72 (C9) expansion carriers and unaffected controls. C9 and control MN cultures showed comparable mRNA levels for MN markers SMI-32, HB9 and ISL1 and similar MN yields (> 50% TUJ1/SMI-32 double-positive MNs). Using whole-cell patch clamp we showed that C9-MNs have normal membrane capacitance, resistance and resting potential. However, immature (day 40) C9-MNs exhibited a hyperexcitable phenotype concurrent with increased release of calcium (Ca2+) from internal stores, but with no changes to NaV and KV currents. Interestingly, this was a transient phenotype. By day 47, maturing C9-MNs demonstrated normal electrophysiological activity, displaying only subtle alterations on mitochondrial Ca2+ release. Together, these findings suggest the potential importance of a developmental component to C9ORF72-related ALS.
Cost-effectiveness of managing HBV reactivation in patients with resolved HBV infection treated with anti-CD20 antibody for B-cell non-Hodgkin lymphoma
Authors: Fujita Misuzu , Kusumoto Shigeru , Ishii Itsuko , Iwata Tadashi , Fujisawa Takehiko , Sugiyama Masaya , Hata Akira , Mizokami Masashi 
Published: May 2022

AbstractThere is no universal recommendation for managing the reactivation of HBV in patients with resolved HBV infection treated with anti-CD20 monoclonal antibodies for B-cell non-Hodgkin lymphoma. This study compared the cost-effectiveness of two commonly used strategies: prophylactic anti-HBV nucleos(t)ide analog therapy (Pro NAT), and HBV DNA monitoring followed by on-demand antiviral therapy (HBV DNA monitoring). Using a decision tree model, the incremental cost-effectiveness ratio (ICER) expressed as cost per quality-adjusted life-year (QALY) gained was calculated. The threshold for cost-effectiveness was set at 5,000,000 JPY, equivalent to 45,662 USD. In a base–case analysis, HBV DNA monitoring was found to be more cost-effective based on the calculation of ICER as 132,048 USD per QALY, a value that far exceeds 45,662 USD. The same results were consistently obtained by a one-way deterministic sensitivity analysis, even after changing each parameter value within the predetermined range. A probabilistic sensitivity analysis with 10,000 simulations also revealed that HBV DNA monitoring is more cost-effective than Pro NAT in 96.8% of cases. Therefore, this study suggests that HBV DNA monitoring is an appropriate managing measure in Japan from a cost-effectiveness perspective.
Admixture and breed traceability in European indigenous pig breeds and wild boar using genome-wide SNP data
Authors: Dadousis Christos , Muñoz Maria , Óvilo Cristina , Fabbri Maria Chiara , Araújo José Pedro , Bovo Samuele , Potokar Marjeta Čandek , Charneca Rui , Crovetti Alessandro , Gallo Maurizio , García-Casco Juan María , Karolyi Danijel , Kušec Goran , Martins José Manuel , Mercat Marie-José , Pugliese Carolina , Quintanilla Raquel , Radović Čedomir , Razmaite Violeta , Ribani Anisa , Riquet Juliet , Savić Radomir , Schiavo Giuseppina , Škrlep Martin , Tinarelli Silvia , Usai Graziano , Zimmer Christoph , Fontanesi Luca , Bozzi Riccardo 
Published: May 2022

AbstractPreserving diversity of indigenous pig (Sus scrofa) breeds is a key factor to (i) sustain the pork chain (both at local and global scales) including the production of high-quality branded products, (ii) enrich the animal biobanking and (iii) progress conservation policies. Single nucleotide polymorphism (SNP) chips offer the opportunity for whole-genome comparisons among individuals and breeds. Animals from twenty European local pigs breeds, reared in nine countries (Croatia: Black Slavonian, Turopolje; France: Basque, Gascon; Germany: Schwabisch-Hällisches Schwein; Italy: Apulo Calabrese, Casertana, Cinta Senese, Mora Romagnola, Nero Siciliano, Sarda; Lithuania: Indigenous Wattle, White Old Type; Portugal: Alentejana, Bísara; Serbia: Moravka, Swallow-Bellied Mangalitsa; Slovenia: Krškopolje pig; Spain: Iberian, Majorcan Black), and three commercial breeds (Duroc, Landrace and Large White) were sampled and genotyped with the GeneSeek Genomic Profiler (GGP) 70 K HD porcine genotyping chip. A dataset of 51 Wild Boars from nine countries was also added, summing up to 1186 pigs (~ 49 pigs/breed). The aim was to: (i) investigate individual admixture ancestries and (ii) assess breed traceability via discriminant analysis on principal components (DAPC). Albeit the mosaic of shared ancestries found for Nero Siciliano, Sarda and Moravka, admixture analysis indicated independent evolvement for the rest of the breeds. High prediction accuracy of DAPC mark SNP data as a reliable solution for the traceability of breed-specific pig products.
Distribution of TAS2R38 bitter taste receptor phenotype and haplotypes among COVID-19 patients
Authors: Risso D. , Carmagnola D. , Morini G. , Pellegrini G. , Canciani E. , Antinucci M. , Henin D. , Dellavia C. 
Published: May 2022

AbstractBitter taste receptor TAS2R38 is expressed in the respiratory tract and can respond to quorum-sensing molecules produced by pathogens, stimulating the release of nitric oxide, with biocidal activity. TAS2R38 presents two main high-frequency haplotypes: the “taster” PAV and the “non-taster” AVI. Individuals carrying the AVI allele could be at greater risk of infections, including SARS-CoV-2. The aim of this study was to assess the frequency of PAV and AVI alleles in COVID-19 patients with severe or non-severe symptoms compared to healthy subjects to further corroborate, or not, the hypothesis that the PAV allele may act as a protecting factor towards SARS-CoV-2 infection while the AVI one may represent a risk factor. After careful selection, 54 individuals were included in the study and underwent genetic analysis and PROP phenotype assessment. Our investigation could not point out at a significant relationship between single nucleotide polymorphisms responsible for PROP bitterness and presence/severity of SARS-CoV-2 infection, as previous studies suggested. Our results uncouple the direct genetic contribution of rs10246939, rs1726866 and rs713598 on COVID-19, calling for caution when proposing a treatment based on TAS2R38 phenotypes.
Dynamic modeling of Nrf2 pathway activation in liver cells after toxicant exposure
Authors: Hiemstra Steven , Fehling-Kaschek Mirjam , Kuijper Isoude A. , Bischoff Luc J. M. , Wijaya Lukas S. , Rosenblatt Marcus , Esselink Jeroen , van Egmond Allard , Mos Jornt , Beltman Joost B. , Timmer Jens , van de Water Bob , Kaschek Daniel 
Published: May 2022

AbstractCells are exposed to oxidative stress and reactive metabolites every day. The Nrf2 signaling pathway responds to oxidative stress by upregulation of antioxidants like glutathione (GSH) to compensate the stress insult and re-establish homeostasis. Although mechanisms describing the interaction between the key pathway constituents Nrf2, Keap1 and p62 are widely reviewed and discussed in literature, quantitative dynamic models bringing together these mechanisms with time-resolved data are limited. Here, we present an ordinary differential equation (ODE) based dynamic model to describe the dynamic response of Nrf2, Keap1, Srxn1 and GSH to oxidative stress caused by the soft-electrophile diethyl maleate (DEM). The time-resolved data obtained by single-cell confocal microscopy of green fluorescent protein (GFP) reporters and qPCR of the Nrf2 pathway components complemented with siRNA knock down experiments, is accurately described by the calibrated mathematical model. We show that the quantitative model can describe the activation of the Nrf2 pathway by compounds with a different mechanism of activation, including drugs which are known for their ability to cause drug induced liver-injury (DILI) i.e., diclofenac (DCF) and omeprazole (OMZ). Finally, we show that our model can reveal differences in the processes leading to altered activation dynamics amongst DILI inducing drugs.
Topography inversion in scanning tunneling microscopy of single-atom-thick materials from penetrating substrate states
Authors: Park Changwon , Yoon Mina 
Published: May 2022

AbstractScanning tunneling microscopy (STM) is one of the indispensable tools to characterize surface structures, but the distinction between atomic geometry and electronic effects based on the measured tunneling current is not always straightforward. In particular, for single-atomic-thick materials (graphene or boron nitride) on metallic substrates, counterintuitive phenomena such as a larger tunneling current for insulators than for metal and a topography opposite to the atomic geometry are reported. Using first-principles density functional theory calculations combined with analytical modeling, we reveal the critical role of penetrating states of metallic substrates that surpass 2D material states, hindering the measurement of intrinsic 2D materials states and leading to topography inversion. Our finding should be instrumental in the interpretation of STM topographies of atomic-thick materials and in the development of 2D material for (opto)electronic and various quantum applications.
Impact of environmental variables on yield related traits and bioactive compounds of the Persian fenugreek (Trigonella foenum-graecum L.) populations
Authors: Rajabihashjin Masoumeh , Zeinalabedini Mehrshad , Asghari Ali , Ghaffari Mohammad Reza , Salekdeh Ghasem Hosseini 
Published: May 2022

AbstractTrigonella foenum-graecum is widely distributed worldwide and grown under a wide range of climatic conditions. The current research was conducted to study the effects of the environmental variables on yield related traits and metabolite contents of 50 different Persian fenugreeks at various geographical locations. Accordingly, multivariate statistical techniques including canonical correspondence analysis (CCA), hierarchical clustering on principal components, and partial least squares regression (PLSR) were applied to determine important proxy variables and establish a relevant model to predict bioactive compounds in fenugreeks. The interrelation of clustered groups emphasized the importance of functional groups of bioactive compounds and several yield related traits. The CCA indicated that two climatic variables of temperature and solar irradiation contributed prominently to 4-hydroxyisoleucine accumulation. The predicted model based on PLSR revealed climatic variables such as temperature, solar, and rain. The precursor of isoleucine was the predictive power for 4-hydroxyisoleucine accumulation while seed weight predicted trigonelline content. The current study's findings may provide helpful information for the breeding strategies of this multipurpose crop.
Characteristics of responders to atropine 0.01% as treatment in Asian myopic children
Authors: Lee Lung-Chi , Hsieh Meng-Wei , Chen Yi-Hao , Chen Po-Liang , Chien Ke-Hung 
Published: May 2022

AbstractRecently, low-concentration atropine (0.01%) has gained increased attention in controlling myopia progression with satisfying effects and minimal side effects. However, studies concerning responders to 0.01% atropine are limited. This retrospective observational cohort study aimed to determine the responder characteristics of 0.01% atropine in Asian children. One hundred forty children (aged between 3 and 15 years) receiving 0.01% atropine were analyzed for the factors influencing annual spherical equivalent changes (SE). The mean age was 9.13 (2.6) years, the mean baseline SE was − 1.56 (1.52) diopters (D), and the mean annual SE change was − 0.52 (0.49) D. A 58.63% responder rate (146/249) of myopic control was achieved with 0.01% atropine in our entire cohort under the criteria of less than 0.5 D of myopic progression annually. The subjects were stratified into 4 subgroups based on a cut-off point of baseline SE of − 1.5 D and baseline age of 9 years. The responder rate differed significantly with the highest being the youngest with the lowest myopia subgroups. Our results demonstrated that children with myopia better than − 1.5 D and younger than 9 years had the highest potential to achieve successful myopic control under 0.01% atropine therapy.