bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient measurement of phononic states with covariance-based stochastic spectroscopy
Authors: Sparapassi Giorgia , Cavaletto Stefano M. , Tollerud Jonathan , Montanaro Angela , Glerean Filippo , Marciniak Alexandre , Giusti Fancesca , Mukamel Shaul , Fausti Daniele 
Published: March 2022

AbstractWe present a novel approach to transient Raman spectroscopy, which combines stochastic probe pulses and a covariance-based detection to measure stimulated Raman signals in alpha-quartz. A coherent broadband pump is used to simultaneously impulsively excite a range of different phonon modes, and the phase, amplitude, and energy of each mode are independently recovered as a function of the pump–probe delay by a noisy-probe and covariance-based analysis. Our experimental results and the associated theoretical description demonstrate the feasibility of 2D-Raman experiments based on the stochastic-probe schemes, with new capabilities not available in equivalent mean-value-based 2D-Raman techniques. This work unlocks the gate for nonlinear spectroscopies to capitalize on the information hidden within the noise and overlooked by a mean-value analysis.
Healthcare professionals’ perceptions of implementing a decision support intervention for cascade screening for beta-thalassemia in Pakistan
Authors: Ahmed Shenaz , Jafri Hussain , Ahmed Wajeeha Naseer , Faran Muhammed , Rashid Yasmin , Ehsan Yasmin , Ahmed Mushtaq 
Published: March 2022

AbstractCounselling relatives of individuals with βeta-Thalassaemia Major (β-TM) about cascade screening is the role of field officers (FOs) in the Punjab Thalassaemia Prevention Project (PTPP). This paper presents FOs’ views about using a ‘decision support intervention for relatives’ (DeSIRe) to facilitate informed decision making, and their perception of its implementation and sustainability. Semi-structured qualitative interviews were conducted with nine FOs (June to July 2021) in seven cities in the Punjab province (Lahore, Sheikhupura, Nankana Sahab, Kasur, Gujranwala, Multan, and Faisalabad) following its use in routine clinical practice. Thematic analysis shows that the FOs were overwhelmingly supportive of the DeSIRe, expressing enthusiasm and identifying benefits of its use, both for their own practice and for relatives. They supported the aim of the intervention to enable them to facilitate relatives’ decision-making about cascade screening, and advocated its use more widely within the PTPP and the other provinces of Pakistan. Overall, the DeSIRe was valued by the FOs for use in routine practice. These findings suggest the DeSIRe is highly likely to be implemented by healthcare professionals more widely in the PTPP and, therefore, is worth evaluating to prove its efficacy. Further research is needed on the extent to which the DeSIRe could be adapted for use by other healthcare professionals with similar responsibilities in the other provinces of Pakistan, and in other low-middle income countries.
Pick up and dispose of pollutants from water via temperature-responsive micellar copolymers on magnetite nanorobots
Authors: Vaghasiya Jayraj V. , Mayorga-Martinez Carmen C. , Matějková Stanislava , Pumera Martin 
Published: March 2022

AbstractNano/micromotor technology is evolving as an effective method for water treatment applications in comparison to existing static mechanisms. The dynamic nature of the nano/micromotor particles enable faster mass transport and a uniform mixing ensuring an improved pollutant degradation and removal. Here we develop thermosensitive magnetic nanorobots (TM nanorobots) consisting of a pluronic tri-block copolymer (PTBC) that functions as hands for pollutant removal. These TM nanorobots are incorporated with iron oxide (Fe3O4) nanoparticles as an active material to enable magnetic propulsion. The pickup and disposal of toxic pollutants are monitored by intermicellar agglomeration and separation of PTBC at different temperatures. The as-prepared TM nanorobots show excellent arsenic and atrazine removal efficiency. Furthermore, the adsorbed toxic contaminants on the TM nanorobots can be disposed by a simple cooling process and exhibit good recovery retention after multiple reuse cycles. This combination of temperature sensitive aggregation/separation coupled with magnetic propulsion opens a plethora of opportunities in the applicability of nanorobots in water treatment and targeted pollutant removal approaches.
Robust Mendelian randomization in the presence of residual population stratification, batch effects and horizontal pleiotropy
Authors: Cinelli Carlos , LaPierre Nathan , Hill Brian L. , Sankararaman Sriram , Eskin Eleazar 
Published: March 2022

AbstractMendelian Randomization (MR) studies are threatened by population stratification, batch effects, and horizontal pleiotropy. Although a variety of methods have been proposed to mitigate those problems, residual biases may still remain, leading to highly statistically significant false positives in large databases. Here we describe a suite of sensitivity analysis tools that enables investigators to quantify the robustness of their findings against such validity threats. Specifically, we propose the routine reporting of sensitivity statistics that reveal the minimal strength of violations necessary to explain away the MR results. We further provide intuitive displays of the robustness of the MR estimate to any degree of violation, and formal bounds on the worst-case bias caused by violations multiple times stronger than observed variables. We demonstrate how these tools can aid researchers in distinguishing robust from fragile findings by examining the effect of body mass index on diastolic blood pressure and Townsend deprivation index.
Reversible dehydrogenation and rehydrogenation of cyclohexane and methylcyclohexane by single-site platinum catalyst
Authors: Chen Luning , Verma Pragya , Hou Kaipeng , Qi Zhiyuan , Zhang Shuchen , Liu Yi-Sheng , Guo Jinghua , Stavila Vitalie , Allendorf Mark D. , Zheng Lansun , Salmeron Miquel , Prendergast David , Somorjai Gabor A. , Su Ji 
Published: March 2022

AbstractDeveloping highly efficient and reversible hydrogenation-dehydrogenation catalysts shows great promise for hydrogen storage technologies with highly desirable economic and ecological benefits. Herein, we show that reaction sites consisting of single Pt atoms and neighboring oxygen vacancies (VO) can be prepared on CeO2 (Pt1/CeO2) with unique catalytic properties for the reversible dehydrogenation and rehydrogenation of large molecules such as cyclohexane and methylcyclohexane. Specifically, we find that the dehydrogenation rate of cyclohexane and methylcyclohexane on such sites can reach values above 32,000 molH2 molPt−1 h−1, which is 309 times higher than that of conventional supported Pt nanoparticles. Combining of DRIFTS, AP-XPS, EXAFS, and DFT calculations, we show that the Pt1/CeO2 catalyst exhibits a super-synergistic effect between the catalytic Pt atom and its support, involving redox coupling between Pt and Ce ions, enabling adsorption, activation and reaction of large molecules with sufficient versatility to drive abstraction/addition of hydrogen without requiring multiple reaction sites.
Mutation-specific reporter for optimization and enrichment of prime editing
Authors: Schene I. F. , Joore I. P. , Baijens J. H. L. , Stevelink R. , Kok G. , Shehata S. , Ilcken E. F. , Nieuwenhuis E. C. M. , Bolhuis D. P. , van Rees R. C. M. , Spelier S. A. , van der Doef H. P. J. , Beekman J. M. , Houwen R. H. J. , Nieuwenhuis E. E. S. , Fuchs S. A. 
Published: March 2022

AbstractPrime editing is a versatile genome-editing technique that shows great promise for the generation and repair of patient mutations. However, some genomic sites are difficult to edit and optimal design of prime-editing tools remains elusive. Here we present a fluorescent prime editing and enrichment reporter (fluoPEER), which can be tailored to any genomic target site. This system rapidly and faithfully ranks the efficiency of prime edit guide RNAs (pegRNAs) combined with any prime editor variant. We apply fluoPEER to instruct correction of pathogenic variants in patient cells and find that plasmid editing enriches for genomic editing up to 3-fold compared to conventional enrichment strategies. DNA repair and cell cycle-related genes are enriched in the transcriptome of edited cells. Stalling cells in the G1/S boundary increases prime editing efficiency up to 30%. Together, our results show that fluoPEER can be employed for rapid and efficient correction of patient cells, selection of gene-edited cells, and elucidation of cellular mechanisms needed for successful prime editing.
The Glycolytic Gatekeeper PDK1 defines different metabolic states between genetically distinct subtypes of human acute myeloid leukemia
Authors: Erdem Ayşegül , Marin Silvia , Pereira-Martins Diego A. , Cortés Roldán , Cunningham Alan , Pruis Maurien G. , de Boer Bauke , van den Heuvel Fiona A. J. , Geugien Marjan , Wierenga Albertus T. J. , Brouwers-Vos Annet Z. , Rego Eduardo M. , Huls Gerwin , Cascante Marta , Schuringa Jan Jacob 
Published: March 2022

AbstractAcute myeloid leukemia remains difficult to treat due to strong genetic heterogeneity between and within individual patients. Here, we show that Pyruvate dehydrogenase kinase 1 (PDK1) acts as a targetable determinant of different metabolic states in acute myeloid leukemia (AML). PDK1low AMLs are OXPHOS-driven, are enriched for leukemic granulocyte-monocyte progenitor (L-GMP) signatures, and are associated with FLT3-ITD and NPM1cyt mutations. PDK1high AMLs however are OXPHOSlow, wild type for FLT3 and NPM1, and are enriched for stemness signatures. Metabolic states can even differ between genetically distinct subclones within individual patients. Loss of PDK1 activity releases glycolytic cells into an OXPHOS state associated with increased ROS levels resulting in enhanced apoptosis in leukemic but not in healthy stem/progenitor cells. This coincides with an enhanced dependency on glutamine uptake and reduced proliferation in vitro and in vivo in humanized xenograft mouse models. We show that human leukemias display distinct metabolic states and adaptation mechanisms that can serve as targets for treatment.
Methionine adenosyltransferase 1a antisense oligonucleotides activate the liver-brown adipose tissue axis preventing obesity and associated hepatosteatosis
Authors: Sáenz de Urturi Diego , Buqué Xabier , Porteiro Begoña , Folgueira Cintia , Mora Alfonso , Delgado Teresa C. , Prieto-Fernández Endika , Olaizola Paula , Gómez-Santos Beatriz , Apodaka-Biguri Maider , González-Romero Francisco , Nieva-Zuluaga Ane , Ruiz de Gauna Mikel , Goikoetxea-Usandizaga Naroa , García-Rodríguez Juan Luis , Gutierrez de Juan Virginia , Aurrekoetxea Igor , Montalvo-Romeral Valle , Novoa Eva M. , Martín-Guerrero Idoia , Varela-Rey Marta , Bhanot Sanjay , Lee Richard , Banales Jesus M. , Syn Wing-Kin , Sabio Guadalupe , Martínez-Chantar María L. , Nogueiras Rubén , Aspichueta Patricia 
Published: March 2022

AbstractAltered methionine metabolism is associated with weight gain in obesity. The methionine adenosyltransferase (MAT), catalyzing the first reaction of the methionine cycle, plays an important role regulating lipid metabolism. However, its role in obesity, when a plethora of metabolic diseases occurs, is still unknown. By using antisense oligonucleotides (ASO) and genetic depletion of Mat1a, here, we demonstrate that Mat1a deficiency in diet-induce obese or genetically obese mice prevented and reversed obesity and obesity-associated insulin resistance and hepatosteatosis by increasing energy expenditure in a hepatocyte FGF21 dependent fashion. The increased NRF2-mediated FGF21 secretion induced by targeting Mat1a, mobilized plasma lipids towards the BAT to be catabolized, induced thermogenesis and reduced body weight, inhibiting hepatic de novo lipogenesis. The beneficial effects of Mat1a ASO were abolished following FGF21 depletion in hepatocytes. Thus, targeting Mat1a activates the liver-BAT axis by increasing NRF2-mediated FGF21 secretion, which prevents obesity, insulin resistance and hepatosteatosis.
ADAP1 promotes latent HIV-1 reactivation by selectively tuning KRAS–ERK–AP-1 T cell signaling-transcriptional axis
Authors: Ramirez Nora-Guadalupe P. , Lee Jeon , Zheng Yue , Li Lianbo , Dennis Bryce , Chen Didi , Challa Ashwini , Planelles Vicente , Westover Kenneth D. , Alto Neal M. , D’Orso Iván 
Published: March 2022

AbstractImmune stimulation fuels cell signaling-transcriptional programs inducing biological responses to eliminate virus-infected cells. Yet, retroviruses that integrate into host cell chromatin, such as HIV-1, co-opt these programs to switch between latent and reactivated states; however, the regulatory mechanisms are still unfolding. Here, we implemented a functional screen leveraging HIV-1’s dependence on CD4+ T cell signaling-transcriptional programs and discovered ADAP1 is an undescribed modulator of HIV-1 proviral fate. Specifically, we report ADAP1 (ArfGAP with dual PH domain-containing protein 1), a previously thought neuronal-restricted factor, is an amplifier of select T cell signaling programs. Using complementary biochemical and cellular assays, we demonstrate ADAP1 inducibly interacts with the immune signalosome to directly stimulate KRAS GTPase activity thereby augmenting T cell signaling through targeted activation of the ERK–AP-1 axis. Single cell transcriptomics analysis revealed loss of ADAP1 function blunts gene programs upon T cell stimulation consequently dampening latent HIV-1 reactivation. Our combined experimental approach defines ADAP1 as an unexpected tuner of T cell programs facilitating HIV-1 latency escape.
Modeling assortative mating and genetic similarities between partners, siblings, and in-laws
Authors: Torvik Fartein Ask , Eilertsen Espen Moen , Hannigan Laurie J. , Cheesman Rosa , Howe Laurence J. , Magnus Per , Reichborn-Kjennerud Ted , Andreassen Ole A. , Njølstad Pål R. , Havdahl Alexandra , Ystrom Eivind 
Published: March 2022

AbstractAssortative mating on heritable traits can have implications for the genetic resemblance between siblings and in-laws in succeeding generations. We studied polygenic scores and phenotypic data from pairs of partners (n = 26,681), siblings (n = 2,170), siblings-in-law (n = 3,905), and co-siblings-in-law (n = 1,763) in the Norwegian Mother, Father and Child Cohort Study. Using structural equation models, we estimated associations between measurement error-free latent genetic and phenotypic variables. We found evidence of genetic similarity between partners for educational attainment (rg = 0.37), height (rg = 0.13), and depression (rg = 0.08). Common genetic variants associated with educational attainment correlated between siblings above 0.50 (rg = 0.68) and between siblings-in-law (rg = 0.25) and co-siblings-in-law (rg = 0.09). Indirect assortment on secondary traits accounted for partner similarity in education and depression, but not in height. Comparisons between the genetic similarities of partners and siblings indicated that genetic variances were in intergenerational equilibrium. This study shows genetic similarities between extended family members and that assortative mating has taken place for several generations.
The impact of age and nodal status on variations in oncotype DX testing and adjuvant treatment
Authors: Iles Kathleen , Roberson Mya L. , Spanheimer Philip , Gallagher Kristalyn , Ollila David W. , Strassle Paula D. , Downs-Canner Stephanie 
Published: March 2022

AbstractOncotype DX (ODX) recurrence score (RS) is a validated tool to guide the use of adjuvant chemotherapy (AC) in hormone receptor+/HER2- breast cancer. In this analysis, we examine (1) characteristics associated with ODX testing and (2) the association between ODX RS and receipt of AC across age and nodal status. Women with HR+/HER2–, early-stage (T1-2, N0-1) breast cancers from 2010–2017 in the National Cancer Database were included. 530,125 met inclusion and 255,971 received ODX testing. Older women were less likely to receive testing; however, nodal positivity increased use of testing. High ODX RS was associated with increased mortality, though the association was not consistent across age and was most strongly associated with mortality among younger, node-negative women. Older women with high ODX RS, regardless of nodal status, were less likely to receive AC. Clinicians may be employing ODX RS to support treatment decisions against the receipt of AC.
Ultrasound-assisted pseudohomogeneous tungstate catalyst for selective oxidation of alcohols to aldehydes
Authors: Rezaei Aram , Mohammadi Yasaman , Ramazani Ali , Zheng Huajun 
Published: March 2022

AbstractThe idea of applying ultrasound (US) as a green activation method in chemical transformations, especially in catalytic alcohol oxidations, technically and ecologically appeals to chemists. In the present work, as an attempt to fulfill the idea of designing an eco-friendly system to oxidize alcoholic substrates into corresponding aldehydes, we developed multifunctional tungstate-decorated CQD base catalyst, A-CQDs/W, and examined its sonooxidation performance in presence of H2O2 as a green oxidant in aqua media. By comparing the catalyst performance in oxidize benzyl alcohol as a testing model to benzaldehyde (BeOH) prior and after US irradiation—trace vs 93%- the key role of ultrasonic irradiation in achieving high yield is completely appreciated. Exceptional thermal and compression condition that is created as a result of acoustic waves is in charge of unparalleled yield results in this type of activation method. The immense degree of reagent interaction in this method, ensures the maximum yield in notably low time, which in turn leads to decrease in the number of unreacted reagents and by-products. Meanwhile, the need for using toxic organic solvents and hazardous oxidants, auxiliaries and phase transfer catalyst (PTC) is completely obviated.
Toolbox for the structure-guided evolution of ferulic acid decarboxylase (FDC)
Authors: Duță Horia , Filip Alina , Nagy Levente Csaba , Nagy Emma Zsófia Aletta , Tőtős Róbert , Bencze László Csaba 
Published: March 2022

AbstractThe interest towards ferulic acid decarboxylase (FDC), piqued by the enzyme’s unique 1,3-dipolar cycloaddition mechanism and its atypic prFMN cofactor, provided several applications of the FDC mediated decarboxylations, such as the synthesis of styrenes, or its diverse derivatives, including 1,3-butadiene and the enzymatic activation of C-H bonds through the reverse carboligation reactions. While rational design-based protein engineering was successfully employed for tailoring FDC towards diverse substrates of interest, the lack of high-throughput FDC-activity assay hinders its directed evolution-based protein engineering. Herein we report a toolbox, useful for the directed evolution based and/or structure-guided protein engineering of FDC, which was validated representatively on the well described FDC, originary fromSaccharomyces cerevisiae(ScFDC). Accordingly, the developed fluorescent plate-assay allows in premiere the FDC-activity screens of a mutant library in a high-throughput manner. Moreover, using the plate-assay for the activity screens of a rationally designed 23-memberedScFDC variant library against a substrate panel comprising of 16, diversely substituted cinnamic acids, revealed several variants of improved activity. The superior catalytic properties of the hits revealed by the plate-assay, were also supported by the conversion values from their analytical scale biotransformations. The computational results further endorsed the experimental findings, showing inactive binding poses of several non-transformed substrate analogues within the active site of thewild-type ScFDC, but favorable ones within the catalytic site of the variants of improved activity. The results highlight several ‘hot-spot’ residues involved in substrate specificity modulation of FDC, such as I189, I330, F397, I398 or Q192, of which mutations to sterically less demanding residues increased the volume of the active site, thus facilitated proper binding and increased conversions of diverse non-natural substrates. Upon revealing which mutations improve the FDC activity towards specific substrate analogues, we also provide key for the rational substrate-tailoring of FDC.
Numerical solution for MHD peristaltic transport in an inclined nanofluid symmetric channel with porous medium
Authors: Abd-Alla A. M. , Thabet Esraa N. , Bayones F. S. 
Published: March 2022

AbstractThe significance of the study is to determine of transferred heat and mass impact on the magneto-hydrodynamic peristalsis of Jeffery nanofluid through porous media with inclined symmetric channels whose walls are induced by peristaltic motion within porous media. The aim of this investagtion is to study the influence of various types of parameters such as Brownian motion, thermophoresis, buoyancy forces, and magnetic fields are studies on concentration, temperature, and axial velocity. The numerical solution has been achieved according to the long-wavelength and low Reynolds number approximation utilizing the MATLAB bvp4c function. The resultant dimensions of nonlinear governing equations were approached numerically through the Runge–Kutta- Fehlberg integration scheme, a MATLAB program. The influence of different factors such as the ratio of relaxation to retardation times, nanoparticle Grashof number, and magnetic field was discussed on concentration, temperature, and velocity profiles. tables and graphs were used to demonstrate the numerically computed numerical results. Plotting graphs were utilized for evaluating the pertinent parameters impacts on the aforementioned quantities based on computational results. According to the findings, the effect of the parameters are significant.
Coordination and equilibrium selection in games: the role of local effects
Authors: Raducha Tomasz , San Miguel Maxi 
Published: March 2022

AbstractWe study the role of local effects and finite size effects in reaching coordination and in equilibrium selection in two-player coordination games. We investigate three update rules — the replicator dynamics (RD), the best response (BR), and the unconditional imitation (UI). For the pure coordination game with two equivalent strategies we find a transition from a disordered state to coordination for a critical value of connectivity. The transition is system-size-independent for the BR and RD update rules. For the IU it is system-size-dependent, but coordination can always be reached below the connectivity of a complete graph. We also consider the general coordination game which covers a range of games, such as the stag hunt. For these games there is a payoff-dominant strategy and a risk-dominant strategy with associated states of equilibrium coordination. We analyse equilibrium selection analytically and numerically. For the RD and BR update rules mean-field predictions agree with simulations and the risk-dominant strategy is evolutionary favoured independently of local effects. When players use the unconditional imitation, however, we observe coordination in the payoff-dominant strategy. Surprisingly, the selection of pay-off dominant equilibrium only occurs below a critical value of the network connectivity and disappears in complete graphs. As we show, it is a combination of local effects and update rule that allows for coordination on the payoff-dominant strategy.