bluuebunny/crossref_metadata_2025 huggingface dataset:
Mineral composites: stay-in-place formwork for concrete using foam 3D printing
Authors: Bedarf Patrick , Calvo-Barentin Cristian , Schulte Dinorah Martinez , Şenol Ayça , Jeoffroy Etienne , Dillenburger Benjamin
Published: February 2023

Optimizing the shape of concrete construction elements is significant in reducing their material consumption and total weight while improving their functional performance. However, the resulting non-standard geometries are difficult and wasteful to fabricate with conventional formwork strategies. This paper presents the novel fabrication method of mineral foam 3D printing (F3DP) of bespoke lost formwork for non-standard, material-efficient, lightweight concrete elements. Many innovative formwork studies have shown that stay-in-place formwork can help to reduce waste and material consumption while adding functionality to building components. Foams are particularly suitable for this application because of their high strength-to-weight ratio, thermal resistance, and good machinability. F3DP allows the waste-free production of geometrically complex formwork elements without long lead times and production-specific tooling. This paper presents the material system and robotic F3DP setup with two experimental case studies: a perforated facade panel and an arched beam slab. Both cases use concrete as structural material and strategically placed custom-printed foam elements. In this first preliminary study, concrete savings of up to 50% and weight reduction of more than 60% could be achieved. This is competitive with standardized solutions such as hollow-core slabs but, in contrast, allows also for non-standard element geometries. Additional functionality, such as programmed perforation, acoustic absorption, and thermal insulation, could be added through the stay-in-place formwork. Moreover, the challenges and future developments of F3DP for sustainable building processes are discussed. Further studies are required to verify the findings. However, considering the urgent need for resource-efficient, low embodied-carbon solutions in the construction industry, this work is an important contribution to the next generation of high-performance building components.
Preclinical-to-Clinical Anti-Cancer Drug Response Prediction and Biomarker Identification Using TINDL
Authors: Hostallero David Earl , Wei Lixuan , Wang Liewei , Cairns Junmei , Emad Amin
Published: February 2023

Prediction of the response of cancer patients to different treatments and identification of biomarkers of drug response are two major goals of individualized medicine. Here, we developed a deep learning framework called TINDL, completely trained on preclinical cancer cell lines (CCLs), to predict the response of cancer patients to different treatments. TINDL utilizes a tissue-informed normalization to account for the tissue type and cancer type of the tumors and to reduce the statistical discrepancies between CCLs and patient tumors. Moreover, by making the deep learning black box interpretable, this model identifies a small set of genes whose expression levels are predictive of drug response in the trained model, enabling identification of biomarkers of drug response. Using data from two large databases of CCLs and cancer tumors, we showed that this model can distinguish between sensitive and resistant tumors for 10 (out of 14) drugs, outperforming various other machine learning models. In addition, our small interfering RNA (siRNA) knockdown experiments on 10 genes identified by this model for one of the drugs (tamoxifen) confirmed that tamoxifen sensitivity is substantially influenced by all of these genes in MCF7 cells, and seven of these genes in T47D cells. Furthermore, genes implicated for multiple drugs pointed to shared mechanism of action among drugs and suggested several important signaling pathways. In summary, this study provides a powerful deep learning framework for prediction of drug response and identification of biomarkers of drug response in cancer. The code can be accessed at https://github.com/ddhostallero/tindl.
Whole-Genome Duplication Reshaped Adaptive Evolution in a Relict Plant Species, Cyclocarya Paliurus
Authors: Qu Yinquan , Shang Xulan , Zeng Ziyan , Yu Yanhao , Bian Guoliang , Wang Wenling , Liu Li , Tian Li , Zhang Shengcheng , Wang Qian , Xie Dejin , Chen Xuequn , Liao Zhenyang , Wang Yibin , Qin Jian , Yang Wanxia , Sun Caowen , Fu Xiangxiang , Zhang Xingtan , Fang Shengzuo
Published: February 2023

Cyclocarya paliurus is a relict plant species that survived the last glacial period and shows a population expansion recently. Its leaves have been traditionally used to treat obesity and diabetes with the well-known active ingredient cyclocaric acid B. Here, we presented three C. paliurus genomes from two diploids with different flower morphs and one haplotype-resolved tetraploid assembly. Comparative genomic analysis revealed two rounds of recent whole-genome duplication events and identified 691 genes with dosage effects that likely contribute to adaptive evolution through enhanced photosynthesis and increased accumulation of triterpenoids. Re  sequencing analysis of 45 C. paliurus individuals uncovered two bottlenecks, consistent with the known events of environmental changes, and many selectively swept genes involved in critical biological functions, including plant defense and secondary metabolite biosynthesis. We also proposed the biosynthesis pathway of cyclocaric acid B based on multi-omics data and identified key genes, in particular gibberellin-related genes, associated with the heterodichogamy in C. paliurus species. Our study sheds light on evolutionary history of C. paliurus and provides genomic resources to study the medicinal herbs.
Identifying RNA Modifications by Direct RNA Sequencing Reveals Complexity of Epitranscriptomic Dynamics in Rice
Authors: Yu Feng , Qi Huanhuan , Gao Li , Luo Sen , Njeri Damaris Rebecca , Ke Yinggen , Wu Wenhua , Yang Pingfang
Published: February 2023

Transcriptome analysis based on high-throughput sequencing of a cDNA library has been widely applied to functional genomic studies. However, the cDNA dependence of most RNA sequencing techniques constrains their ability to detect base modifications on RNA, which is an important element for the post-transcriptional regulation of gene expression. To comprehensively profile the N  6  -methyladenosine (m6A) and N  5  -methylcytosine (m5C) modifications on RNA, direct RNA sequencing (DRS) using the latest Oxford Nanopore Technology was applied to analyze the transcriptome of six tissues in rice. Approximately 94 million reads were generated, with an average length ranging from 619 nt to 1013 nt, and a total of 45,707 transcripts across 34,763 genes were detected. Expression profiles of transcripts at the isoform level were quantified among tissues. Transcriptome-wide mapping of m6A and m5C demonstrated that both modifications exhibited tissue-specific characteristics. The transcripts with m6A modifications tended to be modified by m5C, and the transcripts with modifications presented higher expression levels along with shorter poly(A) tails than transcripts without modifications, suggesting the complexity of gene expression regulation. Gene Ontology analysis demonstrated that m6A- and m5C-modified transcripts were involved in central metabolic pathways related to the life cycle, with modifications on the target genes selected in a tissue-specific manner. Furthermore, most modified sites were located within quantitative trait loci that control important agronomic traits, highlighting the value of cloning functional loci. The results provide new insights into the expression regulation complexity and data resource of the transcriptome and epitranscriptome, improving our understanding of the rice genome.
Lyric Humanity from Virgil to Flaubert
Authors: Langer Ullrich
Published: February 2023

From the Georgics of Virgil to Flaubert's landscapes of happiness, Ullrich Langer argues that lyric representation holds a particular power to address our humanity. Ranging across a vast chronology, the book investigates how such poetry and prose activates our capacities for empathy, equity, irony and reasoning, while educating us in pleasure and helping us comprehend death. Each chapter constitutes a fresh encounter with some of the most celebrated texts of European literary history, demonstrating how the lyrical works, and what it elicits in us. Through deft rhetorical and philological analysis, the study presents the value of literary studies for both ethical purposes and aesthetic ends.
A Divided Poet
Authors: Sanders David
Published: February 2023

Frost's breakthrough book of poetry seen anew as an artistic whole and in the context of the poet's career and development.
American Icon
Authors: Beuka Robert
Published: February 2023

How and why Fitzgerald's novel, initially called a failure, has come to be considered a masterwork of American literature and part of the fabric of the culture.
Three Questions for Sixty-Five Composers
Authors: Varga Bálint András
Published: February 2023

Master interviewer Bálint András Varga poses three probing questions to renowned contemporary composers about their work, and carefully renders their answers in their own words.
The Western Segment of the Precambrian Suture Between the Yangtze and Cathaysia Blocks: Constraints From Magnetotelluric Data in Southwest China
Authors: Xu Shan , Hu Xiangyun , Chen Chaojian , Yang Xin , Sun Heping
Published: February 2023

The western segment of the suture zone between the Yangtze and Cathaysia blocks, which is the most important tectonic boundary related to the formation and rifting of south China, is enigmatic and not fully understood due to the sporadic exposure of Precambrian strata and ophiolites. Three‐dimensional electrical resistivity models derived from inversion of magnetotelluric data identified a lithospheric‐scale conductive zone extending northeastwards beneath the Youjiang basin, which was interpreted as the western segment of the suture zone. The high conductivity and coincident high magnetic anomalies closely match the location of Carlin‐type gold deposits, which can be explained by fluids and gold‐bearing sulfide minerals in a fossil suture zone. Inconsistent with the southeast‐dip resolved at the eastern segment of the suture zone (the Jiangshan‐Shaoxing fault) in the earlier study, the slightly north‐dipping geometry at the western suture zone implies the reactivation by northward subduction and closure of the Paleo‐Tethys Ocean.
The 2022 Hormozgan Doublet Earthquake: Two Blind Thrusts‐Related Folding in Zagros Fold‐And‐Thrust Belt, Southeast Iran
Authors: Yang Ying‐Hui , Li Xiaoyun , Hu Jyr‐Ching , Song Jiawei , Zhao Jingjin , Yassaghi Ali , Pathier Erwan , Xu Qiang , Chen Qiang
Published: February 2023

A doublet earthquake event including two main shocks with a magnitude larger than Mw 6.0 occurred on 1 July 2022 in the Zagros fold‐and‐thrust belt, southeast Iran. The coseismic InSAR deformation field shows that this event caused significant surface uplift due to fault‐related folding in the seismic zone. The estimated preferred faulting model suggests that a higher dip angle fault (maximum slip of ∼1.1 m), and an overlying gentle dipping fault (maximum slip of ∼1.2 m) within the Bandar‐e‐Lengeh Anticline, are responsible for the first and second main shocks, respectively. The calculated Coulomb failure stress change suggests that the first main shock and its Mw 5.7 aftershock have a significantly positive triggering effect in the second main shock. The accumulated interseismic strain should have been partly released by the two main shocks. Finally, the salt diapir activity may affect the generation of the earthquake in the seismic zone.
Augmented Non‐LTE Parameterization of NO Infrared Radiative Cooling Rates
Authors: Eckermann Stephen D.
Published: February 2023

Parameterizations of NO cooling rates in thermospheric models have not changed substantially since the work of Kockarts (1980, https://doi.org/10.1029/GL007i002p0013). We investigate three areas to augment the standard parameterization. The first focuses on cooling‐rate contributions from the first NO “hot band.” Arguments concerning the difficulty or irrelevance of parameterizing hot‐band rates are addressed and either refuted or clarified. Parameterized hot‐band cooling peaks during periods of high solar activity, contributing up to 10%–15% additional cooling, in agreement with published line‐by‐line calculations. The second focuses on collisional NO‐O quenching rates. Recent theoretical calculations predict temperature‐dependent rates similar to those seen in collisional CO2‐O quenching rates. Yet available measurements of NO‐O quenching rates do not reveal clear temperature trends. Quenching rates parameterized with and without temperature dependence produce substantially different thermospheric cooling rates. Further research is needed to resolve these discrepancies. The third involves a linearization of parameterized NO cooling rates around a prescribed state, yielding thermal damping rates for use in parameterizations of subgrid‐scale dynamics. Thermal relaxation rates peak at up to 2 days−1 near 140 km, where they are competitive with corresponding rates due to viscous thermal conduction, consistent with the imputed role of NO in regulating thermospheric climate in response to extraterrestrial energy inputs.
The Behavior of Hydrothermal Mineralization With Spatial Variations of Fluid Pressure
Authors: Xiong Yihui , Zuo Renguang , Miller Stephen A.
Published: February 2023

It is assumed that variable fluid pressure states in space control the spatiotemporal evolution of hydrofracture, and their responses on mineralization. In this study, mineral precipitation caused by rapid fluid pressure reduction is incorporated into a cellular automaton model to explore the effects of various spatially structured fluid pressure rates on the behavior of hydrofracture and mineralization. We explore a range of spatial structures, which vary from essentially random to strong spatial structure. In the model, fluid pressure increase induces local hydrofracture to nearest neighbors, and fluid mass is conserved among the cell affected. As the model evolves, internally connected networks merge and a correlation length is established as the system approaches the failure condition and identifies the percolation threshold. The correlation length of the internally connected network scales with the degree of spatial structure of fluid pressure increase rates, resulting in earlier arrival to the percolation threshold for strong spatial structures. At the percolation threshold, large‐scale fluid pressure reduction induces mineral precipitation and facilitate the formation of the spatially structured geochemical patterns. The degree of spatial structure of geochemical patterns correlates with the spatial structure of fluid pressure increase rates because mineral precipitation from fluid pressure reduction occurs over larger scale. The proposed model offers an intuitive and potentially important tool for understanding the role of spatially structured fluid pressure increase and reduction on hydrothermal mineralization patterns in fault‐related ore systems.
Using Preisach Theory to Evaluate Chemical Remanent Magnetization and Its Behavior During Thellier‐Thellier‐Coe Paleointensity Experiments
Authors: Baker Evelyn B. , Muxworthy Adrian R.
Published: February 2023

The behavior of grain‐growth chemical remanent magnetizations (gCRM) are investigated for different coercivity and magnetostatic‐interaction‐field distributions and acquisition conditions using a thermally activated Preisach model for assemblages of interacting single‐domain grains. A new growth‐rate dependent equation was derived, from which it was found that gCRM intensity is over 10% more sensitive to growth rate than previously modeled. We compare the gCRM results to the behavior of thermoremanences (TRM). gCRMs are two times more sensitive to changes in coercivity distribution, whereas TRMs are four times more sensitive to changes in magnetostatic interactions. The Thellier‐Thellier‐Coe paleointensity protocol was simulated in Preisach space, and gCRMs were found to produce concave‐up Arai plots with pTRM checks which plot to the left of the Arai plot and positive partial‐TRM tail checks that increase with magnetostatic interactions. This often leads to the failure of selection criteria, but high‐temperature segments can pass the criteria for weakly interacting gCRMs; these estimates can underestimate the field by up to 66%.
Pore Pressure Diffusion and Onset of Induced Seismicity
Authors: Stokes Scott M. , Ge Shemin , Brown Megan R. M. , Menezes Elizabeth A. , Sheehan Anne F. , Tiampo Kristy F.
Published: February 2023

The Raton Basin of Southern Colorado and Northern New Mexico experienced a significant increase in seismicity over the last several decades, including two M5+ earthquakes. The increase in seismicity started soon after an increase in wastewater disposal associated with coal‐bed methane production. Twenty‐nine wastewater injection wells have operated in the Basin, with several high‐rate injectors located within a kilometer of the most seismically active regions. We developed a pore pressure model to investigate the relationship between pore pressure diffusion and onset of induced seismicity, with an emphasis on the Trinidad fault zones. Our model indicates that sufficient pore pressure increase had accumulated on the northern extent of the Trinidad fault zone to induce seismicity at the time of early‐stage seismic activity. The hydrogeologic architecture of the Basin played a key role in controlling pore pressure perturbation. The basal sedimentary interval with moderately low diffusivity restricted vertical pore pressure diffusion, creating a substantial lag time between wells becoming active and the expression of perturbation in the fault zones. The spatiotemporal relationship between early‐stage seismicity and wastewater injection in conjunction with modeled pore pressures suggests that the early‐stage seismicity in the Raton Basin was likely triggered by pore pressure diffusion.
Retrieval of Martian Atmospheric CO Vertical Profiles From NOMAD Observations During the First Year of TGO Operations
Authors: Modak Ashimananda , López‐Valverde Miguel Angel , Brines Adrian , Stolzenbach Aurélien , Funke Bernd , González‐Galindo Francisco , Hill Brittany , Aoki Shohei , Thomas Ian , Liuzzi Giuliano , Villanueva Gerónimo , Erwin Justin , Lopez Moreno José Juan , Yoshida Nao , Grabowski Udo , Forget Francois , Daerden Frank , Ristic Bojan , Bellucci Giancarlo , Patel Manish , Trompet Loic , Vandaele Ann‐Carine
Published: February 2023

We present CO density profiles up to about 100 km in the Martian atmosphere obtained for the first time from retrievals of solar occultation measurements by the Nadir and Occultation for Mars Discovery (NOMAD) onboard ExoMars Trace Gas Orbiter (TGO). CO is an important trace gas on Mars, as it is controlled by CO2 photolysis, chemical reaction with the OH radicals, and the global dynamics. However, the measurements of CO vertical profiles have been elusive until the arrival of TGO. We show how the NOMAD CO variations describe very well the Mars general circulation. We observe a depletion of CO in the upper troposphere and mesosphere during the peak period, LS = 190°–200°, more pronounced over the northern latitudes, confirming a similar result recently reported by Atmospheric Chemistry Suite onboard TGO. However, in the lower troposphere around 20 km, and at least at high latitudes of the S. hemisphere, NOMAD CO mixing ratios increase over 1,500 ppmv during the GDS (Global Dust Storm) onset. This might be related to the downwelling branch of the Hadley circulation. A subsequent increase in tropospheric CO is observed during the decay phase of the GDS around LS = 210°–250° when the dust loading is still high. This could be associated with a reduction in the amount of OH radicals in the lower atmosphere due to lack of solar insolation. Once the GDS is over, CO steadily decreases globally during the southern summer season. A couple of distinct CO patterns associated with the Summer solstice and equinox circulation are reported and discussed.
Atmospheric CO2 Concentration Based on Boron Isotopes Versus Simulations of the Global Carbon Cycle During the Plio‐Pleistocene
Authors: Köhler Peter
Published: February 2023

Atmospheric carbon dioxide concentrations (pCO2) beyond ice core records have been reconstructed from δ11B derived from planktic foraminifera found in equatorial sediment cores. Here, I applied a carbon cycle model over the Plio‐Pleistocene to evaluate the assumptions leading to these numbers. During glacials times, simulated atmospheric pCO2 was unequilibrated with pCO2 in the equatorial surface ocean by up to 35 ppm while the δ11B‐based approaches assume unchanged (quasi)equilibrium between both. In the Pliocene, δ11B‐based estimates of surface ocean pH are lower in the Pacific than in the Atlantic resulting in higher calculated pCO2. This offset in pH between ocean basins is not supported by models. To calculate pCO2 in surface waters out of the δ11B‐based pH some assumptions on either total alkalinity or dissolved inorganic carbon are necessary. However, the assumed values of these under‐constrained variables were according to my results partly inconsistent with chemically possible combinations within the marine carbonate system. The model results show glacial/interglacial variability in total alkalinity of the order of 100 μmol/kg, which is rarely applied to proxy reconstructions. Simulated atmospheric pCO2 is tightly (r2 > 0.9) related to equatorial surface‐ocean pH, which can be used for consistency checks. Long‐term trends in volcanic CO2 outgassing and the strength of the continental weathering fluxes are still unconstrained, allowing for a wide range of possible atmospheric pCO2 across the Plio‐Pleistocene. Nevertheless, this carbon cycle analysis suggests that reported atmospheric pCO2 above 500 ppm in the Pliocene might, for various reasons, need to be revised to smaller numbers.
Improved Calculation of Hydraulic Conductivity for Small Disk Tension Infiltrometers
Authors: Nimmo John R. , Voss Paige R.
Published: February 2023

Because tension infiltrometers apply water through a disk of finite size, the infiltrated water moves laterally as well as downward. Only the vertical component of this flow is indicative of the hydraulic conductivity K, so the algorithm for computing K must include a way of isolating that component from the total flow. Some commonly used formulas correct for the multidimensional effects by subtracting an estimate of the laterally spreading flow. For disks smaller than about 200 mm in diameter, however, lateral spreading constitutes so much of the total flow that these subtractive formulas lose considerable accuracy, and sometimes overcorrect so severely as to produce a negative number for K. Other methods rely on empiricisms that are not completely consistent with unsaturated‐flow theory and that require prior knowledge of certain soil properties. We developed a new formula that uses a multiplicative factor instead of a subtracted term to achieve the needed correction. For testing we conducted numerical experiments with synthetic data produced by solving the Richardson‐Richards equation using the code VS2DRTI, for diverse media and a range of disk sizes, including the widely used 45‐mm diameter. We compared K values calculated from our formula to the actual K used to generate the simulated data, as well as to results from other published formulas. This comparison shows that our method provides an algorithm based in unsaturated‐flow theory that produces more reliable values for small disks without requiring prior knowledge of soil properties.
Starry Nights Are Disappearing
Authors: Cartier Kimberly
Published: February 2023

Stars dim as the sky gets brighter, a result of expanding cities and bright LEDs. Simple low-tech changes can help preserve dark night skies.
Acute and long-term exercise adaptation of adipose tissue and skeletal muscle in humans: a matched transcriptomics approach after 8-week training-intervention
Authors: Dreher Simon I. , Irmler Martin , Pivovarova-Ramich Olga , Kessler Katharina , Jürchott Karsten , Sticht Carsten , Fritsche Louise , Schneeweiss Patrick , Machann Jürgen , Pfeiffer Andreas F. H. , Hrabě de Angelis Martin , Beckers Johannes , Birkenfeld Andreas L. , Peter Andreas , Niess Andreas M. , Weigert Cora , Moller Anja
Published: February 2023

Background

Exercise exerts many health benefits by directly inducing molecular alterations in physically utilized skeletal muscle. Molecular adaptations of subcutaneous adipose tissue (SCAT) might also contribute to the prevention of metabolic diseases.

Aim

To characterize the response of human SCAT based on changes in transcripts and mitochondrial respiration to acute and repeated bouts of exercise in comparison to skeletal muscle.

Methods

Sedentary participants (27 ± 4 yrs) with overweight or obesity underwent 8-week supervised endurance exercise 3×1h/week at 80% VO2peak. Before, 60 min after the first and last exercise bout and 5 days post intervention, biopsies were taken for transcriptomic analyses and high-resolution respirometry (n = 14, 8 female/6 male).

Results

In SCAT, we found 37 acutely regulated transcripts (FC > 1.2, FDR < 10%) after the first exercise bout compared to 394, respectively, in skeletal muscle. Regulation of only 5 transcripts overlapped between tissues highlighting their differential response. Upstream and enrichment analyses revealed reduced transcripts of lipid uptake, storage and lipogenesis directly after exercise in SCAT and point to β-adrenergic regulation as potential major driver. The data also suggest an exercise-induced modulation of the circadian clock in SCAT. Neither term was associated with transcriptomic changes in skeletal muscle. No evidence for beigeing/browning was found in SCAT along with unchanged respiration.

Conclusions

Adipose tissue responds completely distinct from adaptations of skeletal muscle to exercise. The acute and repeated reduction in transcripts of lipid storage and lipogenesis, interconnected with a modulated circadian rhythm, can counteract metabolic syndrome progression toward diabetes.
Targeting the E3 ligase NEDD4 as a novel therapeutic strategy for IGF1 signal pathway-driven gastric cancer
Authors: Wang Ke , Yu Yanping , Wang Wei , Jiang Yu , Li Yunlong , Jiang Xunliang , Qiao Yihuan , Chen Le , Zhao Xinhui , Liu Jun , Yang Angang , Li Jipeng , Zhang Rui
Published: February 2023

The IGF1 signal pathway is highly activated in some subtype of gastric cancer(GC) that exhibits poor survival and chemotherapy resistance. Although the results of clinical trials of anti-IGF1R monoclonal antibodies and IGF-1R inhibitors have been mostly disappointing in unselected cancer patients, some patients benefit from anti-IGF1R therapy in these failed studies. Therefore, it is necessary to characterize the complex IGF signaling in GC and help refine the strategies targeting the IGF1 pathway. We found that GC cell lines exhibit differential responses to the specific IGF1R inhibitor OSI906. According to the phosphorylation status of Akt upon the OSI906 treatment, we divided the GC cell lines into IGF1R-dependent and IGF1R-independent cells. Both in vitro and in vivo experiments indicate that Dox-induced knockdown of NEDD4 significantly suppresses tumor growth of IGF1R-dependent GC cells and NEDD4 overexpression promotes tumor growth of IGF1R-dependent GC cells. In contrast, the proliferation of IGF1R-independent GC cells is not affected by NEDD4 silencing and overexpression. The rescue experiments show that a PTEN-IRS1 axis is required for NEDD4-mediated regulation of Akt activation and tumor growth in GC cells. Clinically, NEDD4 is expressed higher in IGF1-high GC tissues compared with IGF1-low GC tissues and normal tissues, and the co-high expression of NEDD4 and IGF1 predicts a worse prognosis in GC patients. Taken together, our study demonstrated that NEDD4 specifically promotes proliferation of GC cells dependent on IGF1/IGF1R signaling by antagonizing the protein phosphatase activity of PTEN to IRS1, and targeting NEDD4 may be a promising therapeutic strategy for IGF1 signal pathway-driven gastric cancer.
Genotype-by-diagnosis interaction influences self-control in human cocaine addiction
Authors: Graczyk Michal M. , Sahakian Barbara J. , Robbins Trevor W. , Ersche Karen D.
Published: February 2023

Not everyone who uses drugs loses control over their intake, which is a hallmark of addiction. Although familial risk studies suggest significant addiction heritability, the genetic basis of vulnerability to drug addiction remains largely unknown. In the present study, we investigate the relationship between self-control, cocaine use, and the rs36024 single nucleotide polymorphism of the noradrenaline transporter gene (SLC6A2). We hypothesize that C-allele-carrying adults show impaired self-control, as measured by the stop-signal task and demonstrated previously in adolescents, and further exacerbated by chronic cocaine use. Patients with cocaine use disorder (CUD, n = 79) and healthy unrelated participants with no history of drug abuse (n = 54) completed the stop-signal task. All participants were genotyped for rs36024 allelic variants (CC/TT homozygotes, CT heterozygotes). We measured mean stop-signal reaction time, reflecting the ability to inhibit ongoing motor responses, reaction times to go stimuli, and the proportion of successful stops. CUD patients showed prolonged stop-signal reaction time, however, there was no main effect of rs36024 genotype. Importantly, there was a significant genotype-by-diagnosis interaction such that CUD patients with CC genotype had longer stop-signal reaction time and fewer successful stops compared with CC healthy controls and TT CUD patients. CT CUD patients showed an intermediate performance. Self-control deficits were associated with cocaine use disorder diagnosis, which interacts with the noradrenaline transporter rs36024 polymorphism. Our findings suggest that rs36024 may represent a potential genetic vulnerability marker, which facilitates the transition from first cocaine use to addiction by weakening the inhibitory control over behavior.
Outcome after allogeneic stem cell transplantation with haploidentical versus HLA-matched donors in patients with higher-risk MDS
Authors: Michel Claire , Robin Marie , Morisset Stephane , Blaise Didier , Maertens Johan , Chevalier Patrice , Castilla-Llorente Cristina , Forcade Edouard , Ceballos Patrice , Yakoug-Agha Ibrahim , Poire Xavier , Carre Martin , Bay Jacques-Olivier , Beguin Yves , Loschi Michael , Huynh Anne , Guillerm Gaëlle , François Sylvie , Mear Jean-Baptiste , Duléry Rémy , Suarez Felipe , Bilger Karin , Cornillon Jérôme , Chalandon Yves , Maillard Natacha , Labussière-Wallet Hélène , Charbonnier Amandine , Turlure Pascal , Berceanu Ana , Chantepie Sylvain , Maury Sébastien , Bazarbachi Ali , Menard Anne-Lise , Nguyen-Quoc Stephanie , Rubio Marie-Thérèse , D’Aveni Maud
Published: February 2023

Allogeneic hematopoietic stem cell transplantation remains the best curative option for higher-risk myelodysplastic syndrome. The presence of monosomal karyotype and/or complex karyotype abnormalities predicts inferior survival after allo-SCT in MDS patients. Haploidentical allo-SCT has been increasingly used in acute leukemia (AL) and has similar results as using HLA-matched donors, but data on higher-risk MDS is sparse. We compared outcomes in 266 patients with higher-risk MDS after HLA-matched sibling donor (MSD, n = 79), HLA-matched unrelated donor (MUD, n = 139) and HLA haploidentical donor (HID, n = 48) from 2010 to 2019. Median donor age differed between the three groups (p < 0.001). The overall survival was significantly different between the three groups with a better OS observed in the MUD group (p = 0.014). This observation could be explained by a higher progression-free survival with MUD (p = 0.014). The cumulative incidence of grade 2–4 acute GvHD was significantly higher in the HID group (p = 0.051). However, in multivariable analysis, patients transplanted using an HID had comparable mortality to patients transplanted using a MUD (subdistribution hazard ratio [sHR]: 0.58 [0.32–1.07]; p = 0.080) and a MSD ([sHR]: 0.56 [0.28–1.11]; p = 0.094). MUD do not remain a significant positive predictor of survival, suggesting that beyond the donor-recipient HLA matching, the donor age might impact recipient outcome.
Psychological impact of risk-stratified screening as part of the NHS Breast Screening Programme: multi-site non-randomised comparison of BC-Predict versus usual screening (NCT04359420)
Authors: French David P. , McWilliams Lorna , Bowers Sarah , Woof Victoria G. , Harrison Fiona , Ruane Helen , Hendy Alice , Evans D. Gareth
Published: February 2023

Background

Adding risk stratification to standard screening via the NHS Breast Screening Programme (NHSBSP) allows women at higher risk to be offered additional prevention and screening options. It may, however, introduce new harms such as increasing cancer worry. The present study aimed to assess whether there were differences in self-reported harms and benefits between women offered risk stratification (BC-Predict) compared to women offered standard NHSBSP, controlling for baseline values.

Methods

As part of the larger PROCAS2 study (NCT04359420), 5901 women were offered standard NHSBSP or BC-Predict at the invitation to NHSBSP. Women who took up BC-Predict received 10-year risk estimates: “high” (≥8%), “above average (moderate)” (5–7.99%), “average” (2–4.99%) or “below average (low)” (<2%) risk. A subset of 662 women completed questionnaires at baseline and at 3 months (n = 511) and 6 months (n = 473).

Results

State anxiety and cancer worry scores were low with no differences between women offered BC-Predict or NHSBSP. Women offered BC-Predict and informed of being at higher risk reported higher risk perceptions and cancer worry than other women, but without reaching clinical levels.

Conclusions

Concerns that risk-stratified screening will produce harm due to increases in general anxiety or cancer worry are unfounded, even for women informed that they are at high risk.
Litchi procyanidins inhibit colon cancer proliferation and metastasis by triggering gut-lung axis immunotherapy
Authors: Yao Yuan , Feng Suya , Li Xuejiao , Liu Taohua , Ye Shengying , Ma Long , Man Shuli
Published: February 2023

Litchi chinensis seed, as a valuable by-product of the subtropical fruit litchi (Litchi chinensis Sonn.), has been confirmed to be rich in procyanidins (LPC). The anticarcinogenic properties of procyanidins has been primarily attributed to their antioxidant and anti-inflammatory activities. However, there is a comparative paucity of information on if and how LPC inhibits colon cancer. Here, LPC significantly inhibited CT26 colon cancer cells proliferation and metastasis in vivo and in vitro. In CT26 lung metastatic mice, the anti-metastatic effect of LPC relied on its regulation of gut microbiota such as increase of Lachnospiraceae UCG-006, Ruminococcus, and their metabolites such as acetic acid, propionic acid and butyric acid. In addition, LPC significantly inhibited CT26 colon cancer cells metastasis through increasing CD8+ cytotoxic T lymphocytes infiltration and decreasing the number of macrophages. Antibiotics treatment demonstrated that the therapeutic effect of LPC depended on the gut microbiota, which regulated T cells immune response. Taken together, LPC had strong inhibitory effects on colon cancer pulmonary metastasis by triggering gut-lung axis to influence the T cells immune response. Our research provides a novel finding for the utilization of procyanidins in the future, that is, supplementing more fruits and vegetables rich in procyanidins is beneficial to the treatment of colon cancer, or it can be used as an adjuvant drug in clinical anti-tumor immunotherapy.
Virtual elastography ultrasound via generative adversarial network for breast cancer diagnosis
Authors: Yao Zhao , Luo Ting , Dong YiJie , Jia XiaoHong , Deng YinHui , Wu GuoQing , Zhu Ying , Zhang JingWen , Liu Juan , Yang LiChun , Luo XiaoMao , Li ZhiYao , Xu YanJun , Hu Bin , Huang YunXia , Chang Cai , Xu JinFeng , Luo Hui , Dong FaJin , Xia XiaoNa , Wu ChengRong , Hu WenJia , Wu Gang , Li QiaoYing , Chen Qin , Deng WanYue , Jiang QiongChao , Mou YongLin , Yan HuanNan , Xu XiaoJing , Yan HongJu , Zhou Ping , Shao Yang , Cui LiGang , He Ping , Qian LinXue , Liu JinPing , Shi LiYing , Zhao YaNan , Xu YongYuan , Zhan WeiWei , Wang YuanYuan , Yu JinHua , Zhou JianQiao
Published: February 2023

Elastography ultrasound (EUS) imaging is a vital ultrasound imaging modality. The current use of EUS faces many challenges, such as vulnerability to subjective manipulation, echo signal attenuation, and unknown risks of elastic pressure in certain delicate tissues. The hardware requirement of EUS also hinders the trend of miniaturization of ultrasound equipment. Here we show a cost-efficient solution by designing a deep neural network to synthesize virtual EUS (V-EUS) from conventional B-mode images. A total of 4580 breast tumor cases were collected from 15 medical centers, including a main cohort with 2501 cases for model establishment, an external dataset with 1730 cases and a portable dataset with 349 cases for testing. In the task of differentiating benign and malignant breast tumors, there is no significant difference between V-EUS and real EUS on high-end ultrasound, while the diagnostic performance of pocket-sized ultrasound can be improved by about 5% after V-EUS is equipped.
A deep learning approach reveals unexplored landscape of viral expression in cancer
Authors: Elbasir Abdurrahman , Ye Ying , Schäffer Daniel E. , Hao Xue , Wickramasinghe Jayamanna , Tsingas Konstantinos , Lieberman Paul M. , Long Qi , Morris Quaid , Zhang Rugang , Schäffer Alejandro A. , Auslander Noam
Published: February 2023

About 15% of human cancer cases are attributed to viral infections. To date, virus expression in tumor tissues has been mostly studied by aligning tumor RNA sequencing reads to databases of known viruses. To allow identification of divergent viruses and rapid characterization of the tumor virome, we develop viRNAtrap, an alignment-free pipeline to identify viral reads and assemble viral contigs. We utilize viRNAtrap, which is based on a deep learning model trained to discriminate viral RNAseq reads, to explore viral expression in cancers and apply it to 14 cancer types from The Cancer Genome Atlas (TCGA). Using viRNAtrap, we uncover expression of unexpected and divergent viruses that have not previously been implicated in cancer and disclose human endogenous viruses whose expression is associated with poor overall survival. The viRNAtrap pipeline provides a way forward to study viral infections associated with different clinical conditions.
Surface engineering of inorganic solid-state electrolytes via interlayers strategy for developing long-cycling quasi-all-solid-state lithium batteries
Authors: Kim Ju-Sik , Yoon Gabin , Kim Sewon , Sugata Shoichi , Yashiro Nobuyoshi , Suzuki Shinya , Lee Myung-Jin , Kim Ryounghee , Badding Michael , Song Zhen , Chang JaeMyung , Im Dongmin
Published: February 2023

Lithium metal batteries (LMBs) with inorganic solid-state electrolytes are considered promising secondary battery systems because of their higher energy content than their Li-ion counterpart. However, the LMB performance remains unsatisfactory for commercialization, primarily owing to the inability of the inorganic solid-state electrolytes to hinder lithium dendrite propagation. Here, using an Ag-coated Li6.4La3Zr1.7Ta0.3O12 (LLZTO) inorganic solid electrolyte in combination with a silver-carbon interlayer, we demonstrate the production of stable interfacially engineered lab-scale LMBs. Via experimental measurements and computational modelling, we prove that the interlayers strategy effectively regulates lithium stripping/plating and prevents dendrite penetration in the solid-state electrolyte pellet. By coupling the surface-engineered LLZTO with a lithium metal negative electrode, a high-voltage positive electrode with an ionic liquid-based liquid electrolyte solution in pouch cell configuration, we report 800 cycles at 1.6 mA/cm2 and 25 °C without applying external pressure. This cell enables an initial discharge capacity of about 3 mAh/cm2 and a discharge capacity retention of about 85%.
Mechanistic insights into RNA surveillance by the canonical poly(A) polymerase Pla1 of the MTREC complex
Authors: Soni Komal , Sivadas Anusree , Horvath Attila , Dobrev Nikolay , Hayashi Rippei , Kiss Leo , Simon Bernd , Wild Klemens , Sinning Irmgard , Fischer Tamás
Published: February 2023

The S. pombe orthologue of the human PAXT connection, Mtl1-Red1 Core (MTREC), is an eleven-subunit complex that targets cryptic unstable transcripts (CUTs) to the nuclear RNA exosome for degradation. It encompasses the canonical poly(A) polymerase Pla1, responsible for polyadenylation of nascent RNA transcripts as part of the cleavage and polyadenylation factor (CPF/CPSF). In this study we identify and characterise the interaction between Pla1 and the MTREC complex core component Red1 and analyse the functional relevance of this interaction in vivo. Our crystal structure of the Pla1-Red1 complex shows that a 58-residue fragment in Red1 binds to the RNA recognition motif domain of Pla1 and tethers it to the MTREC complex. Structure-based Pla1-Red1 interaction mutations show that Pla1, as part of MTREC complex, hyper-adenylates CUTs for their efficient degradation. Interestingly, the Red1-Pla1 interaction is also required for the efficient assembly of the fission yeast facultative heterochromatic islands. Together, our data suggest a complex interplay between the RNA surveillance and 3’-end processing machineries.
Lipid-droplet associated mitochondria promote fatty-acid oxidation through a distinct bioenergetic pattern in male Wistar rats
Authors: Talari Noble Kumar , Mattam Ushodaya , Meher Niroj Kumar , Paripati Arun Kumar , Mahadev Kalyankar , Krishnamoorthy Thanuja , Sepuri Naresh Babu V.
Published: February 2023

Mitochondria empower the liver to regulate lipid homeostasis by enabling fatty acid oxidation during starvation and lipogenesis during nutrient-rich conditions. It is unknown if mitochondria can seamlessly regulate these two distinct processes or if two discrete populations of mitochondria achieve these two functions in the liver. For the first time in the liver, we report the isolation of two distinct populations of mitochondria from male Wistar rats on an ad-libitum diet: cytoplasmic mitochondria and lipid droplet-associated mitochondria. Our studies show that while lipid droplet mitochondria exhibit higher fatty acid oxidation and are marked by enhanced levels of pACC2, MFN2, and CPT1 activity, cytoplasmic mitochondria are associated with higher respiration capacity. Notably, lipid droplet-associated mitochondria isolated from a non-alcoholic fatty liver disease (NAFLD) rat model are compromised for fatty acid oxidation. We demonstrate the importance of functional segregation of mitochondria as any aberration in lipid droplet-associated mitochondria may lead to NAFLD.
Asymmetric eROSITA bubbles as the evidence of a circumgalactic medium wind
Authors: Mou Guobin , Sun Dongze , Fang Taotao , Wang Wei , Zhang Ruiyu , Yuan Feng , Sofue Yoshiaki , Wang Tinggui , He Zhicheng
Published: February 2023

The eROSITA bubbles are detected via the instrument with the same name. The northern bubble shows noticeable asymmetric features, including distortion to the west and enhancement in the eastern edge, while the southern counterpart is significantly dimmer. Their origins are debated. Here, we performed hydrodynamic simulations showing that asymmetric eROSITA bubbles favor a dynamic, circumgalactic medium wind model, but disfavor other mechanisms such as a non-axisymmetric halo gas or a tilted nuclear outflow. The wind from the east by north direction in Galactic coordinates blows across the northern halo with a velocity of about 200 km s−1, and part of it enters the southern halo. This creates a dynamic halo medium and redistributes both density and metallicity within. This naturally explains the asymmetric bubbles in both the morphology and surface brightness. Our results suggest that our Galaxy is accreting low-abundance circumgalactic medium from one side while providing outflow feedback.
Origami-inspired perovskite X-ray detector by printing and folding
Authors: Mescher Henning , Schackmar Fabian , Huber Robert , Eggers Helge , Zuber Marcus , Hamann Elias , Gramlich Georg , Dangelmaier Julian , Zhang Qiaoshuang , Rösch Andres Georg , Zwick Thomas , Hernandez-Sosa Gerardo , Paetzold Ulrich W. , Lemmer Uli
Published: February 2023

X-ray detectors are of pivotal importance for the scientific and technological progress in a wide range of medical, industrial, and scientific applications. Here, we take advantage of the printability of perovskite-based semiconductors and achieve a high X-ray sensitivity combined with the potential of an exceptional high spatial resolution by our origami-inspired folded perovskite X-ray detector. The high performance of our device is reached solely by the folded detector architecture and does not require any photolithography. The design and fabrication of a foldable perovskite sensor array is presented and the detector is characterized as a planar and as a folded device. Exposed to 50 kVp−150 kVp X-ray radiation, the planar detector reaches X-ray sensitivities of 25−35 μC/(Gyaircm2), whereas the folded detector achieves remarkably increased X-ray sensitivities of several hundred μC/(Gyaircm2) and a record value of 1409 μC/(Gyaircm2) at 150 kVp without photoconductive gain. Finally, the potential of an exceptional high spatial resolution of the folded detector of more than 20 lp/mm under 150 kVp X-ray radiation is demonstrated.
Comparison of clinical outcomes in patients with schizophrenia following different long-acting injectable event-driven initiation strategies
Authors: Correll Christoph U. , Benson Carmela , Emond Bruno , Patel Charmi , Lafeuille Marie-Hélène , Lin Dee , Morrison Laura , Ghelerter Isabelle , Lefebvre Patrick , Mavros Panagiotis
Published: February 2023

This retrospective study evaluated the benefit of following different long-acting injectable (LAI) initiation strategies based on the timing of behavioral and clinical events among Medicaid beneficiaries with schizophrenia. Adults with schizophrenia initiating oral antipsychotics (OAPs) after 12 months without antipsychotic use or schizophrenia-related inpatient/emergency room (ER) visits (index date) were identified. Patients were categorized into four event-driven LAI initiation strategy cohorts based on observed sequences of behavioral (i.e., OAP adherence) and clinical (i.e., schizophrenia-related inpatient/ER visits) events between index and LAI initiation or censoring—strategy #1: adherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #2: nonadherent to OAPs without schizophrenia-related inpatient/ER visits; strategy #3: one schizophrenia-related inpatient/ER visit; strategy #4: ≥2 schizophrenia-related inpatient/ER visits. Clinical outcomes (i.e., all-cause inpatient/ER visits) were evaluated between OAP initiation and end of follow-up. Comparisons between LAI initiation strategy cohorts were conducted using a dynamic marginal structural model adjusting for baseline characteristics and time-varying confounders. Among 13,444 eligible patients, 13.1%, 53.6%, 15.7%, and 17.6% were following strategies #1–4, respectively; of these, 21.9%, 4.3%, 9.2%, and 6.5% started an LAI (the remaining were censored). Strategy #1 was associated with a greater clinical benefit, with 43%, 69%, and 80% fewer inpatient days (all p < 0.05); and 57%, 59%, and 79% fewer ER visits (all p < 0.01) vs strategies #2–4, respectively; the clinical benefit was also observed for strategy #2 vs #3–4. Therefore, starting an LAI prior to OAP nonadherence or occurrence of a schizophrenia-related inpatient/ER visit was associated with fewer all-cause inpatient days of inpatient stay and ER visits.