bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unexpected Warming From Land Radiative Management
Authors: Cheng Yu , McColl Kaighin A. 
Published: November 2024

Abstract“Land radiative management” (LRM)—deliberately increasing surface albedo to decrease temperatures—has been proposed as a form of geoengineering to mitigate the effects of regional warming. Here, we show that, contrary to expectations, LRM causes temperatures to increase in surrounding regions. The basic reason for the increase is unintended impacts on precipitation. Precipitation is suppressed over the LRM region, but this effect also extends to nearby areas unprotected by LRM. The reduction in precipitation and soil moisture in these regions leads to higher temperatures than would be expected in the absence of LRM. The resulting warming outside the LRM region is comparable to the cooling achieved inside it. This implies that, if wealthy regions unilaterally adopt LRM to cool, their neighbors may experience warming, worsening heat inequality.
Direction Finding Studies of Simultaneous Auroral 2fce and 3fce Roar Cyclotron Harmonic Radio Emissions
Authors: Godfrey T. M. , LaBelle J. 
Published: November 2024

AbstractAuroral roar originates in Earth's ionosphere at altitudes of several hundred kilometers where the upper hybrid frequency matches a harmonic of the electron gyrofrequency. These radio emissions are important for remote sensing of ionospheric plasma conditions and processes, and their physics is similar to that of astrophysical radio emissions. In this study, direction finding was used to establish the distribution of direction of arrival (DOA) angles for the third harmonic emissions and to compare the direction angles of second harmonic and events when they occur simultaneously. Data were collected for 42 events from 9 May 2022 to 20 May 2023 by a three antenna array in Toolik Lake, AK (68.6°N, 149.6°W, 68.5° magnetic latitude) with a DOA distribution centered overhead. 30% of the events coming from the south, for which azimuth deviations due to refraction are less significant, were on the same azimuth within 10°, the uncertainty of the measurement. This is a lower bound on the fraction of simultaneous harmonic and emissions that come from the same auroral arc. All events coming from the south that had a and azimuth angle of arrival within 10° had a higher elevation than elevation within experimental uncertainty, supporting the mechanism by which these emissions are excited at the “double resonance” points on the bottomside of the ionosphere.
iFLOW: A Framework and GUI to Quantify Effective Thermal Diffusivity and Advection in Permeable Materials From Temperature Time Series
Authors: Bertagnoli A. , Luce C. , van Kampen R. , Schneidewind U. , van Berkel M. , Tranmer A. W. , Vandersteen G. , Krause S. , Tonina D. 
Published: November 2024

AbstractiFLOW is a free, open‐source, and python‐based framework and graphical user interface to visualize and analyze temperature time series, and extract one dimensional thermal velocity, vT, and bulk effective thermal diffusivity, ke. Information of thermal properties of the sediment‐water mixture (bulk) and water allows quantifying the one‐dimensional Darcian flux, q, and seepage velocity, v, from vT. Available software packages were developed to quantify q and ke only based on a specific mathematical model or focused on specific data processing or parameter estimation techniques, and all these steps were lumped together preventing users to identify potential source of errors. iFLOW proposes a novel organizational philosophy with a modular framework that parses the analysis process into three fundamental steps: (a) the mathematical model, (b) signal processing, and (c) parameter estimation. iFLOW houses a suite of models and analysis techniques. This suite can be readily added to and expanded through its modular framework. iFLOW contains a wizard to guide users through the selection process with respect to the three fundamental steps. Users can analyze and visualize intermediate results to identify problematic issues in the time series data and improve data interpretation. Here, we present iFLOW and summarize its performance using a set of one‐dimensional synthetic heat transport simulations.
Genetic contributions to body mass index over adolescence and its associations with adult weight gain: a 25-year follow-up study of Finnish twins
Authors: Obeso Alvaro , Drouard Gabin , Jelenkovic Aline , Aaltonen Sari , Palviainen Teemu , Salvatore Jessica E. , Dick Danielle M. , Kaprio Jaakko , Silventoinen Karri 
Published: November 2024

Abstract

Introduction
High body mass index (BMI) in adolescence is a strong predictor of adult obesity. However, the nature of this association is unclear. We investigated how adolescent BMI is associated with adult weight change using longitudinal data from ages 11.5 to 37 years and examined the genetic factors behind these associations.

Data and Methods
The study cohort consisted of 1400 Finnish twin individuals (40% males) with 494 complete twin pairs who reported their body mass index (BMI) at five ages: 11.5, 14, 17.5, 24, and 37 years. BMI trajectories (defined as BMI changes (i.e., slope) and BMI at baseline age (i.e., intercept)) were calculated in adulthood (from 17.5 to 37 years of age) using linear mixed-effects models. Polygenic Risk Scores of BMI (PRSBMI) and genetic twin models were utilised to analyse the role of genetic factors underlying BMI trajectories and their associations with BMI at 11.5 and 14 years of age.

Results
Mean BMI increased in adulthood (4.06 kg/m2 in men and 3.39 kg/m2 in women). The BMI changes correlated with BMI at the baseline age of 17.5 years (i.e. intercept) (r = 0.24 in men and r = 0.35 in women) as well as with BMI in adolescence (11.5 and 14 years of age). Genetic factors contributed to the BMI changes during adulthood (correlation with PRSBMI
r = 0.25 in men and r = 0.27 in women; heritability estimates 0.63 and 0.64 respectively) as well as to their correlations with BMI at the baseline age (r
A = 0.5 in men and 0.54 in women) and BMI during adolescence (at 11.5 and 14 years of age) (r
A = 0.63–0.64).

Conclusion
We found that genetic factors play a role in BMI change in adulthood, and part of this genetic component overlaps with the genetics of BMI in adolescence. Genetic predisposition to high BMI in adolescence is also related to adult weight gain.
Breathing new insights into the role of mutant p53 in lung cancer
Authors: Chen Tianwei , Ashwood Lauren M. , Kondrashova Olga , Strasser Andreas , Kelly Gemma , Sutherland Kate D. 
Published: November 2024

Abstract
The tumour suppressor gene p53 is one of the most frequently mutated genes in lung cancer and these defects are associated with poor prognosis, albeit some debate exists in the lung cancer field. Despite extensive research, the exact mechanisms by which mutant p53 proteins promote the development and sustained expansion of cancer remain unclear. This review will discuss the cellular responses controlled by p53 that contribute to tumour suppression, p53 mutant lung cancer mouse models and characterisation of p53 mutant lung cancer. Furthermore, we discuss potential approaches of targeting mutant p53 for the treatment of lung cancer.
Polyol pathway-generated fructose is indispensable for growth and survival of non-small cell lung cancer
Authors: Schwab Annemarie , Siddiqui Mohammad Aarif , Ramesh Vignesh , Gollavilli Paradesi Naidu , Turtos Adriana Martinez , Møller Sarah Søgaard , Pinna Luisa , Havelund Jesper F. , Rømer Anne Mette A. , Ersan Pelin Gülizar , Parma Beatrice , Marschall Sabine , Dettmer Katja , Alhusayan Mohammed , Bertoglio Pietro , Querzoli Giulia , Mielenz Dirk , Sahin Ozgur , Færgeman Nils J. , Asangani Irfan A. , Ceppi Paolo 
Published: November 2024

AbstractDespite recent treatment advances, non-small cell lung cancer (NSCLC) remains one of the leading causes of cancer-related deaths worldwide, and therefore it necessitates the exploration of new therapy options. One commonly shared feature of malignant cells is their ability to hijack metabolic pathways to confer survival or proliferation. In this study, we highlight the importance of the polyol pathway (PP) in NSCLC metabolism. This pathway is solely responsible for metabolizing glucose to fructose based on the enzymatic activity of aldose reductase (AKR1B1) and sorbitol dehydrogenase (SORD). Via genetic and pharmacological manipulations, we reveal that PP activity is indispensable for NSCLC growth and survival in vitro and in murine xenograft models. Mechanistically, PP deficiency provokes multifactorial deficits, ranging from energetic breakdown and DNA damage, that ultimately trigger the induction of apoptosis. At the molecular level, this process is driven by pro-apoptotic JNK signaling and concomitant upregulation of the transcription factors c-Jun and ATF3. Moreover, we show that fructose, the PP end-product, as well as other non-glycolytic hexoses confer survival to cancer cells and resistance against chemotherapy via sustained NF-κB activity as well as an oxidative switch in metabolism. Given the detrimental consequence of PP gene targeting on growth and survival, we propose PP pathway interference as a viable therapeutic approach against NSCLC.
DDR1 promotes metastasis of cervical cancer and downstream phosphorylation signal via binding GRB2
Authors: Zhang Jin , Maimaiti Aynuer , Chang Xihan , Sun Pengcheng , Chang Xiaohan 
Published: November 2024

AbstractCervical cancer is a leading cause of cancer-related death among women and its recurrence and metastasis poses challenges to treatment. Discoidin domain receptor 1 (DDR1) was associated with cellular migration and invasion in several types of cancers. However, its function in cervical cancer is still unclear. In this study, we found that DDR1 was significantly more expressed in cervical cancer samples than in normal tissues. SRY-Box transcription factor 2 (SOX2), a known oncogene in cervical cancer, showed a positive correlation with DDR1 and regulated DDR1 transcription, contributing to the elevated expression of DDR1 in cervical cancer. Regarding the function of DDR1 in cervical cancer, the overexpression of DDR1 caused an increase in the migration, invasion, and epithelial-mesenchymal transition (EMT) of cervical cancer cells. In contrast, cervical cancer cells with reduced DDR1 expression exhibited a lower migration rate, fewer invasive cells, and decreased levels of EMT markers. In vivo, mice injected with cervical cancer cells with overexpressed DDR1 showed more pulmonary metastasis and nodule number. Opposite results were found in mice injected with DDR1 silenced cervical cancer cells. Since DDR1 can cause phosphorylation of downstream targets, a phosphorylation omics was employed to reveal the downstream targets of DDR1, including eukaryotic translation initiation factor 4E binding protein 1 and EPH receptor A2. Furthermore, DDR1 bound directly with Src homology 2 domain of growth factor receptor bound protein 2 (GRB2) which mediated the function of DDR1 in the malignant behaviors of cervical cancer and the phosphorylation of downstream targets. In conclusion, DDR1 binds directly to GRB2 and then affects downstream phosphorylation signals, ultimately exacerbating the metastasis of cervical cancer cells. This work sheds light on the mechanism by which DDR1 functions in cervical cancer cells, providing therapeutic strategy for the treatment of cervical cancer.
The outcomes of SGLT-2 inhibitor utilization in diabetic kidney transplant recipients
Authors: Sheu Jia-Yuh , Chang Li-Yang , Chen Jui-Yi , Pan Heng-Chih , Tseng Chi-Shin , Chueh Jeff S. , Wu Vin-Cent 
Published: November 2024

AbstractSodium-glucose cotransporter 2 inhibitors (SGLT-2i) have demonstrated efficacy in reducing cardiovascular events and potentially improving kidney function in diabetic patients. This investigation analyzes the TriNetX database to assess the efficacy of SGLT-2i in diabetic kidney transplant recipients (KTR) concerning all-cause mortality, major adverse cardiac events (MACE), and major adverse kidney events (MAKE). The study includes type 2 diabetic patients over 18 who underwent kidney transplants between June 1, 2015, and June 1, 2023, with a focus on SGLT-2i use within the first three months post-transplant. After propensity score matching, the study compares 1970 SGLT-2i users with matched non-users. With a median follow-up of 3.4 years, SGLT-2i users showed significantly lower rates of all-cause mortality (adjusted hazard ratio [aHR]: 0.32), MACE (aHR: 0.48), and MAKE (aHR: 0.52). These findings indicate that SGLT-2i significantly reduces mortality and adverse events in diabetic KTR, underscoring its potential to improve post-transplant outcomes.
Telomere-to-telomere genome assembly of a male goat reveals variants associated with cashmere traits
Authors: Wu Hui , Luo Ling-Yun , Zhang Ya-Hui , Zhang Chong-Yan , Huang Jia-Hui , Mo Dong-Xin , Zhao Li-Ming , Wang Zhi-Xin , Wang Yi-Chuan , He-Hua EEr , Bai Wen-Lin , Han Di , Dou Xing-Tang , Ren Yan-Ling , Dingkao Renqing , Chen Hai-Liang , Ye Yong , Du Hai-Dong , Zhao Zhan-Qiang , Wang Xi-Jun , Jia Shan-Gang , Liu Zhi-Hong , Li Meng-Hua 
Published: November 2024

AbstractA complete goat (Capra hircus) reference genome enhances analyses of genetic variation, thus providing insights into domestication and selection in goats and related species. Here, we assemble a telomere-to-telomere (T2T) gap-free genome (2.86 Gb) from a cashmere goat (T2T-goat1.0), including a Y chromosome of 20.96 Mb. With a base accuracy of >99.999%, T2T-goat1.0 corrects numerous genome-wide structural and base errors in previous assemblies and adds 288.5 Mb of previously unresolved regions and 446 newly assembled genes to the reference genome. We sequence the genomes of five representative goat breeds for PacBio reads, and use T2T-goat1.0 as a reference to identify a total of 63,417 structural variations (SVs) with up to 4711 (7.42%) in the previously unresolved regions. T2T-goat1.0 was applied in population analyses of global wild and domestic goats, which revealed 32,419 SVs and 25,397,794 SNPs, including 870 SVs and 545,026 SNPs in the previously unresolved regions. Also, our analyses reveal a set of selective variants and genes associated with domestication (e.g., NKG2D and ABCC4) and cashmere traits (e.g., ABCC4 and ASIP).
The inhibitory action of the chaperone BRICHOS against the α-Synuclein secondary nucleation pathway
Authors: Ghosh Dhiman , Torres Felix , Schneider Matthias M. , Ashkinadze Dzmitry , Kadavath Harindranath , Fleischmann Yanick , Mergenthal Simon , Güntert Peter , Krainer Georg , Andrzejewska Ewa A. , Lin Lily , Wei Jiapeng , Klotzsch Enrico , Knowles Tuomas , Riek Roland 
Published: November 2024

AbstractThe complex kinetics of disease-related amyloid aggregation of proteins such as α-Synuclein (α-Syn) in Parkinson’s disease and Aβ42 in Alzheimer’s disease include primary nucleation, amyloid fibril elongation and secondary nucleation. The latter can be a key accelerator of the aggregation process. It has been demonstrated that the chaperone domain BRICHOS can interfere with the secondary nucleation process of Aβ42. Here, we explore the mechanism of secondary nucleation inhibition of the BRICHOS domain of the lung surfactant protein (proSP-C) against α-Syn aggregation and amyloid formation. We determine the 3D NMR structure of an inactive trimer of proSP-C BRICHOS and its active monomer using a designed mutant. Furthermore, the interaction between the proSP-C BRICHOS chaperone and a substrate peptide has been studied. NMR-based interaction studies of proSP-C BRICHOS with α-Syn fibrils show that proSP-C BRICHOS binds to the C-terminal flexible fuzzy coat of the fibrils, which is the secondary nucleation site on the fibrils. Super-resolution fluorescence microscopy demonstrates that proSP-C BRICHOS runs along the fibrillar axis diffusion-dependently sweeping off monomeric α-Syn from the fibrils. The observed mechanism explains how a weakly binding chaperone can inhibit the α-Syn secondary nucleation pathway via avidity where a single proSP-C BRICHOS molecule is sufficient against up to ~7-40 α-Syn molecules embedded within the fibrils.
Analyzing longitudinal trait trajectories using GWAS identifies genetic variants for kidney function decline
Authors: Wiegrebe Simon , Gorski Mathias , Herold Janina M. , Stark Klaus J. , Thorand Barbara , Gieger Christian , Böger Carsten A. , Schödel Johannes , Hartig Florian , Chen Han , Winkler Thomas W. , Küchenhoff Helmut , Heid Iris M. 
Published: November 2024

AbstractUnderstanding the genetics of kidney function decline, or trait change in general, is hampered by scarce longitudinal data for GWAS (longGWAS) and uncertainty about how to analyze such data. We use longitudinal UK Biobank data for creatinine-based estimated glomerular filtration rate from 348,275 individuals to search for genetic variants associated with eGFR-decline. This search was performed both among 595 variants previously associated with eGFR in cross-sectional GWAS and genome-wide. We use seven statistical approaches to analyze the UK Biobank data and simulated data, finding that a linear mixed model is a powerful approach with unbiased effect estimates which is viable for longGWAS. The linear mixed model identifies 13 independent genetic variants associated with eGFR-decline, including 6 novel variants, and links them to age-dependent eGFR-genetics. We demonstrate that age-dependent and age-independent eGFR-genetics exhibit a differential pattern regarding clinical progression traits and kidney-specific gene expression regulation. Overall, our results provide insights into kidney aging and linear mixed model-based longGWAS generally.
Staphylococcus epidermidis alters macrophage polarization and phagocytic uptake by extracellular DNA release in vitro
Authors: Weißelberg Samira , Both Anna , Failla Antonio Virgilio , Huang Jiabin , Linder Stefan , Ohnezeit Denise , Bartsch Patricia , Aepfelbacher Martin , Rohde Holger 
Published: November 2024

AbstractBiofilm formation shields Staphylococcus epidermidis from host defense mechanisms, contributing to chronic implant infections. Using wild-type S. epidermidis 1457, a PIA-negative mutant (1457-M10), and an eDNA-negative mutant (1457ΔatlE), this study examined the influence of biofilm matrix components on human monocyte-derived macrophage (hMDM) interactions. The wild-type strain was resistant to phagocytosis and induced an anti-inflammatory response in hMDMs, while both mutants were more susceptible to phagocytosis and triggered a pro-inflammatory response. Removing eDNA from the 1457 biofilm matrix increased hMDM uptake and a pro-inflammatory reaction, whereas adding eDNA to the 1457ΔatlE mutant reduced phagocytosis and promoted an anti-inflammatory response. Inhibiting TLR9 enhanced bacterial uptake and induced a pro-inflammatory response in hMDMs exposed to wild-type S. epidermidis. This study highlights the critical role of eDNA in immune evasion and the central role of TLR9 in modulating macrophage responses, advancing the understanding of implant infections.
Learning high-accuracy error decoding for quantum processors
Authors: Bausch Johannes , Senior Andrew W. , Heras Francisco J. H. , Edlich Thomas , Davies Alex , Newman Michael , Jones Cody , Satzinger Kevin , Niu Murphy Yuezhen , Blackwell Sam , Holland George , Kafri Dvir , Atalaya Juan , Gidney Craig , Hassabis Demis , Boixo Sergio , Neven Hartmut , Kohli Pushmeet 
Published: November 2024

AbstractBuilding a large-scale quantum computer requires effective strategies to correct errors that inevitably arise in physical quantum systems1. Quantum error-correction codes2 present a way to reach this goal by encoding logical information redundantly into many physical qubits. A key challenge in implementing such codes is accurately decoding noisy syndrome information extracted from redundancy checks to obtain the correct encoded logical information. Here we develop a recurrent, transformer-based neural network that learns to decode the surface code, the leading quantum error-correction code3. Our decoder outperforms other state-of-the-art decoders on real-world data from Google’s Sycamore quantum processor for distance-3 and distance-5 surface codes4. On distances up to 11, the decoder maintains its advantage on simulated data with realistic noise including cross-talk and leakage, utilizing soft readouts and leakage information. After training on approximate synthetic data, the decoder adapts to the more complex, but unknown, underlying error distribution by training on a limited budget of experimental samples. Our work illustrates the ability of machine learning to go beyond human-designed algorithms by learning from data directly, highlighting machine learning as a strong contender for decoding in quantum computers.
Coupling of unactivated alkyl electrophiles using frustrated ion pairs
Authors: Roediger Sven , Le Saux Emilien , Boehm Philip , Morandi Bill 
Published: November 2024

AbstractCross-electrophile coupling reactions have evolved into a major strategy for rapidly assembling important organic molecules1. Two readily accessible electrophiles are coupled to form new C–C bonds, providing a key advantage over traditional cross-coupling strategies that require the preformation of reactive organometallic species. Yet, the formation of C(sp3)–C(sp3) bonds that form the core of nearly all organic compounds remains highly challenging with current approaches, calling for the design of innovative new strategies. Here we report a distinct, transition-metal-free platform to form such bonds without the need for activating or stabilizing groups on the coupling partners. The reaction is enabled by an unusual single-electron transfer in a frustrated ion pair, and it can couple fragments containing functional groups that would be challenging in related transition-metal-catalysed processes. Moreover, we could further leverage this new mechanistic manifold in the design of other reactions, showing the broad potential of this type of reactivity. We anticipate that our results will provide a framework for further exploration of this reactivity pattern to tackle challenging problems in organic synthesis.
Nonlinear receptive fields evoke redundant retinal coding of natural scenes
Authors: Karamanlis Dimokratis , Khani Mohammad H. , Schreyer Helene M. , Zapp Sören J. , Mietsch Matthias , Gollisch Tim 
Published: November 2024

AbstractThe role of the vertebrate retina in early vision is generally described by the efficient coding hypothesis1,2, which predicts that the retina reduces the redundancy inherent in natural scenes3 by discarding spatiotemporal correlations while preserving stimulus information4. It is unclear, however, whether the predicted decorrelation and redundancy reduction in the activity of ganglion cells, the retina’s output neurons, hold under gaze shifts, which dominate the dynamics of the natural visual input5. We show here that species-specific gaze patterns in natural stimuli can drive correlated spiking responses both in and across distinct types of ganglion cells in marmoset as well as mouse retina. These concerted responses disrupt redundancy reduction to signal fixation periods with locally high spatial contrast. Model-based analyses of ganglion cell responses to natural stimuli show that the observed response correlations follow from nonlinear pooling of ganglion cell inputs. Our results indicate cell-type-specific deviations from efficient coding in retinal processing of natural gaze shifts.