bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wnt/β-catenin signalling is required for pole-specific chromatin remodeling during planarian regeneration
Authors: Pascual-Carreras Eudald , Marín-Barba Marta , Castillo-Lara Sergio , Coronel-Córdoba Pablo , Magri Marta Silvia , Wheeler Grant N. , Gómez-Skarmeta Jose Luis , Abril Josep F. , Saló Emili , Adell Teresa 
Published: January 2023

AbstractFor successful regeneration, the identity of the missing tissue must be specified according to the pre-existing tissue. Planarians are ideal for the study of the mechanisms underlying this process; the same field of cells can regrow a head or a tail according to the missing body part. After amputation, the differential activation of the Wnt/β-catenin signal specifies anterior versus posterior identity. Initially, bothwnt1andnotum(Wnt inhibitor) are expressed in all wounds, but 48 hours later they are restricted to posterior or anterior facing wounds, respectively, by an unknown mechanism. Here we show that 12 hours after amputation, the chromatin accessibility of cells in the wound region changes according to the polarity of the pre-existing tissue in a Wnt/β-catenin-dependent manner. Genomic analyses suggest that homeobox transcription factors and chromatin-remodeling proteins are direct Wnt/β-catenin targets, which trigger the expression of posterior effectors. Finally, we identify FoxG as awnt1up-stream regulator, probably via binding to its first intron enhancer region.
Construction of angstrom-scale ion channels with versatile pore configurations and sizes by metal-organic frameworks
Authors: Li Xingya , Jiang Gengping , Jian Meipeng , Zhao Chen , Hou Jue , Thornton Aaron W. , Zhang Xinyi , Liu Jefferson Zhe , Freeman Benny D. , Wang Huanting , Jiang Lei , Zhang Huacheng 
Published: January 2023

AbstractControllable fabrication of angstrom-size channels has been long desired to mimic biological ion channels for the fundamental study of ion transport. Here we report a strategy for fabricating angstrom-scale ion channels with one-dimensional (1D) to three-dimensional (3D) pore structures by the growth of metal-organic frameworks (MOFs) into nanochannels. The 1D MIL-53 channels of flexible pore sizes around 5.2 × 8.9 Å can transport cations rapidly, with one to two orders of magnitude higher conductivities and mobilities than MOF channels of hybrid pore configurations and sizes, including Al-TCPP with 1D ~8 Å channels connected by 2D ~6 Å interlayers, and 3D UiO-66 channels of ~6 Å windows and 9 − 12 Å cavities. Furthermore, the 3D MOF channels exhibit better ion sieving properties than those of 1D and 2D MOF channels. Theoretical simulations reveal that ion transport through 2D and 3D MOF channels should undergo multiple dehydration-rehydration processes, resulting in higher energy barriers than pure 1D channels. These findings offer a platform for studying ion transport properties at angstrom-scale confinement and provide guidelines for improving the efficiency of ionic separations and nanofluidics.
Real-time visualisation of the intracellular dynamics of conjugative plasmid transfer
Authors: Couturier Agathe , Virolle Chloé , Goldlust Kelly , Berne-Dedieu Annick , Reuter Audrey , Nolivos Sophie , Yamaichi Yoshiharu , Bigot Sarah , Lesterlin Christian 
Published: January 2023

AbstractConjugation is a contact-dependent mechanism for the transfer of plasmid DNA between bacterial cells, which contributes to the dissemination of antibiotic resistance. Here, we use live-cell microscopy to visualise the intracellular dynamics of conjugative transfer of F-plasmid in E. coli, in real time. We show that the transfer of plasmid in single-stranded form (ssDNA) and its subsequent conversion into double-stranded DNA (dsDNA) are fast and efficient processes that occur with specific timing and subcellular localisation. Notably, the ssDNA-to-dsDNA conversion determines the timing of plasmid-encoded protein production. The leading region that first enters the recipient cell carries single-stranded promoters that allow the early and transient synthesis of leading proteins immediately upon entry of the ssDNA plasmid. The subsequent conversion into dsDNA turns off leading gene expression, and activates the expression of other plasmid genes under the control of conventional double-stranded promoters. This molecular strategy allows for the timely production of factors sequentially involved in establishing, maintaining and disseminating the plasmid.
Modern temperatures in central–north Greenland warmest in past millennium
Authors: Hörhold M. , Münch T. , Weißbach S. , Kipfstuhl S. , Freitag J. , Sasgen I. , Lohmann G. , Vinther B. , Laepple T. 
Published: January 2023

AbstractThe Greenland Ice Sheet has a central role in the global climate system owing to its size, radiative effects and freshwater storage, and as a potential tipping point1. Weather stations show that the coastal regions are warming2, but the imprint of global warming in the central part of the ice sheet is unclear, owing to missing long-term observations. Current ice-core-based temperature reconstructions3–5 are ambiguous with respect to isolating global warming signatures from natural variability, because they are too noisy and do not include the most recent decades. By systematically redrilling ice cores, we created a high-quality reconstruction of central and north Greenland temperatures from ﻿ad 1000 until 2011. Here we show that the warming in the recent reconstructed decade exceeds the range of the pre-industrial temperature variability in the past millennium with virtual certainty (P < 0.001) and is on average 1.5 ± 0.4 degrees Celsius (1 standard error) warmer than the twentieth century. Our findings suggest that these exceptional temperatures arise from the superposition of natural variability with a long-term warming trend, apparent since ad 1800. The disproportionate warming is accompanied by enhanced Greenland meltwater run-off, implying that anthropogenic influence has also arrived in central and north Greenland, which might further accelerate the overall Greenland mass loss.
A 1.2 Billion Pixel Human-Labeled Dataset for Data-Driven Classification of Coastal Environments
Authors: Buscombe Daniel , Wernette Phillipe , Fitzpatrick Sharon , Favela Jaycee , Goldstein Evan B. , Enwright Nicholas M. 
Published: January 2023

AbstractThe world’s coastlines are spatially highly variable, coupled-human-natural systems that comprise a nested hierarchy of component landforms, ecosystems, and human interventions, each interacting over a range of space and time scales. Understanding and predicting coastline dynamics necessitates frequent observation from imaging sensors on remote sensing platforms. Machine Learning models that carry out supervised (i.e., human-guided) pixel-based classification, or image segmentation, have transformative applications in spatio-temporal mapping of dynamic environments, including transient coastal landforms, sediments, habitats, waterbodies, and water flows. However, these models require large and well-documented training and testing datasets consisting of labeled imagery. We describe “Coast Train,” a multi-labeler dataset of orthomosaic and satellite images of coastal environments and corresponding labels. These data include imagery that are diverse in space and time, and contain 1.2 billion labeled pixels, representing over 3.6 million hectares. We use a human-in-the-loop tool especially designed for rapid and reproducible Earth surface image segmentation. Our approach permits image labeling by multiple labelers, in turn enabling quantification of pixel-level agreement over individual and collections of images.
Brain activity during a working memory task after daily caffeine intake and caffeine withdrawal: a randomized double-blind placebo-controlled trial
Authors: Lin Yu-Shiuan , Weibel Janine , Landolt Hans-Peter , Santini Francesco , Slawik Helen , Borgwardt Stefan , Cajochen Christian , Reichert Carolin Franziska 
Published: January 2023

AbstractAcute caffeine intake has been found to increase working memory (WM)-related brain activity in healthy adults without improving behavioral performances. The impact of daily caffeine intake—a ritual shared by 80% of the population worldwide—and of its discontinuation on working memory and its neural correlates remained unknown. In this double-blind, randomized, crossover study, we examined working memory functions in 20 young healthy non-smokers (age: 26.4 ± 4.0 years; body mass index: 22.7 ± 1.4 kg/m2; and habitual caffeine intake: 474.1 ± 107.5 mg/day) in a 10-day caffeine (150 mg × 3 times/day), a 10-day placebo (3 times/day), and a withdrawal condition (9-day caffeine followed by 1-day placebo). Throughout the 10th day of each condition, participants performed four times a working memory task (N-Back, comprising 3- and 0-back), and task-related blood-oxygen-level-dependent (BOLD) activity was measured in the last session with functional magnetic resonance imaging. Compared to placebo, participants showed a higher error rate and a longer reaction time in 3- against 0-back trials in the caffeine condition; also, in the withdrawal condition we observed a higher error rate compared to placebo. However, task-related BOLD activity, i.e., an increased attention network and decreased default mode network activity in 3- versus 0-back, did not show significant differences among three conditions. Interestingly, irrespective of 3- or 0-back, BOLD activity was reduced in the right hippocampus in the caffeine condition compared to placebo. Adding to the earlier evidence showing increasing cerebral metabolic demands for WM function after acute caffeine intake, our data suggest that such demands might be impeded over daily intake and therefore result in a worse performance. Finally, the reduced hippocampal activity may reflect caffeine-associated hippocampal grey matter plasticity reported in the previous analysis. The findings of this study reveal an adapted neurocognitive response to daily caffeine exposure and highlight the importance of classifying impacts of caffeine on clinical and healthy populations.
A rodent model for Dirofilaria immitis, canine heartworm: parasite growth, development, and drug sensitivity in NSG mice
Authors: Hess Jessica A. , Eberhard Mark L. , Segura-Lepe Marcelo , Grundner-Culemann Kathrin , Kracher Barbara , Shryock Jeffrey , Harrington John , Abraham David 
Published: January 2023

AbstractHeartworm disease, caused by Dirofilaria immitis, remains a significant threat to canines and felines. The development of parasites resistant to macrocyclic lactones (ML) has created a significant challenge to the control of the infection. The goal of this study was to determine if mice lacking a functional immune response would be susceptible to D. immitis. Immunodeficient NSG mice were susceptible to the infection, sustaining parasites for at least 15 weeks, with infective third-stage larvae molting and developing into the late fourth-stage larvae. Proteomic analysis of host responses to the infection revealed a complex pattern of changes after infection, with at least some of the responses directed at reducing immune control mechanisms that remain in NSG mice. NSG mice were infected with isolates of D. immitis that were either susceptible or resistant to MLs, as a population. The susceptible isolate was killed by ivermectin whereas the resistant isolate had improved survivability, while both isolates were affected by moxidectin. It was concluded that D. immitis survives in NSG mice for at least 15 weeks. NSG mice provide an ideal model for monitoring host responses to the infection and for testing parasites in vivo for susceptibility to direct chemotherapeutic activity of new agents.
Hysteroscopic injections of autologous endometrial cells and platelet-rich plasma in patients with thin endometrium: a pilot randomized study
Authors: Efendieva Zulfiia , Vishnyakova Polina , Apolikhina Inna , Artemova Daria , Butov Kirill , Kalinina Elena , Fedorova Tatiana , Tregubova Anna , Asaturova Aleksandra , Fatkhudinov Timur , Sukhikh Gennady 
Published: January 2023

AbstractThe aim of this study was to evaluate the efficacy of hysteroscopically controlled injections of autologous platelet-rich plasma (PRP) and autologous endometrial cells as a treatment for infertile women with thin endometrium. The study enrolled 115 patients with thin endometrium (< 7 mm at implantation window) and infertility, who were divided into groups: Group 1 (the control) underwent conservative therapy; Group 2 received intraendometrial PRP injections instead of the conservative therapy; Group 3 received identical injections after conservative therapy; Group 4 received injections of the autologous endometrial cells suspended in PRP. A single injection dose of PRP contained 0.6–0.7 × 1011of platelets. The levels of PDGF-BB and VEGF in PRP were increased compared with ordinary plasma. The autologous endometrial cells, obtained from pipelle biopsies, constituted heterogeneous cell populations containing stromal and epithelial cells. Intraendometrial PRP injections had significant impact on endometrial thickness and local microcirculation in Group 2 and Group 3. In Group 4, injections of PRP reinforced with endometrial cells also facilitated a significant increase in endometrial thickness. This work describes a novel approach for infertility treatment in patients with refractory thin endometrium. PRP injections and injections of the endometrial cells suspended in PRP into endometrium enhanced cell proliferation and angiogenesis.
Computational analysis of ventricular mechanics in hypertrophic cardiomyopathy patients
Authors: Mojumder Joy , Fan Lei , Nguyen Thuy , Campbell Kenneth S. , Wenk Jonathan F. , Guccione Julius M. , Abraham Theodore , Lee Lik Chuan 
Published: January 2023

AbstractHypertrophic cardiomyopathy (HCM) is a genetic heart disease that is associated with many pathological features, such as a reduction in global longitudinal strain (GLS), myofiber disarray and hypertrophy. The effects of these features on left ventricle (LV) function are, however, not clear in two phenotypes of HCM, namely, obstructive and non-obstructive. To address this issue, we developed patient-specific computational models of the LV using clinical measurements from 2 female HCM patients and a control subject. Left ventricular mechanics was described using an active stress formulation and myofiber disarray was described using a structural tensor in the constitutive models. Unloaded LV configuration for each subject was first determined from their respective end-diastole LV geometries segmented from the cardiac magnetic resonance images, and an empirical single-beat estimation of the end-diastolic pressure volume relationship. The LV was then connected to a closed-loop circulatory model and calibrated using the clinically measured LV pressure and volume waveforms, peak GLS and blood pressure. Without consideration of myofiber disarray, peak myofiber tension was found to be lowest in the obstructive HCM subject (60 kPa), followed by the non-obstructive subject (242 kPa) and the control subject (375 kPa). With increasing myofiber disarray, we found that peak tension has to increase in the HCM models to match the clinical measurements. In the obstructive HCM patient, however, peak tension was still depressed (cf. normal subject) at the largest degree of myofiber disarray found in the clinic. The computational modeling workflow proposed here can be used in future studies with more HCM patient data.
Machine learning approach for quantitative biodosimetry of partial-body or total-body radiation exposures by combining radiation-responsive biomarkers
Authors: Shuryak Igor , Nemzow Leah , Bacon Bezalel A. , Taveras Maria , Wu Xuefeng , Deoli Naresh , Ponnaiya Brian , Garty Guy , Brenner David J. , Turner Helen C. 
Published: January 2023

AbstractDuring a large-scale radiological event such as an improvised nuclear device detonation, many survivors will be shielded from radiation by environmental objects, and experience only partial-body irradiation (PBI), which has different consequences, compared with total-body irradiation (TBI). In this study, we tested the hypothesis that applying machine learning to a combination of radiation-responsive biomarkers (ACTN1, DDB2, FDXR) and B and T cell counts will quantify and distinguish between PBI and TBI exposures. Adult C57BL/6 mice of both sexes were exposed to 0, 2.0–2.5 or 5.0 Gy of half-body PBI or TBI. The random forest (RF) algorithm trained on ½ of the data reconstructed the radiation dose on the remaining testing portion of the data with mean absolute error of 0.749 Gy and reconstructed the product of dose and exposure status (defined as 1.0 × Dose for TBI and 0.5 × Dose for PBI) with MAE of 0.472 Gy. Among irradiated samples, PBI could be distinguished from TBI: ROC curve AUC = 0.944 (95% CI: 0.844–1.0). Mouse sex did not significantly affect dose reconstruction. These results support the hypothesis that combinations of protein biomarkers and blood cell counts can complement existing methods for biodosimetry of PBI and TBI exposures.
A cross-sectional study of inflammatory markers as determinants of circulating kynurenines in the Lung Cancer Cohort Consortium
Authors: Midttun Øivind , Ulvik Arve , Meyer Klaus , Zahed Hana , Giles Graham G. , Manjer Jonas , Sandsveden Malte , Langhammer Arnulf , Sørgjerd Elin Pettersen , Behndig Annelie F. , Johansson Mikael , Freedman Neal D. , Huang Wen-Yi , Chen Chu , Prentice Ross , Stevens Victoria L. , Wang Ying , Le Marchand Loïc , Weinstein Stephanie J. , Cai Qiuyin , Arslan Alan A. , Chen Yu , Shu Xiao-Ou , Zheng Wei , Yuan Jian-Min , Koh Woon-Puay , Visvanathan Kala , Sesso Howard D. , Zhang Xuehong , Gaziano J. Michael , Fanidi Anouar , Robbins Hilary A. , Brennan Paul , Johansson Mattias , Ueland Per M. 
Published: January 2023

AbstractCirculating concentrations of metabolites (collectively called kynurenines) in the kynurenine pathway of tryptophan metabolism increase during inflammation, particularly in response to interferon-gamma (IFN-γ). Neopterin and the kynurenine/tryptophan ratio (KTR) are IFN-γ induced inflammatory markers, and together with C-reactive protein (CRP) and kynurenines they are associated with various diseases, but comprehensive data on the strength of associations of inflammatory markers with circulating concentrations of kynurenines are lacking. We measured circulating concentrations of neopterin, CRP, tryptophan and seven kynurenines in 5314 controls from 20 cohorts in the Lung Cancer Cohort Consortium (LC3). The associations of neopterin, KTR and CRP with kynurenines were investigated using regression models. In mixed models, one standard deviation (SD) higher KTR was associated with a 0.46 SD higher quinolinic acid (QA), and 0.31 SD higher 3-hydroxykynurenine (HK). One SD higher neopterin was associated with 0.48, 0.44, 0.36 and 0.28 SD higher KTR, QA, kynurenine and HK, respectively. KTR and neopterin respectively explained 24.1% and 16.7% of the variation in QA, and 11.4% and 7.5% of HK. CRP was only weakly associated with kynurenines in regression models. In summary, QA was the metabolite that was most strongly associated with the inflammatory markers. In general, the inflammatory markers were most strongly related to metabolites located along the tryptophan–NAD axis, which may support suggestions of increased production of NAD from tryptophan during inflammation.
Clustering by antigen-presenting genes reveals immune landscapes and predicts response to checkpoint immunotherapy
Authors: Gong Xutong , Karchin Rachel 
Published: January 2023

AbstractImmune checkpoint blockade (ICB) has demonstrated efficacy by reinvigorating immune cytotoxicity against tumors. However, the mechanisms underlying how ICB induces responses in a subset of patients remain unclear. Using bulk and single-cell transcriptomic cohorts of melanoma patients receiving ICB, we proposed a clustering model based on the expression of an antigen-presenting machinery (APM) signature consisting of 23 genes in a forward-selection manner. We characterized four APM clusters associated with distinct immune characteristics, cancer hallmarks, and patient prognosis in melanoma. The model predicts differential regulation of APM genes during ICB, which shaped ICB responsiveness. Surprisingly, while immunogenically hot tumors with high baseline APM expression prior to treatment are correlated with a better response to ICB than cold tumors with low APM expression, a subset of hot tumors with the highest pre-ICB APM expression fail to upregulate APM expression during treatment. In addition, they undergo immunoediting and display infiltration of exhausted T cells. In comparison, tumors associated with the best patient prognosis demonstrate significant APM upregulation and immune infiltration following ICB. They also show infiltration of tissue-resident memory T cells, shaping prolonged antitumor immunity. Using only pre-treatment transcriptomic data, our model predicts the dynamic APM-mediated tumor-immune interactions in response to ICB and provides insights into the immune escape mechanisms in hot tumors that compromise the ICB efficacy. We highlight the prognostic value of APM expression in predicting immune response in chronic diseases.
Long distance entanglement and high-dimensional quantum teleportation in the Fermi–Hubbard model
Authors: Abaach Sanaa , Mzaouali Zakaria , El Baz Morad 
Published: January 2023

AbstractThe long distance entanglement in finite size open Fermi–Hubbard chains, together with the end-to-end quantum teleportation are investigated. We show the peculiarity of the ground state of the Fermi–Hubbard model to support maximum long distance entanglement, which allows it to operate as a quantum resource for high fidelity long distance quantum teleportation. We determine the physical properties and conditions for creating scalable long distance entanglement and analyze its stability under the effect of the Coulomb interaction and the hopping amplitude. Furthermore, we show that the choice of the measurement basis in the protocol can drastically affect the fidelity of quantum teleportation and we argue that perfect information transfer can be attained by choosing an adequate basis reflecting the salient properties of the quantum channel, i.e. Hubbard projective measurements.
Impact of physiological parameters on the parotid gland fat fraction in a normal population
Authors: Lee Ari , Choi Yoon Joo , Jeon Kug Jin , Han Sang-Sun , Lee Chena 
Published: January 2023

AbstractQuantifying physiological fat tissue in the organs is important to further assess the organ’s pathologic status. This study aimed to investigate the impact of body mass index (BMI), age, and sex on the fat fraction of normal parotid glands. Patients undergoing magnetic resonance imaging (MRI) of iterative decomposition of water and fat with echo asymmetry and least squares estimation (IDEAL-IQ) due to non-salivary gland-related disease were reviewed. Clinical information of individual patients was categorized into groups based on BMI (under/normal/overweight), age (age I/age II/age III), and sex (female/male) and an inter-group comparison of the fat fraction values of both parotid glands was conducted. Overall, in the 626 parotid glands analyzed, the fat fraction of the gland was 35.80%. The mean fat fraction value increased with BMI (30.23%, 35.74%, and 46.61% in the underweight, normal and overweight groups, respectively [p < 0.01]) and age (32.42%, 36.20%, and 41.94% in the age I, II, and III groups, respectively [p < 0.01]). The fat content of normal parotid glands varies significantly depending on the body mass and age regardless of sex. Therefore, the patient’s age and body mass should be considered when evaluating fatty change in the parotid glands in imaging results.