bluuebunny/crossref_metadata_2025_split huggingface dataset:
Premature thymic functional senescence is a hallmark of childhood acute lymphoblastic leukemia survivorship
Authors: Kientega Tibila , Marcoux Sophie , Bourbonnais Jessica , Montpetit Jade , Caru Maxime , Cardin Guillaume B. , Arbour Nathalie , Marcil Valérie , Curnier Daniel , Laverdière Caroline , Sinnett Daniel , Rodier Francis 
Published: June 2024

AbstractChildhood acute lymphoblastic leukemia (cALL) survivors suffer early-onset chronic diseases classically associated with aging. Normal aging is accompanied by organ dysfunctions, including immunological ones. We hypothesize that thymic immunosenescence occurs in cALL survivors and that its severity may correlate with early-onset chronic diseases. The PETALE study is a cALL survivor cohort with an extensive cardiovascular and metabolic evaluation. The thymic immunosenescence biomarker, signal joint T-cell receptor excision circles (TREC), was evaluated and was highly correlated with age in healthy participants (n = 281) and cALL survivors (n = 248). We observed a systematic thymic immunoage accentuation in each cALL survivor compared to controls ranging from 5.9 to 88.3 years. The immunoage gain was independent of age at diagnosis and treatment modalities and was more severe for females. Thymic aging was associated with several pathophysiological parameters, was greater in survivors suffering from metabolic syndrome, but there was no significant association with global physical condition. The decrease in TREC was independent from blood cell counts, which were normal, suggesting a segmental aging of the thymic compartment. Indeed, increased plasmatic T cell regulatory cytokines IL-6, IL-7 and GM-CSF accompanied high immunoage gain. Our data reveal that cALL or its treatment trigger a rapid immunoage gain followed by further gradual thymic immunosenescence, similar to normal aging. This leads to an enduring shift in accentuated immunoage compared to chronological age. Thus, accentuated thymic immunosenescence is a hallmark of cALL survivorship and TREC levels could be useful immunosenescence biomarkers to help monitoring the health of cancer survivors.
ZFHX3 acts as a tumor suppressor in prostate cancer by targeting FTO-mediated m6A demethylation
Authors: Hu Qingxia , Yin Junling , Zhao Sijie , Wang Yibo , Shi Ruxue , Yan Keqiang , Huang Shuhong 
Published: June 2024

AbstractZinc-finger homeobox 3 (ZFHX3, also known as ATBF1) suppresses prostatic tumorigenesis. ZFHX3 is frequently found to have numerous deletions in human prostate cancer (PCa). However, the underlying molecular function of ZFHX3 during prostatic tumorigenesis is not well understood. N6-methyladenosine (m6A) modification in RNA plays a critical role in the development of cancers; however, the relationship between ZFHX3 and m6A modification is largely unknown in PCa. In this study, we found that ZFHX3 knockdown decreased total m6A levels through enhancing the transcriptional activity of FTO in PCa cells. Importantly, FTO inhibition suppressed cell proliferation and rescued the promoting function of ZFHX3 knockdown on cell proliferation. In vivo, we verified that FTO was upregulated and ZFHX3 was decreased in PCa patients and that a high level of ZFHX3 is indispensable for low FTO expression and is correlated with better patient survival. Through transcriptome sequencing and MeRIP sequencing, we revealed that E2F2 and CDKN2C were the direct targets of FTO-mediated m6A modification and ZFXH3 was required for the regulation of FTO on E2F2 and CDKN2C expression. Unexpectedly, we uncovered that ZFHX3 expression was in return regulated by FTO in an m6A-dependent way. These findings establish a novel crosstalk mechanism between ZFHX3 and FTO in prostatic tumorigenesis.
A non-methanogenic archaeon within the order Methanocellales
Authors: Suzuki Shino , Ishii Shun’ichi , Chadwick Grayson L. , Tanaka Yugo , Kouzuma Atsushi , Watanabe Kazuya , Inagaki Fumio , Albertsen Mads , Nielsen Per H. , Nealson Kenneth H. 
Published: June 2024

AbstractSerpentinization, a geochemical process found on modern and ancient Earth, provides an ultra-reducing environment that can support microbial methanogenesis and acetogenesis. Several groups of archaea, such as the order Methanocellales, are characterized by their ability to produce methane. Here, we generate metagenomic sequences from serpentinized springs in The Cedars, California, and construct a circularized metagenome-assembled genome of a Methanocellales archaeon, termed Met12, that lacks essential methanogenesis genes. The genome includes genes for an acetyl-CoA pathway, but lacks genes encoding methanogenesis enzymes such as methyl-coenzyme M reductase, heterodisulfide reductases and hydrogenases. In situ transcriptomic analyses reveal high expression of a multi-heme c-type cytochrome, and heterologous expression of this protein in a model bacterium demonstrates that it is capable of accepting electrons. Our results suggest that Met12, within the order Methanocellales, is not a methanogen but a CO2-reducing, electron-fueled acetogen without electron bifurcation.
Differences in regional brain structure in toddlers with autism are related to future language outcomes
Authors: Duan Kuaikuai , Eyler Lisa , Pierce Karen , Lombardo Michael V. , Datko Michael , Hagler Donald J. , Taluja Vani , Zahiri Javad , Campbell Kathleen , Barnes Cynthia Carter , Arias Steven , Nalabolu Srinivasa , Troxel Jaden , Ji Peng , Courchesne Eric 
Published: June 2024

AbstractLanguage and social symptoms improve with age in some autistic toddlers, but not in others, and such outcome differences are not clearly predictable from clinical scores alone. Here we aim to identify early-age brain alterations in autism that are prognostic of future language ability. Leveraging 372 longitudinal structural MRI scans from 166 autistic toddlers and 109 typical toddlers and controlling for brain size, we find that, compared to typical toddlers, autistic toddlers show differentially larger or thicker temporal and fusiform regions; smaller or thinner inferior frontal lobe and midline structures; larger callosal subregion volume; and smaller cerebellum. Most differences are replicated in an independent cohort of 75 toddlers. These brain alterations improve accuracy for predicting language outcome at 6-month follow-up beyond intake clinical and demographic variables. Temporal, fusiform, and inferior frontal alterations are related to autism symptom severity and cognitive impairments at early intake ages. Among autistic toddlers, brain alterations in social, language and face processing areas enhance the prediction of the child’s future language ability.
Nicotinamide riboside for peripheral artery disease: the NICE randomized clinical trial
Authors: McDermott Mary M. , Martens Christopher R. , Domanchuk Kathryn J. , Zhang Dongxue , Peek Clara B. , Criqui Michael H. , Ferrucci Luigi , Greenland Philip , Guralnik Jack M. , Ho Karen J. , Kibbe Melina R. , Kosmac Kate , Lloyd-Jones Donald , Peterson Charlotte A. , Sufit Robert , Tian Lu , Wohlgemuth Stephanie , Zhao Lihui , Zhu Pei , Leeuwenburgh Christiaan 
Published: June 2024

AbstractPeople with lower extremity peripheral artery disease (PAD) have increased oxidative stress, impaired mitochondrial activity, and poor walking performance. NAD+ reduces oxidative stress and is an essential cofactor for mitochondrial respiration. Oral nicotinamide riboside (NR) increases bioavailability of NAD+ in humans. Among 90 people with PAD, this randomized double-blind clinical trial assessed whether 6-months of NR, with and without resveratrol, improves 6-min walk distance, compared to placebo, at 6-month follow-up. At 6-month follow-up, compared to placebo, NR significantly improved 6-min walk (+7.0 vs. −10.6 meters, between group difference: +17.6 (90% CI: + 1.8,+∞). Among participants who took at least 75% of study pills, compared to placebo, NR improved 6-min walk by 31.0 meters and NR + resveratrol improved 6-min walk by 26.9 meters. In this work, NR meaningfully improved 6-min walk, and resveratrol did not add benefit to NR alone in PAD. A larger clinical trial to confirm these findings is needed. Clinical Trials.gov registration: NCT03743636.
Bubbles enable volumetric negative compressibility in metastable elastocapillary systems
Authors: Caprini Davide , Battista Francesco , Zajdel Paweł , Di Muccio Giovanni , Guardiani Carlo , Trump Benjamin , Carter Marcus , Yakovenko Andrey A. , Amayuelas Eder , Bartolomé Luis , Meloni Simone , Grosu Yaroslav , Casciola Carlo Massimo , Giacomello Alberto 
Published: June 2024

AbstractAlthough coveted in applications, few materials expand when subject to compression or contract under decompression, i.e., exhibit negative compressibility. A key step to achieve such counterintuitive behaviour is the destabilisations of (meta)stable equilibria of the constituents. Here, we propose a simple strategy to obtain negative compressibility exploiting capillary forces both to precompress the elastic material and to release such precompression by a threshold phenomenon – the reversible formation of a bubble in a hydrophobic flexible cavity. We demonstrate that the solid part of such metastable elastocapillary systems displays negative compressibility across different scales: hydrophobic microporous materials, proteins, and millimetre-sized laminae. This concept is applicable to fields such as porous materials, biomolecules, sensors and may be easily extended to create unexpected material susceptibilities.
Quantum control and Berry phase of electron spins in rotating levitated diamonds in high vacuum
Authors: Jin Yuanbin , Shen Kunhong , Ju Peng , Gao Xingyu , Zu Chong , Grine Alejandro J. , Li Tongcang 
Published: June 2024

AbstractLevitated diamond particles in high vacuum with internal spin qubits have been proposed for exploring macroscopic quantum mechanics, quantum gravity, and precision measurements. The coupling between spins and particle rotation can be utilized to study quantum geometric phase, create gyroscopes and rotational matter-wave interferometers. However, previous efforts in levitated diamonds struggled with vacuum level or spin state readouts. To address these gaps, we fabricate an integrated surface ion trap with multiple stabilization electrodes. This facilitates on-chip levitation and, for the first time, optically detected magnetic resonance measurements of a nanodiamond levitated in high vacuum. The internal temperature of our levitated nanodiamond remains moderate at pressures below 10−5Torr. We have driven a nanodiamond to rotate up to 20 MHz (1.2 × 109rpm), surpassing typical nitrogen-vacancy (NV) center electron spin dephasing rates. Using these NV spins, we observe the effect of the Berry phase arising from particle rotation. In addition, we demonstrate quantum control of spins in a rotating nanodiamond. These results mark an important development in interfacing mechanical rotation with spin qubits, expanding our capacity to study quantum phenomena.
Genomic characterization of cervical lymph node metastases in papillary thyroid carcinoma following the Chornobyl accident
Authors: Morton Lindsay M. , Lee Olivia W. , Karyadi Danielle M. , Bogdanova Tetiana I. , Stewart Chip , Hartley Stephen W. , Breeze Charles E. , Schonfeld Sara J. , Cahoon Elizabeth K. , Drozdovitch Vladimir , Masiuk Sergii , Chepurny Mykola , Zurnadzhy Liudmyla Yu , Dai Jieqiong , Krznaric Marko , Yeager Meredith , Hutchinson Amy , Hicks Belynda D. , Dagnall Casey L. , Steinberg Mia K. , Jones Kristine , Jain Komal , Jordan Ben , Machiela Mitchell J. , Dawson Eric T. , Vij Vibha , Gastier-Foster Julie M. , Bowen Jay , Mabuchi Kiyohiko , Hatch Maureen , Berrington de Gonzalez Amy , Getz Gad , Tronko Mykola D. , Thomas Gerry A. , Chanock Stephen J. 
Published: June 2024

AbstractChildhood radioactive iodine exposure from the Chornobyl accident increased papillary thyroid carcinoma (PTC) risk. While cervical lymph node metastases (cLNM) are well-recognized in pediatric PTC, the PTC metastatic process and potential radiation association are poorly understood. Here, we analyze cLNM occurrence among 428 PTC with genomic landscape analyses and known drivers (131I-exposed = 349, unexposed = 79; mean age = 27.9 years). We show that cLNM are more frequent in PTC with fusion (55%) versus mutation (30%) drivers, although the proportion varies by specific driver gene (RET-fusion = 71%, BRAF-mutation = 38%, RAS-mutation = 5%). cLNM frequency is not associated with other characteristics, including radiation dose. cLNM molecular profiling (N = 47) demonstrates 100% driver concordance with matched primary PTCs and highly concordant mutational spectra. Transcriptome analysis reveals 17 differentially expressed genes, particularly in the HOXC cluster and BRINP3; the strongest differentially expressed microRNA also is near HOXC10. Our findings underscore the critical role of driver alterations and provide promising candidates for elucidating the biological underpinnings of PTC cLNM.
Topological regression as an interpretable and efficient tool for quantitative structure-activity relationship modeling
Authors: Zhang Ruibo , Nolte Daniel , Sanchez-Villalobos Cesar , Ghosh Souparno , Pal Ranadip 
Published: June 2024

AbstractQuantitative structure-activity relationship (QSAR) modeling is a powerful tool for drug discovery, yet the lack of interpretability of commonly used QSAR models hinders their application in molecular design. We propose a similarity-based regression framework, topological regression (TR), that offers a statistically grounded, computationally fast, and interpretable technique to predict drug responses. We compare the predictive performance of TR on 530 ChEMBL human target activity datasets against the predictive performance of deep-learning-based QSAR models. Our results suggest that our sparse TR model can achieve equal, if not better, performance than the deep learning-based QSAR models and provide better intuitive interpretation by extracting an approximate isometry between the chemical space of the drugs and their activity space.
Solution-state methyl NMR spectroscopy of large non-deuterated proteins enabled by deep neural networks
Authors: Karunanithy Gogulan , Shukla Vaibhav Kumar , Hansen D. Flemming 
Published: June 2024

AbstractMethyl-TROSY nuclear magnetic resonance (NMR) spectroscopy is a powerful technique for characterising large biomolecules in solution. However, preparing samples for these experiments is demanding and entails deuteration, limiting its use. Here we demonstrate that NMR spectra recorded on protonated, uniformly 13C labelled samples can be processed using deep neural networks to yield spectra that are of similar quality to typical deuterated methyl-TROSY spectra, potentially providing information for proteins that cannot be produced in bacterial systems. We validate the methodology experimentally on three proteins with molecular weights in the range 42–360 kDa. We further demonstrate the applicability of our methodology to 3D NOESY spectra of Escherichia coli Malate Synthase G (81 kDa), where observed NOE cross-peaks are in good agreement with the available structure. The method represents an advance in the field of using deep learning to analyse complex magnetic resonance data and could have an impact on the study of large biomolecules in years to come.
Hierarchical organic microspheres from diverse molecular building blocks
Authors: Li Yintao , Fan Longlong , Xu Xinyan , Sun Yang , Wang Wei , Li Bin , Veroneau Samuel S. , Ji Pengfei 
Published: June 2024

AbstractMicrospherical structures find broad application in chemistry and materials science, including in separations and purifications, energy storage and conversion, organic and biocatalysis, and as artificial and bioactive scaffolds. Despite this utility, the systematic diversification of their morphology and function remains hindered by the limited range of their molecular building blocks. Drawing upon the design principles of reticular synthesis, where diverse organic molecules generate varied porous frameworks, we show herein how analogous microspherical structures can be generated under mild conditions. The assembly of simple organic molecules into microspherical structures with advanced morphologies represents a grand challenge. Beginning with a partially condensed Schiff base which self-assembles into a hierarchical organic microsphere, we systematically synthesized sixteen microspheres from diverse molecular building blocks. We subsequently explicate the mechanism of hierarchical assembly through which these hierarchical organic microspheres are produced, isolating the initial monomer, intermediate substructures, and eventual microspheres. Furthermore, the open cavities present on the surfaces of these constructs provided distinctive adsorptive properties, which we harnessed for the immobilization of enzymes and bacteriophages. Holistically, these hierarchical organic microspheres provide an approach for designing multi-functional superstructures with advanced morphologies derived from simple organic molecules, revealing an extended length scale for reticular synthesis.
Tissue-intrinsic beta-catenin signals antagonize Nodal-driven anterior visceral endoderm differentiation
Authors: Schumacher Sina , Fernkorn Max , Marten Michelle , Chen Rui , Kim Yung Su , Bedzhov Ivan , Schröter Christian 
Published: June 2024

AbstractThe anterior-posterior axis of the mammalian embryo is laid down by the anterior visceral endoderm (AVE), an extraembryonic signaling center that is specified within the visceral endoderm. Current models posit that AVE differentiation is promoted globally by epiblast-derived Nodal signals, and spatially restricted by a BMP gradient established by the extraembryonic ectoderm. Here, we report spatially restricted AVE differentiation in bilayered embryo-like aggregates made from mouse embryonic stem cells that lack an extraembryonic ectoderm. Notably, clusters of AVE cells also form in pure visceral endoderm cultures upon activation of Nodal signaling, indicating that tissue-intrinsic factors can restrict AVE differentiation. We identify β-catenin activity as a tissue-intrinsic factor that antagonizes AVE-inducing Nodal signals. Together, our results show how an AVE-like population can arise through interactions between epiblast and visceral endoderm alone. This mechanism may be a flexible solution for axis patterning in a wide range of embryo geometries, and provide robustness to axis patterning when coupled with signal gradients.
Johnson-noise-limited cancellation-free microwave impedance microscopy with monolithic silicon cantilever probes
Authors: Shan Jun-Yi , Morrison Nathaniel , Chen Su-Di , Wang Feng , Ma Eric Y. 
Published: June 2024

AbstractMicrowave impedance microscopy (MIM) is an emerging scanning probe technique for nanoscale complex permittivity mapping and has made significant impacts in diverse fields. To date, the most significant hurdles that limit its widespread use are the requirements of specialized microwave probes and high-precision cancellation circuits. Here, we show that forgoing both elements not only is feasible but also enhances performance. Using monolithic silicon cantilever probes and a cancellation-free architecture, we demonstrate Johnson-noise-limited, drift-free MIM operation with 15 nm spatial resolution, minimal topography crosstalk, and an unprecedented sensitivity of 0.26 zF/√Hz. We accomplish this by taking advantage of the high mechanical resonant frequency and spatial resolution of silicon probes, the inherent common-mode phase noise rejection of self-referenced homodyne detection, and the exceptional stability of the streamlined architecture. Our approach makes MIM drastically more accessible and paves the way for advanced operation modes as well as integration with complementary techniques.
Strongly coupled magneto-exciton condensates in large-angle twisted double bilayer graphene
Authors: Li Qingxin , Chen Yiwei , Wei LingNan , Chen Hong , Huang Yan , Zhu Yujian , Zhu Wang , An Dongdong , Song Junwei , Gan Qikang , Zhang Qi , Watanabe Kenji , Taniguchi Takashi , Shi Xiaoyang , Novoselov Kostya S. , Wang Rui , Yu Geliang , Wang Lei 
Published: June 2024

AbstractExcitons, pairs of electrons and holes, undergo a Bose-Einstein condensation at low temperatures. An important platform to study excitons is double-layer two-dimensional electron gases, with two parallel planes of electrons and holes separated by a thin insulating layer. Lowering this separation (d) strengthens the exciton binding energy, however, leads to the undesired interlayer tunneling, resulting in annihilation of excitons. Here, we report the observation of a sequences of robust exciton condensates (ECs) in double bilayer graphene twisted to ~ 10° with no insulating mid-layer. The large momentum mismatch between two graphene layers suppresses interlayer tunneling, reaching a d ~ 0.334 nm. Measuring the bulk and edge transport, we find incompressible states corresponding to ECs when both layers are in half-filled N = 0, 1 Landau levels (LLs). Theoretical calculations suggest that the low-energy charged excitation of ECs can be meron-antimeron or particle-hole pair, which relies on both LL index and carrier type. Our results establish a novel platform with extreme coupling strength for studying quantum bosonic phase.
Micro-optical elements from optical-quality ZIF-62 hybrid glasses by hot imprinting
Authors: Smirnova Oksana , Sajzew Roman , Finkelmeyer Sarah Jasmin , Asadov Teymur , Chattopadhyay Sayan , Wieduwilt Torsten , Reupert Aaron , Presselt Martin , Knebel Alexander , Wondraczek Lothar 
Published: June 2024

AbstractHybrid glasses derived from meltable metal-organic frameworks (MOFs) promise to combine the intriguing properties of MOFs with the universal processing ability of glasses. However, the shaping of hybrid glasses in their liquid state – in analogy to conventional glass processing – has been elusive thus far. Here, we present optical-quality glasses derived from the zeolitic imidazole framework ZIF-62 in the form of cm-scale objects. These allow for in-depth studies of optical transparency and refraction across the ultraviolet to near-infrared spectral range. Fundamental viscosity data are reported using a ball penetration technique, and subsequently employed to demonstrate the fabrication of micro-optical devices by thermal imprinting. Using 3D-printed fused silica templates, we show that concave as well as convex lens structures can be obtained at high precision by remelting the glass without trading-off on material quality. This enables multifunctional micro-optical devices combining the gas uptake and permeation ability of MOFs with the optical functionality of glass. As an example, we demonstrate the reversible change of optical refraction upon the incorporation of volatile guest molecules.
Extreme weather events do not increase political parties' environmental attention
Authors: Wappenhans Tim , Valentim António , Klüver Heike , Stoetzer Lukas F. 
Published: June 2024

AbstractExposure to extreme weather events can make people more aware of environmental changes; however, it remains unclear how such events influence politicians’ behaviour. Combining supervised learning algorithms on over 260,000 press releases by European parties with a difference-in-differences design, we find that apart from Green parties, extreme weather events do not increase attention towards environmental issues. This suggests the consequences of climate change might not directly increase political attention.