bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digital telomere measurement by long-read sequencing distinguishes healthy aging from disease
Authors: Sanchez Santiago E. , Gu Yuchao , Wang Yan , Golla Anudeep , Martin Annika , Shomali William , Hockemeyer Dirk , Savage Sharon A. , Artandi Steven E. 
Published: June 2024

AbstractTelomere length is an important biomarker of organismal aging and cellular replicative potential, but existing measurement methods are limited in resolution and accuracy. Here, we deploy digital telomere measurement (DTM) by nanopore sequencing to understand how distributions of human telomere length change with age and disease. We measure telomere attrition and de novo elongation with up to 30 bp resolution in genetically defined populations of human cells, in blood cells from healthy donors and in blood cells from patients with genetic defects in telomere maintenance. We find that human aging is accompanied by a progressive loss of long telomeres and an accumulation of shorter telomeres. In patients with defects in telomere maintenance, the accumulation of short telomeres is more pronounced and correlates with phenotypic severity. We apply machine learning to train a binary classification model that distinguishes healthy individuals from those with telomere biology disorders. This sequencing and bioinformatic pipeline will advance our understanding of telomere maintenance mechanisms and the use of telomere length as a clinical biomarker of aging and disease.
Repeat controlled human Plasmodium falciparum infections delay bloodstream patency and reduce symptoms
Authors: Ferrer Patricia , Berry Andrea A. , Bucsan Allison N. , Prajapati Surendra K. , Krishnan Karthik , Barbeau Michelle C. , Rickert David M. , Guerrero Sandra Mendoza , Usui Miho , Abebe Yonas , Patil Asha , Chakravarty Sumana , Billingsley Peter F. , Pa’ahana-Brown Faith , Strauss Kathy , Shrestha Biraj , Nomicos Effie , Deye Gregory A. , Sim B. Kim Lee , Hoffman Stephen L. , Williamson Kim C. , Lyke Kirsten E. 
Published: June 2024

AbstractResistance to clinical malaria takes years to develop even in hyperendemic regions and sterilizing immunity has rarely been observed. To evaluate the maturation of the host response against controlled repeat exposures to P. falciparum (Pf) NF54 strain-infected mosquitoes, we systematically monitored malaria-naïve participants through an initial exposure to uninfected mosquitoes and 4 subsequent homologous exposures to Pf-infected mosquitoes over 21 months (n = 8 males) (ClinicalTrials.gov# NCT03014258). The primary outcome was to determine whether protective immunity against parasite infection develops following repeat CHMI and the secondary outcomes were to track the clinical signs and symptoms of malaria and anti-Pf antibody development following repeat CHMI. After two exposures, time to blood stage patency increases significantly and the number of reported symptoms decreases indicating the development of clinical tolerance. The time to patency correlates positively with both anti-Pf circumsporozoite protein (CSP) IgG and CD8 + CD69+ effector memory T cell levels consistent with partial pre-erythrocytic immunity. IFNγ levels decrease significantly during the participants’ second exposure to high blood stage parasitemia and could contribute to the decrease in symptoms. In contrast, CD4-CD8 + T cells expressing CXCR5 and the inhibitory receptor, PD-1, increase significantly after subsequent Pf exposures, possibly dampening the memory response and interfering with the generation of robust sterilizing immunity.
Biotic interactions promote local adaptation to soil in plants
Authors: Dorey Thomas , Frachon Léa , Rieseberg Loren H. , Kreiner Julia M. , Schiestl Florian P. 
Published: June 2024

AbstractAlthough different ecological factors shape adaptative evolution in natural habitats, we know little about how their interactions impact local adaptation. Here we used eight generations of experimental evolution with outcrossingBrassica rapaplants as a model system, in eight treatment groups that varied in soil type, herbivory (with/without aphids), and pollination mode (hand- or bumblebee-pollination), to study how biotic interactions affect local adaptation to soil. First, we show that several plant traits evolved in response to biotic interactions in a soil-specific way. Second, using a reciprocal transplant experiment, we demonstrate that significant local adaptation to soil-type evolved in the “number of open flowers”, a trait used as a fitness proxy, but only in plants that evolved with herbivory and bee pollination. Whole genome re-sequencing of experimental lines revealed that biotic interactions caused a 10-fold increase in the number of SNPs across the genome with significant allele frequency change, and that alleles with opposite allele frequency change in different soil types (antagonistic pleiotropy) were most common in plants with an evolutionary history of herbivory and bee pollination. Our results demonstrate that the interaction with mutualists and antagonists can facilitate local adaptation to soil type through antagonistic pleiotropy.
Red-light-mediated copper-catalyzed photoredox catalysis promotes regioselectivity switch in the difunctionalization of alkenes
Authors: Zhang Tong , Rabeah Jabor , Das Shoubhik 
Published: June 2024

AbstractControlling regioselectivity during difunctionalization of alkenes remains a significant challenge, particularly when the installation of both functional groups involves radical processes. In this aspect, methodologies to install trifluoromethane (−CF3) via difunctionalization have been explored, due to the importance of this moiety in the pharmaceutical sectors; however, these existing reports are limited, most of which affording only the corresponding β-trifluoromethylated products. The main reason for this limitation arises from the fact that −CF3 group served as an initiator in those reactions and predominantly preferred to be installed at the terminal (β) position of an alkene. On the contrary, functionalization of the −CF3 group at the internal (α) position of alkenes would provide valuable products, but a meticulous approach is necessary to win this regioselectivity switch. Intrigued by this challenge, we here develop an efficient and regioselective strategy where the −CF3 group is installed at the α-position of an alkene. Molecular complexity is achieved via the simultaneous insertion of a sulfonyl fragment (−SO2R) at the β-position. A precisely regulated sequence of radical generation using red light-mediated photocatalysis facilitates this regioselective switch from the terminal (β) position to the internal (α) position. Furthermore, this approach demonstrates broad substrate scope and industrial potential for the synthesis of pharmaceuticals under mild reaction conditions.
Simple autonomous agents can enhance creative semantic discovery by human groups
Authors: Ueshima Atsushi , Jones Matthew I. , Christakis Nicholas A. 
Published: June 2024

AbstractInnovation is challenging, and theory and experiments indicate that groups may be better able to identify and preserve innovations than individuals. But innovation within groups faces its own challenges, including groupthink and truncated diffusion. We performed experiments involving a game in which people search for ideas in various conditions: alone, in networked social groups, or in networked groups featuring autonomous agents (bots). The objective was to search a semantic space of 20,000 nouns with defined similarities for an arbitrary noun with the highest point value. Participants (N = 1875) were embedded in networks (n = 125) of 15 nodes to which we sometimes added 2 bots. The bots had 3 possible strategies: they shared a random noun generated by their immediate neighbors, or a noun most similar from among those identified, or a noun least similar. We first confirm that groups are better able to explore a semantic space than isolated individuals. Then we show that when bots that share the most similar noun operate in groups facing a semantic space that is relatively easy to navigate, group performance is superior. Simple autonomous agents with interpretable behavior can affect the capacity for creative discovery of human groups.
Type-printable photodetector arrays for multichannel meta-infrared imaging
Authors: Guo Junxiong , Gu Shuyi , Lin Lin , Liu Yu , Cai Ji , Cai Hongyi , Tian Yu , Zhang Yuelin , Zhang Qinghua , Liu Ze , Zhang Yafei , Zhang Xiaosheng , Lin Yuan , Huang Wen , Gu Lin , Zhang Jinxing 
Published: June 2024

AbstractMultichannel meta-imaging, inspired by the parallel-processing capability of neuromorphic computing, offers considerable advancements in resolution enhancement and edge discrimination in imaging systems, extending even into the mid- to far-infrared spectrum. Currently typical multichannel infrared imaging systems consist of separating optical gratings or merging multi-cameras, which require complex circuit design and heavy power consumption, hindering the implementation of advanced human-eye-like imagers. Here, we present printable graphene plasmonic photodetector arrays driven by a ferroelectric superdomain for multichannel meta-infrared imaging with enhanced edge discrimination. The fabricated photodetectors exhibited multiple spectral responses with zero-bias operation by directly rescaling the ferroelectric superdomain instead of reconstructing the separated gratings. We also demonstrated enhanced and faster shape classification (98.1%) and edge detection (98.2%) using our multichannel infrared images compared with single-channel detectors. Our proof-of-concept photodetector arrays simplify multichannel infrared imaging systems and offer potential solutions in efficient edge detection in human-brain-type machine vision.
Augmented microglial endoplasmic reticulum-mitochondria contacts mediate depression-like behavior in mice induced by chronic social defeat stress
Authors: Zhang Jia-Rui , Shen Shi-Yu , Zhai Meng-Ying , Shen Zu-Qi , Li Wei , Liang Ling-Feng , Yin Shu-Yuan , Han Qiu-Qin , Li Bing , Zhang Yu-Qiu , Yu Jin 
Published: June 2024

AbstractExtracellular ATP (eATP) signaling through the P2X7 receptor pathway is widely believed to trigger NLRP3 inflammasome assembly in microglia, potentially contributing to depression. However, the cellular stress responses of microglia to both eATP and stress itself remain largely unexplored. Mitochondria-associated membranes (MAMs) is a platform facilitating calcium transport between the endoplasmic reticulum (ER) and mitochondria, regulating ER stress responses and mitochondrial homeostasis. This study aims to investigate how MAMs influence microglial reaction and their involvement in the development of depression-like symptoms in response to chronic social defeat stress (CSDS). CSDS induced ER stress, MAMs’ modifications, mitochondrial damage, and the formation of the IP3R3-GRP75-VDAC1 complex at the ER-mitochondria interface in hippocampal microglia, all concomitant with depression-like behaviors. Additionally, exposing microglia to eATP to mimic CSDS conditions resulted in analogous outcomes. Furthermore, knocking down GRP75 in BV2 cells impeded ER-mitochondria contact, calcium transfer, ER stress, mitochondrial damage, mitochondrial superoxide production, and NLRP3 inflammasome aggregation induced by eATP. In addition, reduced GRP75 expression in microglia of Cx3cr1CreER/+Hspa9f/+ mice lead to reduce depressive behaviors, decreased NLRP3 inflammasome aggregation, and fewer ER-mitochondria contacts in hippocampal microglia during CSDS. Here, we show the role of MAMs, particularly the formation of a tripartite complex involving IP3R3, GRP75, and VDAC1 within MAMs, in facilitating communication between the ER and mitochondria in microglia, thereby contributing to the development of depression-like phenotypes in male mice.
Highly sensitive 2D X-ray absorption spectroscopy via physics informed machine learning
Authors: Li Zeyuan , Flynn Thomas , Liu Tongchao , Liu Sizhan , Lee Wah-Keat , Tang Ming , Ge Mingyuan 
Published: June 2024

AbstractImproving the spatial and spectral resolution of 2D X-ray near-edge absorption structure (XANES) has been a decade-long pursuit to probe local chemical reactions at the nanoscale. However, the poor signal-to-noise ratio in the measured images poses significant challenges in quantitative analysis, especially when the element of interest is at a low concentration. In this work, we developed a post-imaging processing method using deep neural network to reliably improve the signal-to-noise ratio in the XANES images. The proposed neural network model could be trained to adapt to new datasets by incorporating the physical features inherent in the latent space of the XANES images and self-supervised to detect new features in the images and achieve self-consistency. Two examples are presented in this work to illustrate the model’s robustness in determining the valence states of Ni and Co in the LiNixMnyCo1-x-yO2 systems with high confidence.
Polymerised forms in the zirconium conversion coatings on cold-rolled steel: proof of concept
Authors: Kraš Ana , Milošev Ingrid , Seyeux Antoine , Marcus Philippe 
Published: June 2024

AbstractThis study validates the proposed polymerised structure, including tetrameric polynuclear species, of solid amorphous oxyhydroxide zirconium conversion coatings on cold-rolled steel using ToF-SIMS. Tetramers are formed at pH near 4 (and possibly higher), with thickness increasing over extended conversion times. EIS in simulated acid rain further demonstrates that optimal coating formation requires a pH of at least 4 and a sufficient conversion time for adequate thickness, confirmed by the high-frequency EIS loop. Tetramer forms were not observed when the coatings were prepared at lower pH or shorter conversion time, proving that the polymerisation step is crucial for obtaining the coatings offering adequate corrosion protection.
Sleep promoting and omics exploration on probiotics fermented Gastrodia elata Blume
Authors: Zhang Chao-Qi , Zhang Xu-Dong , Wang Yan , Liu Yi-Han , Zhang Cun-Li , Zhang Qiang 
Published: June 2024

AbstractFermenting Chinese medicinal herbs could enhance their bioactivities. We hypothesized probiotic-fermented gastrodia elata Blume (GE) with better potential to alleviate insomnia than that of unfermented, thus the changes in chemical composition and the insomnia-alleviating effects and mechanisms of fermented GE on pentylenetetrazole (PTZ)-induced insomnia zebrafish were explored via high-performance liquid chromatography (HPLC) and mass spectroscopy-coupled HPLC (HPLC-MS), phenotypic, transcriptomic, and metabolomics analysis. The results demonstrated that probiotic fermented GE performed better than unfermented GE in increasing the content of chemical composition, reducing the displacement, average speed, and number of apoptotic cells in zebrafish with insomnia. Metabolomic investigation showed that the anti-insomnia effect was related to regulating the pathways of actin cytoskeleton and neuroactive ligand-receptor interactions. Transcriptomic and reverse transcription qPCR (RT-qPCR) analysis revealed that secondary fermentation liquid (SFL) significantly modulated the expression levels of neurod1, msh2, msh3, recql4, ercc5, rad5lc, and rev3l, which are mainly involved in neuron differentiation and DNA repair. Collectively, as a functional food, fermented GE possessed potential for insomnia alleviation.
Evaluation of mRNA-LNP and adjuvanted protein SARS-CoV-2 vaccines in a maternal antibody mouse model
Authors: England Ross N. , Drapeau Elizabeth M. , Alameh Mohamad-Gabriel , Hosseinzadeh Reihaneh , Weissman Drew , Hensley Scott E. 
Published: June 2024

AbstractMaternal antibodies (matAbs) protect against a myriad of pathogens early in life; however, these antibodies can also inhibit de novo immune responses against some vaccine platforms. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) matAbs are efficiently transferred during pregnancy and protect infants against subsequent SARS-CoV-2 infections. It is unknown if matAbs inhibit immune responses elicited by different types of SARS-CoV-2 vaccines. Here, we established a mouse model to determine if SARS-CoV-2 spike-specific matAbs inhibit immune responses elicited by recombinant protein and nucleoside-modified mRNA-lipid nanoparticle (mRNA-LNP) vaccines. We found that SARS-CoV-2 mRNA-LNP vaccines elicited robust de novo antibody responses in mouse pups in the presence of matAbs. Recombinant protein vaccines were also able to circumvent the inhibitory effects of matAbs when adjuvants were co-administered. While additional studies need to be completed in humans, our studies raise the possibility that mRNA-LNP-based and adjuvanted protein-based SARS-CoV-2 vaccines have the potential to be effective when delivered very early in life.
A super-efficient gel adsorbent with over 1000 times the adsorption capacity of activated carbon
Authors: Hu Menghan , Xie Na , Huang Yujia , Yu Yikai 
Published: June 2024

AbstractIt was observed that a super-efficient gel adsorbent system (RRQG@CDC) could be obtained when a matrix material of polyquaternium gel with a flat distribution (RRQG) was loaded onto a skeleton material of cyclodextrin carbide (CDC). The results showed that the adsorption capacity of RRQG@CDC towards dyes was 1250 times higher than that of commonly used activated carbon, enabling highly efficient purification of dyeing wastewater through superior adsorption. In addition, RRQG@CDC demonstrated adaptability to a range of different pH values and salinity conditions, showing super-efficient adsorption abilities towards various types of dyes. Moreover, simulated scale-up tests confirmed the feasibility of this super-efficient adsorbent for practical engineering applications. An enhanced quasi-planar electrostatic adsorption mechanism model was established, which has changed the traditional understanding of adsorption mechanisms. Furthermore, the waste residues of RRQG@CDC, after dye adsorption, can be directly utilized as high-calorific fuels, showcasing the resourcefulness of these residues while eliminating the risk of secondary pollution. In conclusion, this study achieved a remarkably efficient and resource-based purification of dyeing wastewater by developing a highly effective adsorbent system.
Analysis of 10,478 cancer genomes identifies candidate driver genes and opportunities for precision oncology
Authors: Kinnersley Ben , Sud Amit , Everall Andrew , Cornish Alex J. , Chubb Daniel , Culliford Richard , Gruber Andreas J. , Lärkeryd Adrian , Mitsopoulos Costas , Wedge David , Houlston Richard 
Published: June 2024

AbstractTumor genomic profiling is increasingly seen as a prerequisite to guide the treatment of patients with cancer. To explore the value of whole-genome sequencing (WGS) in broadening the scope of cancers potentially amenable to a precision therapy, we analysed whole-genome sequencing data on 10,478 patients spanning 35 cancer types recruited to the UK 100,000 Genomes Project. We identified 330 candidate driver genes, including 74 that are new to any cancer. We estimate that approximately 55% of patients studied harbor at least one clinically relevant mutation, predicting either sensitivity or resistance to certain treatments or clinical trial eligibility. By performing computational chemogenomic analysis of cancer mutations we identify additional targets for compounds that represent attractive candidates for future clinical trials. This study represents one of the most comprehensive efforts thus far to identify cancer driver genes in the real world setting and assess their impact on informing precision oncology.
Effect of manual OCTA segmentation correction to improve image quality and visibility of choroidal neovascularization in AMD
Authors: Deussen Daniel N. , Heinke Anna , Elsner Wyatt , Galang Carlo Miguel B. , Kalaw Fritz Gerald P. , Warter Alexandra , Bartsch Dirk-Uwe , Cheng Lingyun , Freeman William R. 
Published: June 2024

AbstractIn this retrospective case series on neovascular age-related macular degeneration (nAMD), we aimed to improve Choroidal Neovascularization (CNV) visualization in Optical Coherence Tomography Angiography (OCTA) scans by addressing segmentation errors. Out of 198 eyes, 73 OCTA scans required manual segmentation correction. We compared uncorrected scans to those with minimal (2 corrections), moderate (10 corrections), and detailed (50 corrections) efforts targeting falsely segmented Bruch’s Membrane (BM). Results showed that 55% of corrected OCTAs exhibited improved quality after manual correction. Notably, minimal correction (2 scans) already led to significant improvements, with additional corrections (10 or 50) not further enhancing expert grading. Reduced background noise and improved CNV identification were observed, with the most substantial improvement after two corrections compared to baseline uncorrected images. In conclusion, our approach of correcting segmentation errors effectively enhances image quality in OCTA scans of nAMD. This study demonstrates the efficacy of the method, with 55% of resegmented OCTA images exhibiting enhanced quality, leading to a notable increase in the proportion of high-quality images from 63 to 83%.
Plasma circulating tumor DNA unveils the efficacy of PD-1 inhibitors and chemotherapy in advanced gastric cancer
Authors: Jiang Rongqi , Cheng Xu , Li Ping , Meng Enqing , Wu Xinyi , Wu Hao 
Published: June 2024

AbstractProgrammed Death Receptor 1 (PD-1) inhibitors, when combined with chemotherapy, have exhibited notable effectiveness in enhancing the survival outcomes of patients afflicted with advanced gastric cancer. However, it is important to acknowledge that not all patients derive substantial benefits from this therapeutic approach, highlighting the crucial necessity of identifying efficacious biomarkers to inform immunotherapy interventions. In this study, we sought to investigate the predictive utility of circulating tumor DNA (ctDNA) as a biomarker in a cohort of 30 patients diagnosed with advanced gastric cancer, all of whom underwent first-line treatment involving PD-1 inhibitor administration alongside chemotherapy. We procured peripheral blood samples both at baseline and following the completion of two treatment cycles. Additionally, baseline tissue specimens were collected for the purpose of genomic alteration assessment, employing both 47-gene and 737-gene next-generation sequencing panels for plasma and tumor tissue, respectively. We delineated a ctDNA response as the eradication of maximum variant allele frequencies relative to baseline levels. Notably, the objective response rate among individuals exhibiting a ctDNA response proved significantly superior in comparison to non-responders (P = 0.0073). Furthermore, patients who manifested a ctDNA response experienced markedly prolonged progression-free survival (PFS) and overall survival (OS) when juxtaposed with those devoid of a ctDNA response (median PFS: 15.6 vs. 6.0 months, P = 0.003; median OS: not reached [NR] vs. 9.0 months, P = 0.011). In summation, patients with advanced gastric cancer receiving first-line treatment with PD-1 inhibitors and chemotherapy, dynamic changes in ctDNA can serve as a potential biomarker for predicting treatment efficacy and long-term outcomes.
Preparation for shaddock skin polysaccharide derivatives by response surface method
Authors: Huang Gangliang , Lin Bobo 
Published: June 2024

AbstractThe derivation of polysaccharide has an important impact on its properties. The preparation process of phosphorylated-shaddock skin polysaccharides (SSP) and acetylated-SSP was optimized by the response surface method. The constructed model was accurate and reliable in predicting the substitution of acetylated-SSP and the phosphate content of phosphorylated-SSP. This method was simple and easy to operate, which provided a basis for the preparation of a large number of derivatives.