bluuebunny/crossref_metadata_2025_split huggingface dataset:
MarsGT: Multi-omics analysis for rare population inference using single-cell graph transformer
Authors: Wang Xiaoying , Duan Maoteng , Li Jingxian , Ma Anjun , Xin Gang , Xu Dong , Li Zihai , Liu Bingqiang , Ma Qin 
Published: January 2024

AbstractRare cell populations are key in neoplastic progression and therapeutic response, offering potential intervention targets. However, their computational identification and analysis often lag behind major cell types. To fill this gap, we introduce MarsGT: Multi-omics Analysis for Rare population inference using a Single-cell Graph Transformer. It identifies rare cell populations using a probability-based heterogeneous graph transformer on single-cell multi-omics data. MarsGT outperforms existing tools in identifying rare cells across 550 simulated and four real human datasets. In mouse retina data, it reveals unique subpopulations of rare bipolar cells and a Müller glia cell subpopulation. In human lymph node data, MarsGT detects an intermediate B cell population potentially acting as lymphoma precursors. In human melanoma data, it identifies a rare MAIT-like population impacted by a high IFN-I response and reveals the mechanism of immunotherapy. Hence, MarsGT offers biological insights and suggests potential strategies for early detection and therapeutic intervention of disease.
Ton motor conformational switch and peptidoglycan role in bacterial nutrient uptake
Authors: Zinke Maximilian , Lejeune Maylis , Mechaly Ariel , Bardiaux Benjamin , Boneca Ivo Gomperts , Delepelaire Philippe , Izadi-Pruneyre Nadia 
Published: January 2024

AbstractActive nutrient uptake is fundamental for survival and pathogenicity of Gram-negative bacteria, which operate a multi-protein Ton system to transport essential nutrients like metals and vitamins. This system harnesses the proton motive force at the inner membrane to energize the import through the outer membrane, but the mechanism of energy transfer remains enigmatic. Here, we study the periplasmic domain of ExbD, a crucial component of the proton channel of the Ton system. We show that this domain is a dynamic dimer switching between two conformations representing the proton channel’s open and closed states. By in vivo phenotypic assays we demonstrate that this conformational switch is essential for the nutrient uptake by bacteria. The open state of ExbD triggers a disorder to order transition of TonB, enabling TonB to supply energy to the nutrient transporter. We also reveal the anchoring role of the peptidoglycan layer in this mechanism. Herein, we propose a mechanistic model for the Ton system, emphasizing ExbD duality and the pivotal catalytic role of peptidoglycan. Sequence analysis suggests that this mechanism is conserved in other systems energizing gliding motility and membrane integrity. Our study fills important gaps in understanding bacterial motor mechanism and proposes novel antibacterial strategies.
Diffusion-based generative AI for exploring transition states from 2D molecular graphs
Authors: Kim Seonghwan , Woo Jeheon , Kim Woo Youn 
Published: January 2024

AbstractThe exploration of transition state (TS) geometries is crucial for elucidating chemical reaction mechanisms and modeling their kinetics. Recently, machine learning (ML) models have shown remarkable performance for prediction of TS geometries. However, they require 3D conformations of reactants and products often with their appropriate orientations as input, which demands substantial efforts and computational cost. Here, we propose a generative approach based on the stochastic diffusion method, namely TSDiff, for prediction of TS geometries just from 2D molecular graphs. TSDiff outperforms the existing ML models with 3D geometries in terms of both accuracy and efficiency. Moreover, it enables to sample various TS conformations, because it learns the distribution of TS geometries for diverse reactions in training. Thus, TSDiff finds more favorable reaction pathways with lower barrier heights than those in the reference database. These results demonstrate that TSDiff shows promising potential for an efficient and reliable TS exploration.
Biomimetic Bouligand chiral fibers array enables strong and superelastic ceramic aerogels
Authors: Wang Hongxing , Cheng Longdi , Yu Jianyong , Si Yang , Ding Bin 
Published: January 2024

AbstractCeramic aerogels are often used when thermal insulation materials are desired; however, they are still plagued by poor mechanical stability under thermal shock. Here, inspired by the dactyl clubs of mantis shrimp found in nature, which form by directed assembly into hierarchical, chiral and Bouligand (twisted plywood) structure exhibiting superior mechanical properties, we present a compositional and structural engineering strategy to develop strong, superelastic and fatigue resistance ceramic aerogels with chiral fibers array resembling Bouligand architecture. Benefiting from the stress dissipation, crack torsion and mechanical reinforcement of micro-/nano-scale Bouligand array, the tensile strength of these aerogels (170.38 MPa) is between one and two orders of magnitude greater than that of state-of-the-art nanofibrous aerogels. In addition, the developed aerogels feature low density and thermal conductivity, good compressive properties with rapid recovery from 80 % strain, and thermal stability up to 1200 °C, making them ideal for thermal insulation applications.
Large electronegativity differences between adjacent atomic sites activate and stabilize ZnIn2S4 for efficient photocatalytic overall water splitting
Authors: Xin Xu , Li Yuke , Zhang Youzi , Wang Yijin , Chi Xiao , Wei Yanping , Diao Caozheng , Su Jie , Wang Ruiling , Guo Peng , Yu Jiakang , Zhang Jia , Sobrido Ana Jorge , Titirici Maria-Magdalena , Li Xuanhua 
Published: January 2024

AbstractPhotocatalytic overall water splitting into hydrogen and oxygen is desirable for long-term renewable, sustainable and clean fuel production on earth. Metal sulfides are considered as ideal hydrogen-evolved photocatalysts, but their component homogeneity and typical sulfur instability cause an inert oxygen production, which remains a huge obstacle to overall water-splitting. Here, a distortion-evoked cation-site oxygen doping of ZnIn2S4 (D-O-ZIS) creates significant electronegativity differences between adjacent atomic sites, with S1 sites being electron-rich and S2 sites being electron-deficient in the local structure of S1–S2–O sites. The strong charge redistribution character activates stable oxygen reactions at S2 sites and avoids the common issue of sulfur instability in metal sulfide photocatalysis, while S1 sites favor the adsorption/desorption of hydrogen. Consequently, an overall water-splitting reaction has been realized in D-O-ZIS with a remarkable solar-to-hydrogen conversion efficiency of 0.57%, accompanying a ~ 91% retention rate after 120 h photocatalytic test. In this work, we inspire an universal design from electronegativity differences perspective to activate and stabilize metal sulfide photocatalysts for efficient overall water-splitting.
Molecular imaging predicts lack of T-DM1 response in advanced HER2-positive breast cancer (final results of ZEPHIR trial)
Authors: Mileva Magdalena , de Vries Elisabeth G. E. , Guiot Thomas , Wimana Zéna , Deleu Anne-Leen , Schröder Carolien P. , Lefebvre Yolene , Paesmans Marianne , Stroobants Sigrid , Huizing Manon , Aftimos Philippe , Tol Jolien , Van der Graaf Winette T. A. , Oyen Wim J. G. , Vugts Danielle J. , Menke-van der Houven van Oordt C. Willemien , Brouwers Adrienne H. , Piccart-Gebhart Martine , Flamen Patrick , Gebhart Géraldine 
Published: January 2024

AbstractEfficacy of the human epidermal growth factor receptor (HER)2-targeting trastuzumab emtansine (T-DM1) in breast cancer (BC) relies on HER2 status determined by immunohistochemistry or fluorescence in-situ hybridization. Heterogeneity in HER2 expression, however, generates interest in “whole-body” assessment of HER2 status using molecular imaging. We evaluated the role of HER2-targeted molecular imaging in detecting HER2-positive BC lesions and patients unlikely to respond to T-DM1. Patients underwent zirconium-89 (89Zr) trastuzumab (HER2) PET/CT and [18F]-2-fluoro-2-deoxy-D-glucose (FDG) PET/CT before T-DM1 initiation. Based on 89Zr-trastuzumab uptake, lesions were visually classified as HER2-positive (visible/high uptake) or HER2-negative (background/close to background activity). According to proportion of FDG-avid tumor load showing 89Zr-trastuzumab uptake (entire/dominant part or minor/no part), patients were classified as HER2-positive and HER2-negative, respectively. Out of 265 measurable lesions, 93 (35%) were HER2-negative, distributed among 42 of the 90 included patients. Of these, 18 (19%) lesions belonging to 11 patients responded anatomically (>30% decrease in axial diameter from baseline) after three T-DM1 cycles, resulting in an 81% negative predictive value (NPV) of the HER2 PET/CT. In combination with early metabolic response assessment on FDG PET/CT performed before the second T-DM1 cycle, NPVs of 91% and 100% were reached in predicting lesion-based and patient-based (RECIST1.1) response, respectively. Therefore, HER2 PET/CT, alone or in combination with early FDG PET/CT, can successfully identify BC lesions and patients with a low probability of clinical benefit from T-DM1.
Efficient first-principles electronic transport approach to complex band structure materials: the case of n-type Mg3Sb2
Authors: Li Zhen , Graziosi Patrizio , Neophytou Neophytos 
Published: January 2024

AbstractWe present an efficient method for accurately computing electronic scattering rates and transport properties in materials with complex band structures. Using ab initio simulations, we calculate a limited number of electron–phonon matrix elements, and extract scattering rates for acoustic and optical processes based on deformation potential theory. Polar optical phonon scattering rates are determined using the Fröhlich model, and ionized impurity scattering rates are derived from the Brooks-Herring theory. Subsequently, electronic transport coefficients are computed within the Boltzmann transport theory. We exemplify our approach with n-type Mg3Sb2, a promising thermoelectric material with a challenging large unit cell and low symmetry. Notably, our method attains competitive accuracy, requiring less than 10% of the computational cost compared to state-of-the-art ab initio methods, dropping to 1% for simpler materials. Additionally, our approach provides explicit information on individual scattering processes, offering an alternative that combines efficiency, robustness, and flexibility beyond the commonly employed constant relaxation time approximation with the accuracy of fully first-principles calculations.
Rotating square tessellations enabled stretchable and adaptive curved display
Authors: Deng Yang , Xu Kuaile , Jiao Rui , Liu Weixuan , Cheung Yik Kin , Li Yongkai , Wang Xiaoyi , Hou Yue , Hong Wei , Yu Hongyu 
Published: January 2024

AbstractCurved displays can adjust their shape to accommodate different objects and are used in electronics and decorative lighting. Due to the immutable pixel spacing, existing commercial curved displays are flexible but not compatible with undevelopable surfaces. Inspired by kirigami and auxetic structures, we propose an approach that combines luminescent elements and rotating square tessellations to create a stretchable, arbitrary curve adaptive display. We connect square islands by vertical interconnects to relieve the stress concentration and provide extra deformation patterns. The vertical interconnects are patterned on a flexible printed circuit board (FPCB) using laser cutting and folded up via specially designed molds. Further, the freed-up space by folded interconnects allows the structure to be compressed. A prototype stretchable display is demonstrated that it can maintain electrical performance under biaxial strain and adapt to different Gaussian curvature surfaces, including cylindrical, spherical, saddle and arbitrary surfaces. Theoretical models and finite element calculations are established to describe the tensile behavior of the structures under different boundary conditions and agree with the experimental results. This proposed technology paves a feasible solution of mass production of adaptive curved displays and sets the trend for the next-generation display.
Cell-to-cell transmitted alpha-synuclein recapitulates experimental Parkinson’s disease
Authors: Prymaczok Natalia Cecilia , De Francesco Pablo Nicolas , Mazzetti Samanta , Humbert-Claude Marie , Tenenbaum Liliane , Cappelletti Graziella , Masliah Eliezer , Perello Mario , Riek Roland , Gerez Juan Atilio 
Published: January 2024

AbstractParkinson’s disease is characterized by a progressive accumulation of alpha-Synuclein (αSyn) neuronal inclusions called Lewy bodies in the nervous system. Lewy bodies can arise from the cell-to-cell propagation of αSyn, which can occur via sequential steps of secretion and uptake. Here, by fusing a removable short signal peptide to the N-terminus of αSyn, we developed a novel mouse model with enhanced αSyn secretion and cell-to-cell transmission. Expression of the secreted αSyn in the mouse brain was under the control of a novel hybrid promoter in combination with adeno-associated virus serotype 9 (AAV9). This combination of promoter and viral vector induced a robust expression in neurons but not in the glia of injected mice. Biochemical characterization of the secreted αSyn revealed that, in cultured cells, this protein is released to the extracellular milieu via conventional secretion. The released αSyn is then internalized and processed by acceptor cells via the endosome–lysosome pathway indicating that the secreted αSyn is cell-to-cell transmitted. The secreted αSyn is aggregation-prone and amyloidogenic, and when expressed in the brain of wild-type non-transgenic mice, it induces a Parkinson’s disease-like phenotype that includes a robust αSyn pathology in the substantia nigra, neuronal loss, neuroinflammation, and motor deficits, all the key features of experimental animal models of Parkinson’s disease. In summary, a novel animal model of Parkinson’s disease based on enhanced cell-to-cell transmission of αSyn was developed. The neuron-produced cell-to-cell transmitted αSyn triggers all phenotypic features of experimental Parkinson’s disease in mice.
OXTR polymorphisms associated with severity and treatment responses of schizophrenia
Authors: Lv Xue , Hou Yue-Sen , Zhang Zhao-Hui , Yue Wei-Hua 
Published: January 2024

AbstractThe mechanisms generating specific symptoms of schizophrenia remain unclear and genetic research makes it possible to explore these issues at a fundamental level. Taking into account the associations between the oxytocin system and social functions, which are apparently impaired in schizophrenia patients, we hypothesized that the oxytocin receptor gene (OXTR) might be associated with schizophrenia symptoms in both severity and responses to antipsychotics and did this exploratory positional study. A total of 2363 patients with schizophrenia (1181 males and 1182 females) included in our study were randomly allocated to seven antipsychotic treatment groups and received antipsychotic monotherapy for 6 weeks. Their blood DNA was genotyped for OXTR polymorphisms. Their symptom severity was assessed by Positive and Negative Syndrome Scale (PANSS), and the scores were transformed into seven factors (positive, disorganized, negative symptoms apathy/avolition, negative symptoms deficit of expression, hostility, anxiety and depression). Percentage changes in PANSS scores from baseline to week 6 were calculated to quantify antipsychotic responses. We found that OXTR polymorphisms were nominally associated with the severity of overall symptoms (rs237899, β = 1.669, p = 0.019), hostility symptoms (rs237899, β = 0.427, p = 0.044) and anxiety symptoms (rs13316193, β = −0.197, p = 0.038). As for treatment responses, OXTR polymorphisms were nominally associated with the improvement in negative symptoms apathy/avolition (rs2268490, β = 2.235, p = 0.0499). No association between severity or response to treatment and OXTR polymorphisms was found with statistical correction for multiplicity. Overall, our results highlighted the possibility of nominally significant associations of the OXTR gene with the severity and improvement in schizophrenia symptoms. Given the exploratory nature of this study, these associations are indicative of the role of the OXTR gene in the pathology of schizophrenia and may contribute to further elucidate the mechanism of specific symptoms of schizophrenia and to exploit antipsychotics more effective to specific symptoms.
Sex differences in autonomic adverse effects related to antipsychotic treatment and associated hormone profiles
Authors: Johansen Ingrid T. , Steen Nils Eiel , Rødevand Linn , Lunding Synve H. , Hjell Gabriela , Ormerod Monica B. E. G. , Agartz Ingrid , Melle Ingrid , Lagerberg Trine V. , Nerhus Mari , Andreassen Ole A. 
Published: January 2024

AbstractAutonomic adverse effects of antipsychotic drugs (APs) cause clinical challenges, but few studies have investigated sex differences and their underlying biological pathways. Sex-specific regulation of relevant hormones could be involved. We investigated sex differences in autonomic adverse effects related to olanzapine, quetiapine, risperidone, and aripiprazole, and the role of hormones related to APs. Patients with severe mental disorders (N = 1318) were included and grouped based on AP monotherapy: olanzapine (N = 364), quetiapine (N = 211), risperidone (N = 102), aripiprazole (N = 138), and no AP (N = 503). Autonomic symptoms from the Udvalg for Kliniske Undersøgelser (UKU) side effect scale was analyzed with logistic regression, adjusting for age, diagnosis, and polypharmacy. Further, we analyzed associations between autonomic symptoms and hormones related to APs. We found associations between autonomic adverse effects and APs, with sex-specific risk for palpitations/tachycardia associated with hormonal changes related to APs. Results showed increased salivation associated with aripiprazole, reduced salivation with quetiapine, and nausea/vomiting and palpitations/tachycardia with olanzapine, and higher risk of nausea/vomiting, diarrhea, constipation, polyuria/polydipsia, and palpitations/tachycardia in females. Significant sex x AP interaction was found for palpitations/tachycardia, with higher risk in risperidone-treated males, which was associated with different hormone profiles of prolactin, cortisol, and insulin. Our findings implicate a role of several hormones in the sex-specific autonomic adverse effects related to APs.
Epigenetic OCT4 regulatory network: stochastic analysis of cellular reprogramming
Authors: Bruno Simone , Schlaeger Thorsten M. , Del Vecchio Domitilla 
Published: January 2024

AbstractExperimental studies have shown that chromatin modifiers have a critical effect on cellular reprogramming, i.e., the conversion of differentiated cells to pluripotent stem cells. Here, we develop a model of the OCT4 gene regulatory network that includes genes expressing chromatin modifiers TET1 and JMJD2, and the chromatin modification circuit on which these modifiers act. We employ this model to compare three reprogramming approaches that have been considered in the literature with respect to reprogramming efficiency and latency variability. These approaches are overexpression of OCT4 alone, overexpression of OCT4 with TET1, and overexpression of OCT4 with JMJD2. Our results show more efficient and less variable reprogramming when also JMJD2 and TET1 are overexpressed, consistent with previous experimental data. Nevertheless, TET1 overexpression can lead to more efficient reprogramming compared to JMJD2 overexpression. This is the case when the recruitment of DNA methylation by H3K9me3 is weak and the methyl-CpG-binding domain (MBD) proteins are sufficiently scarce such that they do not hamper TET1 binding to methylated DNA. The model that we developed provides a mechanistic understanding of existing experimental results and is also a tool for designing optimized reprogramming approaches that combine overexpression of cell-fate specific transcription factors (TFs) with targeted recruitment of epigenetic modifiers.
mRNA vaccines expressing malaria transmission-blocking antigens Pfs25 and Pfs230D1 induce a functional immune response
Authors: Scaria Puthupparampil V. , Roth Nicole , Schwendt Kim , Muratova Olga V. , Alani Nada , Lambert Lynn E. , Barnafo Emma K. , Rowe Christopher G. , Zaidi Irfan U. , Rausch Kelly M. , Narum David L. , Petsch Benjamin , Duffy Patrick E. 
Published: January 2024

AbstractMalaria transmission-blocking vaccines (TBV) are designed to inhibit the sexual stage development of the parasite in the mosquito host and can play a significant role in achieving the goal of malaria elimination. Preclinical and clinical studies using protein–protein conjugates of leading TBV antigens Pfs25 and Pfs230 domain 1 (Pfs230D1) have demonstrated the feasibility of TBV. Nevertheless, other promising vaccine platforms for TBV remain underexplored. The recent success of mRNA vaccines revealed the potential of this technology for infectious diseases. We explored the mRNA platform for TBV development. mRNA constructs of Pfs25 and Pfs230D1 variously incorporating signal peptides (SP), GPI anchor, and Trans Membrane (TM) domain were assessed in vitro for antigen expression, and selected constructs were evaluated in mice. Only mRNA constructs with GPI anchor or TM domain that resulted in high cell surface expression of the antigens yielded strong immune responses in mice. These mRNA constructs generated higher transmission-reducing functional activity versus the corresponding alum-adjuvanted protein-protein conjugates used as comparators. Pfs25 mRNA with GPI anchor or TM maintained >99% transmission reducing activity through 126 days, the duration of the study, demonstrating the potential of mRNA platform for TBV.
Absolute quantitation of binding antibodies from clinical samples
Authors: Tang Chan , Verwilligen Annemiek , Sadoff Jerald , Brandenburg Boerries , Sneekes-Vriese Eveline , van den Kerkhof Tom , Dillen Lieve , Rutten Lucy , Juraszek Jarek , Callewaert Katleen , Janssen Sarah , Huizingh Jeroen , Euler Zelda , Schilperoord Tom , Verhemeldonck Marc , Langedijk Johannes P. M. , Hendriks Jenny , Stieh Daniel J. 
Published: January 2024

AbstractThe quantitation of antibody responses is a critical requirement for the successful development of vaccines and therapeutics that often relies on the use of standardized reference materials to determine relative quantities within biological samples. The validity of comparing responses across assays using arbitrarily defined reference values is therefore limited. We developed a generalizable method known as MASCALE (Mass Spectrometry Enabled Conversion to Absolute Levels of ELISA Antibodies) for absolute quantitation of antibodies by calibrating ELISA reference sera using mass spectrometry. Levels of proteotypic peptides served as a proxy for human IgG, allowing the conversion of responses from arbitrary values to absolute amounts. Applications include comparison of binding assays at two separate laboratories and evaluation of cross-clade magnitude-breadth responses induced by an investigational HIV-1 vaccine regimen. MASCALE addresses current challenges in the interpretation of immune responses in clinical trials and expands current options available to make suitable comparisons across different settings.