bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic barcoding for clonal diversity monitoring and control in cell-based complex antibody production
Authors: Bauer Niels , Oberist Christoph , Poth Michaela , Stingele Julian , Popp Oliver , Ausländer Simon 
Published: June 2024

AbstractEngineered mammalian cells are key for biotechnology by enabling broad applications ranging from in vitro model systems to therapeutic biofactories. Engineered cell lines exist as a population containing sub-lineages of cell clones that exhibit substantial genetic and phenotypic heterogeneity. There is still a limited understanding of the source of this inter-clonal heterogeneity as well as its implications for biotechnological applications. Here, we developed a genomic barcoding strategy for a targeted integration (TI)-based CHO antibody producer cell line development process. This technology provided novel insights about clone diversity during stable cell line selection on pool level, enabled an imaging-independent monoclonality assessment after single cell cloning, and eventually improved hit-picking of antibody producer clones by monitoring of cellular lineages during the cell line development (CLD) process. Specifically, we observed that CHO producer pools generated by TI of two plasmids at a single genomic site displayed a low diversity (< 0.1% RMCE efficiency), which further depends on the expressed molecules, and underwent rapid population skewing towards dominant clones during routine cultivation. Clonal cell lines from one individual TI event demonstrated a significantly lower variance regarding production-relevant and phenotypic parameters as compared to cell lines from distinct TI events. This implies that the observed cellular diversity lies within pre-existing cell-intrinsic factors and that the majority of clonal variation did not develop during the CLD process, especially during single cell cloning. Using cellular barcodes as a proxy for cellular diversity, we improved our CLD screening workflow and enriched diversity of production-relevant parameters substantially. This work, by enabling clonal diversity monitoring and control, paves the way for an economically valuable and data-driven CLD process.
An efficient plasmid-based system for the recovery of recombinant vesicular stomatitis virus encoding foreign glycoproteins
Authors: Marqués María-Carmen , Andreu-Moreno Iván , Sanjuán Rafael , Elena Santiago F. , Geller Ron 
Published: June 2024

AbstractViral glycoproteins mediate entry into host cells, thereby dictating host range and pathogenesis. In addition, they constitute the principal target of neutralizing antibody responses, making them important antigens in vaccine development. Recombinant vesicular stomatitis virus (VSV) encoding foreign glycoproteins can provide a convenient and safe surrogate system to interrogate the function, evolution, and antigenicity of viral glycoproteins from viruses that are difficult to manipulate or those requiring high biosafety level containment. However, the production of recombinant VSV can be technically challenging. In this work, we present an efficient and robust plasmid-based system for the production of recombinant VSV encoding foreign glycoproteins. We validate the system using glycoproteins from different viral families, including arenaviruses, coronaviruses, and hantaviruses, as well as highlight their utility for studying the effects of mutations on viral fitness. Overall, the methods described herein can facilitate the study of both native and recombinant VSV encoding foreign glycoproteins and can serve as the basis for the production of VSV-based vaccines.
Digital symbol-digit modalities test with modified flexible protocols in patients with CNS demyelinating diseases
Authors: Seo Dayoung , So Jeong Min , Kim Jiyon , Jung Heejae , Jang Inhye , Kim Hyunjin , Kang Dong-Wha , Lim Young-Min , Choi Jaesoon , Lee Eun-Jae 
Published: June 2024

AbstractCognitive impairment (CI) is prevalent in central nervous system demyelinating diseases, such as multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD). We developed a novel tablet-based modified digital Symbol Digit Modalities Test (MD-SDMT) with adjustable protocols that feature alternating symbol-digit combinations in each trial, lasting one or two minutes. We assessed 144 patients (99 with MS and 45 with NMOSD) using both MD-SDMT protocols and the traditional paper-based SDMT. We also gathered participants’ feedback through a questionnaire regarding their preferences and perceived reliability. The results showed strong correlations between MD-SDMT and paper-based SDMT scores (Pearsons correlation: 0.88 for 2 min; 0.85 for 1 min, both p < 0.001). Among the 120 respondents, the majority preferred the digitalized SDMT (55% for the 2 min, 39% for the 1 min) over the paper-based version (6%), with the 2 min MD-SDMT reported as the most reliable test. Notably, patients with NMOSD and older individuals exhibited a preference for the paper-based test, as compared to those with MS and younger patients. In summary, even with short test durations, the digitalized SDMT effectively evaluates cognitive function in MS and NMOSD patients, and is generally preferred over the paper-based method, although preferences may vary with patient characteristics.
Associations of air pollution with acute coronary syndromes based on A/B/AB versus O blood types: case-crossover study
Authors: Bochenek Tomasz , Pytlewski Adam , Bride Daniel , Gruchlik Bartosz , Lelek Michał , Teodorska Małgorzata , Nowok Michał , Wita Krystian , Mizia-Stec Katarzyna , Horne Benjamin D. 
Published: June 2024

AbstractShort-term exposure to air pollutants may contribute to an increased risk of acute coronary syndrome (ACS). This study assessed the role of short-term exposure to fine particulate matter (PM2.5) as well as fine and coarse PM (PM10) air pollution in ACS events and the effect of blood groups on this phenomenon. A retrospectively collected database of 9026 patients was evaluated. The study design was a case-crossover using a conditional logistic regression model. The main analysis focused on PM2.5 levels with a 1 day lag until the ACS event, using threshold-modelled predictor for all patients. Secondary analyses utilized separate threshold-modelled predictors for 2–7-days moving averages and for patients from specific ABO blood groups. Additional analysis was performed with the non-threshold models and for PM10 levels. Short-term exposure to increased PM2.5 and PM10 levels at a 1-day lag was associated with elevated risks of ACS (PM2.5: OR = 1.012 per + 10 µg/m3, 95% CI 1.003, 1.021; PM10: OR = 1.014 per + 10 µg/m3, CI 1.002, 1.025) for all patients. Analysis showed that exposure to PM2.5 was associated with increased risk of ACS at a 1-day lag for the A, B or AB group (OR = 1.012 per + 10 µg/m3, CI 1.001, 1.024), but not O group (OR = 1.011 per + 10 µg/m3, CI 0.994, 1.029). Additional analysis showed positive associations between exposure to PM10 and risk of ACS, with 7-days moving average models stratified by blood group revealing that exposures to PM2.5 and PM10 were associated with elevated risk of ACS for patients with group O. Short-term exposures to PM2.5 and PM10 were associated with elevated risk of ACS. Short-term exposure to PM2.5 was positively associated with the risk of ACS for patients with A, B, or AB blood groups for a 1-day lag, while risk in O group was delayed to 7 days.
Gluten-containing flours and gluten-free flours as a source of calcium, magnesium, iron and zinc
Authors: Mystkowska Iwona , Plażuk Ewa , Szepeluk Adam , Dmitrowicz Aleksandra 
Published: June 2024

AbstractWheat flour is widely used in Poland for the preparation of bread, pasta and other foods. Due to the increasing number of people diagnosed with diet-related diseases, consumer awareness of health-promoting issues and interest in gluten-free products (GFP). There is a dynamic development of the market for these foods with high quality and nutritional value and minerals that benefit human health and prevent deficiencies in patients on a gluten-free diet. The aim of this study was to determine the content of minerals: Ca, Fe, Mg and Zn in flours using the ICP-OES method. The mineral composition of selected GF flours available on the Polish market was analysed. It was tested how they supplement the mineral requirements compared to gluten-containing flours. It was found that these products can be a valuable source of essential minerals, which are often in short supply, especially in patients with gastrointestinal disorders. As our study has shown, flours from the GFP group are a good source of essential minerals, especially in the case of chia and flax flours, as well as buckwheat, amaranth, quinoa, lupin or almonds flours.
Novel Bacillus and Prestia isolates from Dwarf century plant enhance crop yield and salinity tolerance
Authors: Dhar Sanjoy Kumar , Kaur Jaspreet , Singh Gajendra Bahadur , Chauhan Arjun , Tamang Jeewan , Lakhara Nikita , Asyakina Lyudmila , Atuchin Victor , Mudgal Gaurav , Abdi Gholamreza 
Published: June 2024

AbstractSoil salinity is a major environmental stressor impacting global food production. Staple crops like wheat experience significant yield losses in saline environments. Bioprospecting for beneficial microbes associated with stress-resistant plants offers a promising strategy for sustainable agriculture. We isolated two novel endophytic bacteria, Bacillus cereus (ADJ1) and Priestia aryabhattai (ADJ6), from Agave desmettiana Jacobi. Both strains displayed potent plant growth-promoting (PGP) traits, such as producing high amounts of indole-3-acetic acid (9.46, 10.00 µgml−1), ammonia (64.67, 108.97 µmol ml−1), zinc solubilization (Index of 3.33, 4.22, respectively), ACC deaminase production and biofilm formation. ADJ6 additionally showed inorganic phosphate solubilization (PSI of 2.77), atmospheric nitrogen fixation, and hydrogen cyanide production. Wheat seeds primed with these endophytes exhibited enhanced germination, improved growth profiles, and significantly increased yields in field trials. Notably, both ADJ1 and ADJ6 tolerated high salinity (up to 1.03 M) and significantly improved wheat germination and seedling growth under saline stress, acting both independently and synergistically. This study reveals promising stress-tolerance traits within endophytic bacteria from A. desmettiana. Exploiting such under-explored plant microbiomes offers a sustainable approach to developing salt-tolerant crops, mitigating the impact of climate change-induced salinization on global food security.
The role of attachment and personality traits in choosing opiate addiction replacement therapy
Authors: Gizdic Alena , Antičević Vesna , Brajević-Gizdić Igna 
Published: June 2024

AbstractContemporary medical approaches for opioid addiction often include medication-assisted therapy, utilizing methadone and buprenorphine. However, factors influencing patient preferences for starting buprenorphine or methadone therapy are poorly understood. This study aims to explore whether variances in personality traits and attachment styles are related to treatment preferences among individuals undergoing buprenorphine and methadone maintenance therapies. 300 participants completed the Big Five Questionnaire for personality traits and sub-dimensions and the Experiences in Close Relationship Scale for assessing attachment styles. The results indicated that patients with higher levels of Dynamism, Conscientiousness, and Perseverance personality traits were more likely to choose buprenorphine over methadone for achieving and maintaining abstinence. Although attachment styles showed a greater ability to differentiate between groups compared to personality traits, the differences were not significant. However, Conscientiousness stood out for its high discriminant validity, suggesting that scores in this personality dimension could significantly distinguish between groups, with individuals in the buprenorphine group showing higher levels of Conscientiousness compared to the methadone group. The study suggests a partial association between individuals' preference for abstinence therapy and their personality traits. These findings could be considered useful indicators when choosing maintenance therapy to help opiate-addicted patients achieve and maintain abstinence.
Frequency-dependent selection of neoantigens fosters tumor immune escape and predicts immunotherapy response
Authors: Chen Shaoqing , Xie Duo , Li Zan , Wang Jiguang , Hu Zheng , Zhou Da 
Published: June 2024

AbstractCancer is an evolutionary process shaped by selective pressure from the microenvironments. However, recent studies reveal that certain tumors undergo neutral evolution where there is no detectable fitness difference amongst the cells following malignant transformation. Here, through computational modeling, we demonstrate that negative frequency-dependent selection (or NFDS), where the immune response against cancer cells depends on the clonality of neoantigens, can lead to an immunogenic landscape that is highly similar to neutral evolution. Crucially, NFDS promotes high antigenic heterogeneity and early immune evasion in hypermutable tumors, leading to poor responses to immune checkpoint blockade (ICB) therapy. Our model also reveals that NFDS is characterized by a negative association between average clonality and total burden of neoantigens. Indeed, this unique feature of NFDS is common in the whole-exome sequencing (WES) datasets (357 tumor samples from 275 patients) from four melanoma cohorts with ICB therapy and a non-small cell lung cancer (NSCLC) WES dataset (327 tumor samples from 100 patients). Altogether, our study provides quantitative evidence supporting the theory of NFDS in cancer, explaining the high prevalence of neutral-looking tumors. These findings also highlight the critical role of frequency-dependent selection in devising more efficient and predictive immunotherapies.
Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis
Authors: Niu Yang , Pemberton Joshua G , Kim Yeun Ju , Balla Tamas 
Published: June 2024

AbstractPhosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR). Nuclear PS is critical for supporting the translocation of CCTα and Lipin1α, two key enzymes important for phosphatidylcholine (PC) biosynthesis, from the nuclear matrix to the INM and NR in response to oleic acid treatment. We identified the PS-interacting regions within the M-domain of CCTα and M-Lip domain of Lipin1α, and show that lipid droplet formation is altered by manipulations of nuclear PS availability. Our studies reveal an unrecognized regulatory role of nuclear PS levels in the regulation of key PC synthesizing enzymes within the nucleus.
Physiological regulation of neuronal Wnt activity is essential for TDP-43 localization and function
Authors: Zhang Nan , Westerhaus Anna , Wilson Macey , Wang Ethan , Goff Loyal , Sockanathan Shanthini 
Published: June 2024

AbstractNuclear exclusion of the RNA- and DNA-binding protein TDP-43 can induce neurodegeneration in different diseases. Diverse processes have been implicated to influence TDP-43 mislocalization, including disrupted nucleocytoplasmic transport (NCT); however, the physiological pathways that normally ensure TDP-43 nuclear localization are unclear. The six-transmembrane enzyme glycerophosphodiester phosphodiesterase 2 (GDE2 or GDPD5) cleaves the glycosylphosphatidylinositol (GPI) anchor that tethers some proteins to the membrane. Here we show that GDE2 maintains TDP-43 nuclear localization by regulating the dynamics of canonical Wnt signaling. Ablation of GDE2 causes aberrantly sustained Wnt activation in adult neurons, which is sufficient to cause NCT deficits, nuclear pore abnormalities, and TDP-43 nuclear exclusion. Disruption of GDE2 coincides with TDP-43 abnormalities in postmortem tissue from patients with amyotrophic lateral sclerosis (ALS). Further, GDE2 deficits are evident in human neural cell models of ALS, which display erroneous Wnt activation that, when inhibited, increases mRNA levels of genes regulated by TDP-43. Our study identifies GDE2 as a critical physiological regulator of Wnt signaling in adult neurons and highlights Wnt pathway activation as an unappreciated mechanism contributing to nucleocytoplasmic transport and TDP-43 abnormalities in disease.
Senescent endothelial cells promote pathogenic neutrophil trafficking in inflamed tissues
Authors: Rolas Loïc , Stein Monja , Barkaway Anna , Reglero-Real Natalia , Sciacca Elisabetta , Yaseen Mohammed , Wang Haitao , Vazquez-Martinez Laura , Golding Matthew , Blacksell Isobel A , Giblin Meredith J , Jaworska Edyta , Bishop Cleo L , Voisin Mathieu-Benoit , Gaston-Massuet Carles , Fossati-Jimack Liliane , Pitzalis Costantino , Cooper Dianne , Nightingale Thomas D , Lopez-Otin Carlos , Lewis Myles J , Nourshargh Sussan 
Published: June 2024

AbstractCellular senescence is a hallmark of advanced age and a major instigator of numerous inflammatory pathologies. While endothelial cell (EC) senescence is aligned with defective vascular functionality, its impact on fundamental inflammatory responses in vivo at single-cell level remain unclear. To directly investigate the role of EC senescence on dynamics of neutrophil-venular wall interactions, we applied high resolution confocal intravital microscopy to inflamed tissues of an EC-specific progeroid mouse model, characterized by profound indicators of EC senescence. Progerin-expressing ECs supported prolonged neutrophil adhesion and crawling in a cell autonomous manner that additionally mediated neutrophil-dependent microvascular leakage. Transcriptomic and immunofluorescence analysis of inflamed tissues identified elevated levels of EC CXCL1 on progerin-expressing ECs and functional blockade of CXCL1 suppressed the dysregulated neutrophil responses elicited by senescent ECs. Similarly, cultured progerin-expressing human ECs exhibited a senescent phenotype, were pro-inflammatory and prompted increased neutrophil attachment and activation. Collectively, our findings support the concept that senescent ECs drive excessive inflammation and provide new insights into the mode, dynamics, and mechanisms of this response at single-cell level.
Secure energy efficiency maximization for joint ITS and IRS assisted satellite downlink communications
Authors: Yang Shaochuan , Huang Kaizhi , Niu Hehao , Wang Yi , Liu Ya , Chu Zheng 
Published: June 2024

AbstractSatellite communications (SatCom) have been viewed as a promising technique to achieve ubiquitous global coverage in next‐generation wireless systems. This article investigates the secure energy efficient downlink transmission for SatCom where an intelligent transmissive surface‐aided transmitter is deployed at the satellite to perform energy efficient beamforming and an intelligent reflecting surface as well as a cooperative jammer are deployed on the ground to enhance the secure performance. The aim is to maximize the secure energy efficiency by jointly designing ITS beamforming, IRS phase shift, jammer precoding vector, and transmit power allocation. To develop a low‐complexity solution,first, an approximated concave lower bound of the non‐concave objective function is derived by utilizing Dinkelbach's method and a novel successive convex approximation technique. Then the reformulated problem is decoupled using alternating optimization algorithm and the subproblems are solved by adopting Riemannian manifold optimization, element‐wise block coordinate descent, Lagrange dual method and Karush–Kuhn–Tucker conditions. At last, simulation results demonstrate the effectiveness of the proposed scheme.
Robust distributed Nash equilibrium solution for multi‐agent differential graphical games
Authors: Zhang Shouxu , Zhang Zhuo , Cui Rongxin , Yan Weisheng 
Published: June 2024

AbstractThis paper studies the differential graphical games for linear multi‐agent systems with modelling uncertainties. A robust optimal control policy that seeks the distributed Nash equilibrium solution and guarantees the leader‐following consensus is designed. The weighting matrices rely on modelling uncertainties, leading to the Nash equilibrium solution, and the solution can be obtained by solving a decoupled algebraic Riccati equation. Simulation studies are finally reported to illustrate the effectiveness of proposed policy.
A piezoelectric transducer for bone conduction implants designed using finite element analysis
Authors: Shin Dong Ho , Seong Ki Woong 
Published: June 2024

AbstractThis study describes the design of a transducer for bone conduction implants that combines a piezoelectric element and a displacement amplifier. To develop a displacement amplifier with the maximum possible amplification ratio, theoretical analysis was performed to derive the parameters that affect the amplification ratio. Parametric sweep analysis was conducted to calculate the amplification ratio according to changes in the various parameters. The resulting optimal displacement amplifier afforded the maximum amplification ratio when the beam thickness, depth, inclination angle, and length were 0.15 mm, 1.2 mm, 6.5°, and 4 mm, respectively. The displacement amplifier with these optimal parameter values amplified the piezoelectric element displacement by approximately 7.7‐fold. Frequency characteristic analysis by weight was performed to derive a mechanical resonance location with frequency characteristics that appropriately compensated for hearing loss. As a result of this analysis, when a weight of 0.7 g was applied to the displacement amplifier, the mechanical resonance was that required for bone conduction implant transducers.
An improved transformer‐based model for long‐term 4D trajectory prediction in civil aviation
Authors: Luo Aofeng , Luo Yuxing , Liu Hong , Du Wenchao , Wu Xiping , Chen Hu , Yang Hongyu 
Published: June 2024

AbstractFour‐dimensional trajectory prediction is a crucial component of air traffic management, and its accuracy is closely related to the efficiency and safety of air transportation. Although long short‐term memory (LSTM) or its variants have been widely used in recent studies, they may produce unacceptable results in long‐term prediction due to the iterative output that accumulates error. To address this issue, a transformer‐based long‐term trajectory prediction model is proposed here, which utilizes the self‐attention mechanism to extract time series features from historical trajectory data. For long‐term prediction scenarios, we a trajectory stabilization module is introduced to ensure the stationarity of the time series for better predictability. Additionally, the transformer output strategy is improved to generate the prediction sequence by a single step instead of serial dynamic decoding, thus effectively enhancing the precision and inference speed. The proposed model is validated using real data obtained from China's Southwest Air Traffic Management Bureau. The experimental results demonstrate that this model outperforms the benchmark model. Further ablation experiments and visualizations are performed to analyze the impact of trajectory stabilization and one‐step inference strategy.