bluuebunny/crossref_metadata_2025_split huggingface dataset:
IRAK4 is an immunological checkpoint in neuropsychiatric systemic lupus erythematosus
Authors: Ménoret Antoine , Agliano Federica , Karginov Timofey A. , Hu Xiangyou , Vella Anthony T. 
Published: July 2024

AbstractThe search for dementia treatments, including treatments for neuropsychiatric lupus (NPSLE), has not yet uncovered useful therapeutic targets that mitigate underlying inflammation. Currently, NPSLE’s limited treatment options are often accompanied by severe toxicity. Blocking toll-like receptor (TLR) and IL-1 receptor signal transduction by inhibiting interleukin-1 receptor-associated kinase 4 (IRAK4) offers a new pathway for intervention. Using a pre-clinical NPSLE model, we compare lupus-like B6.MRL-Faslpr (MRL) mice with B6.MRL-Faslpr-IRAK4 kinase-dead (MRL-IRAK4-KD) mice, which are were less prone to ‘general’ lupus-like symptoms. We demonstrate that lupus-prone mice with a mutation in the kinase domain of IRAK4 no longer display typical lupus hallmarks such as splenomegaly, inflammation, production of hormones, and anti-double-stranded (ds)DNA antibody. water maze behavioral testing, which measures contextual associative learning, revealed that mice without functional IRAK4 displayed a recovery in memory acquisition deficits. RNA-seq approach revealed that cytokine and hormone signaling converge on the JAK/STAT pathways in the mouse hippocampus. Ultimately, the targets identified in this work may result in broad clinical value that can fill the significant scientific and therapeutic gaps precluding development of cures for dementia.
Enhancing collective entanglement witnesses through correlation with state purity
Authors: Jiráková Kateřina , Černoch Antonín , Barasiński Artur , Lemr Karel 
Published: July 2024

AbstractThis research analyzes the adverse impact of white noise on collective quantum measurements and argues that such noise poses a significant obstacle for the otherwise straightforward deployment of collective measurements in quantum communications. Our findings then suggests addressing this issue by correlating outcomes of these measurements with quantum state purity. To test the concept, a support vector machine is employed to boost the performance of several collective entanglement witnesses by incorporating state purity into the classification task of distinguishing entangled states from separable ones. Furthermore, the application of machine learning allows to optimize specificity of entanglement detection given a target value of sensitivity. A response operating characteristic curve is reconstructed based on this optimization and the area under curve calculated to assess the efficacy of the proposed model. Finally, we test the presented approach on an experimental dataset of Werner states.
The association of breast cancer patients survival and prior menopausal hormone therapy in women with type 2 diabetes
Authors: Hosio Mayu , Urpilainen Elina , Hautakoski Ari , Arffman Martti , Sund Reijo , Ahtikoski Anne , Puistola Ulla , Jukkola Arja , Läärä Esa , Karihtala Peeter 
Published: July 2024

AbstractWe investigated the association of prediagnostic use of menopausal hormone therapy (MHT) with breast cancer survival among women with type 2 diabetes (T2D). The study cohort was identified from a Finnish nationwide diabetes database, and consisted of women with T2D, who were diagnosed with breast cancer between 2000 and 2011 (n = 3189). The patients were classified according to their previous MHT use: systemic MHT, local MHT, and no history of any MHT. The cumulative mortality from breast cancer, cardiovascular diseases, and other causes in three MHT groups was described by the Aalen-Johansen estimator. The cause-specific mortality rates were analyzed by Cox models, and adjusted hazard ratios (HRs) were estimated for the use of MHT. The breast cancer mortality appeared to be lower among systemic MHT users (HR 0.49, 95% Cl 0.36–0.67) compared with non-users of MHT. The mortality from cardiovascular diseases and from other causes of death was found to be lower among systemic MHT users, (HR 0.49, 95% Cl 0.32–0.74), and (HR 0.51, 95% Cl 0.35–0.76), respectively. In conclusion, prediagnostic systemic MHT use is associated with reduced breast cancer, cardiovascular, and other causes of mortality in women with T2D.
Fast, approximation-free molecular simulation of the SPC/Fw water model using non-reversible Markov chains
Authors: Höllmer Philipp , Maggs A. C. , Krauth Werner 
Published: July 2024

AbstractIn a world made of atoms, computer simulations of molecular systems such as proteins in water play an enormous role in science. Software packages for molecular simulation have been developed for decades. They all discretize Hamilton’s equations of motion and treat long-range potentials through cutoffs or discretization of reciprocal space. This introduces severe approximations and artifacts that must be controlled algorithmically. Here, we bring to fruition a paradigm for molecular simulation that relies on modern concepts in statistics to explore the thermodynamic equilibrium with an exact and efficient non-reversible Markov process. It is free of all discretizations, approximations, and cutoffs. We explicitly demonstrate that this approach reaches a break-even point with traditional molecular simulation performed at high precision, but without any of its approximations. We stress the potential of our paradigm for crucial applications in biophysics and other fields, and as a practical approach to molecular simulation. We set out a strategy to reach our goal of rigorous molecular simulation.
Influence of gender on clinical presentation, management practices and outcomes of ocular syphilis
Authors: Shields Melissa K. , Arantes Tiago E. , Lake Stewart R. , Belfort Rubens , Muccioli Cristina , Nascimento Heloisa , de Pinho Queiroz Rafael , Vasconcelos-Santos Daniel V. , Furtado João M. , Smith Justine R. 
Published: July 2024

AbstractOcular syphilis is a re-emerging inflammatory eye disease with a clear gender imbalance, disproportionately affecting men. We investigated the impact of gender on the presentation, management practices and clinical outcomes of this condition. Data generated from a study of patients consecutively diagnosed with ocular syphilis who attended a subspecialist uveitis service at one of four hospitals in Brazil over a 30-month period were disaggregated for analysis by gender. Two-hundred and fourteen eyes (161 men and 53 women) of 127 patients (96 men and 31 women) were included. Posterior uveitis was the most common presentation in both men and women (80.1% vs. 66.7%, p > 0.05), but men were significantly more likely to have vitritis as a feature of their disease (49.4% versus 28.8%, p = 0.019). Three eyes of women had nodular anterior scleritis (p = 0.015). Men were more likely to undergo a lumbar puncture to assess for neurosyphilis (71.9% vs. 51.6%, p = 0.048), but men and women undergoing a lumbar puncture were equally likely to have a cerebrospinal fluid abnormality (36.2% vs. 25.0%, p = 0.393). All patients were treated with aqueous penicillin G or ceftriaxone, and there was a trend towards more men receiving adjunctive systemic corticosteroid treatment as part of their management (65.2% vs. 46.7%, p = 0.071). There were no significant differences in the age of presentation, bilaterality of disease, anatomical classification of uveitis, initial or final visual acuity, and rates of ocular complications between men and women. Our findings indicate that ocular syphilis has comparable outcomes in men and women, but that there are differences in the type of ocular inflammation and management practices between the genders.
Enhancement of the chondrogenic differentiation capacity of human dental pulp stem cells via chondroitin sulfate-coated polycaprolactone-MWCNT nanofibers
Authors: Eldeen Ghada Nour , Elkhooly Tarek A. , El Bassyouni Gehan T. , Hamdy Tamer M. , Hawash Ahmed R. , Aly Riham M. 
Published: July 2024

AbstractMost of the conditions involving cartilaginous tissues are irreversible and involve degenerative processes. The aim of the present study was to fabricate a biocompatible fibrous and film scaffolds using electrospinning and casting techniques to induce chondrogenic differentiation for possible application in cartilaginous tissue regeneration. Polycaprolactone (PCL) electrospun nanofibrous scaffolds and PCL film were fabricated and incorporated with multi-walled carbon nanotubes (MWCNTs). Thereafter, coating of chondroitin sulfate (CS) on the fibrous and film structures was applied to promote chondrogenic differentiation of human dental pulp stem cells (hDPSCs). First, the morphology, hydrophilicity and mechanical properties of the scaffolds were characterized by scanning electron microscopy (SEM), spectroscopic characterization, water contact angle measurements and tensile strength testing. Subsequently, the effects of the fabricated scaffolds on stimulating the proliferation of human dental pulp stem cells (hDPSCs) and inducing their chondrogenic differentiation were evaluated via electron microscopy, flow cytometry and RT‒PCR. The results of the study demonstrated that the different forms of the fabricated PCL-MWCNTs scaffolds analyzed demonstrated biocompatibility. The nanofilm structures demonstrated a higher rate of cellular proliferation, while the nanofibrous architecture of the scaffolds supported the cellular attachment and differentiation capacity of hDPSCs and was further enhanced with CS addition. In conclusion, the results of the present investigation highlighted the significance of this combination of parameters on the viability, proliferation and chondrogenic differentiation capacity of hDPSCs seeded on PCL-MWCNT scaffolds. This approach may be applied when designing PCL-based scaffolds for future cell-based therapeutic approaches developed for chondrogenic diseases.
Comprehensive landscape of m6A regulator-related gene patterns and tumor microenvironment infiltration characterization in gastric cancer
Authors: Peng Bin , Lin Yinglin , Yi Gao , Lin Mingzhen , Xiao Yao , Qiu Yezhenghong , Yao Wenxia , Zhou Xinke , Liu Zhaoyu 
Published: July 2024

AbstractThe epigenetic regulation of N6-methyladenosine (m6A) has attracted considerable interest in tumor research, but the potential roles of m6A regulator-related genes, remain largely unknown within the context of gastric cancer (GC) and tumor microenvironment (TME). Here, a comprehensive strategy of data mining and computational biology utilizing multiple datasets based on 28 m6A regulators (including novel anti-readers) was employed to identify m6A regulator-related genes and patterns and elucidate their underlying mechanisms in GC. Subsequently, a scoring system was constructed to evaluate individual prognosis and immunotherapy response. Three distinct m6A regulator-related patterns were identified through the unsupervised clustering of 56 m6A regulator-related genes (all significantly associated with GC prognosis). TME characterization revealed that these patterns highly corresponded to immune-inflamed, immune-excluded, and immune-desert phenotypes, and their TME characteristics were highly consistent with different clinical outcomes and biological processes. Additionally, an m6A-related scoring system was developed to quantify the m6A modification pattern of individual samples. Low scores indicated high survival rates and high levels of immune activation, whereas high scores indicated stromal activation and tumor malignancy. Furthermore, the m6A-related scores were correlated with tumor mutation loads and various clinical traits, including molecular or histological subtypes and clinical stage or grade, and the score had predictive values across all digestive system tumors and even in all tumor types. Notably, a low score was linked to improved responses to anti-PD-1/L1 and anti-CTLA4 immunotherapy in three independent cohorts. This study has expanded the important role of m6A regulator-related genes in shaping TME diversity and clinical/biological traits of GC. The developed scoring system could help develop more effective immunotherapy strategies and personalized treatment guidance.
QSAR, ADMET, molecular docking, and dynamics studies of 1,2,4-triazine-3(2H)-one derivatives as tubulin inhibitors for breast cancer therapy
Authors: Moussaoui Mohamed , Baammi Soukayna , Soufi Hatim , Baassi Mouna , El Allali Achraf , Belghiti M. E. , Daoud Rachid , Belaaouad Said 
Published: July 2024

AbstractBreast cancer remains a leading cause of cancer-related deaths among women globally, necessitating the development of more effective therapeutic agents with minimal side effects. This study explores novel 1,2,4-triazine-3(2H)-one derivatives as potential inhibitors of Tubulin, a pivotal protein in cancer cell division, highlighting a targeted approach in cancer therapy. Using an integrated computational approach, we combined quantitative structure–activity relationship (QSAR) modeling, ADMET profiling, molecular docking, and molecular dynamics simulations to evaluate and predict the efficacy and stability of these compounds. Our QSAR models, developed through rigorous statistical analysis, revealed that descriptors such as absolute electronegativity and water solubility significantly influence inhibitory activity, achieving a predictive accuracy (R2) of 0.849. Molecular docking studies identified compounds with high binding affinities, particularly Pred28, which exhibited the best docking score of − 9.6 kcal/mol. Molecular dynamics simulations conducted over 100 ns provided further insights into the stability of these interactions. Pred28 demonstrated notable stability, with the lowest root mean square deviation (RMSD) of 0.29 nm and root mean square fluctuation (RMSF) values indicative of a tightly bound conformation to Tubulin. The novelty of this work lies in its methodological rigor and the integration of multiple advanced computational techniques to pinpoint compounds with promising therapeutic potential. Our findings advance the current understanding of Tubulin inhibitors and open avenues for the synthesis and experimental validation of these compounds, aiming to offer new solutions for breast cancer treatment.
Across-environment seed protein stability and genetic architecture of seed components in soybean
Authors: Wu Chengjun , Acuña Andrea , Florez-Palacios Liliana , Harrison Derrick , Rogers Daniel , Mozzoni Leandro , Mian Rouf , Canella Vieira Caio 
Published: July 2024

AbstractThe recent surge in the plant-based protein market has resulted in high demands for soybean genotypes with improved grain yield, seed protein and oil content, and essential amino acids (EAAs). Given the quantitative nature of these traits, complex interactions among seed components, as well as between seed components and environmental factors and management practices, add complexity to the development of desired genotypes. In this study, the across-environment seed protein stability of 449 genetically diverse plant introductions was assessed, revealing that genotypes may display varying sensitivities to such environmental stimuli. The EAAs valine, phenylalanine, and threonine showed the highest variable importance toward the variation in stability, while both seed protein and oil contents were among the explanatory variables with the lowest importance. In addition, 56 single nucleotide polymorphism (SNP) markers were significantly associated with various seed components. Despite the strong phenotypic Pearson’s correlation observed among most seed components, many independent genomic regions associated with one or few seed components were identified. These findings provide insights for improving the seed concentration of specific EAAs and reducing the negative correlation between seed protein and oil contents.
Sustainable synergistic approach to chemolithotrophs—supported bioremediation of wastewater and flue gas
Authors: Barla Rachael J. , Gupta Suresh , Raghuvanshi Smita 
Published: July 2024

AbstractFlue gas emissions are the waste gases produced during the combustion of fuel in industrial processes, which are released into the atmosphere. These identical processes also produce a significant amount of wastewater that is released into the environment. The current investigation aims to assess the viability of simultaneously mitigating flue gas emissions and remediating wastewater in a bubble column bioreactor utilizing bacterial consortia. A comparative study was done on different growth media prepared using wastewater. The highest biomass yield of 3.66 g L−1 was achieved with the highest removal efficiencies of 89.80, 77.30, and 80.77% for CO2, SO2, and NO, respectively. The study investigated pH, salinity, dissolved oxygen, and biochemical and chemical oxygen demand to assess their influence on the process. The nutrient balance validated the ability of bacteria to utilize compounds in flue gas and wastewater for biomass production. The Fourier Transform–Infrared Spectrometry (FT–IR) and Gas Chromatography–Mass Spectrometry (GC–MS) analyses detected commercial-use long-chain hydrocarbons, fatty alcohols, carboxylic acids, and esters in the biomass samples. The nuclear magnetic resonance (NMR) metabolomics detected the potential mechanism pathways followed by the bacteria for mitigation. The techno-economic assessment determined a feasible total capital investment of 245.74$ to operate the reactor for 288 h. The bioreactor’s practicability was determined by mass transfer and thermodynamics assessment. Therefore, this study introduces a novel approach that utilizes bacteria and a bioreactor to mitigate flue gas and remediate wastewater.
Cross-sectional analysis of socioeconomic drivers of PM2.5 pollution in emerging SAARC economies
Authors: Musa Mohammad , Rahman Preethu , Saha Swapan Kumar , Chen Zhe , Ali Muhammad Abu Sufyan , Gao Yanhua 
Published: July 2024

AbstractWithin the intricate interplay of socio-economic, natural and anthropogenic factors, haze pollution stands as a stark emblem of environmental degradation, particularly in the South Asian Association for Regional Cooperation (SAARC) region. Despite significant efforts to mitigate greenhouse gas emissions, several SAARC nations consistently rank among the world’s most polluted. Addressing this critical research gap, this study employs robust econometric methodologies to elucidate the dynamics of haze pollution across SAARC countries from 1998 to 2020. These methodologies include the Pooled Mean Group (PMG) and Augmented Mean Group (AMG) estimator, Panel two-stage least squares (TSLS), Feasible Generalized Least Squares (FGLS) and Dumitrescu–Hurlin (D–H) causality test. The analysis reveals a statistically significant cointegrating relationship between PM2.5 and economic indicators, with economic development and consumption expenditure exhibiting positive associations and rainfall demonstrating a mitigating effect. Furthermore, a bidirectional causality is established between temperature and economic growth, both influencing PM2.5 concentrations. These findings emphasize the crucial role of evidence-based policy strategies in curbing air pollution. Based on these insights, recommendations focus on prioritizing green economic paradigms, intensifying forest conservation efforts, fostering the adoption of eco-friendly energy technologies in manufacturing and proactively implementing climate-sensitive policies. By embracing these recommendations, SAARC nations can formulate comprehensive and sustainable approaches to combat air pollution, paving the way for a healthier atmospheric environment for their citizens.
Time series analysis of COVID-19's impact on physician and dentist visits in Iran
Authors: Rezaei Satar , Ghiasvand Hesam , Brown Heather 
Published: July 2024

AbstractThis study aimed to assess the impact of the COVID-19 pandemic on general practitioner (GP), specialist, and dentist visits among 40 million Iranians covered by the Social Security Organization (SSO). A monthly interrupted time series analysis was conducted over a period of 72 months, including—47 months before the pandemic and 25 months after its onset. The outcomes variables were monthly number of GP, specialist, and dentist visits per 1000 SSO-insured individuals. The analysis was performed by total visits, visits to the SSO direct sector, and visits to the indirect sectors. The study found that in the first month of the pandemic, the number of visits per 1000 insured individuals significantly decreased for visits to GPs (by 51.12, 95% CI −64.42 to −37.88), visits to specialists (by 39.11, 95% CI −51.61 to −26.62), and visits to dentists (by 6.67, 95% CI −8.55 to −4.78). However, during the subsequent months of the pandemic, there was a significant increase in the number of monthly visits for all three categories, with GPs experiencing the highest increase (1.78 visits per 1000 insured), followed by specialists (1.32 visits per 1000 insured), and dentists (0.05 visits per 1000 insured). Furthermore, prior to the pandemic, the number of monthly GP visits per 1000 insured individuals was statistically significantly lower in the indirect sector compared to the direct sector (45.79, 95% CI −52.69 to −38.89). Conversely, the direct sector exhibited lower rates of specialist visits (25.84 visits per 1000 insured individuals, 95% CI 22.87 to 28.82) and dentist visits (0.75 visits per 1000 insured individuals, 95% CI 0.12 to 1.36) compared to the indirect sector. Additionally, the study found that in the first month of the pandemic, the monthly number of GP visits in the indirect sector significantly increased by 34.44 times (95% CI 24.81 to 44.08) compared to the direct sector. For specialist visits and dentist visits, the increase was 3.41 (95% CI −5.87 to 12.69) and 5.01 (95% CI 3.48 to 6.53) per 1000 insured individuals, respectively. Overall, the findings of this study demonstrate statistically significant disruptions in GP, specialist, and dentist visits during the COVID-19 pandemic, although some recovery was observed. Both the direct and indirect sectors experienced decreased visits.
Time pressure and deliberation affect moral punishment
Authors: Philippsen Ana , Mieth Laura , Buchner Axel , Bell Raoul 
Published: July 2024

AbstractThe deliberate-morality account implies that moral punishment should be decreased with time pressure and increased with deliberation while the intuitive-morality account predicts the opposite. In three experiments, moral punishment was examined in a simultaneous one-shot Prisoner’s Dilemma game with a costly punishment option. The players cooperated or defected and then decided whether or not to punish their partners. In Experiment 1, the punishment decisions were made without or with time pressure. In Experiment 2, the punishment decisions were immediate or delayed by pauses in which participants deliberated their decisions. In Experiment 3, participants were asked to deliberate self-interest or fairness before deciding whether to punish their partners. Different types of punishment were distinguished using the cooperation-and-punishment model. In Experiment 1, time pressure decreased moral punishment. In Experiment 2, deliberation increased moral punishment. So far, the evidence supports the deliberate-morality account. Experiment 3 demonstrates that the effect of deliberation depends on what is deliberated. When participants deliberated self-interest rather than fairness, moral punishment was decreased. The results suggest that unguided deliberation increases moral punishment, but the effects of deliberation are modulated by the type of deliberation that takes place. These results strengthen a process-based account of punishment which offers a more nuanced understanding of the context-specific effect of deliberation on moral punishment than the deliberate-morality account.