bluuebunny/crossref_metadata_2025_split huggingface dataset:
Histamine stimulates human microglia to alter cellular prion protein expression via the HRH2 histamine receptor
Authors: Pehar Marcus , Hewitt Melissa , Wagner Ashley , Sandhu Jagdeep K. , Khalili Aria , Wang Xinyu , Cho Jae-Young , Sim Valerie L. , Kulka Marianna 
Published: October 2024

AbstractAlthough the cellular prion protein (PrPC) has been evolutionarily conserved, the role of this protein remains elusive. Recent evidence indicates that PrPC may be involved in neuroinflammation and the immune response in the brain, and its expression may be modified via various mechanisms. Histamine is a proinflammatory mediator and neurotransmitter that stimulates numerous cells via interactions with histamine receptors 1-4 (HRH1-4). Since microglia are the innate immune cells of the central nervous system, we hypothesized that histamine-induced stimulation regulates the expression of PrPC in human-derived microglia. The human microglial clone 3 (HMC3) cell line was treated with histamine, and intracellular calcium levels were measured via a calcium flux assay. Cytokine production was monitored by enzyme-linked immunosorbent assay (ELISA). Western blotting and quantitative reverse transcription-polymerase chain reaction were used to determine protein and gene expression of HRH1-4. Flow cytometry and western blotting were used to measure PrPC expression levels. Fluorescence microscopy was used to examine Iba-1 and PrPC localization. HMC3 cells stimulated by histamine exhibited increased intracellular calcium levels and increased release of IL-6 and IL-8, while also modifying PrPC localization. HMC3 stimulated with histamine for 6 and 24 hours exhibited increased surface PrPC expression. Specifically, we found that stimulation of the HRH2 receptor was responsible for changes in surface PrPC. Histamine-induced increases in surface PrPC were attenuated following inhibition of the HRH2 receptor via the HRH2 antagonist ranitidine. These changes were unique to HRH2 activation, as stimulation of HRH1, HRH3, or HRH4 did not alter surface PrPC. Prolonged stimulation of HMC3 decreased PrPC expression following 48 and 72 hours of histamine stimulation. HMC3 cells can be stimulated by histamine to undergo intracellular calcium influx. Surface expression levels of PrPC on HMC3 cells are altered by histamine exposure, primarily mediated by HRH2. While histamine exposure also increases release of IL-6 and IL-8 in these cells, this cytokine release is not fully dependent on PrPC levels, as IL-6 release is only partially reduced and IL-8 release is unchanged under the conditions of HRH2 blockade that prevent PrPC changes. Overall, this suggests that PrPC may play a role in modulating microglial responses.
Spatial analysis and soft computational modeling for hazard assessment of potential toxic elements in potable groundwater
Authors: Aswal R. S. , Prasad Mukesh , Singh Jaswinder , Singh Hakam , Shrivastava Utpal , Wadhwa Manoj , Pandey Om Prakash , Egbueri Johnbosco C. 
Published: October 2024

AbstractSwiftly increasing population and industrial developments of urban areas has accelerated the worsening of the water quality in recent years. Groundwater samples from different locations of the Doon valley, Garhwal Himalaya were analyzed to measure concentrations of six potential toxic elements (PTEs) viz. chromium (Cr), nickel (Ni), arsenic (As), molybdenum (Mo), cadmium (Cd), and lead (Pb) using Inductively Coupled Plasma Mass Spectrometer (ICP-MS) with the aim to study the spatial distribution and associated hazards. In addition, machine learning algorithms have been used for prediction of water quality and identification of influencing PTEs. The results inferred that the mean values (in the units of µg L−1) of analyzed PTEs were observed in the order of Mo (1.066) > Ni (0.744) > Pb (0.337) > As (0.186) > Cr (0.180) > Cd (0.026). The levels and computed risks of PTEs were found below the safe limits. The radial basis function neural network (RBF-NN) algorithms showed high level of accuracy in the predictions of heavy metal pollution index (HPI), heavy metal evaluation index (HEI), non-carcinogenic (N-CR) and carcinogenic (CR) parameters with determination coefficient values ranged from 0.912 to 0.976. However, the modified heavy metal pollution index (m-HPI) and contamination index (CI) predictions showed comparatively lower coefficient values as 0.753 and 0.657, respectively. The multilayer perceptron neural network (MLP-NN) demonstrated fluctuation in precision with determination coefficient between 0.167 and 0.954 for the prediction of computed indices (HPI, HEI, CI, m-HPI). In contrast, the proficiency in forecasting of non-carcinogenic and carcinogenic hazards for both sub-groups showcased coefficient values ranged from 0.887 to 0.995. As compared to each other, the radial basis function (RBF) model indicated closer alignments between predicted and actual values for pollution indices, while multilayer perceptron (MLP) model portrayed greater precision in prediction of health risk indices.
Association of visceral fat area with early-stage locomotive syndrome across various age groups: a cross-sectional study
Authors: Miyazaki Tadashi , Ozato Naoki , Yamaguchi Tohru , Sugiura Yoko , Kawada Hiromitsu , Katsuragi Yoshihisa , Osaki Noriko , Mikami Tatsuya , Ito Ken , Murashita Koichi , Nakaji Shigeyuki , Tamada Yoshinori 
Published: October 2024

AbstractThe association between visceral fat area (VFA) and locomotive syndrome (LS) has been extensively studied in the older population; however, the association between VFA and early-stage LS (stage 1 [LS1]) remains unclear. In this cross-sectional study, we investigated this association across different age groups. The study involved 1,236 (524 male and 712 female) participants (aged 20–85 years). Multiple regression analysis adjusted for sex, body mass index, skeletal muscle mass index, T-score, exercise habits, smoking status, and alcohol consumption revealed a significant association between LS1 and VFA across all VFA quartiles. The adjusted odds ratio OR for quartiles 2, 3, and 4 was 1.84, 2.68, and 4.12, respectively. The association between LS1 and VFA across the age groups—high VFA (> 73 cm2) and non-older (< 65 years) (OR, 1.87; 95% CI, 1.28–2.72; p = 0.001), low VFA (≤ 73 cm2) and older (≥ 65 years) (OR, 3.16; 95% CI, 1.94–5.14; p < 0.001), and high VFA and older groups (OR, 6.43; 95% CI, 3.98–10.4; p < 0.001)—was significantly stronger than that in the low VFA and non-older group. In summary, our findings suggest that managing VFA through diet and exercise is crucial for preventing LS1 across all age groups.
The Tmem16a chloride channel is required for mucin maturation after secretion from goblet-like cells in the Xenopus tropicalis tadpole skin
Authors: Dubaissi Eamon , Hilton Emma N. , Lilley Sarah , Collins Richard , Holt Charlotte , March Peter , Danahay Henry , Gosling Martin , Grencis Richard K , Roberts Ian S , Thornton David J 
Published: October 2024

AbstractThe TMEM16A chloride channel is proposed as a therapeutic target in cystic fibrosis, where activation of this ion channel might restore airway surface hydration and mitigate respiratory symptoms. While TMEM16A is associated with increased mucin production under stimulated or pro-inflammatory conditions, its role in baseline mucin production, secretion and/or maturation is less well understood. Here, we use the Xenopus tadpole skin mucociliary surface as a model of human upper airway epithelium to study Tmem16a function in mucus production. We found that Xenopus tropicalis Tmem16a is present at the apical membrane surface of tadpole skin small secretory cells that express canonical markers of mammalian “goblet cells” such as Foxa1 and spdef. X. tropicalis Tmem16a functions as a voltage-gated, calcium-activated chloride channel when transfected into mammalian cells in culture. Depletion of Tmem16a from the tadpole skin results in dysregulated mucin maturation post-secretion, with secreted mucins having a disrupted molecular size distribution and altered morphology assessed by sucrose gradient centrifugation and electron microscopy, respectively. Our results show that in the Xenopus tadpole skin, Tmem16a is necessary for normal mucus barrier formation and demonstrate the utility of this model system to discover new biology relevant to human mucosal biology in health and disease.
Characteristics and predictors of persistent somatic symptoms in patients with cardiac disease
Authors: Clifford Caroline , Löwe Bernd , Kohlmann Sebastian 
Published: October 2024

AbstractPersistent somatic symptoms (PSS) are a diagnostic core criterion of the somatic symptom disorder. This longitudinal study aims to determine the frequency of PSS in patients with cardiac disease, identify potential predictive factors, and investigate its impact on healthcare utilization. Somatic symptoms were assessed with the Somatic Symptom Scale-8 four times over the course of three months in consecutively approached cardiac outpatients. Patients were grouped having PSS vs. not having PSS following a psychometric-driven approach based on the SSS-8 cut-off score and a data-driven approach applying cluster analysis. T-tests were performed to compare the characteristics between patients having vs. not having PSS. To identify predictors of group affiliation, we conducted multivariable logistic regressions. Additionally, analyses of covariance were used to further examine associations between healthcare utilization and group affiliation. The study included 95 patients (30.5% female) with a mean age of 60.5 years (SD = 8.7). All patients had at least one of the following cardiac diseases recorded in their medical history: coronary heart disease (n = 51), myocardial infarction (n = 21), valve disease (n = 22), cardiomyopathy (n = 15), cardiac dysrhythmia (n = 43), and heart failure (n = 12). 30 (32%) were grouped having PSS according to the psychometric-driven approach and 27 (28%) according to the data-driven approach. For both approaches, patients with PSS were more likely to be female, unemployed, reporting angina pectoris, having higher depression, and higher anxiety severity (for all: p ≤ 0.05). Predictors of PSS group affiliation were female gender, higher age, depression severity, and angina pectoris (for all: p ≤ 0.015). Patients with PSS more frequently visited general practitioners and cardiologists compared to patients without PSS (p ≤ 0.013). Enhancing our knowledge of PSS in patients with cardiac disease could help to improve identification of patients’ specific needs and the factors to consider in diagnosis and individualized treatment.
Efficiency of multivariate tests in trials in progressive supranuclear palsy
Authors: Yousefi Elham , Gewily Mohamed , König Franz , Höglinger Günter , Hopfner Franziska , Karlsson Mats O. , Ristl Robin , Zehetmayer Sonja , Posch Martin 
Published: October 2024

AbstractMeasuring disease progression in clinical trials for testing novel treatments for multifaceted diseases as progressive supranuclear palsy (PSP), remains challenging. In this study we assess a range of statistical approaches to compare outcomes as measured by the items of the progressive supranuclear palsy rating scale (PSPRS). We consider several statistical approaches, including sum scores, a modified PSPRS rating scale that had been recommended by FDA in a pre-IND meeting, multivariate tests, and analysis approaches based on multiple comparisons of the individual items. In addition, we propose two novel approaches which measure disease status based on Item Response Theory models. We assess the performance of these tests under various scenarios in an extensive simulation study and illustrate their use with a re-analysis of the ABBV-8E12 clinical trial. Furthermore, we discuss the impact of the FDA-recommended scoring of item scores on the power of the statistical tests. We find that classical approaches as the PSPRS sum score demonstrate moderate to high power when treatment effects are consistent across the individual items. The tests based on Item Response Theory (IRT) models yield the highest power when the simulated data are generated from an IRT model. The multiple testing based approaches have a higher power in settings where the treatment effect is limited to certain domains or items. The study demonstrates that there is no one-size-fits-all testing procedure for evaluating treatment effects using PSPRS items; the optimal method varies based on the specific effect size patterns. The efficiency of the PSPRS sum score, while generally robust and straightforward to apply, varies depending on the specific patterns of effect sizes encountered and more powerful alternatives are available in specific settings. These findings can have important implications for the design of future clinical trials in PSP and similar multifaceted diseases.
Brain-to-blood transport of fluorescein in vitro
Authors: Schoknecht Karl , Eilers Jens 
Published: October 2024

AbstractInvestigating blood-brain barrier (BBB) dysfunction has become a pre-clinical and clinical research focus as it accompanies many neurological disorders. Nevertheless, knowledge of how diagnostic BBB tracers cross the endothelium from blood-to-brain or vice versa often remains incomplete. In particular, brain-to-blood transport (efflux) may reduce tracer extravasation of intravascularly (i.v.) applied tracers. Conversely, impaired efflux could mimic phenotypic extravasation. Both processes would affect conclusions on BBB properties primarily attributed to blood-to-brain leakage. Here, we specifically investigated efflux of fluorescent BBB tracers, focusing on the most common non-toxic marker, sodium fluorescein, which is applicable in patients. We used acute neocortical slices from mice and applied fluorescein, sulforhodamine-B, rhodamine-123, FITC dextran to the artificial cerebrospinal fluid. Anionic low molecular weight (MW) fluorescein and sulforhodamine-B, but not ~ 10-fold larger FITC-dextran and cationic low MW rhodamine-123, showed efflux into the lumen of blood vessels. Our data suggest that fluorescein efflux depends on organic anion transporter polypeptides (Oatp) rather than P-glycoprotein. Furthermore, sodium-potassium ATPase inhibition and incomplete oxygen-glucose deprivation (OGD, 20% O2) reduced fluorescein efflux, while complete OGD (0% O2) abolished efflux. We provide evidence for active efflux of fluorescein in vitro. Impaired efflux of fluorescein could thus contribute to the frequently observed BBB dysfunction in neuropathologies in addition to blood-to-brain leakage.
Risk factors for Ascaris lumbricoides infection and its association with nutritional status and IQ in 14-Year old adolescents in Chitwan, Nepal
Authors: Parajuli Rajendra Prasad , Bhandari Shristi , Ward Lauren Marie , Suarez-Lopez Jose Ricardo 
Published: October 2024

AbstractInconsistent results have been obtained from studies investigating the association between soil-transmitted helminths (STHs) and nutritional status and cognitive outcomes. This study aimed to investigate the influence of STHs and nutritional status on the intelligence quotient (IQ) of adolescents in the Chitwan Valley, Nepal. In this birth cohort study from the Chitwan district of Nepal, 74 cohort participants were followed up after 14 years. The presence and egg density of the STHs were investigated following the Kato–Katz method. Full-scale IQ was evaluated using the Wechsler Abbreviated Scale of Intelligence-II (WASI-II). Multivariate regression analysis was also conducted to examine the associations of STHs and nutritional status with IQ scores, adjusting for adverse childhood experiences (ACE) and demographic and socioeconomic factors. The only STHs detected was for Ascaris lumbricoides, which was detected in 16% (12/74) of the study participants. Similarly, 16% (12/73) of participants reported undernutrition (body mass index (BMI) Z score<-2SD), and 33% (25/74) of participants had a developmental deficit (WASI II FSIQ < 69). There were no significant associations between the presence of A. lumbricoides or egg density and IQ scores. However, undernutrition (BMIZ<-2SD) increased the odds of a developmental deficit according to both univariate and adjusted multivariate models [i.e., adjusted odds ratio (aOR) 9.41; 95% CI (2.23 to 39.80)]. While the study primarily examines the association of STHs and nutritional status with IQ, it is important to note that adolescents with educated mothers or higher incomes also showed better cognitive development. The prevalence of undernutrition and associated developmental deficits characterized by an IQ < 69 was alarmingly high in this cohort of adolescents from Chitwan, Nepal. Despite the high prevalence of A. lumbricoides, its infection was not identified as significantly associated with cognition. However, it is noteworthy that a consistent favorable impact of an enriching postnatal environment, approximated by maternal education and family income, may improve neurodevelopmental indicators.
Differential amino acid usage leads to ubiquitous edge effect in proteomes across domains of life that can be explained by amino acid secondary structure propensities
Authors: Morimoto Juliano , Pietras Zuzanna 
Published: October 2024

AbstractAmino acids are the building blocks of proteins and enzymes which are essential for life. Understanding amino acid usage offers insights into protein function and molecular mechanisms underlying life histories. However, genome-wide patterns of amino acid usage across domains of life remain poorly understood. Here, we analysed the proteomes of 5590 species across four domains and found that only a few amino acids are consistently the most and least used. This differential usage results in lower amino acid usage diversity at the most and least frequent ranks, creating a ubiquitous inverted U-shape pattern of amino acid diversity and rank which we call an ‘edge effect’ across proteomes and domains of life. This effect likely stems from protein secondary structural constraints, not the evolutionary chronology of amino acid incorporation into the genetic code, highlighting the functional rather than evolutionary influences on amino acid usage. We also tested other contemporary hypotheses regarding amino acid usage in proteomes and found that amino acid usage varies across life’s domains and is only weakly influenced by growth temperature. Our findings reveal a novel and pervasive amino acid usage pattern across genomes with the potential to help us probe deep evolutionary relationships and advance synthetic biology.
Risk preference and rural livelihood transitions in the hilly and mountainous region of southern China: a case study in Ruijin City
Authors: Wu Zhilong , Chen Hao , Zeng Tian , Yan Yushan , Zhang Mengyuan 
Published: October 2024

AbstractRural livelihood transition towards non-agriculturalization, non-grainization and even anti-urbanization has become a thorny social problem that undermines farmland resources and worldwide food security. Based on a simulation survey, this study explored the risk preferences and the livelihood transition mechanisms of typical farmers in the hilly and mountainous region. The results indicated that: (1) 76.86% of rural households exhibited risk aversion tendencies, with 60.67% being highly risk-averse. The ranking of risk aversion among the three typical farmers is consistent with asset abundance, with non-agriculture oriented households > semi-farmer and semi-labour households > vocational farmer households. (2) The non-grainization of vocational farmer households is significantly and positively correlated with the family labour force, land management area, and housing assets, yet negatively correlated with risk preferences. Compared to traditional grain cultivation, non-grainization in the hilly and mountainous region possesses lower risks and higher profitability for vocational farmer households. (3) The total non-agriculturalization of semi-farmer and semi-labour households correlates negatively with land management area but positively with family income. (4) Anti-urbanization and returning hometowns for farming are still regarded as a livelihood fallback by the non-agriculture oriented households, but excessive gift expenditure has become a heavy burden in rural society. Therefore, practical and systematical countermeasures are proposed in this research to guide sustainable livelihood transition.
Controlling strain localization in thin films with nanoindenter tip sharpness
Authors: Zak Stanislav 
Published: October 2024

AbstractThin film nanoindentation has increased interest due to its usage in various applications. It is virtually impossible to measure thin film elastic modulus without the substrate influence. Several different methods exist to obtain the true thin film’s elastic modulus with no attention given to investigate what parameters can improve insight into thin film mechanical property measurement. A key parameter is the tip radius. This work is aimed at quantifying the influence of the tip radius on the strain field under the indenter. Three Berkovich indentation tips with different tip radii were used for thin multilayer nanoindentation with numerical modelling. The results confirm the existence of the large elastically deformed zone, with a strong localization under the tip. Comparison between the experiments and numerical model shows direct connection between the tip radius and strain localization affecting the experiment, emphasizing importance of knowing the tip radius.
ROI constrained optimal online allocation in sponsored search
Authors: Xu Wenjian , Liu Shui , Chen Zulong , Zhou Ying , Li Liangyue , Wang Yangyang , Lu Quan , Ji Yuyang , Wan Jian 
Published: October 2024

AbstractSponsored search plays a major role in the revenue contribution of e-commerce platforms. Advertising systems are designed to maximize platform revenue, but other goals also need to be considered, such as user experience, advertiser utility, and how to achieve the long-term revenue goal. A key component of a sponsored search system is online allocation, which makes real-time decisions to match users’ search requests with relevant ad campaigns to maximize platform revenue within constraints such as campaign budgets. Although much progress has been made, most of the research work on allocation problem has focused on satisfying guaranteed deals for display ads, and those challenges for allocation problems in sponsored search are not properly addressed. In this paper, we develop a framework to solve the large-scale sponsored search ad allocation problem, consisting of two main parts. One is an optimization problem solved offline by a parameter-server based architecture, and the other is an online strategy to alleviate the conflict with the auction mechanism during online service. Comprehensive offline evaluation on real production data and online A/B testing on real production system have been made. The experimental results demonstrate that through better allocating user queries to appropriate ads, the proposed model can significantly increase the platform’s revenue without sacrificing advertisers’ ROI.