bluuebunny/crossref_metadata_2025_split huggingface dataset:
On the weekly cycle of atmospheric ammonia over European agricultural hotspots
Authors: Van Damme Martin , Clarisse Lieven , Stavrakou Trissevgeni , Wichink Kruit Roy , Sellekaerts Louise , Viatte Camille , Clerbaux Cathy , Coheur Pierre-François 
Published: July 2022

AbstractThe presence of a weekly cycle in the abundance of an atmospheric constituent is a typical fingerprint for the anthropogenic nature of its emission sources. However, while ammonia is mainly emitted as a consequence of human activities, a weekly cycle has never been detected in its abundances at large scale. We expose here for the first time the presence of a weekend effect in the NH3 total columns measured by the IASI satellite sounder over the main agricultural source regions in Europe: northwestern Europe (Belgium-the Netherlands-northwest Germany), the Po Valley, Brittany, and, to a lesser extent, the Ebro Valley. A decrease of 15% relative to the weekly mean is seen on Sunday–Monday observations in northwestern Europe, as a result of reduced NH3 emissions over the weekend. This is confirmed by in situ NH3 concentration data from the National Air Quality Monitoring Network in the Netherlands, where an average reduction of 10% is found around midnight on Sunday. The identified weekend effect presents a strong seasonal variability, with two peaks, one in spring and one in summer, coinciding with the two main (manure) fertilization periods. In spring, a reduction on Sunday–Monday up to 53 and 26% is found in the NH3 satellite columns and in situ concentrations, respectively, as fertilization largely drives atmospheric NH3 abundances at this time of the year.
Connecting nutritional facts with the traditional ranking of ethnobotanically used fodder grasses by local farmers in Central Punjab of Pakistan
Authors: Harun Nidaa , Chaudhry Abdul Shakoor , Shaheen Shabnum , Ahmad Mushtaq , Sahan Zeynep , Bashir Hira 
Published: July 2022

AbstractThe local farmers of Central Punjab, Pakistan have been using indigenous grasses as vital components of ruminant diets, but little is reported about their nutritional potential. Hence this study investigated nutritive potential of a selection of ethnobotanically important fodder grasses. Multiple nutritional parameters (proximate components, fibre fractions), secondary metabolites (phenolics, tannins) and in vitro digestibility values were determined. Furthermore, the legitimacy of ethnobotanical knowledge of local inhabitants about these grasses was also verified. The results suggested that majority (77%) of these grasses can be regarded as good quality fodders because of their high protein (169 g/kg) and good digestibility (457 g/kg) with moderate fibre (≤ 602 g/kg), lignin (≤ 50 g/kg) and secondary metabolites (total phenols ≤ 87 g/kg, total tannins ≤ 78 g/kg, condensed tannins ≤ 61 g/kg). Pearson correlation between nutritional parameters indicated that in vitro digestibility values were positively correlated with crude proteins (IVDMD, r = + 0.83 and IVOMD, r = + 0.83 respectively) and negatively correlated with fibre (NDF, r = − 0.91), ADF, r = − 0.84 and ADL, r = − 0.82) contents. Moreover, a positive relationship was identified between ethnobotanical knowledge and laboratory findings for studied grasses. Spearman correlation test showed that ranking of grasses based on ethnobotanical preferences were highly correlated (r values) with the laboratory results for CP (0.85), NDF (− 0.76), ADF (− 0.72) and ADL (− 0.62). The resilient complementarities between ethnobotanical preferences and nutritive analysis authenticate farmer’s traditional knowledge, which needed to be aligned with the corresponding scientific data. Farmers can use these findings for appropriate fodder selection and development of precise supplements for feeding ruminants within a sustainable and economically viable livestock industry for food security.
A Niclosamide-releasing hot-melt extruded catheter prevents Staphylococcus aureus experimental biomaterial-associated infection
Authors: Vazquez-Rodriguez Jesus Augusto , Shaqour Bahaa , Guarch-Pérez Clara , Choińska Emilia , Riool Martijn , Verleije Bart , Beyers Koen , Costantini Vivian J. A. , Święszkowski Wojciech , Zaat Sebastian A. J. , Cos Paul , Felici Antonio , Ferrari Livia 
Published: July 2022

AbstractBiomaterial-associated infections are a major healthcare challenge as they are responsible for high disease burden in critically ill patients. In this study, we have developed drug-eluting antibacterial catheters to prevent catheter-related infections. Niclosamide (NIC), originally an antiparasitic drug, was incorporated into the polymeric matrix of thermoplastic polyurethane (TPU) via solvent casting, and catheters were fabricated using hot-melt extrusion technology. The mechanical and physicochemical properties of TPU polymers loaded with NIC were studied. NIC was released in a sustained manner from the catheters and exhibited in vitro antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis. Moreover, the antibacterial efficacy of NIC-loaded catheters was validated in an in vivo biomaterial-associated infection model using a methicillin-susceptible and methicillin-resistant strain of S. aureus. The released NIC from the produced catheters reduced bacterial colonization of the catheter as well as of the surrounding tissue. In summary, the NIC-releasing hot-melt extruded catheters prevented implant colonization and reduced the bacterial colonization of peri-catheter tissue by methicillin sensitive as well as resistant S. aureus in a biomaterial-associated infection mouse model and has good prospects for preclinical development.
Activation function 1 of progesterone receptor is required for mammary development and regulation of RANKL during pregnancy
Authors: Lee Shi Hao , Yap Yeannie H. Y. , Lim Chew Leng , Woo Amanda Rui En , Lin Valerie C. L. 
Published: July 2022

AbstractProgesterone receptor (PGR) is a member of the nuclear receptor superfamily of transcription factors. It is critical for mammary stem cells expansion, mammary ductal branching and alveologenesis. The transcriptional activity of PGR is mainly mediated by activation functions AF1 and AF2. Although the discovery of AF1 and AF2 propelled the understanding of the mechanism of gene regulation by nuclear receptors, their physiological roles are still poorly understood. This is largely due to the lack of suitable genetic models. The present study reports gain or loss of AF1 function mutant mouse models in the study of mammary development. The gain of function mutant AF1_QQQ exhibits hyperactivity while the loss of function mutant AF1_FFF shows hypoactivity on mammary development. However, the involvement of AF1 is context dependent. Whereas the AF1_FFF mutation causes significant impairment in mammary development during pregnancy or in response to estrogen and progesterone, it has no effect on mammary development in nulliparous mice. Furthermore, Rankl, but not Wnt4 and Areg is a major target gene of AF1. In conclusion, PGR AF1 is a pivotal ligand-dependent activation domain critical for mammary development during pregnancy and it exerts gene specific effect on PGR regulated genes.
Combination of UV and green light synergistically enhances the attractiveness of light to green stink bugs Nezara spp
Authors: Endo Nobuyuki , Hironaka Mantaro , Honda Yoshiyuki , Iwamoto Tetsuhiro 
Published: July 2022

AbstractThe southern green stink bug Nezara viridula and its congener N. antennata are important agricultural pests worldwide. These species show positive phototaxis and their compound eyes have high sensitivity to UV and green lights. The attractiveness of monochromatic UV, green lights and combined UV and green light to stink bugs was investigated under field conditions. The number of stink bugs caught increased with the number of UV LEDs, but very few bugs were caught using green light, irrespective of the number of LEDs. However, the most stink bugs were caught when both colors were combined. These results indicate that monochromatic green light is less attractive to Nezara bugs, but when mixed with UV light, it synergistically enhances the attractiveness of UV light. This finding contributes to the construction of reliable and highly specific light traps to monitor Nezara bugs. The addition of green light hardly affected the attractiveness of the UV light to other insects, such as Anomala beetles, which are often caught in light traps. We conclude that the spectral composition of light that is attractive to nocturnal insects depends on the species, hence it is possible to make ecologically friendly light traps that are target specific.
Protective effects of rituximab on puromycin-induced apoptosis, loss of adhesion and cytoskeletal alterations in human podocytes
Authors: Jeruschke Stefanie , Alex Dana , Hoyer Peter Friedrich , Weber Stefanie 
Published: July 2022

AbstractPodocytes are highly specialized cells playing a key role in the filtration function of the kidney. A damaged podocyte ultrastructure is associated with a reorganization of the actin cytoskeleton and accompanied with a loss of adhesion to the glomerular basement membrane leading to proteinuria in many forms of glomerular diseases, e.g. nephrotic syndrome. If the first-line therapy with glucocorticoids fails, alternative immunosuppressive agents are used, which are known to have the potential to stabilize the actin cytoskeleton. A new option for preventing relapses in steroid dependent nephrotic syndrome is the monoclonal antibody rituximab, which, in addition to its B-cell depleting effect, is assumed to have direct effects on podocytes. We here provide data on the non-immunological off-target effects of the immunosuppressant rituximab on podocyte structure and dynamics in an in vitro puromycin aminonucleoside model of podocyte injury. A conditionally immortalized human podocyte cell line was used. Differentiated podocytes were treated with puromycin aminonucleoside and rituximab. Our studies focussed on analyzing the structure of the actin cytoskeleton, cellular adhesion and apoptosis using immunofluorescence staining and protein biochemistry methods. Treatment with rituximab resulted in a stabilization of podocyte actin stress fibers in the puromycin aminonucleoside model, leading to an improvement in cell adhesion. A lower apoptosis rate was observed after parallel treatment with puromycin aminonucleoside and rituximab visualized by reduced nuclear fragmentation. Consistent with this data, Western-blot analyses demonstrated that rituximab directly affects the caspase pathways by inhibiting the activation of Caspases-8, -9 and -3, suggesting that rituximab may inhibit apoptosis. In conclusion, our results indicate an important role of the immunosuppressant rituximab in terms of stability and morphogenesis of podocytes, involving apoptosis pathways. This could help to improve therapeutical concepts for patients with proteinuria mediated by diseased podocytes.
Conformational landscape of the yeast SAGA complex as revealed by cryo-EM
Authors: Vasyliuk Diana , Felt Joeseph , Zhong Ellen D. , Berger Bonnie , Davis Joseph H. , Yip Calvin K. 
Published: July 2022

AbstractSpt-Ada-Gcn5-Acetyltransferase (SAGA) is a conserved multi-subunit complex that activates RNA polymerase II-mediated transcription by acetylating and deubiquitinating nucleosomal histones and by recruiting TATA box binding protein (TBP) to DNA. The prototypical yeast Saccharomyces cerevisiae SAGA contains 19 subunits that are organized into Tra1, core, histone acetyltransferase, and deubiquitination modules. Recent cryo-electron microscopy studies have generated high-resolution structural information on the Tra1 and core modules of yeast SAGA. However, the two catalytical modules were poorly resolved due to conformational flexibility of the full assembly. Furthermore, the high sample requirement created a formidable barrier to further structural investigations of SAGA. Here, we report a workflow for isolating/stabilizing yeast SAGA and preparing cryo-EM specimens at low protein concentration using a graphene oxide support layer. With this procedure, we were able to determine a cryo-EM reconstruction of yeast SAGA at 3.1 Å resolution and examine its conformational landscape with the neural network-based algorithm cryoDRGN. Our analysis revealed that SAGA adopts a range of conformations with its HAT module and central core in different orientations relative to Tra1.
PDA modification and properties of α-AlH3
Authors: Qin Mingna , Yao Bingjie , Shi Qiang , Tang Wang , Chen Shaoli , Guo Tao , Wang Wei , Zhang Yan , Ge Zhongxue 
Published: July 2022

AbstractWe present a novel surface coating to resolve the stability of α-AlH3. Inspired by the strong chemical adhesion of mussels, the polymerization of dopamine was first introduced to coat α-AlH3 through simple situ polymerization. The α-AlH3 was used as a substrate. In-depth characterizations confirmed the formation of polydopamine (PDA) on the α-AlH3 surface. The coated α-AlH3 sample was characterized by X-ray diffraction X-ray photoelectron spectrometry and Scanning Electron Microscope. The results show that a strong PDA film is formed on the surface of α-AlH3, and PDA@α-AlH3 retains its primary morphology. The crystal form of α-AlH3 does not change after coating with PDA. The XPS analysis results show that N1 s appears on the material after coating with PDA, indicating that polydopamine is formed on the surface of α-AlH3. The moisture absorption tests show that the moisture absorption rate of α-AlH3 is greatly reduced after being coated with PDA. The excellent intact ability of PDA prevents α-AlH3 from reacting with water in air. The thermal stability of α-AlH3 before and after coating was analyzed by DSC. This work demonstrates the successful applications of dopamine chemistry to α-AlH3, thereby providing a potential method for metastable materials.
Structured assessment of modifiable lifestyle habits among patients with mental illnesses in primary care
Authors: Pikkemaat Miriam , Nymberg Veronica Milos , Nymberg Peter 
Published: July 2022

AbstractPatients with mental illness have an increased risk of cardiovascular morbidity. The Swedish-developed Health Dialogue is a pedagogical tool to individualize lifestyle counselling, used in specific age-groups to improve lifestyle habits and decrease mortality, but not tested specifically for patients with mental illness. Patients > 18 years old seeking primary care due to symptoms related to mental illness and diagnosed with depression, sleeping disorders, stress and anxiety, were included. A nurse-led health dialogue was conducted, focusing on lifestyle habits, anthropometric measurements, and blood samples, resulting in tailored advice regarding the individual’s risk profile. All 64 participants had lifestyle areas with increased risk level. Approximately 20% had elevated fasting glucose, blood pressure or cholesterol levels, and over 40% had highest risk level in Waist–Hip-Ratio. 30% were overweight, or physical inactive. The results suggest the need of a larger cohort study with long-term follow up, to establish potentially positive effects on wellbeing, and decreased cardiovascular risk in patients with mental illness.Clinical trial registration: The study was registered at ClinicalTrials.gov January 6th, 2022, registration number NCT05181254.
Predicting mortality among ischemic stroke patients using pathways-derived polygenic risk scores
Authors: Li Jiang , Chaudhary Durgesh , Griessenauer Christoph J. , Carey David J. , Zand Ramin , Abedi Vida 
Published: July 2022

AbstractWe aim to determine whether ischemic stroke(IS)-related PRSs are also associated with and further predict 3-year all-cause mortality. 1756 IS patients with European ancestry were randomly split into training (n = 1226) and testing (n = 530) groups with 3-year post-event observations. Univariate Cox proportional hazards regression model (CoxPH) was used for primary screening of individual prognostic PRSs. Only the significantly associated PRSs and clinical risk factors with the same direction for a causal relationship with IS were used to construct a multivariate CoxPH. Feature selection was conducted by the LASSO method. After feature selection, a prediction model with 11 disease-associated pathway-specific PRSs outperformed the base model, as demonstrated by a higher concordance index (0.751, 95%CI [0.693–0.809] versus 0.729, 95%CI [0.676–0.782]) in the testing sample. A PRS derived from endothelial cell apoptosis showed independent predictability in the multivariate CoxPH (Hazard Ratio = 1.193 [1.027–1.385], p = 0.021). These PRSs fine-tuned the model by better stratifying high, intermediate, and low-risk groups. Several pathway-specific PRSs were associated with clinical risk factors in an age-dependent manner and further confirmed some known etiologies of IS and all-cause mortality. In conclusion, Pathway-specific PRSs for IS are associated with all-cause mortality, and the integrated multivariate risk model provides prognostic value in this context.
Methods for stroke severity assessment by chart review in the Atherosclerosis Risk in Communities study
Authors: Koton Silvia , Patole Shalom , Carlson Julia M. , Haight Taylor , Johansen Michelle , Schneider Andrea L. C. , Pike James Russell , Gottesman Rebecca F. , Coresh Josef 
Published: July 2022

AbstractStroke severity is the most important predictor of post-stroke outcome. Most longitudinal cohort studies do not include direct and validated measures of stroke severity, yet these indicators may provide valuable information about post-stroke outcomes, as well as risk factor associations. In the Atherosclerosis Risk in Communities (ARIC) study, stroke severity data were retrospectively collected, and this paper outlines the procedures used and shares them as a model for assessment of stroke severity in other large epidemiologic studies. Trained physician abstractors, who were blinded to other clinical events, reviewed hospital charts of all definite/probable stroke events occurring in ARIC. In this analysis we included 1,198 ischemic stroke events occurring from ARIC baseline (1987–1989) through December 31, 2009. Stroke severity was categorized according to the National Institutes of Health Stroke Scale (NIHSS) score and classified into 5 levels: NIHSS ≤ 5 (minor), NIHSS 6–10 (mild), NIHSS 11–15 (moderate), NIHSS 16–20 (severe), and NIHSS > 20 (very severe). We assessed interrater reliability in a subgroup of 180 stroke events, reviewed independently by the lead abstraction physician and one of the four secondary physician abstractors. Interrater correlation coefficients for continuous NIHSS score as well as percentage of absolute agreement and Cohen Kappa Statistic for NIHSS categories were presented. Determination of stroke severity by the NIHSS, based on data abstracted from hospital charts, was possible for 97% of all ischemic stroke events. Median (25%-75%) NIHSS score was 5 (2–8). The distribution of NIHSS category was NIHSS ≤ 5 = 58.3%, NIHSS 6–10 = 24.5%, NIHSS 11–15 = 8.9%, NIHSS 16–20 = 4.7%, NIHSS > 20 = 3.6%. Overall agreement in the classification of severity by NIHSS category was present in 145/180 events (80.56%). Cohen’s simple Kappa statistic (95% CI) was 0.64 (0.55–0.74) and weighted Kappa was 0.79 (0.72–0.86). Mean (SD) NIHSS score was 5.84 (5.88), with a median score of 4 and range 0–31 for the lead reviewer (rater 1) and mean (SD) 6.16 (6.10), median 4.5 and range 0–36 in the second independent assessment (rater 2). There was a very high correlation between the scores reported in both assessments (Pearson r = 0.90). Based on our findings, we conclude that hospital chart-based retrospective assessment of stroke severity using the NIHSS is feasible and reliable.
Class I PI3K regulatory subunits control differentiation of dendritic cell subsets and regulate Flt3L mediated signal transduction
Authors: Thummar Keyur , Rathinam Chozha Vendan 
Published: July 2022

AbstractDendritic cells (DCs) play pivotal roles in initiating and shaping both innate and adaptive immune responses. The spatiotemporal expression of transcription factor networks and activation of specific signal transduction pathways determine the specification, distribution and differentiation of DC subsets. Even though pioneering studies have established indispensable roles for specific catalytic subunits (p110δ and p110γ) in immune cells, functions of the regulatory subunits, particularly of Class I PI3K, within the hematopoietic system remain incompletely understood. In the study presented here, we deleted the key regulatory subunits—p85α and p85β of the Class IA PI3K in hematopoietic cells and studied its impact on DC differentiation. Our studies identify that a deficiency of p85 causes increased differentiation of conventional DC (cDC) 2 and plasmacytoid DC (pDC) subsets in the spleen. On the other hand, DC numbers in the bone marrow (BM), thymus and lymph nodes were decreased in p85 mutant mice. Analysis of DC-specific progenitors and precursors indicated increased numbers in the BM and spleen of p85 deficient mice. In-vitro differentiation studies demonstrated augmented DC-differentiation capacities of p85 deficient BM cells in the presence of GM-CSF and Flt3L. BM chimera studies established that p85 deficiency affects DC development through cell intrinsic mechanisms. Molecular studies revealed increased proliferation of DCs and common DC progenitors (CDPs) in the absence of p85 and altered signal transduction pathways in p85 mutant DC subsets in response to Flt3L. In essence, data presented here, for the first time, unequivocally establish that the P85α subunit of class IA PI3Ks has an indispensable role in the development and maintenance of DCs.
Determination of starting dose of the T cell-redirecting bispecific antibody ERY974 targeting glypican-3 in first-in-human clinical trial
Authors: Komatsu Shun-ichiro , Kayukawa Yoko , Miyazaki Yoko , Kaneko Akihisa , Ikegami Hisashi , Ishiguro Takahiro , Nakamura Mikiko , Frings Werner , Ono Natsuki , Sakata Kiyoaki , Fujii Toshihiko , Kishishita Shohei , Kitazawa Takehisa , Endo Mika , Sano Yuji 
Published: July 2022

AbstractCurrently, ERY974, a humanized IgG4 bispecific T cell-redirecting antibody recognizing glypican-3 and CD3, is in phase I clinical trials. After a first-in-human clinical trial of an anti-CD28 agonist monoclonal antibody resulting in severe life-threatening adverse events, the minimal anticipated biological effect level approach has been considered for determining the first-in-human dose of high-risk drugs. Accordingly, we aimed to determine the first-in-human dose of ERY974 using both the minimal anticipated biological effect level and no observed adverse effect level approaches. In the former, we used the 10% effective concentration value from a cytotoxicity assay using the huH-1 cell line with the highest sensitivity to ERY974 to calculate the first-in-human dose of 4.9 ng/kg, at which maximum drug concentration after 4 h of intravenous ERY974 infusion was equal to the 10% effective concentration value. To determine the no observed adverse effect level, we conducted a single-dose study in cynomolgus monkeys that were intravenously infused with ERY974 (0.1, 1, and 10 μg/kg). The lowest dose of 0.1 μg/kg was determined as the no observed adverse effect level, and the first-in-human dose of 3.2 ng/kg was calculated, considering body surface area and species difference. For the phase I clinical trial, we selected 3.0 ng/kg as a starting dose, which was lower than the first-in-human dose calculated from both the no observed adverse effect level and minimal anticipated biological effect level. Combining these two methods to determine the first-in-human dose of strong immune modulators such as T cell-redirecting antibodies would be a suitable approach from safety and efficacy perspectives.Clinical trial registration: JapicCTI-194805/NCT05022927.