bluuebunny/crossref_metadata_2025_split huggingface dataset:
Systematic decoding of cis gene regulation defines context-dependent control of the multi-gene costimulatory receptor locus in human T cells
Authors: Mowery Cody T. , Freimer Jacob W. , Chen Zeyu , Casaní-Galdón Salvador , Umhoefer Jennifer M. , Arce Maya M. , Gjoni Ketrin , Daniel Bence , Sandor Katalin , Gowen Benjamin G. , Nguyen Vinh , Simeonov Dimitre R. , Garrido Christian M. , Curie Gemma L. , Schmidt Ralf , Steinhart Zachary , Satpathy Ansuman T. , Pollard Katherine S. , Corn Jacob E. , Bernstein Bradley E. , Ye Chun Jimmie , Marson Alexander 
Published: May 2024

AbstractCis-regulatory elements (CREs) interact with trans regulators to orchestrate gene expression, but how transcriptional regulation is coordinated in multi-gene loci has not been experimentally defined. We sought to characterize the CREs controlling dynamic expression of the adjacent costimulatory genes CD28, CTLA4 and ICOS, encoding regulators of T cell-mediated immunity. Tiling CRISPR interference (CRISPRi) screens in primary human T cells, both conventional and regulatory subsets, uncovered gene-, cell subset- and stimulation-specific CREs. Integration with CRISPR knockout screens and assay for transposase-accessible chromatin with sequencing (ATAC-seq) profiling identified trans regulators influencing chromatin states at specific CRISPRi-responsive elements to control costimulatory gene expression. We then discovered a critical CCCTC-binding factor (CTCF) boundary that reinforces CRE interaction with CTLA4 while also preventing promiscuous activation of CD28. By systematically mapping CREs and associated trans regulators directly in primary human T cell subsets, this work overcomes longstanding experimental limitations to decode context-dependent gene regulatory programs in a complex, multi-gene locus critical to immune homeostasis.
Characterization of two novel Salmonella phages having biocontrol potential against Salmonella spp. in gastrointestinal conditions
Authors: Zhang Yujie , Chu Mackenna , Liao Yen-Te , Salvador Alexandra , Wu Vivian C. H. 
Published: May 2024

AbstractSalmonella is a primary enteric pathogen related to the contamination of poultry and other food products in numerous foodborne outbreaks. The continuous emergence of multidrug-resistant bacteria has become a serious issue due to the overuse of antibiotics. Hence, lytic phages are considered alternative biocontrol agents against these bacterial superbugs. Here, two Salmonella phages—S4lw and D5lw—were subjected to genomic and biological characterization and further encapsulated to improve the stability under acidic conditions mimicking gastrointestinal conditions. The two lytic phages, S4lw and D5lw, taxonomically belong to new species under the Guernseyvirinae and Ackermannviridae families, respectively. Each phage showed antimicrobial activities against diverse Salmonella spp., such as S. Enteritidis and S. Typhimurium, achieving 1.7–3.4 log reduction after 2–6 h of treatment. The phage cocktail at a multiplicity of infection (MOI) of 100 or 1000 completely inhibited these Salmonella strains for at least 14 h at 25 °C. Additionally, the bead-encapsulated phage cocktail could withstand low pH and different simulated gut environments for at least 1 h. Overall, the newly isolated phages can potentially mitigate Salmonella spp. under the gastrointestinal environments through encapsulation and may be further applied via oral administration to resolve common antimicrobial resistance issues in the poultry production chain.
Aripiprazole as protector against COVID-19 mortality
Authors: Loucera-Muñecas C. , Canal-Rivero M. , Ruiz-Veguilla M. , Carmona R. , Bostelmann G. , Garrido-Torres N. , Dopazo J. , Crespo-Facorro B. 
Published: May 2024

AbstractThe relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18 years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15 days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 [adjusted odds ratio (OR) = 0.86; 95% CI, 0.79–0.93, multiple-testing adjusted p-value < 0.05]. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.
The impact of presentation modes on mental rotation processing: a comparative analysis of eye movements and performance
Authors: Stark Philipp , Bozkir Efe , Sójka Weronika , Huff Markus , Kasneci Enkelejda , Göllner Richard 
Published: May 2024

AbstractMental rotation is the ability to rotate mental representations of objects in space. Shepard and Metzler’s shape-matching tasks, frequently used to test mental rotation, involve presenting pictorial representations of 3D objects. This stimulus material has raised questions regarding the ecological validity of the test for mental rotation with actual visual 3D objects. To systematically investigate differences in mental rotation with pictorial and visual stimuli, we compared data of $$N=54$$

N
=
54

university students from a virtual reality experiment. Comparing both conditions within subjects, we found higher accuracy and faster reaction times for 3D visual figures. We expected eye tracking to reveal differences in participants’ stimulus processing and mental rotation strategies induced by the visual differences. We statistically compared fixations (locations), saccades (directions), pupil changes, and head movements. Supplementary Shapley values of a Gradient Boosting Decision Tree algorithm were analyzed, which correctly classified the two conditions using eye and head movements. The results indicated that with visual 3D figures, the encoding of spatial information was less demanding, and participants may have used egocentric transformations and perspective changes. Moreover, participants showed eye movements associated with more holistic processing for visual 3D figures and more piecemeal processing for pictorial 2D figures.
Electrospun nanofiber mats caged the mammalian macrophages on their surfaces and prevented their inflammatory responses independent of the fiber diameter
Authors: Ayaz Furkan , Demir Didem , Bölgen Nimet 
Published: May 2024

AbstractPoly-ε-caprolactone (PCL) has been widely used as biocompatible materials in tissue engineering. They have been used in mammalian cell proliferation to polarization and differentiation. Their modified versions had regulatory activities on mammalian macrophages in vitro. There are also studies suggesting different nanofiber diameters might alter the biological activities of these materials. Based on these cues, we examined the inflammatory activities and adherence properties of mammalian macrophages on electrospun PCL nanofibrous scaffolds formed with PCL having different nanofiber diameters. Our results suggest that macrophages could easily attach and get dispersed on the scaffolds. Macrophages lost their inflammatory cytokine TNF and IL6 production capacity in the presence of LPS when they were incubated on nanofibers. These effects were independent of the mean fiber diameters. Overall, the scaffolds have potential to be used as biocompatible materials to suppress excessive inflammatory reactions during tissue and organ transplantation by caging and suppressing the inflammatory cells.
Investigating surface proteins and antibody combinations for detecting circulating tumor cells of various sarcomas
Authors: Le Minh-Chau N. , Smith Kierstin A. , Dopico Pablo J. , Greer Beate , Alipanah Morteza , Zhang Yang , Siemann Dietmar W. , Lagmay Joanne P. , Fan Z. Hugh 
Published: May 2024

AbstractCirculating tumor cells (CTCs) have gathered attention as a biomarker for carcinomas. However, CTCs in sarcomas have received little attention. In this work, we investigated cell surface proteins and antibody combinations for immunofluorescence detection of sarcoma CTCs. A microfluidic device that combines filtration and immunoaffinity using gangliosides 2 and cell surface vimentin (CSV) antibodies was employed to capture CTCs. For CTC detection, antibodies against cytokeratins 7 and 8 (CK), pan-cytokeratin (panCK), or a combination of panCK and CSV were used. Thirty-nine blood samples were collected from 21 patients of various sarcoma subtypes. In the independent samples study, samples were subjected to one of three antibody combination choices. Significant difference in CTC enumeration was found between CK and panCK + CSV, and between panCK and panCK + CSV. Upon stratification of CK+ samples, those of metastatic disease had a higher CTC number than those of localized disease. In the paired samples study involving cytokeratin-positive sarcoma subtypes, using panCK antibody detected more CTCs than CK. Similarly, for osteosarcoma, using panCK + CSV combination resulted in a higher CTC count than panCK. This study emphasized deliberate selection of cell surface proteins for sarcoma CTC detection and subtype stratification for studying cancers as heterogeneous as sarcomas.
3D imaging of SARS-CoV-2 infected hamster lungs by X-ray phase contrast tomography enables drug testing
Authors: Reichmann Jakob , Sarrazin Clement , Schmale Sebastian , Blaurock Claudia , Balkema-Buschmann Anne , Schmitzer Bernhard , Salditt Tim 
Published: May 2024

AbstractX-ray Phase Contrast Tomography (XPCT) based on wavefield propagation has been established as a high resolution three-dimensional (3D) imaging modality, suitable to reconstruct the intricate structure of soft tissues, and the corresponding pathological alterations. However, for biomedical research, more is needed than 3D visualisation and rendering of the cytoarchitecture in a few selected cases. First, the throughput needs to be increased to cover a statistically relevant number of samples. Second, the cytoarchitecture has to be quantified in terms of morphometric parameters, independent of visual impression. Third, dimensionality reduction and classification are required for identification of effects and interpretation of results. To address these challenges, we here design and implement a novel integrated and high throughput XPCT imaging and analysis workflow for 3D histology, pathohistology and drug testing. Our approach uses semi-automated data acquisition, reconstruction and statistical quantification. We demonstrate its capability for the example of lung pathohistology in Covid-19. Using a small animal model, different Covid-19 drug candidates are administered after infection and tested in view of restoration of the physiological cytoarchitecture, specifically the alveolar morphology. To this end, we then use morphometric parameter determination followed by a dimensionality reduction and classification based on optimal transport. This approach allows efficient discrimination between physiological and pathological lung structure, thereby providing quantitative insights into the pathological progression and partial recovery due to drug treatment. Finally, we stress that the XPCT image chain implemented here only used synchrotron radiation for validation, while the data used for analysis was recorded with laboratory $$\mu$$
μ
CT radiation, more easily accessible for pre-clinical research.
Valorization of Eichhornia crassipes for the production of cellulose nanocrystals further investigation of plethoric biobased resource
Authors: Hemida Mohamed H. , Moustafa Hesham , Mehanny Sherif , Morsy Mohamed , Abd EL Rahman Eid N. , Ibrahim Mohamed M. 
Published: May 2024

AbstractChemical processing is among the significant keys to tackle agro-residues utilization field, aiming to obtain value-added materials. Extraction of cellulose nanocrystals (CNCs) is an emerging route to valorize lignocellulosic wastes into high value particles. In this investigation, effect of acidic hydrolysis duration was monitored on size and morphology of obtained crystals; namely: CNCs from Nile roses fibers (NRFs) (Eichhornia crassipes). Different acidic hydrolysis duration range or different characterization techniques set this article apart from relevant literature, including our group research articles. The grinded NRFs were firstly subjected to alkaline and bleaching pretreatments, then acid hydrolysis process was carried out with varied durations ranging from 5 to 30 min. Microcrystalline cellulose (MCC) was used as reference for comparison with NRFs based samples. The extracted CNCs samples were investigated using various techniques such as scanning electron microscopy (SEM), Atomic force microscopy (AFM), Raman spectroscopy, and thermogravimetric (TGA) analysis. The figures gotten from SEM and AFM depicted that NRFs based CNCs appeared as fibril-like shapes, with reduced average size when the NRFs underwent pulping and bleaching processes. This was indicated that the elimination of hemicellulose and lignin components got achieved successfully. This outcome was proven by chemical composition measurements and TGA/DTG curves. On the other hand, AFM-3D images indicated that CNCs topology and surface roughness were mostly affected by increasing hydrolysis durations, besides smooth and homogeneous surfaces were noticed. Moreover, Raman spectra demonstrated that the particle size and crystallinity degree of NRFs based CNCs can be affected by acidic hydrolysis durations and optimum extraction time was found to be 10 min. Thermal stability of extracted CNCs-NRFs and CNCs-MCC was measured by TGA/DTG and the kinetic models were suggested to identify the kinetic parameters of the thermal decomposition of CNCs for each acid hydrolysis duration. Increasing hydrolysis duration promoted thermal stability, particularly for NRFs based CNCs. Results showcased in this article add new perspective to Nile rose nanocellulose and pave down the way to fabricate NRFs based humidity nano-sensors.
DFT study on CO2 capture using boron, nitrogen, and phosphorus-doped C20 in the presence of an electric field
Authors: Rezaee Parham , Asl Shervin Alikhah , Javadi Mohammad Hasan , Rezaee Shahab , Morad Razieh , Akbari Mahmood , Arab Seyed Shahriar , Maaza Malik 
Published: May 2024

AbstractBurning fossil fuels emits a significant amount of $$\hbox {CO}_{2}$$

CO
2

, causing climate change concerns. $$\hbox {CO}_{2}$$

CO
2

Capture and Storage (CCS) aims to reduce emissions, with fullerenes showing promise as $$\hbox {CO}_{2}$$

CO
2

adsorbents. Recent research focuses on modifying fullerenes using an electric field. In light of this, we carried out DFT studies on some B, N, and P doped $$\hbox {C}_{20}$$

C
20

($$C_{20-n}X_n$$

C

20
-
n

X
n

, n = 0, 1, 2, and 3; X = B, N, and P) in the absence and presence of an electric field in the range of 0-0.02 a.u.. The cohesive energy was calculated to ensure their thermodynamic stability showing, that despite having lesser cohesive energies than $$\hbox {C}_{20}$$

C
20

, they appear in a favorable range. Moreover, the charge distribution for all structures was depicted using the ESP map. Most importantly, we evaluated the adsorption energy, height, and $$\hbox {CO}_{2}$$

CO
2

angle, demonstrating the B and N-doped fullerenes had the stronger interaction with $$\hbox {CO}_{2}$$

CO
2

, which by far exceeded $$\hbox {C}_{20}$$

C
20

’s, improving its physisorption to physicochemical adsorption. Although the adsorption energy of P-doped fullerenes was not as satisfactory, in most cases, increasing the electric field led to enhancing $$\hbox {CO}_{2}$$

CO
2

adsorption and incorporating chemical attributes to $$\hbox {CO}_{2}$$

CO
2

-fullerene interaction. The HOMO–LUMO plots were obtained by which we discovered that unlike the P-doped $$\hbox {C}_{20}$$

C
20

, the surprising activity of B and N-doped $$\hbox {C}_{20}$$

C
20

s against $$\hbox {CO}_{2}$$

CO
2

originates from a high concentration of the HOMO-LUMO orbitals on B, N and neighboring atoms. In the present article, we attempt to introduce more effective fullerene-based materials for $$\hbox {CO}_{2}$$

CO
2

adsorption as well as strategies to enhance their efficiency and revealing adsorption nature over B, N, and P-doped fullerenes and in the end, hope to encourage more experimental research on these materials within growing electric field for $$\hbox {CO}_{2}$$

CO
2

capture in the future.
Transmural collaborative care model for the review of antipsychotics: a feasibility study of a complex intervention
Authors: Jakobs Kirsti M. , van den Brule-Barnhoorn Karlijn J. , van Lieshout Jan , Janzing Joost G. E. , Cahn Wiepke , van den Muijsenbergh Maria , Biermans Marion C. J. , Bischoff Erik W. M. A. 
Published: May 2024

AbstractGeneral practitioners (GPs) are often unaware of antipsychotic (AP)-induced cardiovascular risk (CVR) and therefore patients using atypical APs are not systematically monitored. We evaluated the feasibility of a complex intervention designed to review the use of APs and advise on CVR-lowering strategies in a transmural collaboration. A mixed methods prospective cohort study in three general practices in the Netherlands was conducted in 2021. The intervention comprised three steps: a digital information meeting, a multidisciplinary meeting, and a shared decision-making visit to the GP. We assessed patient recruitment and retention rates, advice given and adopted, and CVR with QRISK3 score and mental state with MHI-5 at baseline and three months post-intervention. GPs invited 57 of 146 eligible patients (39%), of whom 28 (19%) participated. The intervention was completed by 23 (82%) and follow-up by 18 participants (64%). At the multidisciplinary meeting, 22 (78%) patients were advised to change AP use. Other advice concerned medication (other than APs), lifestyle, monitoring, and psychotherapy. At 3-months post-intervention, 41% (28/68) of this advice was adopted. Our findings suggest that this complex intervention is feasible for evaluating health improvement in patients using AP in a trial.
Beneficial effect of heat-killed Lactiplantibacillus plantarum L-137 on intestinal barrier function of rat small intestinal epithelial cells
Authors: Watanabe Mototsugu , Nakai Hiroko , Ohara Tatsuya , Kawasaki Kengo , Murosaki Shinji , Hirose Yoshitaka 
Published: May 2024

AbstractHeat-killed Lactiplantibacillus plantarum L-137 (HK L-137) has been suggested to enhance the intestinal barrier in obese mice, leading to improvement of metabolic abnormalities and adipose tissue inflammation, and in healthy humans with overweight, leading to improvement of systemic inflammation. However, its detailed mechanism of action has not been clarified. Therefore, this study investigated the effects of HK L-137 on the permeability of rat small intestinal epithelial IEC-6 cells, tight junction-related gene and protein expression and localization, and intracellular signaling pathways involved in barrier function. Treatment of IEC-6 cells with HK L-137 for 26 h significantly reduced the permeability to fluorescein isothiocyanate-dextran (FD-4). HK L-137 also increased gene and protein expression of zonula occludens-1 (ZO-1), an important tight junction protein, without affecting the localization. Furthermore, inhibition of the extracellular signal-regulated kinase (ERK)1/2 pathway in IEC-6 cells canceled the HK L-137-related reduction in permeability to FD-4. Phosphorylation of ERK in IEC-6 cells was induced 15 min after the addition of HK L-137. These results suggest that HK L-137 reduces intestinal permeability partly through activating the ERK pathway and increasing expression of the ZO-1 gene and protein. Enhancement of intestinal barrier function with HK L-137 might be effective in preventing and treating leaky gut, for which no specific therapeutic tool has been established.
Locating carbon neutral mobility hubs using artificial intelligence techniques
Authors: Bencekri Madiha , Kim Sion , Fan Yee Van , Lee Seungjae 
Published: May 2024

AbstractThis research proposes a novel, three-tier AI-based scheme for the allocation of carbon–neutral mobility hubs. Initially, it identified optimal sites using a genetic algorithm, which optimized travel times and achieved a high fitness value of 77,000,000. Second, it involved an Ensemble-based suitability analysis of the pinpointed locations, using factors such as land use mix, densities of population and employment, and proximities of parking, biking, and transit. Each factor is weighted by its carbon emissions contribution, then incorporated into a suitability analysis model, generating scores that guide the final selection of the most suitable mobility hub sites. The final step employs a traffic assignment model to evaluate these sites’ environmental and economic impacts. This includes measuring reductions in vehicle kilometers traveled and calculating other cost savings. Focusing on addressing sustainable development goals 11 and 9, this study leverages advanced techniques to enhance transportation planning policies. The Ensemble model demonstrated strong predictive accuracy, achieving an R-squared of 95% in training and 53% in testing. The identified hubs’ sites reduced daily vehicle travel by 771,074 km, leading to annual savings of 225.5 million USD. This comprehensive approach integrates carbon-focused analyses and post-assessment evaluations, thereby offering a comprehensive framework for sustainable mobility hub planning.
Genetic relationships and introgression events between wild and cultivated grapevines (Vitis vinifera L.): focus on Italian Lambruscos
Authors: Schneider A. , Ruffa P. , Tumino G. , Fontana M. , Boccacci P. , Raimondi S. 
Published: May 2024

AbstractResearch efforts on genomic structure and ecology of wild populations of Vitis vinifera L. offer insights on grape domestication processes and on the assortment evolution of the cultivated forms. Attention is also paid to the origin of traditional, long-cultivated varieties, often producing renowned and valuable wines. The genetic relationships between 283 Vitis vinifera cultivated varieties (subsp. sativa) and 65 individuals from 9 populations of the sylvestris subspecies mainly from northern Italy were explored by means of molecular markers (27 nuclear and 4 chloroplastic microsatellites). Several episodes of contamination of the wild germplasm by the pollen of specific grape cultivars were detected, implying concern for maintaining the purity of the wild form. At the same time, events of introgression from the wild subspecies resulted playing a crucial role in the emergence of several cultivated varieties with a clear admixed genome ancestry sativa-sylvestris. These included Lambruscos originated from the flat areas crossed by the Po and Adige rivers in northern Italy, while other cultivars still called Lambrusco but typical of hilly areas did not show the same admixed genome. Historical and ecological evidences suggesting an adaptative recent post-domestication process in the origin of several Italian Lambruscos are discussed.