bluuebunny/crossref_metadata_2025_split huggingface dataset:
Computational modeling and synthesis of Pyridine variants of Benzoyl-Phenoxy-Acetamide with high glioblastoma cytotoxicity and brain tumor penetration
Authors: IV Charles Ingraham , Stalinska Joanna , Carson Sean , Colley Susan , Rak Monika , Lassak Adam , Reiss Krzysztof , Jursic Branko 
Published: April 2023

Abstract
Glioblastomas are highly aggressive brain tumors for which therapeutic options are very limited. In a quest for new anti-glioblastoma drugs, we focused on specific structural modifications of benzoyl-phenoxy-acetamide (BPA) present in a common lipid-lowering drug, fenofibrate, and in our first prototype glioblastoma drug, PP1. Here, we propose extensive computational analyses to improve selection of the most effective glioblastoma drug candidates. Initially over 100 structural BPA variations were analyzed and their physicochemical properties such as water solubility (-logS), calculated partition coefficient (ClogP), probability for BBB crossing (BBB_SCORE), probability for CNS penetration (CNS-MPO) and calculated cardiotoxicity (hERG), were evaluated. This integrated approach allowed us to select pyridine variants of BPA that show improved BBB penetration, water solubility, and low cardiotoxicity. Herein the top 24 compounds were synthesized and analyzed in cell culture. Six of them demonstrated glioblastoma toxicity with IC50 ranging from 0.59 to 3.24mM. Importantly, one of the compounds, HR68, accumulated in the brain tumor tissue at 3.7+/-0.5mM, which exceeds its glioblastoma IC50 (1.17mM) by over 3-fold.
Thin Nacreous Films with Enhanced Mechanical Properties for Highly Efficient Durable Radiative Cooling
Authors: Deng Hua , Xiong Lianhu , Wei Yun , Chen Chuanliang , Chen Xin , Fu Qiang 
Published: April 2023

Abstract
Passive daytime radiative cooling (PDRC) is a promising path to tackle energy, environment and security issues originated from global warming. However, the contradiction between optical properties (especially desired high solar reflectivity) and other applicable performance (e.g. strength, modulus, durability and thickness) limits the practical applications of PDRC. Herein, we demonstrate a nacreous PDRC film integrating aramid nanofibers (ANFs) network with core-shell TiO2-coated mica microplatelet (Mica@TiO2) scatterers via a “Solvent exchange-Reprotonation” processing strategy for enhancing mechanical strength and durability without compromising optical performance. The slow but complete two-step protonation transition regulates the three-dimensional dendritic ANFs network with strong fibrillar joints, where overloaded scatterers (> 50 wt%) are stably grasped and anchored in alignment, thereby resulting in a high strength of ~ 112 MPa. Meanwhile, the strong backward scattering excited by multiple interfaces of core-shell Mica@TiO2 and interlamellar micropores guarantees a balanced reflectivity (~ 92%) and thickness (~ 25 µm). Notably, such design renders excellent environmental durability, including high temperature, UV radiation, water rinsing and scratch damage, to meet the realistic requirements. The practical PDRC cooling capability is further revealed by outdoor tests where attainable subambient temperature drops are ~ 3.35 ℃ for daytime and ~ 6.11 ℃ for nighttime, thus providing possibility for thermal protection of vehicles, mobile phones and cables exposed to direct sunlight. Consequently, both the cooling capacity which equals those of state-of-the-art PDRC designs and comprehensive outdoor-services performance, greatly push PDRC towards practical applications.
Objective Cognitive Functioning in Patients with Stress-Related Disorders: A Cross-Sectional Study Using Remote Digital Cognitive Testing
Authors: Föyen Ludwig Franke , Sennerstam Victoria , Kontio Evelina , Lekander Mats , Hedman-Lagerlöf Erik , Lindsäter Elin 
Published: April 2023

Abstract
Background

Patients with stress-related mental disorders often report cognitive impairment, but studies investigating objective cognitive impairment in patients with stress-related disorders have produced inconsistent findings.

Aim

The primary aim of this study was to investigate objective cognitive functioning in patients diagnosed with the stress-related disorders adjustment disorder or exhaustion disorder, compared to a healthy normative group. Secondary aims were to conduct subgroup analyses of cognitive functioning between the diagnostic groups and explore associations between self-reported symptoms and cognitive functioning.

Methods

Cognitive test results on a digitally self-administered cognitive test battery from 266 patients (adjustment disorder, n = 131; exhaustion disorder, n = 135) were cross-sectionally compared with results from a healthy normative group (N =184 to 692) using one-tailed t-tests. ANOVAs were conducted for subgroup analyses, and regression analyses for associations between self-reported symptoms and cognitive functioning. Effect sizes were calculated.

Results

Patients performed significantly worse than the normative group on all measures with small to moderate effect sizes ranging from d = -.13 to -.57. Those diagnosed with exhaustion disorder performed worse than norms on more measures than did patients with adjustment disorder, but no significant differences between diagnostic groups were found on any measure. Self-reported memory impairment was weakly associated with one of two memory measures. No clear associations between self-reported burnout symptoms and objective cognitive functioning were found.

Conclusions

This study adds to the literature indicative of small to moderate objective cognitive impairments in patients diagnosed with stress-related mental disorders. Further exploration into mechanisms of cognitive functioning in different populations is needed for development of theoretical models that may explain the weak correlation between self-reported symptoms and objective measures.

Study registration

This study was pre-registered on Open Science Framework (osf.io) with DOI 10.17605/OSF.IO/TQXZV
Microbiome-metabolomics analysis reveals abatement effects of itaconic acid on odorous compound production
Authors: Zhu Xin , Zhang Yinhang , Liu Haiying , Yang Guiqin , Li Lin 
Published: April 2023

Abstract
Background: Public complaints concerning odor emissions from intensive livestock and poultry farms continue to grow, as nauseous odorous compounds have adverse impacts on the environment and human health. Itaconic acid is a metabolite from the citric acid cycle of the host and shows volatile odor-reducing effects during animal production operations. However, the specific role of itaconic acid in decreasing intestinal odorous compound production remains unclear. A total of 360 one-day-old chicks were randomly divided into 6 treatments: control group (basal diet) and itaconic acid groups (basal diet + 2, 4, 6, 8 and 10 g/kg itaconic acid, respectively). The feeding experiment lasted for 42 d.
Results: Dietary itaconic acid supplementation linearly and quadratically decreased (P < 0.05) the cecal concentrations of indole and skatole but did not affect (P> 0.05) those of lactic, acetic, propionic and butyric acids. The cecal microbial shift was significant in response to 6 g/kg itaconic acid supplementation, in that the abundances of Firmicutes, Ruminococcus and Clostridiumwas increased (P < 0.05), while that of Bacteroidetes, Escherichia-Shigella and Bacteroides were decreased (P < 0.05), indicative of increased microbial richness and diversity. Furthermore, a total of 35 significantly (P < 0.05) modified metabolites were obtained by metabolomic analysis. Itaconic acid decreased (P < 0.05) the levels of nicotinic acid, nicotinamide, glucose-6-phosphate, fumatic acid and malic acid and increased (P< 0.05) 5-methoxytroptomine, dodecanoic acid and stearic acid, which are connected with the glycolytic pathway, citrate acid cycle and tryptophan metabolism. Correlation analysis indicated significant correlations between the altered cecal microbiota and metabolites; Firmicutes, Ruminococcus and Clostridiumwere shown to be negatively correlated with indole and skatole production, while Bacteroidetes, Escherichia-Shigellaand Bacteroides were positively correlated with indole and skatole production.
Conclusions: Itaconic acid decreased cecal indole and skatole levels and altered the microbiome and metabolome in favor of odorous compound reduction. These findings provide new insight into the role of itaconic acid and expand its application potential in broilers.
Malignant Otitis Externa in an Adult Diabetic Patient Caused by Escherichia coli: a Case Report
Authors: Batinović Franko , Kujundžić Sanja Lovrić , Golec Nikolina , Sunara Davor 
Published: April 2023

Abstract
Introduction: Malignant otitis externa (MOE) is commonly presented as invasive external otitis resistant to local treatment that classically affects elderly diabetic patients.
Case presentation: We presented a 55-year-old man with a history of diabetes mellitus (DM) and ear scratching, initially manifesting with left-sided nocturnal otalgia, purulent otorrhea, and external auditory canal (EAC) edema. A diagnosis of MOE was made based on Levenson's criteria and radiological findings. Antibiotics were given intravenously based on bacterial cultures from ear swabs, with repeated cultures growing Escherichia coli (E. coli). The patient's MOE caused by E. coli improved after two months of ear toilets, DM management, parenteral and local antibiotics, and hyperbaric oxygen therapy (HBOT). We detected that the MOE was caused by self-inflicted local trauma to the EAC on the same side as the dominant hand.
Conclusion: The isolation of E. coli from the EAC as the causative organism of MOE with a favorable response to HBOT as an adjunction to antibiotic therapy was previously unreported and could present a novel treatment strategy.
Physical mapping of the wheat genes in low recombination regions: Radiation Hybrid mapping of the C-locus
Authors: Kajla Anmol , Schoen Adam , Paulson Carl , Yadav Inderjit Singh , Neelam Kumari , Riera-Lizarazu Oscar , Leonard Jeff , Gill Bikram , Venglat Prakash , Datla Raju , Poland Jesse , Coleman Gary , Rawat Nidhi , Tiwari Vijay 
Published: April 2023

Abstract
Mapping wheat genes, in the centromeric and pericentromeric regions (~2/3rd of a given chromosome), poses a formidable challenge due to highly suppressed recombination. Using an example of compact spike locus (C-locus), this study provides an approach to precisely map wheat genes in the pericentromeric and centromeric regions that house ~30% of wheat genes. In Club-wheat, spike compactness is controlled by the dominant C-locus, but previous efforts have failed to localize it, on a particular arm of chromosome 2D. We integrated radiation hybrid (RH) and high-resolution genetic mapping to locate C-locus on the short arm of chromosome 2D. Flanking markers of the C-locus span a physical distance of 11.0 Mb (231.0-242 Mb interval) and contain only 11 high-confidence annotated genes. This work demonstrates the value of this integrated strategy in mapping dominant genes in the low-recombination regions of the wheat genome. A comparison of the mapping resolutions of the RH and genetic maps using common anchored markers indicated that the RH map provides ~9 times better resolution that the genetic map even with much smaller population size. This study provides a broadly applicable approach to fine-map wheat genes in regions of suppressed recombination.
Authentic Leadership and Nurses’ Caring Behavior in China: The Mediating Effect of Psychological Capital
Authors: Zhang Guo-wen , Zhang Xiao-hong , Lin Wen-feng , Chen Juan-juan , Li Hui-ping , Sun Li-qin , Cheng Bao-zhen , Ding Hui , Song Gui-qi 
Published: April 2023

Abstract
Background An increasing number of studies are indicating that caring behavior is an important indicator of quality nursing care and positive outcomes for patients and nurses. For this reason, identifying the factors that predict nurses’ caring behavior is crucial. Studies showed authentic leadership and psychological capital are the predictors of nurses’ caring behaviors, but the three relationships are still unclear.Methods An online survey was conducted in December 2021 with 3,495 registered nurses working in Ahhui Province, China. The Authentic Leadership Questionnaire, Psychological Capital Questionnaire, and Caring Behavior Inventory were used in this study. Structural Equation Modeling (SEM) and the bootstrapping procedure were utilized to examine the role of psychological capital in mediating the relationship between authentic leadership and nurses’ caring behaviour.Results Authentic leadership, psychological capital, and caring behavior among nurses exhibited significant correlations. Furthermore, psychological capital showed a significant mediating impact (β = 0.378, p < 0.001) on the correlation between authentic leadership and nurses’ caring behavior.Conclusion According to the findings of this research, enhancing psychological capital could help nurses who experience an authentic leadership style improve their caring behaviors effectively. This finding suggests that nursing managers should actively develop an authentic leadership style and take actions or provide education to increase the psychological capital of nurses, which can effectively promote nurses’ caring behaviors toward patients in clinical practice.
Terahertz Four-Way Out-of-phase Waveguide Power Combiner with Low Insertion Loss
Authors: Song Kaijun , Zhao Meng , Fan Yong 
Published: April 2023

Abstract

A terahertz four-way out-of-phase waveguide power combiner has been proposed and analyzed in this paper. The input return loss of the circuit is improved greatly by the power combiner through the metal matching square column in the center of the circuit node, and the four output ports are reversed in equal amplitude. A simple equivalent circuit model for this power-combining structure has been developed. In order to verify the validity of the proposed structure, a four-way power combiner structure with the center frequency of 145GHz has been designed and fabricated with conventional machining. The measured input return loss of the circuit is greater than 16dB from 130GHz to 162GHz. And the insertion loss is less than 0.5dB from 140GHz to 160GHz, which corresponds to a power-combining efficiency of 90%.
Incomplete immune reconstitution and its predictors in people living with HIV in Wuhan, China
Authors: Zhang Wenyuan , Yan Jisong , Luo Hong , Wang Xianguang , Ruan Lianguo 
Published: April 2023

Abstract
Objective This study aimed to build and validate a nomogram model to predict the risk of incomplete immune reconstitution in people living with HIV (PLWH).Methods Totally 3783 individuals with a confirmed diagnosis of HIV/AIDS were included. A predictive model was developed based on a retrospective set (N = 2678) and was validated using the remaining cases (N = 1105). Univariable and multivariable logistic regression analyses were performed to determine valuable predictors among the collected clinical and laboratory variables. The predictive model was presented as a nomogram, and internally validated using another independent dataset. The predictive value of the model was evaluated by determining the area under the curve (AUC). Besides, calibration curve and decision curve (DCA) analyses were performed in both the training and test sets.Results The final model comprised 5 predictors, including baseline CD4, age at ART initiation, BMI, HZ and TBIL. The AUC of the nomogram model was 0.902 in the training cohort, versus 0.926 in the validation cohort. The calibration accuracy and diagnostic performance were satisfactory in both the training and test sets.Conclusions This predictive model based on a retrospective study was internally validated using 5 readily available clinical indicators. It showed high performance in predicting the risk of incomplete immune reconstitution.
Improving the Collection of National Health Data: The Case for the Middle Eastern and North African Checkbox in the United States
Authors: Kindratt Tiffany B 
Published: April 2023

Abstract
Objectives
To describe public comments posted in relation to the Office of Management and Budget (OMB) Statistical Policy Directive 15 proposals regarding the addition of a separate Middle Eastern and North African (MENA) checkbox on the US Census and other required federal forms.
Methods
A public comment period outlining changes to the collection of race and ethnicity data on the US Census and other federal forms opened in January 2023. Public comments posted in February and March 2023 were reviewed to determine whether MENA was mentioned, whether comments supported a MENA checkbox, and whether comments mentioned support for health-related reasons.
Results
There were 3,062 comments reviewed. Most (71.49%) mentioned adding a MENA checkbox. Of those, 98.86% supported adding a MENA checkbox. Among those, 31.98% mentioned adding a MENA checkbox for health-related reasons.
Conclusions
Overall, the comments reviewed demonstrated strong support for the addition of a MENA checkbox on federal forms. These findings are encouraging yet further review is needed to contribute to the OMB’s final decision on whether to add the checkbox and uncover the health of this underrepresented population.
The human acetylcholinesterase c-terminal T30 peptide activates neural growth through an alpha 7 nicotinic acetylcholine receptor mTOR pathway
Authors: Graur Alexandru , Sinclair Patricia , Kabbani Nadine 
Published: April 2023

AbstractAcetylcholinesterase (AChE) is a highly conserved enzyme responsible for the regulation of acetylcholine signaling within the brain and periphery. AChE has also been shown to participate in non-enzymatic activity and contribute to cellular development and aging. In particular, enzymatic cleavage of the carboxy terminal region of the synaptic AChE isoform, AChE-T, is shown to generate a bioactive T30 peptide that binds to the ⍺7 nicotinic acetylcholine receptor (nAChR) at synapses. Here, we explore intracellular mechanisms of T30 signaling within the human cholinergic neural cell line SH-SY5Y using high performance liquid chromatography (HPLC) coupled to electrospray ionization mass spectrometry (ESI-MS/MS). Proteomic analysis of cells exposed to (100nM) T30 for 3-days reveals significant changes within proteins important for cell growth. Specifically, bioinformatic analysis identifies proteins that converge onto the mammalian target of rapamycin (mTOR) pathway signaling. Functional experiments confirm that T30 regulates neural cell growth via mTOR signaling and ⍺7 nAChR activation. In addition, T30 was found promote mTORC1 pro-growth signaling through an increase in phosphorylated elF4E, and a decrease in autophagy LC3B-II level. Taken together, our findings define mTOR as a novel pathway activated by the T30 cleavage peptide of AChE and suggest a role for mTOR signaling in cholinergic aspects of brain development, as well as disease.
Integrating single-cell and bulk RNA sequencing to predict prognosis and immunotherapy response in prostate cancer
Authors: Wen Xiao Yan , Wang Ru Yi , Yu Bei , Yang Yue , Yang Jin , Zhang Chao 
Published: April 2023

Abstract
Prostate cancer (PCa) is one of the leading causes of death for men worldwide. Cancer-associated fibroblasts (CAFs) are considered to be closely connected to tumour growth, invasion, and metastasis. We explored the role and characteristics of CAFs in PCa through bioinformatics analysis and built a CAFs-based risk model to predict prognostic treatment and treatment response in PCa patients. First, we downloaded the signal-cell RNA sequencing (scRNA-seq) data of PCa from the GEO database. We extracted bulk RNA-seq data and microarray data of PCa from the TCGA and GEO databases respectively, and adopted "ComBat" to remove batch effects. Then, we created a Seurat object for the scRNA-seq data using the package "Seurat" of R and identified CAF clusters based on the CAF-related genes (CAFRGs). Based on CAFRGs, a prognostic model was constructed by univariate Cox, LASSO, and multivariate Cox analyses. And the model was validated internally and externally by Kaplan-Meier analysis, respectively. We further performed GO and KEGG analysis of differentially expressed genes between risk groups. Besides, we investigated differences in somatic mutations between different risk groups. We explored differences in the immune microenvironment landscape and immune checkpoint gene expression levels in the different groups. Final, we predicted the response to immunotherapy and the sensitivity of antitumour drugs between the different groups.We screened 4 CAF clusters and identified 463 CAFRGs in PCa scRNA-seq. We constructed a model containing 10 prognostic CAFRGs by univariate Cox, LASSO, and multivariate Cox analysis. Somatic mutation analysis revealed that TTN and TP53 were significantly more mutated in the high-risk group than in the low-risk group, suggesting that the high-risk group may have a poor prognosis. Finally, we screened 31 chemotherapeutic drugs and targeted therapeutic drugs for PCa.In conclusion, we identified four clusters based on CAFs and constructed a new CAFs-based prognostic signature that could predict PCa patient prognosis and response to immunotherapy and might suggest meaningful clinical options for the treatment of PCa.
Adapting Physiologically-Based Pharmacokinetic Models for Machine Learning Applications
Authors: Habiballah Sohaib , Reisfeld Brad 
Published: April 2023

Abstract
Both machine learning and physiologically-based pharmacokinetic models are becoming essential components of the drug development process. Integrating the predictive capabilities of physiologically-based pharmacokinetic (PBPK) models within machine learning pipelines could offer significant benefits in improving the accuracy and scope of drug screening and evaluation procedures. Here, we describe the development and testing of a self-contained machine learning module capable of faithfully recapitulating summary pharmacokinetic (PK) parameters produced by a full PBPK model, given a set of input drug-specific and regimen-specific information. Because of its widespread use in characterizing the disposition of orally administered drugs, the PBPK model chosen to demonstrate the methodology was an open-source implementation of a state-of-the-art compartmental and transit model called OpenCAT. The model was tested for drug formulations spanning a large range of solubility and absorption characteristics, and was evaluated for concordance against predictions of OpenCAT and relevant experimental data. In general, the values predicted by the ML models were within 20% of those of the PBPK model across the range of drug and formulation properties. However, summary PK parameter predictions from both the ML model and full PBPK model were occasionally poor with respect to those derived from experiments, suggesting deficiencies in the underlying PBPK model.