bluuebunny/crossref_metadata_2025_split huggingface dataset:
Machine Learning-Based Metabolic Pattern Recognition Predicts Mode of Action for Anti-Cancer Drug Candidates
Authors: Balcke Gerd , Saoud Mohamad , Grau Jan , Rennert Robert , Mueller Thomas , Yousefi Mohammad , Davari Mehdi D. , Hause Bettina , Csuk Rene , Rashan Luay , Grosse Ivo , Tissier Alain , Wessjohann Ludger 
Published: January 2024

Abstract
A bottleneck in the development of new anti-cancer drugs is the recognition of their mode of action (MoA). We combined metabolomics and machine learning to predict MoAs of novel anti-proliferative drug candidates, focusing on human prostate cancer cells (PC-3). As proof of concept, we studied 38 drugs with known effects on 16 key processes of cancer metabolism, profiling low molecular weight intermediates of the central carbon and cellular energy metabolism (CCEM) by LC-MS/MS. These metabolic patterns unveiled distinct MoAs, enabling accurate MoA predictions for novel agents by machine learning. We validate the transferability of MoA predictions from PC-3 to two other cancer cell models and show that correct predictions are still possible, but at the expense of prediction quality. Furthermore, metabolic profiles of treated cells yield insights into intracellular processes, exemplified for drugs inducing different types of mitochondrial dysfunction. Specifically, we predict that pentacyclic triterpenes inhibit oxidative phosphorylation and affect phospholipid biosynthesis, as supported by respiration parameters, lipidomics, and molecular docking. Using biochemical insights from individual drug treatments, our approach offers new opportunities, including the optimization of combinatorial drug applications.
The molecular architecture of the kidney slit diaphragm
Authors: Birtasu Alexandra N. , Wieland Konstantin , Ermel Utz H. , Scheffer Margot P. , Grahammer Florian , Frangakis Achilleas S. 
Published: January 2024

Abstract
Vertebrate life depends on renal function to filter excess fluid and remove low molecular-weight waste products. An essential component of the kidney filtration barrier is the slit diaphragm (SD), a specialized cell-cell junction between podocytes. Although the constituents of the SD have recently been identified, its molecular architecture remains elusive. Here, we use cryo-electron tomography of vitreous lamellae from high-pressure frozen native murine glomeruli to analyse the molecular architecture of the SD. In our tomographic reconstructions, the “central dot” of the SD resembles a fishnet pattern. After sub-tomogram averaging and molecular dynamics flexible fitting of Nephrin and Neph1, the main constituents of the SD, an ordered crisscross arrangement can be seen. The resulting molecular model of the SD suggests at least four contact sites for each Nephrin and two contact sites for each Neph1 and renders the SD as a quasi-crystalline, sheet-like molecular polymer that is able to compensate for mechanical forces. Our architectural understanding of the murine SD reconciles previous findings and provides a mechanistic framework for the understanding of renal disease.
Metal-Optic Nanophotonic Modulators in Standard CMOS Technology
Authors: Trajtenberg-Mills Sivan , ElKabbash Mohamed , Harris Isaac , Bandyopadhyay Saumil , Ibrahim Mohamed , Wang Archer , Chen Xibi , Brabec Cole , Han Ruonan , Englund Dirk 
Published: January 2024

Abstract

Integrating nanophotonics with electronics promises revolutionary applications ranging from light detection and ranging (LiDAR) to holographic displays. Although semiconductor manufacturing of nanophotonics in Silicon Photonic foundries is maturing, realizing active nanophotonics in the ubiquitous bulk
CMOS processes remains challenging. We introduce a fabless approach to embed active nanophotonics in bulk CMOS by co-designing the back-end-of-line metal layers for optical functionality. Without changing any of the design rules imposed by a 65 nm CMOS process, we realize plasmonic liquid crystal modulators that exhibit switching speeds 100 times faster than commercial technologies. Our approach, which embeds ’zero-change’ nanophotonics into the most ubiquitous platform for integrated electronics, democratizes fabrication of metal-optic
nanophotonics, opens the path to mass production of active nanophotonic components, and overcomes major packaging challenges that have previously hindered the realization of complex metal-optic optoelectronic systems.
Pain relief in children: pharmacokinetic extrapolation supported by real-world evidence
Authors: Lai John Chi Keung , Rasche Stefanie , Fish Nicola , Wagner Kerstin , Bermin Jenny , Spegel Christer 
Published: January 2024

Abstract

Background
Relieving pain quickly in children suffering from childhood aches and pains is high priority for parents and caregivers. However, conducting controlled pain relief studies in children to investigate the time it takes for the onset of pain relief presents ethical and reproducibility considerations. The aim of this work was to research the ability of paracetamol pain relievers to quickly (in under 30 minutes) relieve pain in pediatric populations.
Methods
Onset of pain relief in children aged 6 years and above was determined using a pharmacokinetic/pharmacodynamic model to extrapolate data from adults who were treated with paracetamol in clinical studies. Perception of pain relief in 2- to 5-year-old children was collected via questionnaire from caregivers who had administered paracetamol to their child for pain.
Results
Pharmacokinetic/pharmacodynamic modeling generated with data from paracetamol adult pain relief studies and pharmacokinetic studies of paracetamol fast dissolving tablet and suspension demonstrated that the onset of pain relief would be reached within 30 minutes in children 6 years and above. In the 2- to 5-year-old group, 89% of parents and caregivers perceived their child felt relief from pain in less than 30 minutes after being administered paracetamol pain reliever.
Conclusions
Paracetamol-containing pain reliever in tablet and suspension formulations provide relief from pain in less than 30 minutes in the pediatric population.
Patient-reported outcome measures in an outpatient parenteral antimicrobial therapy program– a prospective cohort study
Authors: Burch Andrea R. , Ledergerber Bruno , Ringer Martin , Zinkernagel Annelies S. , Eberhard Nadia , Kaelin Marisa B. , Hasse Barbara 
Published: January 2024

Abstract
Objectives To evaluate the influence of our local Outpatient Parenteral Antimicrobial Therapy (OPAT) program on Health-Related Quality of Life (HRQoL) using Patient Reported Outcomes (PROs).
Design Prospective cohort study.
Setting A public tertiary care hospital in Switzerland.
Participants Patients enrolled in the University Hospital Zurich’s OPAT program between October 2020 and September 2022. They were interviewed pre-discharge and 7-14 days post-dis using a shortened, four-domain-version of the validated Short Form-36 (SF-36) questionnaire, complemented by four additional questions gauging patient satisfaction.
Main outcome measures The primary outcomes were the scores in four domains of the SF-36 questionnaire.
Results Thirty-three patients participated in the study. Univariate analysis revealed substantial improvement in three of the four SF-36 domains. Specifically, participants reported enhanced role emotional (p=0.038), social functioning (p=0.003) and emotional well-being (p=0.003). Furthermore, 97% of patients would recommend OPAT to others.
Conclusion OPAT significantly impacts HRQoL and yields high patient satisfaction. Hospitals considering new OPAT programs should include both patient satisfaction and HRQoL impact in their argument repertoire for the introduction of OPAT.
Alzheimer's disease transcriptional landscape in ex-vivo human microglia
Authors: Roussos Panos , Kosoy Roman , Fullard John , Bendl Jaroslav , Kleopoulos Steven , Shao Zhiping , Argyriou Stathis , Mathur Deepika , Vicari James , Ma Yixuan , Humphrey Jack , Brophy Erica , Raj Towfique , Katsel Pavel , Voloudakis Georgios , Lee Donghoon , Bennett David , Haroutunian Vahram , Hoffman Gabriel 
Published: January 2024

Abstract
Microglia are resident immune cells of the brain and are implicated in the etiology of Alzheimer’s Disease (AD) and other diseases. Yet the cellular and molecular processes regulating their function throughout the course of the disease are poorly understood. Here, we present the transcriptional landscape of primary microglia from 189 human postmortem brains, including 58 healthy aging individuals and 131 with a range of disease phenotypes, including 63 patients representing the full spectrum of clinical and pathological severity of AD. We identified transcriptional changes associated with multiple AD phenotypes, capturing the severity of dementia and neuropathological lesions. Transcript-level analyses identified additional genes with heterogeneous isoform usage and AD phenotypes. We identified changes in gene-gene coordination in AD, dysregulation of co-expression modules, and disease subtypes with distinct gene expression. Taken together, these data further our understanding of the key role of microglia in AD biology and nominate candidates for therapeutic intervention.
Tomato mutants reveal root and shoot strigolactones involvement in branching and broomrape resistance
Authors: Karniel Uri , Koch Amit , Nun Nurit Bar , Zamir Dani , Hirschberg Joseph 
Published: January 2024

Abstract

The phytohormones strigolactones (SLs) control root and shoot branching and are exuded from roots into the rhizosphere to stimulate interaction with mycorrhizal fungi. The exuded SLs serve as signaling molecules for the germination of parasitic plants. The broomrape Phelipanche aegyptiaca is a widespread noxious weed in several crop plants, including tomato (Solanum lycopersicum). 'In silico' screening of tomato (M82) mutants identified three lines that showed significantly increased branching. Two mutants, SHOOT BRANCHING 1 (sb1) and SHOOT BRANCHING 2 (sb2), lack SLs due to loss of function mutations in the genes for the carotenoid cleavage dioxygenase enzymes CCD7, and CCD8, respectively. Beyond the increased branching, these mutants were completely resistant to infection by P. aegyptiaca. The third branching mutant, SHOOT BRANCHING 3 (sb3), carried a point mutation in the SLs receptor DWARF14 and was found to be highly susceptible to P. aegyptiaca. SL concentration in roots of the sb3 was two-fold higher than in the wild type due to the upregulation of transcription of SL biosynthesis genes. This phenomenon suggests that the steady-state level of SLs is regulated by a feedback mechanism that involves the SL signaling pathway. Grafting experiments showed that sb1 and sb2 rootstocks protected wild-type tomato scions from P. aegyptiaca infection without a significant yield loss, offering a solution to the broomrape crisis. These results also demonstrate that strigolactones synthesized in the shoots are involved in the control of shoot branching.
Mental Health Literacy Among Urban and Rural Residents of Guangdong Province, China
Authors: He Xiao-Yan , wen YanTan , Guo Li-Li , Ji Ying-Ying , Jia Fu-Jun , Wang Shi-Bing 
Published: January 2024

Abstract

Background.
The study aims to understanding the levels of mental health literacy among residents of Guangdong Province, the first major province in China, and its influencing factors is crucial. Such understanding will serve as a solid foundation for mental health promotion initiatives and enhancing the overall mental health literacy levels among residents across the province.
Method
A multi-stage stratified equal-volume random sampling method was adopted in October-December 2022 to select permanent residents aged 18 years and above in Guangdong Province for the questionnaire survey, which consisted of a general demographic information questionnaire and a national mental health literacy questionnaire. Rao-Scott χ test with correction based on sampling design, independent samples t-test and binary multivariate logistic regression analysis were performed.
Results
A total of 51744 individuals completed the questionnaire, including 31822 (61.4%) urban residents and 19200 (38.6%) rural residents. The rate of achievement of mental health literacy was 13.6% among urban residents, which was significantly higher compared to the rate of 8.6% among rural residents. Logistic regression analysis showed that being female, having an education level of 12 years or higher, being mental worker, being a retiree, having a higher monthly household income, maintaining a regular diet, and using electronic products for 2–6 hours per day were all protective factors for mental health literacy attainment in urban residents, while having chronic diseases, being a smoker, having a history of drinking, and being were identified as risk factors in urban residents. Among in rural residents, being married, being younger, having an education level of 12 years or higher, being mental worker and using electronic products for 2–6 hours per day, maintaining a regular diet, and engaging in regular exercise were protective factors for achieving mental health literacy. Additionally, previous smoking was identified as a risk factor.
Conclusion
The study revealed a low level of mental health literacy among urban and rural residents of Guangdong Province, with a significant disparity between the two areas. These findings highlight the need for continuing efforts to increase the dissemination of mental health knowledge in rural communities and improve levels of mental health literacy.
Pesticide labels do not effectively communicate toxicity risks
Authors: Hosni Hanin , Segovia Michelle , Zhao Shuoli , Palma Marco A , Skevas Theodoros 
Published: January 2024

Abstract

We show consumers inadvertently misperceive the risk associated with over-the-counter pesticides under the current labeling policy. Through an incentivized framed field experiment with eye tracking, we evaluate the effectiveness of existing pesticide labels that convey risk using signal words, finding they are ineffective in communicating toxicity information. We introduce two novel label display formats using traffic light colors and a skull intensity symbol and show that the new pictorial labels perform better than the existing signal word label in terms of consumers identifying the appropriate level of toxicity. Specifically, consumers’ correct assessment of toxicity level dramatically improves from 56% under the existing signal word label to 88% under the traffic light and 87% under the skull intensity symbol labels. We also find that participants are more likely to choose less toxic alternatives under the new labels, suggesting the current labeling system may have unintended adverse effects to human health.
Predicting two-year neurodevelopmental outcomes in preterm infants using multimodal structural brain magnetic resonance imaging with local connectivity: A machine learning approach
Authors: Jang Yong Hun , Ham Jusung , Kasani Payam Hosseinzadeh , Kim Hyuna , Lee Joo Young , Lee Gang Yi , Kim Bung-Nyun , Lee Hyun Ju 
Published: January 2024

Abstract
Determine brain structural networks in extremely preterm (EP; <28 weeks), very-to-late preterm (V-LP; ≥28 and < 37 weeks), and all preterm infants at term-equivalent age. Predict 2-year neurodevelopmental scores using multimodal predictors. Prospective cross-sectional study with MRI and diffusion MRI on 61 EP and 131 V-LP infants. Constructed a multimodal feature set through volumetric and structural network analysis. Linear and nonlinear machine learning models used for predicting Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) scores, assessing predictive power and feature importance. Prediction models, incorporating local connectivity features, demonstrated high predictive performance for cognitive scores in preterm (RMSE 13.352; variance explained 17%) and V-LP (RMSE 11.205; variance explained 17%) infants. For motor scores, models with local connectivity features had the highest predictive performance for EP (RMSE 11.363; variance explained 15%). A model with only local connectivity features showed high predictive performance for language scores in preterm infants (RMSE 11.792; variance explained 15%). BSID-III prediction performance and feature importance varied across preterm groups, emphasizing the efficacy of multimodal feature sets with local connectivity. Leveraging machine learning in this context enhances our understanding of microstructural alterations and their link to neurodevelopmental outcomes, facilitating risk stratification.
Tumor size does not affect overall survival of patients undergoing resection for a single hepatocellular carcinoma without microscopic vascular invasion.
Authors: Yen Yi-Hao , Kuo Fang-Ying , Eng Hock-Liew , Liu Yueh-Wei , Yong Chee-Chien , Wang Chih-Chi , Li Wei-Feng , Lin Chih-Yun 
Published: January 2024

Abstract
Purpose
Whether tumor size affects the survival of patients undergoing liver resection (LR) for a single hepatocellular carcinoma (HCC) without microscopic vascular invasion (MVI), i.e., pathological T1N0M0, is controversial. We aimed to clarify this issue.
Methods
We enrolled 626 patients with HCC of pathological stage T1N0M0 of the 7th edition of American Joint Committee on Cancer staging who underwent LR between 2011 and 2021 at our institution. The overall survival (OS) of patients with T1N0M0 HCC > 5.0 cm and those with T1N0M0 HCC ≤ 5.0 cm was compared using the Kaplan–Meier estimator and log-rank test both before and after propensity score matching (PSM).
Results
Ninety-two (14.7%) patients had T1N0M0 HCC > 5.0 cm. The proportion of patients with cirrhosis was lower in the T1N0M0 HCC > 5.0 cm group than in the T1N0M0 HCC ≤ 5.0 cm group (16.3% vs 41.2%, p < 0.001). The former also had a lower proportion of patients showing anti-HCV positivity than the latter (17.4% vs 33.9%, p = 0.002). Five-year OS did not differ significantly between the two groups before PSM (82% vs 84%, p = 0.857) or after PSM (82% vs 92%, p = 0.274).
Conclusion
Tumor size did not affect the OS of patients undergoing LR for T1N0M0 HCC.
Donkey-like kirkovirus is associated with diarrhea in piglets
Authors: Tong Panpan , Wang Zunbao , Dang Yueyi , Zhang Lei , Song Guangwei , Song Xiaozhen , Pan Juanjuan , Kuang Ling , Li Junhui , Lu Gang , Xie Jinxin 
Published: January 2024

Abstract
Kirkovirus (kirV), a seemingly novel virus family, has been found in horses and donkeys. The objectives of the study intend to investigate the presence of the virus in swine. In this study, donkey-like kirV was detected in rectal swabs of piglets with diarrhea, and the positive rate was found to be 100% (149/149), however this virus was detected in only one of 261 clinically healthy piglets, which suggested a strong relationship between the kirV and the diarrheic disease. We obtained the whole-genome sequences of three kirVs (named Cj-D5, Cj-D32 and Cj-D43), with length of 3750 nt and sharing 99.9% nucleotide (nt)-identity with donkey kirVs. Furthermore, the three viruses shared 88.5–100%, and 23–51% of the Rep protein sequence identity with available reference strains of the families Kirkoviridae, Circoviridae, respectively. Moreover, like horse and donkey kirVs, RCR domain and P-loop NTPase domains of Rep protein and nonanucleotide motif (CAATATTAC), of the three viruses, were similar to those of Circoviruses and Cycloviruses. Phylogenetic analysis showed that these viruses could be potentially grouped together with members in the proposed family Kirkoviridae. This is the first report to describe that kirV can circulate in piglets with diarrhea and future studies are needed to determine the pathogenesis of this virus.
Intracellular adhesion molecule-1 and Vascular adhesion molecule-1 profile in uncomplicated malaria cases in Lagos, Nigeria
Authors: Igbasi Uche Thecla , Oyibo Wellington A. 
Published: January 2024

Abstract

Objectives: High levels of endothelial activation markers have been reported mostly in severe malaria cases and associated with several malaria syndromes following Plasmodium falciparum infected erythrocytes sequestration into blood vessels of deep tissues and organs. Data on their roles in uncomplicated malaria is scarce. This study evaluated levels of vascular endothelial adhesion molecule-1 (VCAM-1) and intracellular adhesion molecule-1 (ICAM-1) in uncomplicated malaria and their relationship with host factors.
Results: Mean levels of ICAM-1 (1.03x106±20689.2 pg/ml) and median level of VCAM-1 (1.11x106 pg/ml, range 3,725-6,273,725 pg/ml) were both significantly increased in malaria cases compared to the malaria negative group (p<0.01). The geometric mean parasite density was 11,183 parasites /μl, ICAM-1 and VCAM-1 levels did not correlate with parasite density, p=0.125, p=0.945; r=0.138, r=0.006 respectively. Mean PCV was significantly lower (P=0.042) in malaria positive cases than negative cases. A negative correlation was seen between ICAM-1 and PCV (r = -0.167, p =0.026; VCAM-1) and PCV (r=-0.173, p = 0.021). However, ICAM-1 and VCAM-1 levels were negatively associated with age (r =-0.314, p= 0.000; r = -0.160, p=0.033) respectively. This study showed increased VCAM-1 and ICAM-1 levels in uncomplicated malaria, an indication of endothelial activation, which plays a significant role in malaria pathogenesis.
Experimental study of Three-Nucleon Dynamics in the dp breakup reaction
Authors: Barbara Barbara 
Published: January 2024

Abstract
The data analysis is in progress with the aim to determine the differential cross sections for the 1H(d,pp)n breakup reaction at four deuteron beam energies between 300 and 400 MeV. The data havebeen measured with the use of the WASA detector at COSY-Jülich. This work is focused on the beam energy of 380 MeV (190 MeV/nucleon). Set of proton-proton coincidences registered at the Forward Detector is analysed on a dense grid of kinematic variables. The one of the main steps of the analysis is efficiency study. Their impact on the final accuracy of the result is discussed.
Is a talented employee happy? - Talent and life satisfaction among European team workers
Authors: Talik Wieslaw , Wiechetek Michal 
Published: January 2024

Abstract

This article presents a study of employees in small and medium-sized companies, specifically team members, in terms of their talent and life satisfaction. The main objective of the research was to assess the specific links between talent and life satisfaction in employees from five European countries. The study surveyed 298 individuals from Belgium (N = 69), Cyprus (N = 52), the Czech Republic (N = 61), Poland (N = 54), and the UK (N = 62) using the Satisfaction With Life Scale - SWLS (Diener, Emmons, Larsen, & Griffin, 1985) and the ComTal-Team Member test (Talik, Wiechetek, & Dean, 2018), an electronic tool that measures the components of talent: competence, commitment, and contribution. Employees of small and medium-sized companies show a positive correlation between talent and life satisfaction. Differences in talent components and dimensions exist among team members from different European countries.