bluuebunny/crossref_metadata_2025 huggingface dataset:
Isotopic evidence of high reliance on plant food among Later Stone Age hunter-gatherers at Taforalt, Morocco
Authors: Moubtahij Zineb , McCormack Jeremy , Bourgon Nicolas , Trost Manuel , Sinet-Mathiot Virginie , Fuller Benjamin T. , Smith Geoff M. , Temming Heiko , Steinbrenner Sven , Hublin Jean-Jacques , Bouzouggar Abdeljalil , Turner Elaine , Jaouen Klervia
Published: April 2024

The transition from hunting-gathering to agriculture stands as one of the most important dietary revolutions in human history. Yet, due to a scarcity of well-preserved human remains from Pleistocene sites, little is known about the dietary practices of pre-agricultural human groups. Here we present the isotopic evidence of pronounced plant reliance among Late Stone Age hunter-gatherers from North Africa (15,000–13,000 cal BP), predating the advent of agriculture by several millennia. Employing a comprehensive multi-isotopic approach, we conducted zinc (δ66Zn) and strontium (87Sr/86Sr) analysis on dental enamel, bulk carbon (δ13C) and nitrogen (δ15N) and sulfur (δ34S) isotope analysis on dentin and bone collagen, and single amino acid analysis on human and faunal remains from Taforalt (Morocco). Our results unequivocally demonstrate a substantial plant-based component in the diets of these hunter-gatherers. This distinct dietary pattern challenges the prevailing notion of high reliance on animal proteins among pre-agricultural human groups. It also raises intriguing questions surrounding the absence of agricultural development in North Africa during the early Holocene. This study underscores the importance of investigating dietary practices during the transition to agriculture and provides insights into the complexities of human subsistence strategies across different regions.
Influence of COVID-19 on trust in routine immunization, health information sources and pandemic preparedness in 23 countries in 2023
Authors: Lazarus Jeffrey V. , White Trenton M. , Wyka Katarzyna , Ratzan Scott C. , Rabin Kenneth , Larson Heidi J. , Martinon-Torres Federico , Kuchar Ernest , Abdool Karim Salim S. , Giles-Vernick Tamara , Müller Selina , Batista Carolina , Myburgh Nellie , Kampmann Beate , El-Mohandes Ayman
Published: April 2024

It is unclear how great a challenge pandemic and vaccine fatigue present to public health. We assessed perspectives on coronavirus disease 2019 (COVID-19) and routine immunization as well as trust in pandemic information sources and future pandemic preparedness in a survey of 23,000 adults in 23 countries in October 2023. The participants reported a lower intent to get a COVID-19 booster vaccine in 2023 (71.6%), compared with 2022 (87.9%). A total of 60.8% expressed being more willing to get vaccinated for diseases other than COVID-19 as a result of their experience during the pandemic, while 23.1% reported being less willing. Trust in 11 selected sources of vaccine information each averaged less than 7 on a 10-point scale with one’s own doctor or nurse and the World Health Organization, averaging a 6.9 and 6.5, respectively. Our findings emphasize that vaccine hesitancy and trust challenges remain for public health practitioners, underscoring the need for targeted, culturally sensitive health communication strategies.
Abstract deliberation by visuomotor neurons in prefrontal cortex
Authors: Charlton Julie A. , Goris Robbe L. T.
Published: April 2024

During visually guided behavior, the prefrontal cortex plays a pivotal role in mapping sensory inputs onto appropriate motor plans. When the sensory input is ambiguous, this involves deliberation. It is not known whether the deliberation is implemented as a competition between possible stimulus interpretations or between possible motor plans. Here we study neural population activity in the prefrontal cortex of macaque monkeys trained to flexibly report perceptual judgments of ambiguous visual stimuli. We find that the population activity initially represents the formation of a perceptual choice before transitioning into the representation of the motor plan. Stimulus strength and prior expectations both bear on the formation of the perceptual choice, but not on the formation of the action plan. These results suggest that prefrontal circuits involved in action selection are also used for the deliberation of abstract propositions divorced from a specific motor plan, thus providing a crucial mechanism for abstract reasoning.
Preclinical evaluation of novel synthesised nanoparticles based on tyrosine poly(ester amide) for improved targeted pulmonary delivery
Authors: Dahmash Eman Zmaily , Achkar Nour Radwan , Ali Dalia Khalil , Jarrar Qais , Iyire Affiong , Assaf Shereen M. , Alyami Hamad
Published: April 2024

Fixed dose combinations (FDCs) incorporating two or three medicines in a single inhaler have been created to enhance patient compliance and hence clinical outcomes. However, the development of dry powder inhalers (DPIs), particularly for FDCs, faces challenges pertinent to formulation uniformity and reproducibility. Therefore, this project aimed to employ nanotechnology to develop a FDC of DPIs for market-leading medicines—fluticasone propionate (FP) and salmeterol xinafoate (SAL)—for asthma management. Nanoaggregates were prepared using a novel biocompatible and biodegradable poly(ester amide) based on the amino acid tyrosine, utilising a one-step interfacial polymerisation process. The produced tyrosine poly (ester amide) drug-loaded nanoparticles were evaluated for content uniformity, PSA, FTIR, TEM, DSC, XRD and aerodynamic performance (in vitro and in vivo). The optimised formulation demonstrated high entrapment efficiency– > 90%. The aerodynamic performance in terms of the emitted dose, fine particle fraction and respirable dose was superior to the carrier-based marketed product. In-vivo studies showed that FP (above the marketed formulation) and SAL reached the lungs of mice in a reproducible manner. These results highlight the superiority of novel FDC FP/SAL nanoparticles prepared via a one-step process, which can be used as a cost-effective and efficient method to alleviate the burden of asthma.
Machine learning approach for recognition and morphological analysis of isolated astrocytes in phase contrast microscopy
Authors: Yakovlev Egor V. , Simkin Ivan V. , Shirokova Anastasiya A. , Kolotieva Nataliya A. , Novikova Svetlana V. , Nasyrov Artur D. , Denisenko Ilya R. , Gursky Konstantin D. , Shishkov Ivan N. , Narzaeva Diana E. , Salmina Alla B. , Yurchenko Stanislav O. , Kryuchkov Nikita P.
Published: April 2024

Astrocytes are glycolytically active cells in the central nervous system playing a crucial role in various brain processes from homeostasis to neurotransmission. Astrocytes possess a complex branched morphology, frequently examined by fluorescent microscopy. However, staining and fixation may impact the properties of astrocytes, thereby affecting the accuracy of the experimental data of astrocytes dynamics and morphology. On the other hand, phase contrast microscopy can be used to study astrocytes morphology without affecting them, but the post-processing of the resulting low-contrast images is challenging. The main result of this work is a novel approach for recognition and morphological analysis of unstained astrocytes based on machine-learning recognition of microscopic images. We conducted a series of experiments involving the cultivation of isolated astrocytes from the rat brain cortex followed by microscopy. Using the proposed approach, we tracked the temporal evolution of the average total length of branches, branching, and area per astrocyte in our experiments. We believe that the proposed approach and the obtained experimental data will be of interest and benefit to the scientific communities in cell biology, biophysics, and machine learning.
Symptomatic HIV infection and in-hospital outcomes for patients with acute myocardial infarction undergoing percutaneous coronary intervention from national inpatient sample
Authors: Cui Mingzhi , Qi Haohong , Zhang Ting , Wang Shixiong , Zhang Xiao , Cao Xiangmei , Ma Xueping , Huang Hui , Yan Ru , Jia Shaobin , Cong Guangzhi
Published: April 2024

Human immunodeficiency virus (HIV) infection increases the risk of acute myocardial infarction (AMI). However, little is known about its association with in-hospital outcomes and temporal trends in patients with AMI undergoing percutaneous coronary intervention (PCI). We queried patients with AMI who underwent PCI from the National Inpatient Sample Database (2003–2015) and stratified them into three groups: symptomatic, asymptomatic, and HIV-negative. After 1:2 case–control matching (CCM), logistic regression analysis was conducted to determine how HIV infection affected in-hospital outcomes. We also evaluated their recent trends from 2003 to 2015. The total weighted national estimate of 2,191,129 AMI cases included 2,178,995 HIV/AIDS-negative, 4994 asymptomatic, and 7140 symptomatic HIV cases. Symptomatic but not asymptomatic patients with HIV suffered more than triple the in-hospital mortality (adjusted odds ratio (aOR) 3.6, 95% confidence interval (CI) 2.5–5.2), over one-fold incidence of acute kidney injury (aOR 2.6 95% CI 1.9–3.4) and cardiogenic shock risk (aOR 1.9, 95% CI 1.3–2.7), a longer length of hospital stay (beta 1.2, 95% CI 1.0–1.5), and had more procedures (beta 1.3, 95% CI 1.2–1.5). These disparities relating to symptomatic HIV infection persisted from 2003 to 2015. In patients with AMI who underwent PCI, symptomatic HIV infection was associated with higher in-hospital mortality and more severe outcomes.
Exploring indirect effects of a classic trophic cascade between urchins and kelp on zooplankton and whales
Authors: Hildebrand Lisa , Derville Solène , Hildebrand Ines , Torres Leigh G.
Published: April 2024

Kelp forest trophic cascades have been extensively researched, yet indirect effects to the zooplankton prey base and gray whales have not been explored. We investigate the correlative patterns of a trophic cascade between bull kelp and purple sea urchins on gray whales and zooplankton in Oregon, USA. Using generalized additive models (GAMs), we assess (1) temporal dynamics of the four species across 8 years, and (2) possible trophic paths from urchins to kelp, kelp as habitat to zooplankton, and kelp and zooplankton to gray whales. Temporal GAMs revealed an increase in urchin coverage, with simultaneous decline in kelp condition, zooplankton abundance and gray whale foraging time. Trophic path GAMs, which tested for correlations between species, demonstrated that urchins and kelp were negatively correlated, while kelp and zooplankton were positively correlated. Gray whales showed nuanced and site-specific correlations with zooplankton in one site, and positive correlations with kelp condition in both sites. The negative correlation between the kelp-urchin trophic cascade and zooplankton resulted in a reduced prey base for gray whales. This research provides a new perspective on the vital role kelp forests may play across multiple trophic levels and interspecies linkages.
Simplified Spectrum Score (S3) app for pathogen-agnostic antimicrobial drug spectrum ranking to assess for antimicrobial de-escalation events
Authors: de Lorenzi-Tognon Mikaël , Schrenzel Jacques
Published: April 2024

Antimicrobial/antibiotic de-escalation (ADE) is a key feature of antimicrobial stewardship programs (ASP) that relies mainly on individual panels for determining ADE events based on subjective ranking of antibiotics’ spectrum activity. The lack of consensus among ASP experts leads to reproducibility issues in the measure of this clinical outcome, making difficult to assess its real impact on patient care. The S3 score (Simplified Spectrum Score) app was developed to allow an objective ranking of antibiotics. Ranking was achieved by developing a database harboring pairs of bacteria-antibiotics for which each molecule was assigned a score based on published and clinically validated data from a recognized international committee. S3 score shows a strong correlation relationship and substantial agreement to a clinically validated spectrum score, and its framework enables any person to use it for ADE detection without assuming prior knowledge or training. In addition, its design enables regular updates and sustainability.
Fate and preservation of the Late Pleistocene cave bears from Niedźwiedzia Cave in Poland, through taphonomy, pathology, and geochemistry
Authors: Marciszak Adrian , Mackiewicz Paweł , Borówka Ryszard K. , Capalbo Chiara , Chibowski Piotr , Gąsiorowski Michał , Hercman Helena , Cedro Bernard , Kropczyk Aleksandra , Gornig Wiktoria , Moska Piotr , Nowakowski Dariusz , Ratajczak-Skrzatek Urszula , Sobczyk Artur , Sykut Maciej T. , Zarzecka-Szubińska Katarzyna , Kovalchuk Oleksandr , Barkaszi Zoltán , Stefaniak Krzysztof , Mazza Paul P. A.
Published: April 2024

This comprehensive study examines fossil remains from Niedźwiedzia Cave in the Eastern Sudetes, offering detailed insights into the palaeobiology and adversities encountered by the Pleistocene cave bear Ursus spelaeus ingressus. Emphasising habitual cave use for hibernation and a primarily herbivorous diet, the findings attribute mortality to resource scarcity during hibernation and habitat fragmentation amid climate shifts. Taphonomic analysis indicates that the cave was extensively used by successive generations of bears, virtually unexposed to the impact of predators. The study also reveals that alkaline conditions developed in the cave during the post-depositional taphonomic processes. Mortality patterns, notably among juveniles, imply dwindling resources, indicative of environmental instability. Skeletal examination reveals a high incidence of forelimb fractures, indicating risks during activities like digging or confrontations. Palaeopathological evidence unveils vulnerabilities to tuberculosis, abscesses, rickets, and injuries, elucidating mobility challenges. The cave’s silts exhibit a high zinc concentration, potentially derived from successive bear generations consuming zinc-rich plants. This study illuminates the lives of late cave bears, elucidating unique environmental hurdles faced near their species’ end.
Rho kinase inhibitor Y-27632 downregulates IL-1β expression in mice with experimental autoimmune myocarditis
Authors: Li Yanjun , Gao Ge , Han Yiru , Xiao Bingshuai , Shen Liyuan , Yang Xiangxin , Liu Yangqing , Mu Yaqin , Zhang Nianping , Niu Chunhong , Wang Yuxing
Published: April 2024

Autoimmune myocarditis is the limited or diffuse inflammation of the myocardium due to dysfunctional cellular and humoral immunity mechanisms. We constructed mouse models of experimental autoimmune myocarditis (EAM) using peptide MyHC-α614-629. On the day after secondary immunization, the mice were intraperitoneally injected with Rho kinase (ROCK) inhibitor Y-27632. On day 21, the cardiac tissues were harvested and weighed. The hearts of EAM mice were significantly enlarged and whitened. Furthermore, body weight (BW) slowly increased during the treatment period, the heart weight (HW) and the ratio of HW/eventual BW were increased, and inflammatory infiltration and fibrosis were aggravated in the myocardial tissue. Y-27632 treatment improved the aforementioned phenotypic and pathological features of EAM mice. Mechanistic analysis revealed a significant increase in Notch1, Hes1, Jag2, Dil1, Toll-like receptor (Tlr) 2, and interleukin (IL)-1β expression in the myocardial tissue of EAM mice. Notably, IL-1β expression was correlated with that of Notch1 and Tlr2. Following Y-27632 treatment, the expression of key target genes of the Notch signaling pathway (Notch1, Hes1, Dil1, and Jag2) and Tlr2 were obviously decreased. Y-27632 treatment also decreased the number of monocytes in the spleen of EAM mice. Thus, ROCK inhibitor Y-27632 exerted a protective effect in EAM mice by downregulating IL-1β expression. This study aimed to provide a reference point for the future treatment of myocarditis in clinical settings.
The mediating effect of internet addiction and the moderating effect of physical activity on the relationship between alexithymia and depression
Authors: Liu Yang , Duan Liangfan , Shen Qingxin , Ma Yuanyuan , Chen Yiyi , Xu Lei , Wu Yawen , Zhang Tiancheng
Published: April 2024

There is a certain relationship between alexithymia and depression, but further investigation is needed to explore their underlying mechanisms. The aims of this study was to explore the mediating role of internet addiction between alexithymia and depression and the moderating role of physical activity. A total of 594 valid responses were included in the analysis, with a mean age of 18.72 years (SD = 1.09). The sample comprised 250 males (42.09%) and 344 females (57.91%). These responses were utilized for descriptive analysis, correlation analysis, regression analysis, and the development of mediation and moderation models. Alexithymia showed positive correlations with depression and internet addiction, and physical activity was negatively correlated with internet addiction and depression. Internet addiction partially mediated the relationship between alexithymia and depression, while physical activity weakened the association between internet addiction and depression, acting as a moderator. Our findings suggest that excessive Internet engagement may mediate the relationship between alexithymia and depression as an emotional regulatory coping strategy, and that physical activity attenuates the predictive effect of Internet addiction on depression.
Sensitivity analysis of natural convection in a porous cavity filled with nanofluid and equipped with horizontal fins using various optimization methods and MRT-LB
Authors: Sajjadi H. , Mansouri N. , Nabavi S. N. , Delouei A. Amiri , Atashafrooz M.
Published: April 2024

In the present study, natural convection heat transfer is investigated in a porous cavity filled with Cu/water nanofluid and equipped with horizontal fins. Optimization and sensitivity analysis of the fin’s geometry, porous medium and nanofluid properties to maximize heat transfer rate is the aim of this work. To achieve this purpose, a design space is created by input parameters which include length, number of fins, distance between fins, porosity, Darcy number and volumetric fraction of the nanoparticles. Several tools have been used to implement optimization methods including the Taguchi method (TM) for design points generation, sensitivity analysis of design variables by using signal-to-noise ratio (SNR) and analysis of variance (ANOVA), response surface method (RSM) for interpolation and regression by using nonparametric regression, and genetic algorithm (GA) for finding optimum design point. The double multi-relaxation time lattice Boltzmann method (MRT-LBM) is used to analyze and simulate the flow field and heat transfer in each design point. The results show that the optimal configuration leads to an average Nusselt number of 5.56. This optimal configuration is at the length of fins L/2, the number of fins 2, the distance between fins L/12, porosity 0.8, Darcy number 0.1, and the volumetric fraction of the nanoparticles 0.02. By using the SNR results, the Darcy number and the number of fins have the most and the least effect in maximizing the average Nusselt number, respectively. The ANOVA results and global sensitivity analysis (GSA) findings further validated this conclusion.
Gestational diabetes-related gut microbiome dysbiosis is not influenced by different Asian ethnicities and dietary interventions: a pilot study
Authors: Gupta Abhishek , Chan Shiao Yng , Toh Rachel , Low Jia Ming , Liu Isabella Ming Zhen , Lim Su Lin , Lee Le Ye , Swarup Sanjay
Published: April 2024

Gut microbiome dysbiosis contributes to the pathophysiology of both gestational diabetes mellitus (GDM) and its associated adverse outcomes in the woman and offspring. Even though GDM prevalence, complications, and outcomes vary among different ethnic groups, limited information is available about the influence of ethnicity on gut microbiome dysbiosis in pregnancies complicated by GDM. This pilot prospective cohort study examined the impact of ethnicity on gut dysbiosis in GDM among three Asian ethnic groups (Chinese, Malay, Indian) living in Singapore, and investigated the potential modulatory roles of diet and lifestyle modifications on gut microbiome post-GDM diagnosis. Women with GDM (n = 53) and without GDM (n = 16) were recruited. Fecal samples were collected at 24–28- and 36–40-weeks’ gestation and analyzed by targeted 16S rRNA gene-based amplicon sequencing. Permutational multivariate analysis of variance (PERMANOVA) analysis was performed to evaluate differences between groups. Differentially abundant taxa were identified by DeSeq2 based analysis. Functional prediction was performed using the phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt2). Among women with GDM, gut microbiome from different ethnicities harbored common microbial features. However, among those without GDM, there was contrasting microbiome composition between ethnic groups. Microbial members such as Collinsella, Blautia, Ruminococcus, Ruminococcus gnavus, Ruminococcus torques, and Eubacterium hallii groups were differentially enriched (p < 0.05) in women with GDM compared to those without. Among women with GDM, no differences in alpha- and beta- diversity were observed when comparing 24–28 weeks’ samples with 36–40 weeks’ samples, a period covering intense dietary and lifestyle modification, suggesting an inability to modulate gut microbiota through classic GDM management. Women with GDM have a distinct gut microbiome profile which harbours common features across different Asian ethnic groups, consistent with the notion that specific microbes are involved in the pathogenesis of insulin resistance, pro-inflammatory conditions, and other metabolic dysregulation known to be present in GDM.
Process and mechanism of preparing metallized blast furnace burden from metallurgical dust and sludge
Authors: Gao Xing , Chai Yifan , Wang Yici , Luo Guoping , An Shengli , Peng Jun
Published: April 2024

Metallurgical dust and sludge are solid waste resources with recycling value. In recent years, rotary hearth furnace has become the most important means to treat metallurgical dust and sludge because of its wide range of raw materials and strong treatment capacity. In this study blast furnace ash and converter sludge were selected as the research objects, and high-quality metallized pellets were prepared based on the rotary hearth furnace process. The strength changed of pellets, the reduction process of iron oxides and the removal process of zinc during the roasting of pellets in rotary hearth furnace were studied. To explore the reasonable roasting condition for preparing metallized pellets in rotary hearth furnace. The optimum roasting temperature of the pellets was 1250℃ and the roasting time was 25 min. The compressive strength, metallization rate and dezincification rate of metallized pellets reached 1361N, 97.44% and 95.67%, respectively. The efficient resource utilization of various metallurgical dust and sludge is realized.
A support vector machine based drought index for regional drought analysis
Authors: A Alshahrani Mohammed , Laiq Muhammad , Noor-ul-Amin Muhammad , Yasmeen Uzma , Nabi Muhammad
Published: April 2024

The increased global warming has increased the likelihood of recurrent drought hazards. Potential links between the frequency of extreme weather events and global warming have been suggested by earlier research. The spatial variability of meteorological factors over short distances can cause distortions in conclusions or limit the scope of drought analysis in a particular region when extreme values predominate. Therefore, it is challenging to make trustworthy judgments regarding the spatiotemporal characteristics of regional drought. This study aims to improve the quality and accuracy of regional drought characterization and the process of continuous monitoring. The new drought indicator presented in this study is called the Support Vector Machine based drought index (SVM-DI). It is created by adding different weights to an SVM-based X-bar chart that is displayed with regional precipitation aggregate data. The SVM-DI application site is located in Pakistan's northern area. Using the Pearson correlation coefficient for pairwise comparison, the study compares the SVM-DI and the Regional Standard Precipitation Index (RSPI). Interestingly, compared to RSPI, SVM-DI shows more pronounced regional characteristics in its correlations with other meteorological stations, with a significantly lower Coefficient of Variation. These results confirm that SVM-DI is a useful tool for regional drought analysis. The SVM-DI methodology offers a unique way to reduce the impact of extreme values and outliers when aggregating regional precipitation data.
Static magnetic field-induced IL-6 secretion in periodontal ligament stem cells accelerates orthodontic tooth movement
Authors: Luo Shitong , Li Zhilian , Liu Lizhiyi , Zhao Juan , Ge Wenbin , Zhang Kun , Zhou Zhi , Liu Yali
Published: April 2024

Static magnetic field (SMF) promoting bone tissue remodeling is a potential non-invasive therapy technique to accelerate orthodontic tooth movement (OTM). The periodontal ligament stem cells (PDLSCs), which are mechanosensitive cells, are essential for force-induced bone remodeling and OTM. However, whether and how the PDLSCs influence the process of inflammatory bone remodeling under mechanical force stimuli in the presence of SMFs remains unclear. In this study, we found that local SMF stimulation significantly enhanced the OTM distance and induced osteoclastogenesis on the compression side of a rat model of OTM. Further experiments with macrophages cultured with supernatants from force-loaded PDLSCs exposed to an SMF showed enhanced osteoclast formation. RNA-seq analysis showed that interleukin-6 (IL-6) was elevated in force-loaded PDLSCs exposed to SMFs. IL-6 expression was also elevated on the pressure side of a rat OTM model with an SMF. The OTM distance induced by an SMF was significantly decreased after injection of the IL-6 inhibitor tocilizumab. These results imply that SMF promotes osteoclastogenesis by inducing force-loaded PDLSCs to secrete the inflammatory cytokine IL-6, which accelerates OTM. This will help to reveal the mechanism of SMF accelerates tooth movement and should be evaluated for application in periodontitis patients.
Enhancing effect of natural adjuvant, panduratin A, on antibacterial activity of colistin against multidrug-resistant Acinetobacter baumannii
Authors: Thadtapong Nalumon , Chaturongakul Soraya , Napaswad Chanita , Dubbs Padungsri , Soodvilai Sunhapas
Published: April 2024

Colistin- and carbapenem-resistant Acinetobacter baumannii is a serious multidrug resistant (MDR) bacterium in clinical settings. Discovery of new antibacterial drugs against MDR is facing multiple challenges in drug development. Combination of known antibiotics with a robust adjuvant might be an alternative effective strategy for MDR treatment. In the study herein, we report an antibiotic adjuvant activity of a natural compound panduratin A from fingerroot (Boesenbergia rotunda) as a potent adjuvant to colistin. The present study investigated the antibiotic adjuvant effect of panduratin A against 10 colistin- and carbapenem-resistant A. baumannii. Antibacterial activities were tested by broth microdilution method. Biofilm assay was used to determine the efficacy of panduratin A in biofilm formation inhibition on two representative strains Aci46 and Aci44. Genomic and transcriptomic analyses of colistin- and carbapenem-resistant A. baumannii strains were used to identify potential resistance and tolerance mechanism in the bacteria. Panduratin A-colistin combination showed an increased effect on antibacterial in the A. baumannii. However, panduratin A did not improve the antibacterial activity of imipenem. In addition, panduratin A improves anti-biofilm activity of colistin against Aci44 and Aci46, the colistin- and carbapenem-resistant A. baumannii. Panduratin A markedly enhances bactericidal and anti-biofilm activity of colistin against colistin- resistant A. baumannii. Based on genome comparisons, single nucleotide polymorphism (SNP) patterns in six genes encoding biofilm and lipid A biosynthesis were shared in Aci44 and Aci46. In Aci44, we identified a partial sequence of pmrB encoding a polymyxin resistant component PmrB, whereas a full length of pmrB was observed in Aci46. RNA-seq analyses of Aci44 revealed that panduratin A-colistin combination induced expression of ribosomal proteins and oxidative stress response proteins, whereas iron transporter and MFS-type transporter systems were suppressed. Panduratin A-colistin combination could promote intracellular reactive oxygen species (ROS) accumulation could lead to the cidal effect on colistin-resistant A. baumannii. Combination of panduratin A and colistin showed a significant increase in colistin efficacy against colistin- resistant A. baumannii in comparison of colistin alone. Genomic comparison between Aci44 and Aci46 showed mutations and SNPs that might affect different phenotypes. Additionally, based on RNA-Seq, panduratin A-colistin combination could lead to ROS production and accumulation. These findings confirmed the potency of panduratin as colistin adjuvant against multidrug resistant A. baumannii.
A novel hybrid supervised and unsupervised hierarchical ensemble for COVID-19 cases and mortality prediction
Authors: Yakovyna Vitaliy , Shakhovska Nataliya , Szpakowska Aleksandra
Published: April 2024

Though COVID-19 is no longer a pandemic but rather an endemic, the epidemiological situation related to the SARS-CoV-2 virus is developing at an alarming rate, impacting every corner of the world. The rapid escalation of the coronavirus has led to the scientific community engagement, continually seeking solutions to ensure the comfort and safety of society. Understanding the joint impact of medical and non-medical interventions on COVID-19 spread is essential for making public health decisions that control the pandemic. This paper introduces two novel hybrid machine-learning ensembles that combine supervised and unsupervised learning for COVID-19 data classification and regression. The study utilizes publicly available COVID-19 outbreak and potential predictive features in the USA dataset, which provides information related to the outbreak of COVID-19 disease in the US, including data from each of 3142 US counties from the beginning of the epidemic (January 2020) until June 2021. The developed hybrid hierarchical classifiers outperform single classification algorithms. The best-achieved performance metrics for the classification task were Accuracy = 0.912, ROC-AUC = 0.916, and F1-score = 0.916. The proposed hybrid hierarchical ensemble combining both supervised and unsupervised learning allows us to increase the accuracy of the regression task by 11% in terms of MSE, 29% in terms of the area under the ROC, and 43% in terms of the MPP metric. Thus, using the proposed approach, it is possible to predict the number of COVID-19 cases and deaths based on demographic, geographic, climatic, traffic, public health, social-distancing-policy adherence, and political characteristics with sufficiently high accuracy. The study reveals that virus pressure is the most important feature in COVID-19 spread for classification and regression analysis. Five other significant features were identified to have the most influence on COVID-19 spread. The combined ensembling approach introduced in this study can help policymakers design prevention and control measures to avoid or minimize public health threats in the future.
Modeling spillover dynamics: understanding emerging pathogens of public health concern
Authors: Saldaña Fernando , Stollenwerk Nico , Van Dierdonck Joseba Bidaurrazaga , Aguiar Maíra
Published: April 2024

The emergence of infectious diseases with pandemic potential is a major public health threat worldwide. The World Health Organization reports that about 60% of emerging infectious diseases are zoonoses, originating from spillover events. Although the mechanisms behind spillover events remain unclear, mathematical modeling offers a way to understand the intricate interactions among pathogens, wildlife, humans, and their shared environment. Aiming at gaining insights into the dynamics of spillover events and the outcome of an eventual disease outbreak in a population, we propose a continuous time stochastic modeling framework. This framework links the dynamics of animal reservoirs and human hosts to simulate cross-species disease transmission. We conduct a thorough analysis of the model followed by numerical experiments that explore various spillover scenarios. The results suggest that although most epidemic outbreaks caused by novel zoonotic pathogens do not persist in the human population, the rising number of spillover events can avoid long-lasting extinction and lead to unexpected large outbreaks. Hence, global efforts to reduce the impacts of emerging diseases should not only address post-emergence outbreak control but also need to prevent pandemics before they are established.
SLKIR: A framework for extracting key information from air traffic control instructions Using small sample learning
Authors: Jiang Peiyuan , Zeng Chen , Pan Weijun , Han Boyuan , Zhang Jian
Published: April 2024

In air traffic control (ATC), Key Information Recognition (KIR) of ATC instructions plays a pivotal role in automation. The field's specialized nature has led to a scarcity of related research and a gap with the industry's cutting-edge developments. Addressing this, an innovative end-to-end deep learning framework, Small Sample Learning for Key Information Recognition (SLKIR), is introduced for enhancing KIR in ATC instructions. SLKIR incorporates a novel Multi-Head Local Lexical Association Attention (MHLA) mechanism, specifically designed to enhance accuracy in identifying boundary words of key information by capturing their latent representations. Furthermore, the framework includes a task focused on prompt, aiming to bolster the semantic comprehension of ATC instructions within the core network. To overcome the challenges posed by category imbalance in boundary word and prompt discrimination tasks, tailored loss function optimization strategies are implemented, effectively expediting the learning process and boosting recognition accuracy. The framework's efficacy and adaptability are demonstrated through experiments on two distinct ATC instruction datasets. Notably, SLKIR outperforms the leading baseline model, W2NER, achieving a 3.65% increase in F1 score on the commercial flight dataset and a 12.8% increase on the training flight dataset. This study is the first of its kind to apply small-sample learning in KIR for ATC and the source code of SLKIR will be available at: https://github.com/PANPANKK/ATC_KIR.
Diffusion-weighted imaging as a potential non-gadolinium alternative for immediate assessing the hyperacute outcome of MRgFUS ablation for uterine fibroids
Authors: Huang Yaoqu , Zhou Shouguo , Su Yinghua , Pang Zhuochao , Cai Shihua
Published: April 2024

The aim of this study was to investigate the value of diffusion-weighted imaging (DWI) as a potential non-gadolinium alternative for promptly assessing the hyperacute outcome of magnetic resonance-guided focused ultrasound (MRgFUS) treatment for uterine fibroids. In this retrospective study we included 65 uterine fibroids from 44 women, who underwent axial DWI (b-value: 800 s/mm2) and contrast-enhanced (CE) MR within 15 min post-ablation. Two blinded observers independently reviewed the DWI findings of ablated necrotic lesions and measured their volumes on DWI and CE images. The post-ablation DWI images revealed clear depiction of ablative necrotic lesions in all fibroids, which were classified into two types: the bull’s eye sign (type 1) and the bright patch sign (type 2). The inter-observer intraclass correlation coefficient for classifying DWI signal types was 0.804 (p < 0.001). Volumetric analysis of ablated necrosis using DWI and CE T1-weighted imaging showed no significant variance, nor did the non-perfused volume ratios (all p > 0.05). Bland–Altman analysis revealed a mean difference of 2.38% and 1.71% in non-perfused volume ratios between DWI and CE, with 95% limits of agreement from − 19.06 to 23.82% and − 18.40 to 21.82%, respectively. The findings of this study support the potential of DWI as a viable non-gadolinium alternative for evaluating the hyperacute outcomes of MRgFUS ablation in uterine fibroids.
Wasted efforts of elite Marathon runners under a warming climate primarily due to atmospheric oxygen reduction
Authors: Wang Shixin , Gao Meng , Xiao Xiang , Jiang Xiaodong , Luo Jingjia
Published: April 2024

Meteorological conditions exert influences on sport performances via complex processes. Previous studies conventionally investigate the effects of weather conditions on marathon performance by following events held at the same places, which brings large uncertainties due to the changed participants. Via following each athlete to eliminate these uncertainties, we show that elite athletes’ marathon-running performance tends to monotonically worsen as ambient temperature rises except when it is extremely cold based on the best 16 athletes from each of the sex continents. It worsens by 0.56 (0.39 for men and 0.71 for women) min/°C when it rises beyond 15 °C. Theoretical analysis based on global marathon performance and weather observation datasets shows that more than half of this effect is mediated by reduced oxygen partial density as warmer temperature expands air and increases vapor pressure for both the men and women athletes, which is confirmed by the methods of Baron–Kenny. This atmospheric thermodynamic mechanism has not been emphasized previously. We also show that world-top athletes’ marathon performance approximately linearly worsens as ambient pressure decreases and slightly worsens as relative humidity rises if not extremely wet. These results substantially differ from the previous ones following the events instead of each athlete. Multi-variable changes in climate system are projected to slow Olympic marathon athletes by 2.51 and 1.06 min by the end of the 21st century in relative to 2020 under the high and intermediate emission scenario, respectively. Therefore, future progression of marathon performance is likely to be substantially slowed or even halted by climate changes without efficient greenhouse gas mitigation.
Evidence-based health messages increase intention to cope with loneliness in Germany: a randomized controlled online trial
Authors: Liu Shuyan , Haucke Matthias , Wegner Luisa , Gates Jennifer , Bärnighausen Till , Adam Maya
Published: April 2024

Loneliness poses a formidable global health challenge in our volatile, post-pandemic world. Prior studies have identified promising interventions to alleviate loneliness, however, little is known about their effectiveness. This study measured the effectiveness of educational entertainment (“edutainment”) and/or evidence-based, written health messages in alleviating loneliness and increasing intention to cope with loneliness. We recruited 1639 German participants, aged 18 years or older. We compared three intervention groups who received: (A) edutainment and written health messages, (B) only edutainment, or (C) only written health messages, against (D) a control group that received nothing. The primary outcomes were loneliness and intention to cope with loneliness. Participants were also invited to leave comments about the interventions or about their perception or experiences with loneliness. We found a small (d = 0.254) but significant effect of the written messages on increased intention to cope with loneliness (b = 1.78, t(1602) = 2.91, P = 0.004), while a combination of edutainment and written messages significantly decreased loneliness scores (b = −0.25, t(1602) = −2.06, P = 0.04) when compared with the control, even after adjusting for covariables including baseline values, self-esteem, self-efficacy, and hope. We also observed significantly higher self-esteem scores after exposure to a combination of edutainment and written messages (b = 0.821, t(1609) = 1.76, one-tailed P = 0.039) and significantly higher hope scores after exposure to edutainment-only (b = 0.986, t(1609) = 1.85, one-tailed P = 0.032) when compared with the control group. Our study highlights the benefits of using written messages for increasing intention to cope with loneliness and a combination of edutainment and written messages for easing loneliness. Even in small “doses” (less than 6 min of exposure), edutainment can nurture hope, and edutainment combined with written messages can boost self-esteem.
Collimated muon beam proposal for probing neutrino charge-parity violation
Authors: Ruzi Alim , Yang Tianyi , Fu Dawei , Qian Sitian , Gao Leyun , Li Qiang
Published: April 2024

The phenomenon of neutrino oscillation is of great theoretical and experimental interest for our understand of the nature of the neutrino and its implication for physics beyond the standard Model. Currently available neutrino oscillation experiments can already constrain neutrino mixing parameters with a confidence level up to 3 standard deviations (σ). However, it remains challenging to provide a deterministic constraint on the Charge-Parity (CP) violation phase of the neutrino mixing matrix. Here, we propose an experimental setup that exploits collimated muon beams to probe neutrino CP-violation. In our proposed acceleration experiment, a 45 GeV positron source with additional muon collimation, interfaces with near-future neutrino detectors like DUNE and T2K, to probe neutrino CP-violation phase with a significantly higher sensitivity than obtained with the neutrino detectors alone, and to determine tau neutrino properties. Simulations estimate the collection of 104 tau (anti-) neutrino in 5 years, and a sensitivity of over 7 standard deviations for δCP = ∣π/2∣ in 5 years. Collecting ντ appearance events from μ− and μ+ beams over 10 years can attain a 3-4 standard deviation sensitivity. This proposal may serve as a tau factory.
Deep learning detects premalignant lesions in the Fallopian tube
Authors: Bogaerts Joep M. A. , Bokhorst John-Melle , Simons Michiel , van Bommel Majke H. D. , Steenbeek Miranda P. , de Hullu Joanne A. , Linmans Jasper , Bart Joost , Bentz Jessica L. , Bosse Tjalling , Bulten Johan , Chien Yen-Wei , Desouki Mohamed Mokhtar , Lastra Ricardo R. , Numan Tricia A. , Schoolmeester J. Kenneth , Schwartz Lauren E. , Shih Ie-Ming , Soong T. Rinda , Turashvili Gulisa , Vang Russell , Volchek Mila , van der Laak Jeroen A. W. M.
Published: April 2024

Tubo-ovarian high-grade serous carcinoma is believed to originate in the fallopian tubes, arising from precursor lesions like serous tubal intraepithelial carcinoma (STIC) and serous tubal intraepithelial lesion (STIL). Adequate diagnosis of these precursors is important, but can be challenging for pathologists. Here we present a deep-learning algorithm that could assist pathologists in detecting STIC/STIL. A dataset of STIC/STIL (n = 323) and controls (n = 359) was collected and split into three groups; training (n = 169), internal test set (n = 327), and external test set (n = 186). A reference standard was set for the training and internal test sets, by a panel review amongst 15 gynecologic pathologists. The training set was used to train and validate a deep-learning algorithm (U-Net with resnet50 backbone) to differentiate STIC/STIL from benign tubal epithelium. The model’s performance was evaluated on the internal and external test sets by ROC curve analysis, achieving an AUROC of 0.98 (95% CI: 0.96–0.99) on the internal test set, and 0.95 (95% CI: 0.90–0.99) on the external test set. Visual inspection of all cases confirmed the accurate detection of STIC/STIL in relation to the morphology, immunohistochemistry, and the reference standard. This model’s output can aid pathologists in screening for STIC, and can contribute towards a more reliable and reproducible diagnosis.
Glucose hypometabolism prompts RAN translation and exacerbates C9orf72-related ALS/FTD phenotypes
Authors: Nelson Andrew T , Cicardi Maria Elena , Markandaiah Shashirekha S , Han John YS , Philp Nancy J , Welebob Emily , Haeusler Aaron R , Pasinelli Piera , Manfredi Giovanni , Kawamata Hibiki , Trotti Davide
Published: April 2024

The most prevalent genetic cause of both amyotrophic lateral sclerosis and frontotemporal dementia is a (GGGGCC)nnucleotide repeat expansion (NRE) occurring in the first intron of theC9orf72gene (C9). Brain glucose hypometabolism is consistently observed in C9-NRE carriers, even at pre-symptomatic stages, but its role in disease pathogenesis is unknown. Here, we show alterations in glucose metabolic pathways and ATP levels in the brains of asymptomatic C9-BAC mice. We find that, through activation of the GCN2 kinase, glucose hypometabolism drives the production of dipeptide repeat proteins (DPRs), impairs the survival of C9 patient-derived neurons, and triggers motor dysfunction in C9-BAC mice. We also show that one of the arginine-rich DPRs (PR) could directly contribute to glucose metabolism and metabolic stress by inhibiting glucose uptake in neurons. Our findings provide a potential mechanistic link between energy imbalances and C9-ALS/FTD pathogenesis and suggest a feedforward loop model with potential opportunities for therapeutic intervention.
NBR1-mediated selective autophagy of ARF7 modulates root branching
Authors: Ebstrup Elise , Ansbøl Jeppe , Paez-Garcia Ana , Culp Henry , Chevalier Jonathan , Clemmens Pauline , Coll Núria S , Moreno-Risueno Miguel A , Rodriguez Eleazar
Published: April 2024

Auxin dictates root architecture via the Auxin Response Factor (ARF) family of transcription factors, which control lateral root (LR) formation. In Arabidopsis, ARF7 regulates the specification of prebranch sites (PBS) generating LRs through gene expression oscillations and plays a pivotal role during LR initiation. Despite the importance of ARF7 in this process, there is a surprising lack of knowledge about how ARF7 turnover is regulated and how this impacts root architecture. Here, we show that ARF7 accumulates in autophagy mutants and is degraded through NBR1-dependent selective autophagy. We demonstrate that the previously reported rhythmic changes to ARF7 abundance in roots are modulated via autophagy and might occur in other tissues. In addition, we show that the level of co-localization between ARF7 and autophagy markers oscillates and can be modulated by auxin to trigger ARF7 turnover. Furthermore, we observe that autophagy impairment prevents ARF7 oscillation and reduces both PBS establishment and LR formation. In conclusion, we report a novel role for autophagy during development, namely by enacting auxin-induced selective degradation of ARF7 to optimize periodic root branching.