bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving biodiversity in Central and Eastern European domestic gardens needs regionally scaled strategies
Authors: Varga-Szilay Zsófia , Barševskis Arvīds , Benedek Klára , Bevk Danilo , Jojczyk Agata , Krištín Anton , Růžičková Jana , Jelaska Lucija Šerić , Veromann Eve , Vilumets Silva , Fetykó Kinga Gabriela , Szövényi Gergely , Pozsgai Gábor 
Published: July 2024

AbstractAmid ongoing urbanisation and increasing anthropogenic activities, domestic gardens, while they cannot replace undisturbed habitats, play a valuable role in enhancing urban biodiversity by supplementing green areas and improving landscape connectivity. Moreover, biodiversity-friendly gardens also improve human well-being and foster connections between nature and people. To study these benefits, we distributed an online questionnaire between 2022 and 2023, and used a scoring system to evaluate the ecological value of gardens, garden owners’ motivations, and pesticide use habits. We used machine learning to explore how these indices interact and what sociodemographic factors drive them across nine Central and Eastern European (CEE) countries. Additionally, we explored the differences and similarities between the ecological values of gardens and gardening practices in building high biodiversity. Our findings reveal significant variability both between and within countries, across all three indices with Romania faring low and Czechia reaching high scores in all three indices. Domestic pesticide use was ubiquitous across all CEE and largely unaffected by sociodemographic factors. However, increased time spent with gardening was associated with reduced pesticide use and a greater potential for fostering high biodiversity. Garden owners over 55 tended to follow and uphold longstanding conventional practices and thus lowered both pesticide and garden index scores. The local-scale differences we observed emphasise the need for regionally tailored guidelines for biodiversity-friendly gardening over standardized regulations across Europe. Optimal strategies for effective environmental educational and community programs can be developed based on local biodiversity and the three indices used in this study. To maximize their impact and meet local needs, these programs should educate garden owners about the environmental and health effects of pesticides and offer comprehensive biodiversity-related information across all regions and social strata. This is particularly crucial in Central and Eastern Europe (CEE), where such initiatives are currently underrepresented.HighlightsDomestic gardens can enhance biodiversity and support human well-being.Study conducted across nine Central and Eastern European countries.Significant variability both between and within countries in gardening practices.Improving biodiversity in domestic gardens needs regionally scaled strategies.Reducing pesticide use and increasing awareness are key.
SARS-CoV-2 entry and fusion are independent of ACE2 localization to lipid rafts
Authors: Bolland William , Marechal Inès , Petiot Chloé , Porrot Françoise , Guivel-Benhassine Florence , Casartelli Nicoletta , Schwartz Olivier , Buchrieser Julian 
Published: July 2024

ABSTRACTMembrane fusion occurs at the early stages of SARS-CoV-2 replication, during entry of the virus, and later during the formation of multinucleated cells called syncytia. Fusion is mediated by the binding of the viral Spike protein to its receptor ACE2. Lipid rafts are dynamic nanodomains enriched in cholesterol and sphingolipids. Rafts can act as platforms for entry of dìerent viruses by localizing virus receptors, and attachment factors to the same membrane microdomains. Here, we first demonstrate that cholesterol depletion by methyl-beta-cyclodextrin inhibits Spike mediated fusion and entry. To further study the role of ACE2 lipid raft localization in SARS-CoV-2 fusion and entry, we design a GPI-anchored ACE2 construct. Both ACE2 and ACE2-GPI proteins are similarly expressed at the plasma membrane. Through membrane flotation assays, we show that in dìerent cell lines, ACE2-GPI localises predominantly to raft domains of the plasma membrane while ACE2 is non-raft associated. We then compare the ability of ACE2 and ACE2-GPI to permit SARS-CoV-2 pseudovirus entry and syncytia formation and replication of dìerent viral variants. We find little dìerence in the two proteins. Our results demonstrate that SARS-CoV-2 entry and fusion are a cholesterol dependent and raft-independent process.IMPORTANCERafts are often exploited by viruses and used as platforms to enhance their entry into the cell or spread from cell-to-cell. The membrane localization of ACE2 and the role of lipid rafts in SARS-CoV-2 entry and cell-to-cell spread is poorly understood. The function of lipid rafts in viral fusion is often studied through their disruption by cholesterol-depleting agents. However, this process may have ò-target impacts on viral fusion independently of lipid-raft disruption. Therefore, we created an ACE2 construct that localizes to lipid rafts using a GPI anchor. Conversely, wild-type ACE2 was non-raft associated. We find that the localization of ACE2 to lipid rafts does not modify the fusion dynamics of SARS-CoV-2.
Distinct genetic profiles influence body mass index between infancy and adolescence
Authors: Wang Geng , McEwan Samuel , Zeng Jian , Haile-Mariam Mekonnen , Yengo Loic , Goddard Michael E , Kemper Kathryn E , Warrington Nicole M 
Published: July 2024

AbstractBody mass index (BMI) changes throughout life with age-varying genetic contributions. We aimed to investigate the genetic contribution to BMI across early life using repeated measures from the Avon Longitudinal Study of Parents and Children (ALSPAC) cohort. Random regression modelling was used to estimate the genetic covariance matrix (Kg) of BMI trajectories from ages one to 18 years with 65,930 repeated BMI measurements from 6,291 genotyped ALSPAC participants. TheKgmatrix was used to estimate SNP-based heritabilityat yearly intervals from 1-18 years and genetic correlations across early life. We also performed an eigenvalue decomposition ofKgto identify age-varying genetic patterns of BMI. Finally, we investigated the impact of a polygenic score derived from adult BMI on the estimated genetic components across early life. Thewas relatively constant across early life, between 23-30%. The genetic contribution to BMI in early childhood is different to that in later childhood, indicated by the diminishing strength of genetic correlation across different ages. The eigenvalue decomposition revealed that the primary axis of variation (explaining 89% of the genetic variance inKg) increases with age from zero and reaches a plateau in adolescence, while the second eigenfunction (explaining around 9% ofKg) represents factors with opposing effects on BMI between early and later ages. Adjusting for the adult BMI polygenic score attenuated thefrom late childhood; for example,is 29.8% (SE=6.5%) at 18 years of age and attenuates to 14.5% (SE=6.3%) after adjusting for the adult BMI polygenic score. Although common genetic variation explains around 23-30% of BMI variability across early life, our findings indicate that there is a different genetic profile operating during infancy compared to later childhood and adolescence.
Lost in Transplantation: Characterizing Racial Gaps in Physician Organ Offer Acceptance
Authors: Adam Hammaad , Bermea Rene S. , Yang Ming Ying , Celi Leo Anthony , Ghassemi Marzyeh 
Published: July 2024

AbstractBackground.There are known racial disparities in the organ transplant allocation system in the United States. However, prior work has yet to establish if transplant center decisions on offer acceptance—the final step in the allocation process— contribute to these disparities.ObjectiveTo estimate racial differences in the acceptance of organ offers by transplant center physicians on behalf of their patients.DesignRetrospective cohort analysis using data from the Scientific Registry of Transplant Recipients (SRTR) on patients who received an offer for a heart, liver, or lung transplant between January 1, 2010 and December 31, 2020.SettingNationwide, waitlist-based.Patients32,268 heart transplant candidates, 102,823 liver candidates, and 25,780 lung candidates, all aged 18 or older.Measurements1) Association between offer acceptance and two race-based variables: candidate race and donor-candidate race match; 2) association between offer rejection and time to patient mortality.ResultsBlack race was associated with significantly lower odds of offer acceptance for livers (OR=0.93, CI: 0.88-0.98) and lungs (OR=0.80, CI: 0.73-0.87). Donor-candidate race match was associated with significantly higher odds of offer acceptance for hearts (OR=1.11, CI: 1.06-1.16), livers (OR=1.10, CI: 1.06-1.13), and lungs (OR=1.13, CI: 1.07-1.19). Rejecting an offer was associated with lower survival times for all three organs (heart hazard ratio=1.16, CI: 1.09-1.23; liver HR=1.74, CI: 1.66-1.82; lung HR=1.21, CI: 1.15-1.28).LimitationsOur study analyzed the observational SRTR dataset, which has known limitations.ConclusionOffer acceptance decisions are associated with inequity in the organ allocation system. Our findings demonstrate the additional barriers that Black patients face in accessing organ transplants and demonstrate the need for standardized practice, continuous distribution policies, and better organ procurement.
Single-molecule live-cell RNA imaging with CRISPR-Csm
Authors: Xia Chenglong , Colognori David , Jiang Xueyang , Xu Ke , Doudna Jennifer A. 
Published: July 2024

AbstractHigh-resolution, real-time imaging of RNA is essential for understanding the diverse, dynamic behaviors of individual RNA molecules in single cells. However, single-molecule live-cell imaging of unmodified endogenous RNA has not yet been achieved. Here, we present single-molecule live-cell fluorescencein situhybridization (smLiveFISH), a robust approach that combines the programmable RNA-guided, RNA-targeting CRISPR-Csm complex with multiplexed guide RNAs for efficient, direct visualization of single RNA molecules in a range of cell types, including primary cells. Using smLiveFISH, we tracked individual endogenousNOTCH2andMAP1BmRNA transcripts in living cells and identified two distinct localization mechanisms: co-translational translocation ofNOTCH2mRNA at the endoplasmic reticulum, and directional transport ofMAP1BmRNA toward the cell periphery. This method has the potential to unlock principles governing the spatiotemporal organization of native transcripts in health and disease.
Multiomic analyses uncover immunological signatures in kidney transplantation
Authors: Tinel Claire , Varin Alexis , Anglicheau Dany , Callemeyn Jasper , De Loor Jetty , Gwinner Wilfried , Marquet Pierre , Rabant Marion , Sauvaget Virginia , Loon Elisabet Van , Lamarthée Baptiste , Naesens Maarten 
Published: July 2024

AbstractIdentifying biomarkers in kidney transplant patients is essential for early detection of rejection, personalized treatment and improved overall outcomes. It improves our ability to monitor the health of the transplanted organ and tailor interventions to the specific needs of each patient. Here we compiled a multicenter, multiomic dataset of the kidney transplant landscape. Using multi-omics factor analysis (MOFA), we sought to uncover sources of biological variability in patients’ blood, urine and allograft at the epigenetic and transcriptomic levels. MOFA reveals multicellular immune signatures characterized by distinct monocyte, natural killer and T cell substates explaining a large proportion of inter-patient variance. We also identified specific factors that reflect allograft rejection, complement activation or induction treatment. Factor 1 mainly explained the molecular variations in patients’ circulation and discriminated antibody-mediated rejection from T-cell mediated rejection. Factor 2 captured some of the molecular variation occurring within the allograft and associated with complement/monocytes crosstalk. Factor 4 captured the impact of ATG induction. These data provide proof-of-concept of MOFA’s ability to reveal multicellular immune profiles in kidney transplantation, opening up new directions for mechanistic, biomarker and therapeutic studies.
Neural mass modelling reveals that hyperexcitability underpins slow-wave sleep changes in children with epilepsy
Authors: Dunstan Dominic M , Chan Samantha YS , Goodfellow Marc 
Published: July 2024

AbstractObjectiveThe relationship between sleep and epilepsy is important but imperfectly understood. We sought to understand why children with epilepsy have altered sleep homeostasis.MethodsWe used neural mass models to replicate sleep EEG recorded from 15 children with focal lesional epilepsies and 16 healthy age-matched controls.ResultsThe models revealed that sleep EEG differences are driven by enhanced firing rates in the neuronal populations of patients, which arise predominantly due to enhanced excitatory synaptic currents. These differences were more marked in patients who had seizures within 72 hours after the sleep recording. Furthermore, models inferred from patients resided closer in parameter space to models of a typical seizure rhythm.SignificanceThese results demonstrate that brain mechanisms relating to epilepsy manifest in the interictal EEG in slow-wave sleep, and that EEG recorded from patients can be mapped to synaptic deficits that may explain their predisposition to seizures. Neural mass models inferred from sleep EEG data have the potential to generate new biomarkers to predict seizure occurrence or inform treatment decisions.1.Key PointsThe mechanisms that differentiate children with epilepsy from controls during slow-wave sleep can be understood using a mathematical model.The observed spectral power shifts in patients are predominately explained by greater excitatory synaptic currents.These differences in currents place patients’ models closer to seizure rhythms.Ultimately, this framework could help foster the development of biomarkers to guide intervention in epilepsy.
Dynamic Individual Prediction of Conversion from Mild Cognitive Impairment to Probable Alzheimer’s Disease using Joint Modeling
Authors: Mouiha Abderazzak , Potvin Olivier , Duchesne Simon ,   the Alzheimer’s Disease Neuroimaging Initiative
Published: July 2024

ABSTRACTBackgroundWe propose a joint model predicting the risk of conversion from MCI to AD that considers the association between biomarker evolution and disease progression.MethodsWe selected 814 MCI subjects (285 progressives, 529 stables) who had at least four follow-up MRI visits from the ADNI dataset. The values of Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-Cog) were used as a surrogate of time. A mixed linear model was fitted for bilateral hippocampal volumes (HC) versus ADAS-Cog, education, age and sex and a Cox model for risk progression. The association between HC evolution and risk conversion was estimated by fitting a joint model.ResultsOur results show (1) significant association (p< .0001, C.I.= [0.0864; 0.1217]) between bilateral HC and risk of conversion; (2) on average, the risk of progression increased as HC decreased; and (3) the individual prediction of the risk is dynamic, i.e., updated at each follow-up. The AUC of our model for the whole group increased to reach 0.789 at the last follow-up.ConclusionsApplicable to AD and generalizable to other biomarkers and covariates, this joint methodology has a direct application in the clinical estimation of individual risk.
Evaluating acute medical service performance against assessment time metrics: the Society for Acute Medicine Benchmarking Audit 2023 (SAMBA23)
Authors: Atkin Catherine , Subbe Chris , Holland Mark , Varia Ragit , Cooksley Tim , Gebril Adnan , Kennedy Adrian , Knight Thomas , Lasserson Daniel 
Published: July 2024

AbstractPerformance within acute medicine services is impacted by ongoing pressures on acute care services. Data from the Society for Acute Medicine Benchmarking Audit 2023 (SAMBA23), was used to assess performance of acute medicine services compared to key clinical quality indicators, comparing performance by initial assessment location. Data was analysed for 8213 unplanned attendances across 161 hospitals. Comparing by initial assessment location, performance against the clinical quality indicators was unchanged from 2022. Only 29% of daytime arrivals assessed within the Emergency Department received consultant review within target times. Delays were seen in transfer between acute care locations. 29% of patients requiring admission were not admitted to the AMU. There is ongoing variation in acute medical service performance nationally, with significant delays in patient access to appropriate assessment locations.
A comparative analysis of the prevalence of suicidal ideation among depressed and non-depressed pregnant women in rural Bangladesh
Authors: Mumu Rifa Tamanna , Shaikh Md Parvez , Mitra Dipak Kumar 
Published: July 2024

AbstractBackgroundMore than 300 million people all over the world succumbed to depressive disorders in 2015. 680 per 100,000 expectant mothers worldwide bear suicidal ideation during the antenatal period. Despite suicidal ideation being a consequence of antenatal depression, there is a scarcity of information on the prevalence of suicidal ideation in depressed and non-depressed pregnant women in rural Bangladesh.ObjectiveThis study is directed to evaluate the point prevalence of suicidal ideation and compare the prevalence between depressed and non-depressed pregnant women in rural Bangladesh.MethodA cross-sectional study was performed in Lohagara, a rural subdistrict in Bangladesh between January 08 and 17, 2024. 351 pregnant women of various trimesters were recruited for the study. The Bengali-translated version of the Edinburgh Postnatal Depression Scale (EPDS) and another structured questionnaire were used for data collection. Data analyses were done by STATA version 17.ResultThe point prevalence of suicidal ideation is 11.4% (95% CI: 8.5% to 15.2%). It reveals a similarity between depressed and non-depressed pregnant women. The prevalence of suicidal thoughts in antenatally depressed women accounts for 10.2% (95% CI: 6.1% to 16.6%) and in non-depressed pregnant women it is 12.2% (95% CI: 8.4% to 17.3%) -obtained after analysis.ConclusionThe considerable prevalence of suicidal thoughts among depressed and non-depressed rural pregnant women in Bangladesh underscores the necessity of ensuring additional counseling, care, and support to expectant mothers during their antepartum.
Structural insight into sodium ion pathway in the bacterial flagellar stator from marineVibrio
Authors: Nishikino Tatsuro , Takekawa Norihiro , Kishikawa Jun-ichi , Hirose Mika , Kojima Seiji , Homma Michio , Kato Takayuki , Imada Katsumi 
Published: July 2024

AbstractMany bacteria swim in liquid or swarm on surface using the flagellum rotated by a motor driven by specific ion flow. The motor consists of the rotor and stator, and the stator converts the energy of ion flow to mechanical rotation. However, the ion pathway and the mechanism of stator rotation coupled with specific ion flow are still obscure. Here, we determined the structures of the Na+-driven stator ofVibrio, namely PomAB, in the presence and absence of sodium ions and the structure with its specific inhibitor, phenamil, by cryo-electron microscopy. The structures and following functional analysis revealed the sodium ion pathway, the mechanism of ion selectivity, and the inhibition mechanism by phenamil. We propose a model of sodium ion flow coupled with the stator rotation based on the structures. This work provides insights into the molecular mechanisms of ion specificity and conversion of the electrochemical potential into mechanical functions.
Efficacy and mechanism of action of cipargamin as an antibabesial drug candidate
Authors: Li Hang , Ji Shengwei , Ariefta Nanang R. , Galon Eloiza May S. , El-Sayed Shimaa AES , Do Thom , Jia Lijun , Sakaguchi Miako , Asada Masahito , Nishikawa Yoshifumi , Qin Xin , Liu Mingming , Xuan Xuenan 
Published: July 2024

AbstractBabesiosis is a disease brought on by intraerythrocytic parasites of the genusBabesia. Current chemotherapies are accompanied by side effects and parasite relapse. Therefore, it is crucial to develop highly effective drugs againstBabesia. Cipargamin (CIP) has shown inhibition against apicomplexan parasites, mainlyPlasmodiumandToxoplasma. This study evaluated the growth-inhibiting properties of CIP againstBabesiaspp. and investigated the mechanism of CIP onB. gibsoni. The half inhibitory concentration (IC50) values of CIP against thein vitrogrowth ofB. bovisandB. gibsoniwere 20.2 ± 1.4 nM and 69.4 ± 2.2 nM, respectively. CIP significantly inhibited the growth ofB. microtiandB. rodhaini in vivo.Resistance was conferred by L921V and L921I mutations inBgATP4, which reduced the sensitivity to CIP by 6.1- and 12.8-fold. The inhibitory potency of CIP againstBgATP4-associated ATPase activity was moderately reduced in mutant strains, with a 1.3-fold and 2.4-fold decrease inBgATP4L921VandBgATP4L921Icompared to that ofBgATP4WT, respectively. Anin silicoinvestigation revealed reductions in affinity for CIP binding toBgATP4L921VandBgATP4L921Icompared toBgATP4WT. Resistant strains showed no significant cross-resistance to atovaquone (ATO) or tafenoquine (TQ), with less than a onefold change in IC50values. Combining CIP with TQ effectively eliminatedB. microtiinfection in SCID mice, no relapse, and parasite DNA was not detected by qPCR within 90 days post-infection. Our findings reveal the efficacy of CIP as an anti-babesial agent, its limitations as a monotherapy due to resistance development, and the potential of combination therapy with TQ to overcome resistance and achieve complete parasite clearance.
2,3-bis (phenylamino) quinoxaline - containing compounds display potent activity against Methicillin-resistantStaphylococcus aureus,Enterococcus faecalisand their biofilms
Authors: Padalino Gilda , Duggan Katrina , Mur Luis A. J. , Maillard Jean-Yves , Brancale Andrea , Hoffmann Karl F. 
Published: July 2024

AbstractAntimicrobial resistance remains a global challenge threatening the ability to control diseases caused by bacterial infections. Here, we explored the antimicrobial activity of 2,3-N,N-diphenyl quinoxaline derivatives against representative Gram-positive, Gram-negative andMycobacteriumspecies. Two quinoxaline derivatives (compounds25and31) demonstrated particularly potent activity against mostStaphylococcus aureus,Enterococcus faeciumandEnterococcus faecalisstrains tested (MIC values between 0.25 to 1 mg/l). These compounds also demonstrated potent antibacterial activity against methicillin-resistantS. aureus(MRSA) and vancomycin-resistantE. faecium/E. faecalis(VRE) strains. Against an extensive panel of clinically relevant isolates, they further showed comparable or better activity to four currently used antibiotics (vancomycin, teicoplanin, daptomycin and linezolid). Finally, they performed better in preventingS. aureusandE. faecalisbiofilm formation when compared to several other antibiotics. In conclusion, these two quinoxaline derivatives have promising activities that could be further explored as part of efforts to identify urgently needed new antibacterial agents.