bluuebunny/crossref_metadata_2025_split huggingface dataset:
Site Effects in Multisite Fetal Brain MRI: Morphological Insights into Early Brain Development
Authors: Xu Xinyi , Sun Cong , Yu Hong , Yan Guohui , Zhu Qingqing , Kong Xianglei , Pan Yibin , Xu Haoan , Zheng Tianshu , Zhou Chi , Wang Yutian , Xiao Jiaxin , Chen Ruike , Li Mingyang , Zhang Songying , Hu Hongjie , Zou Yu , Wang Jingshi , Wang Guangbin , Wu Dan 
Published: December 2023

AbstractBackgroundMultisite MRI studies have become prevalent given their advantage in revealing reliable biological or clinical findings. Adult and adolescent multisite studies have demonstrated inevitable site-related non-biological effects that introduce bias. However, the site effect on fetal brain MRI remains unknown.PurposeTo identify crucial acquisition factors affecting fetal brain structural measurements and developmental patterns, while assessing the effectiveness of existing harmonization methods in mitigating site effects.Materials and MethodsBetween May 2017 and March 2022, T2-weighted fast spin-echo sequences in-utero MRI were performed in healthy fetuses from prospectively recruited pregnant volunteers on four different scanners at four sites. A generalized additive model (GAM) was used to quantitatively assess site effects, including field strength (FS), manufacture (M), in-plane resolution (R), and slice thickness (ST), on subcortical volume and cortical morphological measurements, including cortical thickness, curvature, and sulcal depth. Growth models were selected to elucidate developmental trajectories of these morphological measurements. Welch’s test was performed to evaluate the influence of site effects on developmental trajectories. ComBat-GAM harmonization method was applied to mitigate site-related biases.ResultsThe final analytic sample consisted of 340 MRI scans from 218 fetuses (mean gestational age, 30.1 weeks ± 4.4 [range, 21.7–40 weeks]). GAM results showed that low FS and low spatial resolution led to overestimations in selected brain regions of subcortical volumes and cortical morphological measurements, and cortical measurements were more susceptible to site effects than subcortical volumes. Only the peak cortical thickness in developmental trajectories was significantly influenced by the effects of FS and R. Notably, ComBat-GAM harmonization effectively removed site effects while preserving developmental patterns.ConclusionOur findings pinpointed the key acquisition factors in in-utero fetal brain MRI and underscored the necessity of data harmonization when pooling multisite data for fetal brain morphology investigations.
Fast and accurate estimation of selection coefficients and allele histories from ancient and modern DNA
Authors: Vaughn Andrew H. , Nielsen Rasmus 
Published: December 2023

AbstractWe here present CLUES2, a full-likelihood method to infer natural selection from sequence data that is an extension of the method CLUES. We make several substantial improvements to the CLUES method that greatly increases both its applicability and its speed. We add the ability to use ARGs on ancient data as emissions to the underlying HMM, which enables CLUES2 to use both temporal and linkage information to make estimates of selection coefficients. We also fully implement the ability to estimate distinct selection coefficients in different epochs, which allows for the analysis of changes in selective pressures through time. In addition, we greatly increase the computational efficiency of CLUES2 over CLUES using several approximations to the forward-backward algorithms and develop a new way to reconstruct historic allele frequencies by integrating over the uncertainty in the estimation of the selection coefficients. We illustrate the accuracy of CLUES2 through extensive simulations and validate the importance sampling framework for integrating over the uncertainty in the inference of gene trees. We also show that CLUES2 is well-calibrated by showing that under the null hypothesis, the distribution of log-likelihood ratios follows a chi-squared distribution with the appropriate degrees of freedom. We run CLUES2 on a set of recently published ancient human data from Western Eurasia and test for evidence of changing selection coefficients through time. We find significant evidence of changing selective pressures in several genes correlated with the introduction of agriculture to Europe and the ensuing dietary and demographic shifts of that time. In particular, our analysis supports previous hypotheses of strong selection on lactase persistence during periods of ancient famines and attenuated selection in more modern periods.
Ketamine potentiates a central glutamatergic presynapse
Authors: Eshra Abdelmoneim , Lipstein Noa , Hallermann Stefan 
Published: December 2023

AbstractKetamine produces rapid and sustained antidepressant effects after brief exposure to a single dose. Counterintuitively, while ketamine acts primarily as a blocker of postsynaptic N-methyl-D-aspartate receptors (NMDARs), increased signalling at glutamatergic synapses has been reported. Due to technical limitations, however, it remains unclear whether ketamine directly increases presynaptic glutamate release or acts via postsynaptic or network-level mechanisms. To address this knowledge gap, we used presynaptic capacitance measurements to directly monitor glutamate release in a cerebellar synapse. Ketamine increased glutamate release within minutes and this effect persisted >30 minutes after washout. MK-801, another NMDAR blocker, had no effect on glutamate release. Mechanistically, we show that the ketamine-mediated enhancement of presynaptic release results from an increase in both calcium influx and the number of release-ready vesicles. Our data uncover a rapid effect of ketamine on key presynaptic properties of central glutamatergic synapses, which has important implications for the development of antidepressant drugs.
Homeostatic mitophagy scales mitochondrial networks
Authors: Thomas R.L. , Bishop B.C. , Andre L.M. , Nolte H. , Graef M. 
Published: December 2023

AbstractCells scale organelle sizes to ensure physiological function. Here, we uncover a dual role for autophagy in controlling mitochondrial network size with a key function for homeostatic mitophagy. During starvation, non-selective autophagy sustains mitochondrial biogenesis in non-dividing yeast cells resulting in mitochondrial network expansion. Strikingly, Atg32/Bcl2L13-mediated mitophagy scales mitochondria back to pre-starvation size. Without mitophagy, mitochondria size increases two-fold while retaining wildtype-like structural, compositional, and metabolic features. In turn, synthetically elevated mitophagy only mildly reduces mitochondria size, suggesting cells maintain a minimal network size by compensatory biogenesis. Single-cell analysis predicts two metabolically tunable setpoints, mitochondria-to-cell and mitochondria-to-cytosol volume ratios, for mitochondria scaling by autophagy-driven biogenesis and degradation, respectively. Our work reveals how cells use autophagy to scale mitochondria to metabolic and cellular size parameters.One Sentence SummaryA homeostatic form of mitophagy controls the network size of mitochondria during starvation.
STIE: Single-cell level deconvolution, convolution, and clustering in spatial transcriptomics by aligning spot level transcriptome to nuclear morphology
Authors: Zhu Shijia , Kubota Naoto , Wang Shidan , Wang Tao , Xiao Guanghua , Hoshida Yujin 
Published: December 2023

AbstractIn spot-based spatial transcriptomics, spots that are of the same size and printed at the fixed location cannot precisely capture the actual randomly located single cells, therefore failing to profile the transcriptome at the single-cell level. The current studies primarily focused on enhancing the spot resolution in size via computational imputation or technical improvement, however, they largely overlooked that single-cell resolution, i.e., resolution in cellular or even smaller size, does not equal single-cell level. Using both real and simulated spatial transcriptomics data, we demonstrated that even the high-resolution spatial transcriptomics still has a large number of spots partially covering multiple cells simultaneously, revealing the intrinsic non-single-cell level of spot-based spatial transcriptomics regardless of spot size. To this end, we present STIE, an EM algorithm that aligns the spatial transcriptome to its matched histology image-based nuclear morphology and recovers missing cells from up to ∼70% gap area between spots via the nuclear morphological similarity and neighborhood information, thereby achieving the real single-cell level and whole-slide scale deconvolution/convolution and clustering for both low- and high-resolution spots. On both real and simulation spatial transcriptomics data, STIE characterizes the cell-type specific gene expression variation and demonstrates the outperforming concordance with the single-cell RNAseq-derived cell type transcriptomic signatures compared to the other spot- and subspot-level methods. Furthermore, STIE enabled us to gain novel insights that failed to be revealed by the existing methods due to the lack of single-cell level, for instance, lower actual spot resolution than its reported spot size, the additional contribution of cellular morphology to cell typing beyond transcriptome, unbiased evaluation of cell type colocalization, superior power of high-resolution spot in distinguishing nuanced cell types, and spatially resolved cell-cell interactions at the single-cell level other than spot level. The STIE code is publicly available as an R package athttps://github.com/zhushijia/STIE.
Antibiotics at Clinical Concentrations Show Limited Effectivity Against Acute and Chronic IntracellularS. aureusInfections in Osteocytes
Authors: Zelmer Anja R. , Yang Dongqing , Gunn Nicholas J. , Solomon L. Bogdan , Nelson Renjy , Kidd Stephen P. , Richter Katharina , Atkins Gerald J. 
Published: December 2023

AbstractObjectivesCase numbers of osteomyelitis are rising and chronic infections remain difficult to cure. While it is known that the major pathogenStaphylococcus aureuscan persist intracellularly in osteocytes, the effectivity of antibiotics against this condition remains largely unknown. We sought to determine if current clinically utilised antibiotics were capable of clearing an intracellular osteocyteS. aureusinfection.MethodsRifampicin, vancomycin, levofloxacin, ofloxacin, amoxicillin, oxacillin, doxycycline, linezolid, gentamicin and tigecycline were assessed for their MIC and minimum bactericidal concentrations (MBC) against 11S. aureusclinical isolates and the reference strain ATCC 25923, at pH 5.0 and 7.2 to mimic lysosomal and cytoplasmic environments, respectively. Those antibiotics whose bone achievable concentration was commonly above their respective MICs for the strains tested were further assayed in a human osteocyte infection model under either acute or chronic conditions. Osteocyte-like cells were treated at 1, 4 and 10x the MIC for 1 and 7 days following infection (acute model), or after 14 days of infection (chronic model). The intracellular effectivity of each antibiotic was measured in terms of colony forming unit (CFU) reduction, small colony variant (SCV) formation and bacterial mRNA expression change.ResultsOnly rifampicin, levofloxacin and linezolid reduced intracellular CFU numbers significantly in the acute model. The effect was larger after 7 days compared to 1 day of treatment. However, no treatment reduced the quantity of bacterial mRNA, nor prevented non-culturable bacteria from returning to a culturable state.DiscussionThese findings indicate thatS. aureusadapts phenotypically during intracellular infection of osteocytes, adopting a reversible quiescent state which is protected against antibiotics, even at 10x their MIC. Thus, new therapeutic approaches are necessary to cureS. aureusintracellular infections in osteocytes.
Coevolution of age-structured tolerance and virulence
Authors: Buckingham Lydia J. , Ashby Ben 
Published: December 2023

AbstractHosts can evolve a variety of defences against parasitism, including resistance (which prevents or reduces the spread of infection) and tolerance (which protects against virulence). Some organisms have evolved different levels of tolerance at different life-stages, which is likely to be the result of coevolution with pathogens, and yet it is currently unclear how coevolution drives patterns of age-specific tolerance. Here, we use a model of tolerance-virulence coevolution to investigate how age structure influences coevolutionary dynamics. Specifically, we explore how coevolution unfolds when tolerance and virulence (disease-induced mortality) are age-specific compared to when these traits are uniform across the host lifespan. We find that coevolutionary cycling is relatively common when host tolerance is age-specific, but cycling does not occur when tolerance is the same across all ages. We also find that age-structured tolerance can lead to selection for higher virulence in shorter-lived than in longer-lived hosts, whereas non-age-structured tolerance always leads virulence to increase with host lifespan. Our findings therefore suggest that age structure can have substantial qualitative impacts on host-pathogen coevolution.
Cryptosporidium Life Cycle Small Molecule Probing Implicates Translational Repression And An Apetala 2 Transcription Factor In Sexual Differentiation
Authors: Hasan Muhammad M. , Mattice Ethan B. , Teixeira José E. , Jumani Rajiv S. , Stebbins Erin E. , Klopfer Connor , Franco Sebastian , Love Melissa S. , McNamara Case W. , Huston Christopher D. 
Published: December 2023

AbstractThe apicomplexan parasiteCryptosporidiumis a leading cause of childhood diarrhea in developing countries. Current treatment options are inadequate and multiple preclinical compounds are being actively pursued as potential drugs for cryptosporidiosis. Unlike most apicomplexans,Cryptosporidiumspp. sequentially replicate asexually and then sexually within a single host to complete their lifecycles. Anti-cryptosporidial compounds are generally identified or tested through in vitro phenotypic assays that only assess the asexual stages. Therefore, compounds that specifically target the sexual stages remain unexplored. In this study, we leveraged the ReFRAME drug repurposing library against a newly devised multi-readout imaging assay to identify small-molecule compounds that modulate sexual differentiation and maturation. mRNA-seq studies confirmed selective modulation of sexual differentiation for 10 hit compounds (9 inhibitors and 1 accelerator). The collective transcriptomic profiles of these compounds indicates that translational repression accompaniesCryptosporidiumsexual differentiation, which we validated experimentally. Additionally, cross comparison of the RNA-seq data with promoter sequence analysis for stage-specific genes converged on a key role for an Apetala 2 (AP2) transcription factor (cgd2_3490) in sexual differentiation. Finally, drug annotation for the ReFRAME hits indicates that an elevated supply of energy equivalence in the host cell is critical for gamont formation.
Camel milk affects serum metabolites by modulating the intestinal microflora
Authors: Yue Haitao , Zhang Jiaxue , Wang Ruiqi , Zhao Luyu , Kou Yuxuan , Li Runye , Yang Zhengyang , Qian Yurong , Li Xinhui , Wang Xiao , Yasheng Pazilaiti , Wu Jieyi , Xing Xiangxiang , Xie Lei , Niu Hao , Chen Gangliang , Yang Jie , Liu Ying , Shi Tian , Gao Feng 
Published: December 2023

AbstractGut microbes play a vital role in human health and are influenced by numerous factors including diet, genetics, and environment. (Fermented) Camel milk, which is abundant in nutrients and lacks allergenic proteins, has been consumed for its edible and medicinal properties for centuries. Research on camel milk’s impact on gut microbiota and host metabolism is still limited. The results found that sour camel milk contained various beneficial bacteria such asLactobacillus helveticus, Acinetobacter lwoffii, Eubacterium coprostanoligenesgroup, Lachnospiraceae, which could be transported to the recipient’s intestines by diet. This study specified that the transportation of microbiome happened both intra- and inter-species and played a principal role in the formation of progeny gut microflora. An investigation on type 2 diabetic rats revealed that the composition of gut microflora and serum metabolites of those fed with high-dose camel whey was closer to that of the normal.Eubacterium limnetica, which can reduce the risk of diseases by producing MtcB protein, was found in the gut microflora of the ones taking camel milk. These results evidenced the high potential of camel milk as a functional food.
Experimental and theoretical investigation of two thioether-based Schiff bases as anti-corrosion agents for carbon steel in HCl electrolyte
Authors: Morovati Halime , Noorbala Mohammad Reza , Namazian Mansoor , Zare Hamid R. , Dehghani-Firouzabadi Ahmad Ali 
Published: December 2023

Purpose
The main purpose of the present work is to introduce two new Schiff bases as corrosion inhibitors (CIs) for carbon steel (CS). The anti-corrosion performance of these Schiff bases having N and S heteroatoms in their structures was investigated and compared in 2 M HCl electrolyte. The inhibitory activity of these Schiff bases was also assessed.

Design/methodology/approach
Common electrochemical assays like potentiodynamic polarization and electrochemical impedance measurements were used to evaluate the ability of compounds in reduction of the rate of corrosion. Quantum chemical calculations (QCCs) were also used to examine the corrosion inhibitive and the process related to the electrical and structural characteristics of the molecules acting as CIs.

Findings
The electrochemical measurements indicate that both Schiff bases acted as the efficient CIs of CS in 2 M HCl electrolyte. The adsorption of the Schiff base on the surface of the CS caused the corrosion to be inhibited. The change of Gibbs energies indicated that both physical and chemical interactions are involved in the adsorption of NNS and SNS on CS surfaces. The predicted QCCs of the CIs neutral and positively charged versions were well-aligned with those obtained by electrochemical experiments.

Originality/value
Using electrochemical experiments and quantum chemical modelings, two new Schiff bases, N-2-((2-nitrophenyl)thio)phenyl)-1-(pyrrole-2-yl)methanimine (NNS) and N-2-((2-nitrophenyl)thio)phenyl)-1-(thiophen-2-yl)methanimine (SNS), were evaluated as anti-corrosion agents for CS in 2 M HCl electrolyte. The DFT calculations were considered to compute the quantum chemical parameters of the inhibitors.
Understanding leader–member exchange on job satisfaction: while work interfaces between home and life?
Authors: Goswami Munmun , Jena Lalatendu Kesari 
Published: December 2023

PurposeThis study is aimed at decoding the impact of supportive leadership behavior (leader–member exchange [LMX]) on job satisfaction (JS) through the mediating role of the work–nonwork interface (work-to-nonwork conflict [WNC] and work-to-nonwork enrichment [WNE]), within the work-from-home context in India.Design/methodology/approach Multiphased data collected from 232 full-time working Indian dual-working parents (with one or more children) were analyzed using structural equation modeling.FindingsOverall, the hypothesized model receives empirical support from the data. LMX positively influenced WNE and simultaneously negatively influenced WNC. WNE, in turn, positively impacted JS, and WNC negatively influenced JS. Results supported only the mediating role of WNE between LMX and JS but not WNC. Women reported greater JS than men, and respondents staying in a joint family reported decreased WNC.Research limitations/implications The current study takes a multiphased, multidomain approach to understand the underlying mechanisms of leadership’s impact while working from home.Practical implications By adopting a tailored approach, organizations can ensure better alignment between employee goals and the desired outcomes of the organization. This entails considering extended family requirements and designing HR interventions and strategies that accommodate the specific challenges faced by dual-working parents.Originality/value This study helps to shed light on the sparsely researched arena of the role of leadership in the work-from-home context, more so for Indian dual-working households. Hence, it makes significant contributions to theory and practice.
The internal and external effect of environmental complexity on business responses: a PLS-SEM and artificial neural network approach
Authors: Bui My-Trinh , Tran Thi-Thanh-Huyen 
Published: December 2023

PurposeIn the wake of severe socio-economic damage, many firms have made creative and technological progress in their responses to the COVID-19 crisis. This paper examines internal and external environmental complexity elements as antecedents of business responses and builds a framework for tourism firms to respond to the pandemic crisis.Design/methodology/approachThis study obtained survey data from 395 respondents in the Vietnamese tourism and hospitality industry. A partial least squares structural equation modeling–artificial neural network approach was used to examine various combinations of internal and external environmental complexity elements that have different impacts on business responses and firms' performance.FindingsThe knowledge and practice created by the firm's employees (individual creativity), obtained from traditional contexts (traditionality) were identified as internal environmental complexity factors while practice learned from other firms (mimetic pressure), information processing (status certainty) and digital transformation (digital technology speed) were treated as external environmental complexity factors. Internal and external environmental complexity factors influence business responses and firms' performance positively but differently.Practical implicationsThis study demonstrates that firms should integrate their internal environment of creativity and traditionality with external environmental factors of mimetic pressure, status certainty and digital technology speed to create better business responses, and thus firm performance in the COVID-19 era.Originality/valueThis investigation contributes to environmental research and narrows the existing research gap relating to the association between types of environmental complexity and firms' responsive action, which then influence firms' performance in terms of sustainable competitiveness.