bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a prioritization system for mild traumatic brain injury case ascertainment from emergency department records
Authors: MacMillan Katherine , Klotz Tasha , Silverberg Noah D.
Published: November 2024

Objective

To evaluate modifications to a tiered priority chart review system designed to efficiently identify patients with mild traumatic brain injury (mTBI), via medical chart review, that presented to an emergency department or urgent and primary care center (ED/UPCC) for research purposes.

Methods

We initially created a tiered priority chart review system and applied it to screening N=17,072 electronic ED/UPCC medical charts in study 1 (Clinicaltrials.govID#NCT04704037). Chief complaints with high positive predictive value (PPV) for correctly identifying possible/probable mTBI cases were moved to a higher tier and those with low positive predictive value were downgraded to create a tiered priority chart review system. This revised system was then used in a second research study (Clinicaltrials.govID#NCT05365776), and PPV values were calculated for the new sample (N=4,434). The original and revised tiered priority system were compared with respect to overall efficiency.

Results

PPV for specific chief complaint key terms varied markedly from 0% to 61% and resulted in an empirically-driven resorting of the priority tiers. After excluding clearly ineligible participants, 49% of charts reviewed in the first study and 60% of charts reviewed in the second study were identified as a possible or probable mTBI. This indicates an improvement in overall efficiency (12%; χ2(1)=114.7, p<.001) compared to the original system.

Conclusion

The revised tiered priority chart review system was more efficient at identifying patients with mTBI for the purposes of mTBI study recruitment.
Bivalent interaction through an intrinsically disordered linker promotes transcription activation complex assembly in Notch signaling
Authors: Cook Cyril , Ramsey Kristen M. , Barrick Doug
Published: November 2024

The Notch signaling pathway regulates cellular differentiation by activating transcription through an unusual heterotrimeric complex comprising the Notch receptor’s intracellular domain (NICD), the DNA-binding protein CSL, and the coactivator MAML. NICD has two binding sites for CSL, a short motif in the RAM region and an ankyrin domain (ANK), connected by an intrinsically disordered linker and which form a bivalent ternary complex with CSL and MAML. Although bivalency is required for maximal transcription activation, the energetic contributions of bivalency and heterotrimer formation within this essential complex are unknown. To elucidate the energetics of bivalency we first determine the free energy of the CSL-ANK-MAML heterotrimer, using isothermal titration calorimetry and developing an obligate heterotrimer model to analyze the data. By comparing this heterotrimerization reaction with binding reactions involving different regions of RAMANK, we determine the energetic contribution of bivalency to heterotrimer assembly. We show that bivalency through the disordered linker increases the effective concentration of ANK, and that the bivalent interaction enhances occupancy of RAM and ANK at their binding sites on CSL by about three orders of magnitude. By redefining the standard state to a lower, more physiological protein concentration, we reveal the importance of the RAMANK intrinsically disordered linker for assembly of the Notch transcription activation complex. This work provides a framework whereby the energetic contributions of intrinsically disordered linkers to higher-order multivalent assembly may be analyzed.
Assessment of the Genetic Diversity of Atlantic Bottlenose Dolphin (Tursiops truncatus) Strandings in the Mississippi Sound (USA)
Authors: Arick Mark A. , Landrau-Giovannetti Nelmarie , Hsu Chuan-Yu , Grover Corrinne E. , Reichley Stephen , Magbanua Zenaida V. , Pechanova Olga , Moore Debra , Kayal Ehsan , Linhoss Anna , Madrigal Theresa , Peterman Mark , Ozdemir Ozan , Peterson Daniel G. , Solangi Moby , Lawrence Mark , Karsi Attila
Published: November 2024

The common bottlenose dolphin (Tursiops truncatus) is a key marine mammal species in the northern Gulf of Mexico, playing an essential role as a top predator. This study focuses on the genetic diversity and population structure of bottlenose dolphins stranded in the Mississippi Sound from 2010 to 2021. A total of 511 tissue samples (muscle, liver, lung, kidney, and brain) were collected from stranded dolphins, and mitochondrial DNA (mtDNA) was extracted for analysis. Using high-throughput sequencing methods, 417 samples were successfully amplified and sequenced, producing 386 complete mitogenomes. Genetic diversity metrics, such as nucleotide and haplotype diversity, were calculated, and population structure was inferred for both mitochondrial control region (mtCR) and whole mitogenome sequences. Using the whole mitogenome, the study identified four genetically distinct populations within the Mississippi Sound, demonstrating regional variation in dolphin populations. Notably, some individuals likely originated from populations outside the sampled area. The use of whole mitogenomes allowed for improved resolution of genetic diversity and population differentiation compared to previous studies using partial mtDNA sequences. These findings provide critical insights into the genetic structure of bottlenose dolphins in the region and highlight the value of using stranded animals for population genetic studies.
Pfs230 Domain 12 is a potent malaria transmission-blocking vaccine candidate
Authors: Inklaar Maartje R. , de Jong Roos M. , Da Dari F. , Hubregtse Lisanne L. , Meijer Maartje , Teelen Karina , van de Vegte-Bolmer Marga , van Gemert Geert-Jan , Stoter Rianne , Nagaoka Hikaru , Tsuboi Takafumi , Takashima Eizo , Spruijt Cornelia G. , Vermeulen Michiel , Dabire Roch K. , Arinaitwe Emmanuel , Cohuet Anna , Bousema Teun , Jore Matthijs M.
Published: November 2024

Malaria transmission-blocking vaccines (TBV) target sexual stage parasites that are transmitted to mosquitoes and critical for spread of the pathogen. The clinically most advanced TBV candidate contains part of the Pro-domain (Pro) and Domain 1 (D1) ofPlasmodium falciparumsurface protein Pfs230. Subunit vaccines that contain other domains of Pfs230 have so far failed to induce functional antibodies. Here, we produced eight single domain fragments of Pfs230 inDrosophila melanogasterS2 cells and assessed their immunogenicity in mouse immunizations. In addition to D1-specific antibodies, antibodies raised against Domain 12 (D12) showed strong recognition of Pfs230 on the surface of female parasites. Importantly, D12-specific antibodies showed strong functional transmission-reducing activity in membrane feeding assays with cultured parasites, an activity that was complement-dependent. Murine D12-specific antibodies further reduced mosquito transmission of parasites acquired from naturally infected parasite carriers. The D12 antigen was recognized by sera from an all-age cohort of individuals who had been naturally exposed toPlasmodium falciparumwith antibody levels increasing with age. In conclusion, we identified Pfs230D12 as a promising new TBV candidate.

Impact statement

Pfs230 Domain 12 induces antibodies in mice that strongly reduce transmission of lab-cultured and naturally circulating malaria parasites to mosquitoes.
Stability of the polarization agent AsymPolPOK in intact and lysed mammalian cells
Authors: Lagasca Dominique , Ghosh Rupam , Xiao Yiling , Frederick Kendra K.
Published: November 2024

Dynamic nuclear polarization (DNP) solid-state NMR enables detection of proteins at endogenous concentrations in cells through sensitivity enhancement from nitroxide biradical polarization agents. AsymPolPOK, a novel water-soluble asymmetric nitroxide biradical, offers superior sensitivity and faster build-up times compared to existing agents like AMUPol. Here, we characterize AsymPolPOK in mammalian HEK293 cells, examining its cellular distribution, reduction kinetics, and DNP performance. We demonstrate that electroporation achieves uniform cellular delivery of AsymPolPOK, including nuclear permeation, with no cytotoxicity at millimolar concentrations. However, the cellular environment rapidly reduces AsymPolPOK to its monoradical form, with one nitroxide center showing greater reduction resistance than the other. While AsymPolPOK maintains high DNP enhancements and short build-up times in lysates, its performance in intact cells depends critically on delivery method and exposure time to cellular constituents. Electroporation yields higher, more uniform enhancements compared to incubation, but prolonged exposure to the cellular environment diminishes DNP performance in both cases. These findings establish the potential of AsymPolPOK as a polarization agent for in-cell DNP NMR while highlighting the need for developing more bio-resistant polarization agents to further advance cellular structural biology studies.
Movement ecology of captive-bred axolotls in restored and artificial wetlands: conservation insights for amphibian reintroductions and translocations
Authors: Ramos Alejandra G. , Mena Horacio , Schneider David , Zambrano Luis
Published: November 2024

Amphibians are among the most endangered vertebrates globally due to habitat loss, environmental degradation, and urban expansion. The Mexican axolotl (Ambystoma mexicanum), a critically endangered aquatic species endemic to Xochimilco, exemplifies these challenges. This study evaluates the viability of restored and artificial wetlands for axolotl conservation by comparing movement patterns, home range sizes, and habitat use. Using VHF telemetry, we tracked captive-bred axolotls released into both environments. Axolotls survived and foraged successfully in both sites, with those in La Cantera Oriente (LCO) exhibiting larger home ranges and greater daily distances traveled than those in Xochimilco. A quadratic relationship between water temperature and movement indicated a narrow thermal preference. Additionally, age and sex influenced movement patterns, with younger axolotls and females traveling greater distances. Recaptured individuals gained weight, suggesting successful adaptation, although two axolotls were lost to avian predation in Xochimilco after the study concluded. These findings highlight the potential of artificial wetlands like LCO for axolotl conservation by providing stable conditions that may mitigate habitat degradation and climate change impacts. The study recommends integrating native and artificial habitats into conservation strategies, incorporating predator awareness training before release, and ongoing habitat monitoring to enhance survival outcomes for this iconic species.
The metabolic pathways underlying dynamic heterosis for plant height are robust biomarkers in rice
Authors: Dan Zhiwu , Chen Yunping , Huang Wenchao
Published: November 2024

Robust biomarkers for complex phenotypes enable accurate predictions not only across different populations and environments but also developmental stages because quantitative changes in specific molecules over time are directly connected to phenotypic transformations that determine outcomes of both crop agronomic traits and human diseases. In this study, we conducted a network analysis of untargeted metabolite profiles to investigate dynamic heterosis for rice plant height, a trait that varies during development and contributes to yield heterosis. We found that the levels of pyruvaldehyde were predictive of height heterosis at the seedling stage, while 4-hydroxycinnamic acid showed significant positive correlations with height heterosis across all four developmental stages examined. Our analysis identified metabolic pathways associated with height heterosis, revealing that metabolomic variations at the elongation stage had a more substantial impact than those at other stages. We developed 11 significantly enriched pathways into metabolomic biomarkers with robust predictability for mature hybrids from another population grown under different conditions. This work elucidates the metabolomic landscape of dynamic height heterosis in rice and provides a practical strategy for identifying biomarkers capable of predicting complex phenotypes, irrespective of discrepancies in population, environment, and developmental stage.
Estimating the Treatment Effects of Multiple Drug Combinations on Multiple Outcomes in Hypertension
Authors: Liu Ruoqi , Li Lang , Zhang Ping
Published: November 2024

Hypertension poses a significant global health challenge, and its management is often complicated by the complexity of treatment strategies involving multiple drug combinations and the need to consider multiple outcomes. Traditional treatment effect estimation (TEE) methods struggle to address this complexity, as they typically focus on binary treatments and binary outcomes. To overcome these limitations, we introduce METO, a novel framework designed for TEE in the context of multiple drug combinations and multiple outcomes. METO employs a multi-treatment encoding mechanism to effectively handle various drug combinations and their sequences, and differentiates between effectiveness and safety outcomes by explicitly learning the outcome type when predicting the treatment outcomes. Furthermore, to address confounding bias in outcome prediction, we employ an inverse probability weighting method tailored for multiple treatments, assigning each patient a balance weight derived from their propensity score against different drug combinations. Our comprehensive evaluation using a real-world patient dataset demonstrates that METO outperforms existing TEE methods, with an average improvement of 5.0% in area under the precision-recall curve and 6.4% in influence function-based precision of estimating heterogeneous effects. A case study demonstrates that our method successfully identifies personalized optimal antihypertensive dual regimens, achieving maximal efficacy and minimal drug-related safety risks. This showcases its potential for improving treatment strategies and outcomes in hypertension management.
Entangled adaptive landscapes facilitate the evolution of gene regulation by exaptation
Authors: Westmann Cauã Antunes , Goldbach Leander , Wagner Andreas
Published: November 2024

Exaptation, the co-option of existing traits for new functions, is a central process in Darwinian evolution. However, the molecular changes leading to exaptations remain unclear. Here, we investigated the potential of bacterial transcription factor binding sites (TFBSs) to evolve exaptively for the three globalE. colitranscription factors (TFs) CRP, Fis, and IHF. Using a massively parallel reporter assay, we mapped three combinatorially complete adaptive landscapes, encompassing all intermediate sequences between three pairs of strong TFBSs for each TF. Our results revealed that these landscapes are smooth and navigable, with a monotonic relationship between mutations and their impact on gene regulation. Starting from a strong TFBS for one of our TFs, Darwinian evolution can create a strong TFBS for another TF through a small number of individually adaptive mutations. Notably, most intermediate genotypes are prone to transcriptional crosstalk – gene regulation mediated by both TFs. Because our landscapes are smooth, Darwinian evolution can also easily create TFBSs that show such crosstalk whenever it is adaptive. Our study presents the first in vivo evidence that new TFBSs can evolve exaptively through multiple small and adaptive mutational steps. It also highlights the importance of regulatory crosstalk for the diversification of bacterial gene regulation.
Spatio-temporal dynamics of the fibrotic niche in cardiac repair
Authors: Chan Andy Shing Fung , Greiner Joachim , Brennan Tomas , Agrawal Ankit , Hemmer Helene , Sinning Katrin , Marschhäuser Lisa , Cheung Wing Lam , Iqbal Zafar , Klesen Alexander , Seidel Thomas , Vaeth Martin , Rog-Zielinska Eva , Kohl Peter , Schneider-Warme Franziska , Grün Dominic
Published: November 2024

The heart is one of the least regenerative organs in humans, and ischemic heart disease is the leading cause of death worldwide. Understanding the cellular and molecular processes that occur during cardiac wound healing is an essential prerequisite to reducing health burden and improve cardiac function after myocardial tissue damage. By integrating single-cell RNA-sequencing with imaging-based spatial transcriptomics, we reconstructed the spatio-temporal dynamics of the fibrotic niche after ventricular injury in adult mice. Our analysis reveals dynamic regulation of local cell communication niches over time. We identified interactions that regulate cardiac repair, including fibroblast proliferation silencing byTrem2highmacrophages that prevents excessive fibrosis. Moreover, we discovered a rare population of dedifferentiating cardiomyocytes during early post-lesion stages, which was sustained by signals from myeloid and lymphoid cells. Culturing non-regenerative mouse cardiomyocytes or human heart tissue with these niche factors reactivated progenitor gene expression and cell cycle activity. In summary, this spatio-temporal cell type atlas provides valuable insights into the heterocellular interactions that control cardiac repair.

Highlights

scRNA-seq and in situ sequencing reveal spatio-temporal dynamics of heart repair

Local heterocellular communication niches coordinate overall wound response

Fibroblast cell cycle silencing byTrem2highmacrophages suppresses excessive fibrosis

Cardiomyocyte plasticity is promoted by myeloid and lymphoid cells
Prenatal Arsenic Exposure and Gene Expression in Fetal Liver, Heart, Lung, and Placenta
Authors: Rychlik K. A. , Kashiwagi C. , Liao J. , Mathur A. , Illingworth E. J. , Sanchez S. S. , Kleensang A. , Maertens A. , Sillé F. C. M.
Published: November 2024

Prenatal arsenic exposure has been linked to a myriad of negative health effects. There is relatively little insight into the mechanisms and signaling alterations across different fetal organs that drive long-term immune-related issues following prenatal arsenic exposure. Therefore, the effects of this exposure window on gene expression in the liver, placenta, heart, and lung of gestation day (GD) 18 C57BL/6 mouse fetuses were investigated. From two weeks prior to mating until tissue collection at GD18, mice were exposed to 0 or 100 ppb sodium (meta) arsenite in drinking water. Genes of interest were analyzed by RT-qPCR, complemented with untargeted Agilent 44K microarray analysis. Data cleanup and analysis was performed in RStudio. Differentially expressed mRNAs were queried in the String Database and using Cytoscape to create interaction networks and identify significantly enriched biological pathways. A total of 251, 165, 158, and 41 genes were significantly altered in the liver, placenta, heart, and lung, respectively, when treated samples were compared to controls. Many altered pathways were immune-related, supporting prior research. Most notably, gene expression of Gbp3, a key player in the cellular response to interferon gamma, was found to be reduced in placentas of female fetuses exposed to arsenic compared to controls (p=0.0762).

Impact

This is the first study comparing alterations in gene expression across multiple organs following prenatal exposure to environmentally relevant levels of arsenic. These findings, elucidating the multi-organ impact of prenatal arsenic exposure on predominantly immune-related pathways, further our mechanistic understanding of the long-term health effects observed in early-life arsenic-exposed populations.
Implication ofTITINVariations in Dilated Cardiomyopathy: Integrating Whole Exome Sequencing With Molecular Dynamics Simulation Study
Authors: Mukhopadhyay Amrita , Devi Bharti , Baidya Anurag TK , Yadav Manohar Lal , Kumar Rajnish , Mohapatra Bhagyalaxmi
Published: November 2024

Dilated cardiomyopathy (DCM) is one of the leading causes of heart failure, characterized by ventricular dilation and impaired systolic function. Variations in theTITIN(TTN)gene, which encodes the giant muscle protein TTN, play a pivotal role in the genetic underpinnings of DCM. We conducted WES on 15 patients (5 familial and 10 sporadic) diagnosed with idiopathic DCM and identified 88 exonic variants including four novel variants. These variants were predominantly located in the A-band region (39 variants) of TTN, a critical region for its mechanical stability and interaction with other sarcomeric proteins, followed by the I-band domain (33 variants), Z-disc domain (7 variants) and M-band region (9 variants). To discern the functional repercussions of these variations, we performed several bioinformatics analyses including pathogenicity prediction, protein stability, and protein-protein docking followed by MD simulations on both wild-type and mutant TTN fragments with their corresponding interacting partners (TCAP, MYH7, LMNA). We revealed that variations in the A-band domain significantly alter the protein’s structural dynamics, leading to decreased mechanical stability and altered protein-protein interactions. These changes are likely to disrupt sarcomere function, thereby elucidating their role in the pathogenesis of DCM.

Graphical abstract
A revision of the AfricanRussula radicansand allies in subgen.Heterophyllidiaeprovides an example of a clade that exhibits recent diversification and extensive phenotypic plasticity
Authors: Buyck B , Henkel TW , Manz C , Cao SQ , Amalfi M , Wang XH
Published: November 2024

RussulasubsectionRadicantinaeis described forR. radicansand allies, while subsectionAureotactinaeis again restricted toR. aureotacta, the subsectional type species that has never been recollected since its original description.Russula radicans,originally described from Madagascar, as well as the Central AfricanR. brunneoannulata,are epitypified.Russula xylophilais the first confirmed annulate species belonging to Sect.Ingrataeand a close relative toR. oleifera.An ITS sequence has been obtained from theR. xylophilaholotype collection made in 1928, but it is slightly different from those obtained from all new collections. For this reason and some minor morphological differences, we refrained from epitypification.Russula acriannulata, another species attributed toAureotactinaein the past, is now also excluded from the subsection, but needs more sequencing to solve its systematic placement. The MalagasyRussula cibaensisandR. tapiae, as well as the Central AfricanR. cameroonensisandR. afrovinaceaare new species inRadicantinae.At least three more undescribed species are revealed by environmental sequences. The West AfricanR. sankaraeis reduced to a form ofR. radicans. The latter species exhibits an impressive phenotypic plasticity in response to differences in habitat or host associations. It has a very wide distribution covering littoral rain forest in eastern Madagascar (formaradicans), Zambezian woodlands in Central and Eastern Africa (formamiomboensisfo. nov.) and gallery forests in West Africa (formasankarae).
Cell-context dependent in silico organelle localization in label-free microscopy images
Authors: Elmalam Nitsan , Zaritsky Assaf
Published: November 2024

In silico labeling prediction of organelle fluorescence from label-free microscopy images has the potential to revolutionize our understanding of cells as integrated complex systems. However, out-of-distribution data caused by changes in the intracellular organization across cell types, cellular processes or perturbations, can lead to altered label-free images and impaired in silico labeling. We demonstrated that incorporating biological meaningful cell contexts, via a context-dependent model that we call CELTIC, enhanced in silico labeling prediction and enabled downstream analysis of out-of-distribution data such as cells undergoing mitosis, and cells located at the edge of the colony. These results suggest a link between cell context and intracellular organization. Using CELTIC to generate single cell images transitioning between different contexts enabled us to overcome inter-cell variability toward integrated characterization of organelles’ alterations in cellular organization. The explicit inclusion of context has the potential to harmonize multiple datasets, paving the way for generalized in silico labeling foundation models.
4-Methylpyrazole-mediated inhibition of Cytochrome P450 2E1 protects renal epithelial cells, but not bladder cancer cells, from cisplatin toxicity
Authors: Akakpo Jephte Y. , Abbott Erika , Woolbright Ben L. , Ramachandran Anup , Rick Schnellmann G. , Wallace Darren P. , Taylor John A.
Published: November 2024

Cisplatin is an effective chemotherapeutic drug for the treatment of bladder cancer, though cisplatin-induced nephrotoxicity (CIN) occurs in approximately 20-30% of patients, limiting its clinical use. Evidence has shown that cytochrome P450 2E1 (CYP2E1), a drug metabolism enzyme expressed in proximal tubules, mediates the production of reactive oxygen species (ROS) during cisplatin-induced injury. Previously, we showed that the repurposed drug 4-methylpyrazole (4MP; fomepizole) blocks CYP2E1 activity and prevents acetaminophen-induced liver injury. Here, we investigated the potential protective effects of 4MP against CIN. Male and female C57BL/6J mice were treated with a single 20 mg/kg dose of cisplatin for 3 days (acute) or 9 mg/kg/week for 4 weeks (repeated dosing regimen) with or without a co-treatment of 50 mg/kg 4MP. Our findings revealed that acute treatment with cisplatin induced severe histological tubular damage and elevated plasma BUN and creatinine levels in male mice, but not in female mice. This difference correlated with higher basal CYP2E1 expression in the kidneys of male mice compared to female mice. We also found that cisplatin increased renal CYP2E1 activity and that inhibition of CYP2E1 with 4MP significantly reduced cisplatin induced cell death in male mice and primary normal human kidney cells. By contrast, human bladder cancer cells do not express CYP2E1, and treatment with 4MP did not interfere with cisplatin anti-cancer effects in human bladder cancer HTB9 cells. This study highlights the critical role of CYP2E1 in CIN and suggests that its inhibition with 4MP in the kidney is a potential prophylactic therapeutic option to prevent CIN in bladder cancer patients without affecting its anti-neoplastic effect.
Resuscitation-promoting factor (Rpf) terminates dormancy among diverse soil bacteria
Authors: Lennon Jay T. , Lehmkuhl Brent K. , Chen Lingling , Illingworth Melissa , Kuo Venus , Muscarella Mario E.
Published: November 2024

Microorganisms often inhabit environments that are suboptimal for growth and reproduction. To survive when challenged by such conditions, individuals may engage in dormancy where they enter a metabolically inactive state. For this persistence strategy to confer an evolutionary advantage, microorganisms must be able to resuscitate and reproduce when conditions improve. Among bacteria in the phylum Actinomycetota, dormancy can be terminated by resuscitation-promoting factor (Rpf), an exoenzyme that hydrolyzes glycosidic bonds in the peptidoglycan of the cell wall. We characterized Rpf fromMicrococcusKBS0714, a bacterium isolated from agricultural soil. Compared to previous studies, the Rpf elicited activity at relatively high concentrations, yet demonstrated high substrate affinity. Site-directed mutations at conserved catalytic sites significantly reduced or abolished resuscitation, as did the deletion of repeating motifs in a lectin-encoding linker region. We then tested the effects of recombinant Rpf fromMicrococcusKBS0714 on a diverse set of dormant soil bacteria. Patterns of resuscitation mapped onto strain phylogeny, which reflected core features of the cell envelope. Additionally, the direction and magnitude of the Rpf effect were associated with functional traits, in particular, aspects of the moisture niche and biofilm production, which are critical for understanding persistence and resuscitation during dormancy. These findings expand our understanding of how Rpf may affect seed-bank dynamics and have implications for the diversity and functioning of soil ecosystems.
Discordance between biomarkers of iron status in plasma and myocardium across iron replete, iron deficiency, and iron replacement states
Authors: Tomkova Kristina , Cabolis Katerina , Sajic Maria , Wozniak Marcin J , Richards Toby , Murphy Gavin J
Published: November 2024

It is unclear whether plasma measures of iron status reflect iron status in tissues. This study compared the effects of iron deficiency or treatment with intravenous iron on plasma versus myocardial measures of iron metabolism and mitochondrial dysfunction in mice and humans. The human study included 31 people undergoing cardiac surgery. Twenty-two (71%) were iron deficient. The mouse study included 88 mice randomly allocated to iron replete diet group (Controls, n=29), an Iron Deficient diet (n=31) or an iron deficient diet followed by IV Iron administration (n=28). Outcomes included plasma iron and ferritin concentrations, and myocardial total iron, ferritin, IRP1 binding, and mitochondrial complex activity and DNA damage. In the human study, plasma ferritin positively correlated with myocardial ferritin (r2=0.155, p=0.012). People with iron deficiency had significantly lower myocardial ferritin levels than those without iron deficiency. There were no differences or significant correlations for other outcomes. In the mouse study, plasma ferritin negatively correlated with myocardial ferritin (r2=0.113, p=0.004), and iron deficiency reduced myocardial ferritin levels (p=0.018) as well as the binding affinity of myocardial IRP1 to the Ferritin heavy chain mRNA (p=0.033). Intravenous iron had divergent effects on plasma (increased) and myocardial (decreased) ferritin levels, and increased IRP1 binding affinity and mitochondrial respiratory complex activity (p=0.049). These finding suggest that measures of iron metabolism and iron deficiency in plasma do not consistently reflect myocardial iron status across iron replete, iron deficient, and iron replacement states.
Temporal loss of genome-wide and immunogenetic diversity in a near-extinct parrot
Authors: Silver Luke W. , Farquharson Katherine A. , Peel Emma , Gilbert M. Thomas P. , Belov Katherine , Morales Hernán E. , Hogg Carolyn J.
Published: November 2024

Loss of genetic diversity threatens a species' adaptive potential and long-term resilience. Predicted to be extinct by 2038, the orange-bellied parrot (Neophema chrysogaster) is a Critically Endangered migratory bird threatened by numerous viral, bacterial and fungal diseases. The species has undergone multiple population crashes, reaching a low of three wild-born females and 13 males in 2016 and is now represented by only a single wild population and individuals in the captive breeding program. Here we used our high-quality long-read reference genome, and contemporary and historical resequenced genomes from as early as 1829, to track the long-term genomic erosion and immunogenetic diversity decline in this species. 62% of genomic diversity was lost between historical (mean autosomal heterozygosity = 0.00149 ± 0.000699 SD) and contemporary (0.00057 ± 0.000026) parrots. A greater number and length of runs of homozygosity in contemporary samples was also observed. A temporal reduction of the number of alleles at Toll-like receptor genes was found (historical average alleles = 5.78 ± 2.73; contemporary = 3.89 ± 2.10), potentially exacerbating disease susceptibility in the contemporary population. Of particular concern is the new threat of avian influenza strain (HPAI) to Australia. We discuss the conservation implications of our findings and propose that hybridization and synthetic biology may be required to address the catastrophic loss of genetic diversity that has occurred this species in order to prevent extinction.
Polystyrene nanoplastics promote neurodegeneration by catalyzing TDP43 hyperphosphorylation
Authors: Winanto  , Tan Li-Yi , Chooi Wai Hon , Lee Cheryl Yi-Pin , Ho Wan Yun , Lim Yong Shan , Soh Boon Seng , Sanford Emma , Tan Chong-Lun , Liou Yih-Cherng , Huang Cathy Chia-Yu , Ling Shuo-Chien , Ng Shi-Yan
Published: November 2024

The ubiquity of polystyrene nanoplastics (PS-NPs) in our environment raises substantial concerns about their potential impact on human health. Recent studies have shown that PS-NPs cross the blood-brain-barrier and accumulate in the central nervous system (CNS), raising the concerns on the causal role of PS-NP exposure and neurodegenerative diseases. In this study, we utilized human-induced pluripotent stem cell-derived neurons to examine the effects of PS-NPs on neuronal function and health. Our results revealed that PS-NPs penetrate neuronal cells in a size-dependent manner, and are bound by various cellular proteins, including TDP43, a key protein implicated in amyotrophic lateral sclerosis (ALS). Interestingly, CK1 and GSK3β kinases that are known to phosphorylate TDP-43 were found to be associated with PS-NPs. This observation suggests that PS-NPs may play a role in facilitating conditions that lead to TDP43 phosphorylation. We further demonstrate that exposure to healthy motor neurons with PS-NPs resulted in ALS-like phenotypes, characterized by hyperphosphorylated TDP-43, disrupted neuronal morphology, impaired mitochondrial respiration, and accelerated motor neuron death. These findings suggest that PS-NPs contribute to the pathogenesis of neurodegenerative diseases such as ALS and highlight the urgent need for strategies to limit human exposure to nanoplastics.
More with less: Simulation-based inference enables accurate diffusion-weighted MRI with minimal acquisition time
Authors: Eggl Maximilian F. , De Santis Silvia
Published: November 2024

Diffusion-weighted magnetic resonance imaging (dw-MRI) is an essential tool in neuroimaging, providing non-invasive insights into brain microstructure. However, obtaining reproducible and accurate maps requires lengthy acquisition due to the need to massively oversample the parameter space. This means that tensor-based dw-MRI accessibility is still relatively low in daily practice, and more advanced approaches with increased sensitivity and specificity to microstructure are seldom applied in research and clinical contexts. Motivated by recent advances in simulation-based inference (SBI) methods, this work uses neural networks to model the posterior distribution of key diffusion parameters when provided experimental data, allowing accurate estimation with fewer measurements and without the need to train on real data. We find that SBI outperforms standard non-linear least squares fitting under noisy and sparse data conditions in both diffusion tensor and kurtosis imaging, reducing imaging time by 90% while maintaining high accuracy and robustness. Demonstrated on simulated and real data in healthy and pathological brains, this approach can substantially impact radiology by:i)increasing dw-MRI access to more patients, including those unable to undergo long exams;ii)promoting advanced dw-MRI protocols for greater microstructure sensitivity; andiii)rescuing older data where noise hindered analysis. Combining SBI with dw-MRI could greatly improve clinical MRI workflows by reducing patient discomfort, enhancing scan efficiency, and enabling advanced imaging approaches in a data and privacy friendly way.
Evaluating the relationship between visual privacy and work-process interactions in open-plan offices: a space syntax approach
Authors: Yenel Güler Gizem , Demirkan Halime
Published: November 2024

Purpose

Previous studies on privacy in offices have primarily focused on the characteristics of generic visibility, examining the entire visible space from each workspace in 360 degrees. Nevertheless, employees in their workspaces investigate the visual targets within their binocular vision at 120 degrees. Therefore, by adopting the affordances perspective, this study aims to examine deeply generic and targeted visibility in open-plan offices and their relationship to interactions.

Design/methodology/approach

The study consisted of two phases utilizing space syntax techniques. Initially, work-process interactions of the employees were determined through the survey. The survey data underwent spatial analysis to calculate the number of work-process interactions. Subsequently, DepthMapX software was used for visibility analyses. A new Python script for DepthMapX was developed to analyse the targeted visibility ratio. Multiple regression analyses were conducted to examine the relationship between the number of work-process interactions with generic and targeted visibility parameters.

Findings

The findings revealed that a higher number of visible employees within the 120-degree and 360-degree fields of vision corresponded to a lower number of work-process interactions in open-plan offices. Furthermore, the study establishes a direct link between visual privacy and interaction, indicating that increased visibility leads to decreased visual privacy.

Originality/value

The current research concluded that the relationship between visual privacy and interaction in open-plan offices differs from the previous studies, as employees with low visual privacy and high visibility tend to engage in fewer interactions. Overall, this study highlights that increased employee visibility is not directly associated with increased interaction in open-plan offices unless adequate visual privacy is provided.
Engaging tourists through destination social responsibility: the moderating role of self-congruence
Authors: Kumar Vikas , Kaushal Vikrant , Sharma Mohit
Published: November 2024

Purpose

Engaging tourists with a destination brand can offer innumerable benefits. Based on stakeholder and social exchange theories, this study aims to comprehend destination social responsibility’s (DSR) role in inducing destination brand engagement (DBE) and favorable behavioral intentions, i.e. destination advocacy and revisit intentions. Further, the study examines self-congruence as a boundary condition to DSR’s impact on DBE.

Design/methodology/approach

Data were collected through an online survey of individuals in India and analyzed using structural equation modeling.

Findings

Findings highlight the importance of stakeholder and social exchange theories for socially responsible destinations by establishing a link between DSR and DBE, which adds to scholarship and holds practical relevance. Results confirm the moderating effects of self-congruence.

Research limitations/implications

The study did not assume the variation of tourists based on their characteristics and types while examining the moderation effects.

Originality/value

Research adds value by establishing the importance of DSR in engaging tourists with a destination. Furthermore, the study demonstrates how engaged tourists can showcase favorable responses toward the destination.
Leadership canvas: towards a leadership meta-theory
Authors: Bagchi Soumendra N. , Sharma Rajeev
Published: November 2024

Purpose

The voluminous research on leadership, along with multiple theories, makes it challenging for organizational leaders, managers, and trainers to keep track of and reconcile the different theories of leadership to derive benefits from them. We propose a leadership canvas as a meta-theory of leadership theories, integrating the major existing theories by highlighting the unifying principles that underpin these theories.

Design/methodology/approach

This paper has been triggered by students’ and executives’ questions regarding leadership theories and how they choose one over the other. In this paper, we have coded the leadership theories and plotted them on the two-dimensional framework using two dimensions: (1) the collaboration between leader and followers engrained in the theories, and (2) the leader focus, as implied by the different theorists.

Findings

Our proposed two-dimensional leadership canvas reveals that concepts in theories lower on the canvas are necessary conditions for theories higher on the leadership canvas. Thus, our framework illustrates how different leadership theories are part of a continuum rather than distinct from each other.

Originality/value

The proposed framework ensures a bird’s eye view of the theories, facilitating rapid comprehension of existing leadership theories regardless of readers’ prior knowledge. It also incorporates environmental complexity and leader focus in a single framework.
Students' thinking dispositions and teacher's approaches in conflict situations: a case study of a secondary school mathematics class in Japan
Authors: Toyoshima Marie
Published: November 2024

Purpose

This study aims to depict the process of creating a culture of thinking in relation to developing thinking dispositions, focusing on conflicts between students and teachers at the beginning of the school year.

Design/methodology/approach

This study conducted a year-long fieldwork in a secondary school in Tokyo, Japan, including participatory observation of a mathematics class and a semi-structured interview with a teacher. The classroom discourse is analyzed to interpret the students’ thinking dispositions and the teacher's approaches in context using eight lessons. A situation in which the teacher attempts to change the method or direction of students’ thinking is defined as a conflict.

Findings

Five conflict situations are found, namely (1) listening, (2) mathematical explanation, (3) disclosure, (4) giving up and (5) examining ideas. They reveal three characteristics about students’ thinking dispositions: closed-minded, correct answer-ism and mathematical immaturity. Against such students’ thinking, the teacher tried to make them listen carefully to, understand and examine peer ideas, aiming to discuss mathematically. Through these conflicts, the classroom culture moves toward a community of thinking and discussing mathematically.

Originality/value

This study emphasizes the cultural and contextual aspects of thinking dispositions as shaped by a classroom culture. By depicting “conflict” as a new analysis unit, this study reveals students’ thinking dispositions and how they are enacted in what situations and how teacher’s approaches to them create a culture of thinking.
The power of many: analyzing the impact of shared leadership on project teams
Authors: Zhou Qiwei , Wu Qiong , Sun Yuyuan , Cormican Kathryn
Published: November 2024

Purpose

Shared leadership has received significant empirical and theoretical attention in the project management literature. However, a dearth of studies reveals how shared leadership promotes project performance. Drawing on the theory of conservation of resources, this research proposes a serial mediation model that investigates the relationship between shared leadership and project performance through team failure learning and team resilience.

Design/methodology/approach

A field study was conducted that surveyed 79 project teams in various industries (comprising 380 project team members and 79 project managers) using a multisource, time-lagged survey design.

Findings

Our findings show that shared leadership has a positive impact on project performance. More importantly, team failure learning and team resilience play sequential mediating roles in the relationship between shared leadership and project performance.

Practical implications

This research offers new ways for project managers to manage project performance effectively. Project managers are encouraged to recognize the benefits of shared leadership. To do this, they should facilitate team failure learning and improve team resilience, which serves to boost project performance.

Originality/value

This research provides a novel perspective on how shared leadership influences project performance. To the best of our knowledge, we are among the first to explore the serial mediating effects of team failure learning and team resilience on the relationship between shared leadership and project performance.
An analytical approach to incomplete spherical conformal contact: application on self-lubricating spherical plain bearings
Authors: Xue Yahong , Kang Dongzhuang
Published: November 2024

Purpose

Contact pressure is a critical factor that significantly influences the wear of self-lubricating spherical plain bearings. The purpose of this paper is to address the issue of conformal contact in spherical plain bearings with a self-lubricating fabric liner, and then a universal theoretical analytical model for conformal contact between frictionless spheres is proposed.

Design/methodology/approach

This study establishes an analytical model to calculate the conformal contact in spherical plain bearings and verifies the new model by finite element analysis.

Findings

The new model proposed in this paper overcomes the limitations of elastic half-space and small-deformation assumptions. After conducting accuracy validation, it was observed that the computational error of the new model has significantly decreased in comparison to the Johnson model. For a conformal contact with a clearance of 0, the error is nearly 0.

Practical implications

The analytical model can calculate the contact pressure distribution of self-lubricating spherical plain bearings bonded with a self-lubricating layer and can be extended to the conformal contact problem of spherical contact surfaces in biomechanics and other fields.

Originality/value

The model presented here overcomes the limitations of the elastic half-space and small deformation assumptions. It accurately calculates the contact pressure distribution of self-lubricating spherical bearings. Moreover, the complex nonlinear relationship between variables such as normal force, clearance, maximum contact pressure and contact radius was investigated using this model. The model can also be extended and applied to the conformal contact problem of spherical contact surfaces in various fields, including biomechanics.

Peer review

The peer review history for this article is available at: https://publons.com/publon/10.1108/ILT-08-2024-0296/
How hotel VR photography previews enhance customers’ immediate booking intention through mental imagery and perceived value
Authors: Wu Xiaohong , Lai Ivan Ka Wai , Chen Junwei
Published: November 2024

Purpose

The purpose of this study is to examine how a hotel virtual reality photography (VRP) preview enhances customers’ immediate booking intention compared to a picture preview.

Design/methodology/approach

Data were collected using a one-factor between-subject experimental design and time-based systematic sampling. Respondents were asked to read a scenario on an iPad and assess a hotel preview (VRPs vs pictures) before answering the questionnaire.

Findings

The results show that a hotel VRP preview generates more mental imagery than a picture preview in terms of quantity, vividness, modality and valence. These four dimensions of mental imagery indirectly influence customers’ immediate booking intentions through perceived utilitarian value and hedonic value, among which modality has the greatest influence on utilitarian value and valence has the greatest influence on hedonic value. Moreover, utilitarian value has a stronger impact on customers’ immediate booking intentions than does hedonic value.

Originality/value

The results obtained in this study contribute to hospitality research by using cognitive consistency theory as the overarching framework, combining mental imagery theory, media richness theory and perceived value theory to explain the mechanism of tourists’ hotel booking decision-making from hotel previews. Comparing this study’s results with previous studies shows the difference in the effects of 360° (head-mounted) videos, VRPs and pictures on evoking mental imagery across tourism and hotel products, updating our knowledge of VR technology in tourism marketing.