bluuebunny/crossref_metadata_2025 huggingface dataset:
Key factors for sustainable working conditions in emergency departments: an EUSEM-initiated, Europe-wide consensus survey
Authors: Weigl Matthias , Lifschitz Michael , Dodt Christoph
Published: July 2024

Background and importance

Modern emergency medicine (EM) is a complex, demanding, and occasionally stressful field of work. Working conditions, provider well-being, and associated health and performance outcomes are key factors influencing the establishment of a sustainable emergency department (ED) working environment.

Objectives

This multinational European Delphi survey aimed to identify unequivocal major factors for good and poor ED working conditions and their possible effects on health care provider well-being.

Design/setting and participants

A total of 18 experts from six European countries (Belgium, Finland, Germany, Italy, Romania, and the UK) covering three different hospital sizes (small, medium, and large) in their respective countries participated in the two-round Delphi survey. All panelists held leadership roles in EM.

Outcome measures and analysis

The first step involved conducting an extensive literature search on ED working conditions. The second step involved the first Delphi round, which consisted of structured interviews with the panelists. The survey was designed to obtain information concerning important working conditions, comments regarding work-life factors identified from the literature, and ratings of their importance. Interviews were transcribed and analyzed following a standardized protocol. In the second Delphi round, experts rated the relevance of items consolidated from the first Delphi round (classified into ED work system factors, provider health outcomes, and ED work-life intervention approaches).

Results

A nearly unequivocal consensus was obtained in four ED work condition categories, including positive (e.g. job challenges, personal motivation, and case complexities) and negative (e.g. overcrowding, workflow interruptions/multitasking, medical errors) ED work conditions. The highly relevant adverse personal health events identified included physical fatigue, exhaustion, and burnout. Concerning intervention practices, the panelists offered a wide spectrum of opportunities with less consensus.

Conclusion

Work system conditions exert positive and negative effects on the work life of ED providers across Europe. Although most European countries have varying health care systems, the expert-based survey results presented herein strongly suggest that improvement strategies should focus on system-related external stressors common in various countries. Our findings lay the scientific groundwork for future intervention studies at the local and systemic levels to improve ED provider work life.
Concept Analysis of Woman-Centered Care
Authors: Sposato Margaret F. , Miller Wendy R.
Published: July 2024

Approximately two-thirds of pregnancy-related deaths in the United States occur during the postpartum period, yet there is minimal research focusing on the postpartum hospital stay, a critical point of contact between women and the health care system and an important opportunity for intervention. A new approach to postpartum care is needed. “Woman-centered” postpartum care is recommended to improve maternal outcomes, but the concept of woman-centered care is not well-defined. Using Walker & Avant's method of concept analysis, we identified four defining attributes of woman-centered care in the literature: 1) choice, control, and involvement in decision-making; 2) communication and collaboration in the caregiver–woman relationship; 3) individualized and holistic care; and 4) continuity of care. Using these findings, we offer a conceptual definition of woman-centered care and apply the attributes to the postpartum hospitalization in the model and contrary cases. We discuss the potential of the concept to improve maternal health care during this critical period.
HETEROGENEOUS EXPANSION OF POLYMORPHONUCLEAR MYELOID-DERIVED SUPPRESSOR CELLS DISTINGUISHES HIGH-RISK SEPSIS IMMUNOPHENOTYPES IN UGANDA
Authors: Cummings Matthew J. , Guichard Vincent , Owor Nicholas , Ochar Thomas , Kiwubeyi Moses , Nankwanga Rittah , Kibisi Richard , Kassaja Charles , Ross Jesse E. , Postler Thomas S. , Kayiwa John , Reynolds Steven J. , Nakibuuka Martina Cathy , Nakaseegu Joweria , Lutwama Julius J. , Lipkin W. Ian , Ghosh Sankar , Bakamutumaho Barnabas , O’Donnell Max R.
Published: July 2024

Background: Understanding of immune cell phenotypes associated with inflammatory and immunosuppressive host responses in sepsis is imprecise, particularly in low- and middle-income countries, where the global sepsis burden is concentrated. In these settings, elucidation of clinically relevant immunophenotypes is necessary to determine the relevance of emerging therapeutics and refine mechanistic investigations of sepsis immunopathology. Methods: In a prospective cohort of adults hospitalized with suspected sepsis in Uganda (N = 43; median age 46 years [IQR 36–59], 24 [55.8%] living with HIV, 16 [37.2%] deceased at 60 days), we combined high-dimensional flow cytometry with unsupervised machine learning and manual gating to define peripheral immunophenotypes associated with increased risk of 60-day mortality. Results: Patients who died showed heterogeneous expansion of polymorphonuclear myeloid-derived suppressor cells, with increased and decreased abundance of CD16−PD-L1dim and CD16brightPD-L1bright subsets, respectively, significantly associated with mortality. While differences between CD16−PD-L1dim cell abundance and mortality risk appeared consistent throughout the course of illness, those for the CD16brightPD-L1bright subset were more pronounced early after illness onset. Independent of HIV co-infection, depletion of CD4+ T cells, dendritic cells, and CD56−CD16bright NK cells were significantly associated with mortality risk, as was expansion of immature, CD56+CD16−CD11c+ NK cells. Abundance of T cells expressing inhibitory checkpoint proteins (PD-1, CTLA-4, LAG-3) was similar between patients who died versus those who survived. Conclusions: This is the first study to define high-risk immunophenotypes among adults with sepsis in sub-Saharan Africa, an immunologically distinct region where biologically informed treatment strategies are needed. More broadly, our findings highlight the clinical importance and complexity of myeloid derived suppressor cell expansion during sepsis and support emerging data that suggest a host-protective role for PD-L1 myeloid checkpoints in acute critical illness.
Further evidence of the role of microRNA in schizophrenia: a case report
Authors: Sanjuan-Ortiz Cecilia , Rojo-Bofill Luis M. , Rosello Monica , Orellana Carmen , Iranzo-Tatay Carmen
Published: July 2024

According to the neurodevelopmental hypothesis of schizophrenia, genetic predisposing factors cause abnormalities in neural functions, leading to the disease. A 2-year follow-up of a young woman with schizophrenia is presented. Karyotype, Affymetrix CytoScanTM 750K SNP array, and optical genome mapping ultra-high molecular weight were carried out. The case presented a severe and resistant to treatment schizophrenia. A 404 kbp microduplication in 2q13 (chr2 : 112088944-112492811; Hg19) was revealed, which includes an only gene (MIR4435-2HG, OMIM 617144). The Positive and Negative Syndrome Scale of Schizophrenia questionnaire showed a moderate improvement after 2 years, but functioning was still poor. The presented case had a microduplication of copy number variants at 2q13, previously linked to schizophrenia, but it only involved one gene, encoding a microRNA, which regulates the expression of candidate genes associated to neurodevelopment. This case provides further evidence of the importance of microRNA in the pathogenesis of schizophrenia.
Explaining the emergence of land-use frontiers
Authors: Meyfroidt Patrick , Abeygunawardane Dilini , Baumann Matthias , Bey Adia , Buchadas Ana , Chiarella Cristina , Junquera Victoria , Kronenburg García Angela , Kuemmerle Tobias , le Polain de Waroux Yann , Oliveira Eduardo , Picoli Michelle , Qin Siyu , Rodriguez García Virginia , Rufin Philippe
Published: July 2024

Land-use expansion is linked to major sustainability concerns including climate change, food security and biodiversity loss. This expansion is largely concentrated in so-called ‘frontiers’, defined here as places experiencing marked transformations owing to rapid resource exploitation. Understanding the mechanisms shaping these frontiers is crucial for sustainability. Previous work focused mainly on explaining how active frontiers advance, in particular, into tropical forests. Comparatively, our understanding of how frontiers emerge in territories considered marginal in terms of agricultural productivity and global market integration remains weak. We synthesize conceptual tools explaining resource and land-use frontiers, including theories of land rent and agglomeration economies, of frontiers as successive waves, spaces of territorialization, friction and opportunities, anticipation and expectation. We then propose a new theory of frontier emergence, which identifies exogenous pushes, legacies of past waves and actors’ anticipations as key mechanisms by which frontiers emerge. Processes of differential rent creation and capture and the built-up of agglomeration economies then constitute key mechanisms sustaining active frontiers. Finally, we discuss five implications for the governance of frontiers for sustainability. Our theory focuses on agriculture and deforestation frontiers in the tropics but can be inspirational for other frontier processes including for extractive resources, such as minerals.
Insights into the production and evolution of lantibiotics from a computational analysis of peptides associated with the lanthipeptide cyclase domain
Authors: Maheshwari Nikunj , Jermiin Lars S. , Cotroneo Chiara , Gordon Stephen V. , Shields Denis C.
Published: July 2024

Lanthipeptides are a large group of ribosomally encoded peptides cyclized by thioether and methylene bridges, which include the lantibiotics, lanthipeptides with antimicrobial activity. There are over 100 experimentally characterized lanthipeptides, with at least 25 distinct cyclization bridging patterns. We set out to understand the evolutionary dynamics and diversity of lanthipeptides. We identified 977 peptides in 2785 bacterial genomes from short open-reading frames encoding lanthipeptide modifiable amino acids (C, S and T) that lay chromosomally adjacent to genes encoding proteins containing the cyclase domain. These appeared to be synthesized by both known and novel enzymatic combinations. Our predictor of bridging topology suggested 36 novel-predicted topologies, including a single-cysteine topology seen in 179 lanthionine or labionin containing peptides, which were enriched for histidine. Evidence that supported the relevance of the single-cysteine containing lanthipeptide precursors included the presence of the labionin motif among single cysteine peptides that clustered with labionin-associated synthetase domains, and the leader features of experimentally defined lanthipeptides that were shared with single cysteine predictions. Evolutionary rate variation among peptide subfamilies suggests that selection pressures for functional change differ among subfamilies. Lanthipeptides that have recently evolved specific novel features may represent a richer source of potential novel antimicrobials, since their target species may have had less time to evolve resistance.
Third-party arbitration and forgiving strategies increase cooperation when perception errors are common
Authors: Lenfesty Hillary , Mathew Sarah , Fikes Thomas , Ross Cody T. , Boyd Robert
Published: July 2024

Humans cooperate in groups in which mutual monitoring is common, and this provides the possibility of third-party arbitration. Third-party arbitration stabilizes reciprocity in at least two ways: first, when it is accurate, it reduces the frequency of misunderstandings resulting from perception errors, and second, even when it is inaccurate, it provides a public signal that allows pairs to align their expectations about how to behave after errors occur. Here, we describe experiments that test for these two effects. We find that in an iterated, sequential Prisoner’s Dilemma game with errors, players with the highest average payoffs are those who make use of third-party arbitration and who also employ forgiving strategies. The combination of these two behaviours reduces the detrimental effects of errors on reciprocity, resulting in more cooperation.
The blushing brain: neural substrates of cheek temperature increase in response to self-observation
Authors: Nikolić Milica , di Plinio Simone , Sauter Disa , Keysers Christian , Gazzola Valeria
Published: July 2024

Darwin proposed that blushing—the reddening of the face owing to heightened self-awareness—is ‘the most human of all expressions’. Yet, relatively little is known about the underlying mechanisms of blushing. Theories diverge on whether it is a rapid, spontaneous emotional response that does not involve reflection upon the self or whether it results from higher-order socio-cognitive processes. Investigating the neural substrates of blushing can shed light on the mental processes underlying blushing and the mechanisms involved in self-awareness. To reveal neural activity associated with blushing, 16–20 year-old participants (n= 40) watched pre-recorded videos of themselves (versus other people as a control condition) singing karaoke in a magnetic resonance imaging scanner. We measured participants’ cheek temperature increase—an indicator of blushing—and their brain activity. The results showed that blushing is higher when watching oneself versus others sing. Those who blushed more while watching themselves sing had, on average, higher activation in the cerebellum (lobule V) and the left paracentral lobe and exhibited more time-locked processing of the videos in early visual cortices. These findings show that blushing is associated with the activation of brain areas involved in emotional arousal, suggesting that it may occur independently of higher-order socio-cognitive processes. Our results provide new avenues for future research on self-awareness in infants and non-human animals.
Sexually selected weapons can wear out, decreasing their effectiveness in combat
Authors: McEvoy Isaac , Daniels Lana , Emberts Zachary
Published: July 2024

Sexual selection has resulted in some of the most elaborate traits seen in animals, many of which are used as weapons. These weapons can be incredibly diverse, even within species. Such morphological variation has largely been attributed to the environment in which individuals are reared and their genetics. However, variation in weapon form could also be the result of a weapon wearing out from usage. This mechanism has received relatively little attention. In this study, we demonstrate that sexually selected weapons can wear out from repeated use, providing experimental evidence that weapon usage can contribute to the diversity of weapon shapes observed within species. In a second experiment, we demonstrate that having a worn-out weapon decreases an individual’s fighting ability. This finding illustrates that the shape of a weapon can have an important role in determining contest outcomes. Overall, these results suggest that individuals are limited in the number of times they can effectively use their weapons, which may be one factor (among others) influencing how frequently an animal engages in a fight.
Mapping the Escherichia coli DnaA-binding landscape reveals a preference for binding pairs of closely spaced DNA sites
Authors: Stringer Anne M. , Fitzgerald Devon M. , Wade Joseph T.
Published: July 2024

DnaA is a widely conserved DNA-binding protein that is essential for the initiation of DNA replication in many bacterial species, including Escherichia coli. Cooperative binding of ATP-bound DnaA to multiple 9mer sites (‘DnaA boxes’) at the origin of replication results in local unwinding of the DNA and recruitment of the replication machinery. DnaA also functions as a transcription regulator by binding to DNA sites upstream of target genes. Previous studies have identified many sites of direct positive and negative regulation by E. coli DnaA. Here, we use a ChIP-seq to map the E. coli DnaA-binding landscape. Our data reveal a compact regulon for DnaA that coordinates the initiation of DNA replication with expression of genes associated with nucleotide synthesis, replication, DNA repair and RNA metabolism. We also show that DnaA binds preferentially to pairs of DnaA boxes spaced 2 or 3 bp apart. Mutation of either the upstream or downstream site in a pair disrupts DnaA binding, as does altering the spacing between sites. We conclude that binding of DnaA at almost all target sites requires a dimer of DnaA, with each subunit making critical contacts with a DnaA box.
Bridging the gap: a prospective trial comparing programmable targeted long-read sequencing and short-read genome sequencing for genetic diagnosis of cerebellar ataxia
Authors: Rafehi Haloom , Fearnley Liam G. , Read Justin , Snell Penny , Davies Kayli C. , Scott Liam , Gillies Greta , Thompson Genevieve C. , Field Tess A. , Eldo Aleena , Bodek Simon , Butler Ernest , Chen Luke , Drago John , Goel Himanshu , Hackett Anna , Halmagyi G. Michael , Hannaford Andrew , Kotschet Katya , Kumar Kishore R. , Kumble Smitha , Lee-Archer Matthew , Malhotra Abhishek , Paine Mark , Poon Michael , Pope Kate , Reardon Katrina , Ring Steven , Ronan Anne , Silsby Matthew , Smyth Renee , Stutterd Chloe , Wallis Mathew , Waterston John , Wellings Thomas , West Kirsty , Wools Christine , Wu Kathy H. C. , Szmulewicz David J. , Delatycki Martin B. , Bahlo Melanie , Lockhart Paul J.
Published: July 2024

The cerebellar ataxias (CA) are a heterogeneous group of disorders characterized by progressive incoordination. Seventeen repeat expansion (RE) loci have been identified as the primary genetic cause and account for >80% of genetic diagnoses. Despite this, diagnostic testing is limited and inefficient, often utilizing single gene assays. This study evaluated the effectiveness of long- and short-read sequencing as diagnostic tools for CA. We recruited 110 individuals (48 females, 62 males) with a clinical diagnosis of CA. Short-read genome sequencing (SR-GS) was performed to identify pathogenic RE and also non-RE variants in 356 genes associated with CA. Independently, long-read sequencing with adaptive sampling (LR-AS) and performed to identify pathogenic RE. SR-GS identified pathogenic variants in 38% of the cohort (40/110). RE caused disease in 33 individuals, with the most common condition being SCA27B (n=24). In comparison, LR-AS identified pathogenic RE in 29 individuals. RE identification for the two methods was concordant apart from four SCA27B cases not detected by LR-AS due to low read depth. For both technologies manual review of the RE alignment enhanced diagnostic outcomes. Orthogonal testing for SCA27B revealed a 16% and 0% false positive rate for SR-GS and LR-AS respectively. In conclusion, both technologies are powerful screening tools for CA. SR-GS is a mature technology currently utilized by diagnostic providers, requiring only minor changes in bioinformatic workflows to enable CA diagnostics. LR-AS offers considerable advantages in the context of RE detection and characterization but requires optimization prior to clinical implementation.
CT-Perfusion absolute Ghost Infarct Core is a rare phenomenon associated with poor collateral status in acute ischemic stroke patients
Authors: Busto Giorgio , Morotti Andrea , Casetta Ilaria , Poggesi Anna , Gadda Davide , Ginestroni Andrea , Arcara Giorgio , Rustici Arianna , Zini Andrea , Padovani Alessandro , Fainardi Enrico
Published: July 2024

Background

CT-Perfusion (CTP) overestimation of core volume >10 mL compared to the final infarct volume (FIV) size is the current definition of the ghost infarct core (GIC) phenomenon. However, subsequent infarct growth might influence FIV. We aimed to report a more reliable assessment of GIC occurrence, defined as the lack of FIV at 24 hours follow-up imaging, compared to CTP core volume at admission. This phenomenon was named absolute GIC (aGIC) and we investigated its prevalence and predictors.

Methods

A total of 652 consecutive stroke patients with large vessel occlusion who achieved successful recanalization (mTICI 2b-3) after Endovascular Treatment (EVT) and non-contrast CT (NCCT) follow-up imaging at 24 hours were retrospectively analyzed. Ischemic core volume was automatically generated from CTP, and FIV was manually determined on follow-up NCCT. Multivariable logistic regression was used to explore aGIC predictors.

Results

We included 652 patients (53.3% female, median age 75 years), of whom 35 (5.3%) had an aGIC. The aGIC group showed higher ASPECTS (p<0.001), shorter (<3 hours) onset-to-imaging time (p<0.001), poorer collaterals (p<0.001), higher hypoperfusion intensity ratio (p=0.001) compared to the non-aGIC group. In multivariate analysis, ASPECTS (odds ratio [OR], 1.87; p<0.001), onset-to-imaging time (OR, 0.99; p=0.013), collateral score (OR, 0.45; p<0.004) and hypoperfusion intensity ratio (OR, 23.2; p<0.001) were independently associated with aGIC.

Conclusion

aGIC is a more reliable evaluation of infarct core volume overestimation assessed on admission CTP and represents a rare phenomenon, associated with ultra-early presentation and poor collaterals.
Serum Glial Fibrillary Acidic Protein: Potential to Determine Stroke-Type, Time-Line and Tissue-Impact in Acute Stroke
Authors: Paul Julien F. , Ducroux Célina , Correia Pamela , Daigneault Audrey , Larochelle Catherine , Stapf Christian , Gioia Laura C.
Published: July 2024

Background

Interest is emerging regarding the role of blood biomarkers in acute stroke. The aim of this pilot study was to determine the feasibility of biomarker acquisition in suspected acute stroke, using modern ultrasensitive immunoassay techniques, and explore their potential usefulness for stroke diagnosis and management.

Methods

In 62 patients with suspected acute stroke, blood samples were prospectively obtained upon arrival and prior to neuroimaging. Serum levels (pg/mL) of glial fibrillary acidic protein (GFAP) and neurofilament light chain (NfL) were analyzed according to time of symptom onset, neuroimaging, and final diagnosis.

Results

Acute ischemic stroke (AIS) was diagnosed in 35 patients, 10 with large-vessel occlusion (LVO). The remaining were diagnosed with intracerebral hemorrhage (ICH) (n = 12), transient ischemic attack (n=4), and stroke mimics (n=11). Median(IQR) GFAP levels were significantly higher in ICH (2,877.8 [1,002.1-10,402.5] pg/mL) compared to others diagnoses. In AIS, GFAP levels appear to increase over time from symptom onset, and were higher in patients with more extensive ischemic changes on baseline CT (ASPECTS ≤ 7) than those without, particularly in LVO stroke. NfL values were similar across groups.

Conclusions

In acute stroke, serum GFAP shows potential as an adjunct tool for the distinction between ICH and AIS. Specific to AIS, GFAP may also offer insight into time from onset, and extent of ischemic tissue injury on neuroimaging, particularly in LVO stroke. These preliminary findings merit further study.
Measuring the Immune Memory Response of In Vitro Polarized Th1, Th2, and Th17 Cells in the Face of OVA TransgenicLeishmania major inMouse Model
Authors: Tedla Mebrahtu G. , Nahar Musammat F. , Every Alison L. , Scheerlinck Jean-Pierre Y.
Published: July 2024

Th1 and Th2 cytokines determine the outcome ofLeishmania majorinfection and immune protection depends mainly on memory T cells induced during vaccination. This largely hinges on the nature and type of memory T cells produced. In this study, transgenicLeishmania majorexpressing membrane associated ovalbumin (mOVA) and soluble ovalbumin (sOVA) are used as a model to study whether fully differentiated Th1/ Th2 &Th17 cells can recall immune memory and tolerate pathogen manipulation. Naïve OT-II T cells werein vitropolarised into Th1/Th2, and these cells were transferred adoptively into recipient mice. Following transferring the memory cells, recipient mice were challenged with OVA transgenicLeishmania majorand wild type parasite was used a control. Thein vitropolarised T helper cells continued to produce the same cytokine signatures after challenged by both forms of OVA-expressingLeishmania majorparasitesin vivo. This suggests antigen-experienced cells cells remain the same or unaltered in the face of OVA transgenicLeishmania major. Such ability of the antigen-experienced cells to remain resilient to manipulation by the parasite signifies that vaccines might be able to produce immune memory responses and withstand against the parasite immune manipulation and protect the host from infection.
Restoring data balance via generative models of T-cell receptors for antigen-binding prediction
Authors: Loffredo Emanuele , Pastore Mauro , Cocco Simona , Monasson Rémi
Published: July 2024

Unveiling the specificity in T-cell-receptor and antigen recognition represents a major step to understand the immune system response. Many supervised machine learning approaches have been designed to build sequence-based predictive models of such specificity using binding and non-binding examples of data. Due to the presence of few specific and many non-specific T-cell receptors for each antigen, available datasets are heavily imbalanced and make the goal of achieving solid predictive performances very challenging. Here, we propose to restore data balance through data augmentation using generative unsupervised models. We then use these augmented data to train supervised models for prediction of peptide-specific T-cell receptors and binding pairs of peptide and T-cell receptors sequences. We show that our pipeline yields increased performance in terms of T-cell receptors specificity prediction tasks. More broadly, our work provides a general framework to restore balance in computational problems involving biological sequence data.

Significance Statement

The adaptive immune system carries a diverse set of T-cell receptors capable of recognizing pathogens and protect the host from diseases. Predicting whether a receptor binds a pathogenic peptide is a fundamental computational problem, made difficult by the imbalance in available data: relatively few binding pairs are known compared to all possible pairs of receptors and peptides. Here, we propose to mitigate this imbalance problem by generating putative binding pairs through data augmentation machine-learning methods. We show that these extra data helps training binding prediction models and improves their performances. Our framework for sequence data augmentation is generic and could be applied to other biological computational problems.
Physical activity modulates early visual response and improves target detection in humans
Authors: Weischner Tom , Che Xinyun , Schmid Paul , Reichert Christoph , Scholz Annemarie , Knight Robert T. , Dürschmid Stefan
Published: July 2024

Brain state changes affect visual perception by altering spatial resolution. Attention enhances the spatial resolution decorrelating neuronal activity in early nonhuman primate (NHP) visual cortex. Physical activity (PA) amplifies these attentional effects in rodents but impact of PA on visual perception in humans remains uncertain. We investigated the relationship between broadband high-frequency activity (BHA: 80-150 Hz) recorded with magnetoencephalography (MEG) and visual detection performance. We found that PA enhanced visual target detection predicted by a reduction of early BHA responses (<90 msec). This effect may be due to reduced interneuronal correlation to improve spatial resolution. Moreover, PA improved spatial integration time, as indicated by a linear relationship between reaction times and BHA variation with target eccentricity. These findings provide evidence that PA influences neuronal activity critical for early visual perception, optimizing visual processing at the initial stages of the visual hierarchy.
Uneven Walking is Challenging: step-ups or extended steps that is the question
Authors: Hosseini-Yazdi Seyed-Saleh
Published: July 2024

Uneven terrain presents significant challenges for walkers, resulting in increased energy expenditures. Given that Center of Mass (COM) work reflects this energy demand, it's reasonable to assume that individuals also seek strategies to minimize mechanical work. One such strategy involves deciding between extending step length to avoid terrain irregularities or simply traversing over them. Each approach carries its own mechanical cost, leading to the adoption of the less costly option. To investigate this, we conducted a simulation focusing on COM mechanical work under the assumption that gait energy is entirely provided through pre-emptive push-off. We examined the COM work required for step length extension, ranging from nominal to twice its magnitude, and compared it with the mechanical work needed for step-ups from zero to 0.05 m. The simulation revealed a critical threshold for a given walking velocity and perturbation amplitude: below it, extending step length was more favorable, while beyond it, landing atop perturbations became the preferred choice. As perturbation amplitude rose, the magnitude of the threshold also increased.
Determining potential immunomodulatory drug efficacy in sepsis using ELISpot
Authors: Walton AH , Mazer MB , Remy KE , Davitt EB , Griffith TS , Gould RW , Badovinac VP , Brakenridge SC , Drewry AM , Loftus TJ , Efron PA , Moldawer LL , Caldwell CC , Hotchkiss RS
Published: July 2024

Purpose

This study evaluated the ability of ELISpot to identify immuno-modulatory drug therapies for their potential efficacy in patients with sepsis.

Methods

ELISpot was performed using diluted whole blood from 61 septic patients and 48 healthy matched controls. Innate and adaptive immunity were evaluated byex vivostimulated production of TNF-α and IFN-γ respectively. Potential drug efficacy was determined by the drugs’ effects to increase or decrease the number of cytokine-producing cells and amount of cytokine produced per cell as determined by spot size and intensity. The corticosteroid dexamethasone was evaluated for its ability to down modulate TNF-α and IFN-γ production. The TLR7/8 agonist resiquimod (R848) and T-cell stimulants IL-7 and anti-PD-1 mAb were tested for their ability to enhance immune responses in sepsis.

Results

Spontaneous production of TNF-α and IFN-γ varied among healthy subjects and septic patients. LPS or resiquimod stimulation increased total TNF-α production in septic patients by 1,648% and 1,929% respectively. Conversely, dexamethasone diminished the responses to LPS or resiquimod by 71% and 61% respectively. IL-7, but not anti-PD-1 mAb markedly increased IFN-γ production in both healthy subjects (127%) and septic patients (79%). Dexamethasone also reduced anti-CD3/CD28 mAb stimulated IFN-γ production by 54%; while IL-7 ameliorated dexamethasone-induced suppression. IL-7 significantly enhanced lymphocyte function in over 90% of septic patients.

Conclusion

ELISpot can reveal host immune response patterns and the effects of drugs to selectively down– or up-regulate patient immunity. Furthermore, the ability of ELISpot to detect the effect of specific immuno-modulatory drugs to independently regulate the innate and adaptive host response could enable precision-based immune drug therapies in sepsis.
Robust coexistence in ecological competitive communities
Authors: Lechón-Alonso Pablo , Kundu Srilena , Lemos-Costa Paula , Capitán José A. , Allesina Stefano
Published: July 2024

The notions of intraspecific competition and population self-regulation play a central role in ecological theory, leading to foundational concepts such as limiting similarity and niche differentiation[1–6]. They also are crucial for coexistence: for example, May[7] showed that ecological dynamics can be stabilized by imposing sufficiently strong intraspecific competition, and that for large systems with random interactions the transition from instability to stability is sharp[7–9], and achieved at a critical value of intraspecific competition.

Here we consider the existence of an equilibrium and its stability as the strength of intraspecific competitionαis increased. We show that an ecological system can gain or lose a coexistence equilibrium as intraspecific competition becomes more prevalent, but that for any competitive system there exists a critical valueαFafter which the existence of an equilibrium is guaranteed, in analogy to stability.

Having derived results on general systems, we turn to ecological systems with random interactions, and compute the probability that a system would display a coexistence equilibrium, given the level of intraspecific interaction, the size of the systemn, and the statistics on the distribution of interactions—thereby extending, generalizing and refining results that have been accumulating for decades[10–16]. We show that the transition to feasibility is smooth, contrary to what is found for stability, and that the existence of an equilibrium almost invariably guarantees its stability[10, 11, 14] This has strong consequences for the dynamics of such large ecological systems: coexistence via limit cycles or chaos[17, 18] is precluded, and dynamics always converge to an equilibrium. The surviving competitors coexist extremely robustly; the ecological community will return to equilibrium after any perturbation, can be assembled from the ground-up, and is resistant to invasions[19, 20].
First-male sperm precedence in polyandrousSpodoptera frugiperdaallows sterile males induce population suppression
Authors: Sun Hao , Bu Ling-Ao , Zhang Xin-Yue , Zhang Zhi-Ruo , Zhu Ling-Yi , Su Shao-Cong , Guo Di , Hu Gao , Gao Cong-Fen , Palli Subba Reddy , Champer Jackson , Wu Shun-Fan
Published: July 2024

Males respond to intense sperm competition by adapting reproductive strategies to promote fertilization success, which is critical for population reproduction. Thus, investigating the patterns and mechanisms of sperm competition is crucial for the development and application of pest population management techniques. In this study, we analyzed the sperm precedence pattern of a major pest, the fall armyworm, and used this pattern to manage the pest population. First, we found that females had a post-mating response and did not gain direct benefit through multiple mating. Next, in a double mating experiment, we used a molecular marker created by CRISPR/Cas9 to determine that most females use only the sperm of the first male to produce offspring. To further explore the role of fertilizing sperm in sperm competition, we constructed a sterile male line with eupyrene sperm defect by knocking out theB2tgene. Interestingly, two round mating assays showed that first mating withB2t-null males inhibited sperm fertilization from a second wild-type male. In other words, prior mating withB2t-null males significantly reduced the fertility and fecundity of females. Based on this finding, we continued to explore whether sperm-deficient sterile males could be used in the management of FAW populations. Cage experiments and mathematical modeling analyses showed that the release of excessB2t-null males induced population suppression. Our study expands our knowledge of sperm competition patterns in lepidopteran. In addition, our study provides a paradigm to develop and apply genetic control methods based on sperm competition outcome in polyandrous pests.

Significance

Sperm competition is essential for maintaining population reproduction. Understanding patterns and mechanisms of sperm competition facilitates the development of appropriate pest genetic control methods. Here, we describe that a globally major pest, the fall armyworm displays the first-male sperm precedence pattern. Interestingly, first mating withB2t-null males, which produces non-functional eupyrene sperm, significantly reduces the fertility and fecundity of females. That means that the ejaculate of the first male, even if its eupyrene sperm are defective, can inhibit sperm fertilization from a second wild-type male. Based on this, the release of excessB2t-null males significantly suppresses FAW populations. These results suggest that future development of genetic control techniques based on targeting nucleated sperm can effectively control FAW populations.
Identification of Southeast AsianAnophelesmosquito species with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using a cross-correlation approach
Authors: Chaumeau Victor , Sawasdichai Sunisa , Min Thu Zar Ma Ma Moe , Kularbkeeree Thithiwarada , Jaruwan Naw , Gloria Naw , Lee Naw Yu , Trackoolchengkaew Muesuwa , Phanaphadungtham Monticha , Rongthong Patcharamai , Inta Aritsara , Watthanaworawit Wanitda , Nosten François
Published: July 2024

Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is proposed for mosquito species identification. The absence of public repositories for sharing mass spectra and of open-source data analysis pipelines for fingerprint matching to mosquito species limits widespread use of this technology. The objective of this study was to develop an open-source data analysis pipeline forAnophelesspecies identification with MALDI-TOF MS. Malaria mosquitos were captured in 33 villages in Karen (Kayin) state in Myanmar. 359 specimens were identified with DNA barcodes and assigned to 21 sensu stricto species and 5 sibling species pairs or complexes. 3584 mass spectra of the head of these specimens identified with DNA barcoding were acquired and the similarity between mass spectra was quantified using a cross-correlation approach adapted from the published literature. A simulation experiment was carried out to evaluate the performance of species identification with MALDI-TOF MS at varying thresholds of cross-correlation index for the algorithm to output an identification result and with varying numbers of technical replicates for the tested specimens, considering PCR identification results as the reference. With one spot and a threshold value of −14 for the cross-correlation index on the log scale, the sensitivity was 0.99 (95%CrI: 0.98 to 1.00), the predictive positive value was 0.99 (95%CrI: 0.98 to 0.99) and the accuracy was 0.98 (95%CrI: 0.97 to 0.99). It was not possible to directly estimate the sensitivity and negative predictive value because there was no true negative in the assessment. In conclusion, the modified cross-correlation approach can be used for matching mass spectral fingerprints to predefined taxa and MALDI-TOF MS is a valuable tool for rapid, accurate and affordable identification of malaria mosquitos.
Self-Logical Consistent GPT-4 Enables Human-Level Classification of Patient Feedback
Authors: Loi Zeno , Morquin David , Derzko Xavier , Corbier Xavier , Gauthier Sylvie , Taourel Patrice , Prin-Lombardo Emilie , Mercier Grégoire , Yauy Kévin
Published: July 2024

Patient satisfaction feedback is crucial for hospital service quality, but human-led reviews are time-consuming and traditional natural language processing remains ineffective. Large Language Models (LLM) offer potential, but their tendency to generate illogical thoughts limits their use in healthcare. Here we describe Self-Logical Consistency Assessment (SLCA), a method ensuring a reproducible LLM classification explained by a logically-structured chain of thought. In an analysis targeting extrinsic faithfulness hallucinations, SLCA mitigated the 16% GPT-4 hallucination rate, leaving only three residual cases across 12,600 classifications from 100 diverse patient feedbacks. In a benchmark designed to evaluate classification accuracy, SLCA applied to GPT-4 outperformed best algorithms, with a 88% precision rate and a 71% recall rate across 49,140 classifications from 1,170 sampled patient feedbacks. This method provides a reliable, scalable solution for improving hospital services and shows potential for accurate, explainable text classifications without fine-tuning.
Influence of salinity on the thermal tolerance of aquatic organisms
Authors: Farias Luan , Beszteri Bánk , Burfeid Castellanos Andrea M. , Doliwa Annemie , Enss Julian , Feld Christian K. , Grabner Daniel , Lampert Kathrin P. , Mayombo Serge , Prati Sebastian , Schürings Christian , Smollich Esther , Schäfer Ralf B. , Sures Bernd , Yen Le T.T.
Published: July 2024

Aquatic organisms are challenged by changes in the external environment, such as temperature and salinity fluctuations. The response of an organism to temperature changes can be modified by salinity, thus pointing at the potential interaction of both variables. In the present study, we tested this assumption for freshwater, brackish, and marine organisms, including algae, macrophytes, heterotrophic protists, parasites, invertebrates, and fish. We reviewed the existing body of literature on potential interactions between temperature and salinity and performed a meta-analysis that compared the thermal tolerance (characterized by the temperature optima, lower and upper temperature limits, and thermal breadths). The final database includes 90 relevant publications (algae: 15; heterotrophic protists: 1; invertebrates: 43; and fish: 31). Relevant publications for microphytes and parasites were not available. Overall, our results show that decreasing salinity significantly increased the lower temperature limits and decreased the upper temperature limits irrespective of the organism groups. These findings mainly reflect the response to salinity changes in brackish and marine systems that dominate our database. Although the number of studies on freshwater species was limited, they showed negative, although statistically nonsignificant, effects of an increased salinity on the thermal tolerance of these species (i.e. increased lower limits and decreased upper limits). In addition, our meta-analysis shows nonsignificant differences in the responsiveness of thermal tolerance to salinity changes among different groups of organisms, but the sensitivity of thermal tolerance to salinity changes generally followed the order: algae > invertebrates > fish. Facing the impact of climate change, our findings point at adverse effects of salinity changes on the temperature tolerance of aquatic organisms. Further studies that investigate the thermal performance of freshwater species at various salinity gradients are required to broaden the evidence for interactions between salinity and temperature tolerance. This also applies to the influence of parasitic infections, which have been found to modulate the temperature tolerance of aquatic invertebrates and fish.
TOR Inhibition Enhances Autophagic Flux and Immune Response in Tomato Plants Against PSTVd Infection
Authors: Silva-Valencia Samanta , Prol Francisco Vázquez , Rodrigo Ismael , Lisón Purificación , Belda-Palazón Borja
Published: July 2024

Viroids are small, non-coding RNA pathogens known for their ability to cause severe plant diseases. Despite their simple structure, viroids like Potato Spindle Tuber Viroid (PSTVd) can interfere plant cellular processes, including both transcriptional and post-transcriptional mechanisms, thereby impacting plant growth and yield. In this study, we have investigated the role of the Target Of Rapamycin (TOR) signalling pathway in modulating viroid pathogenesis in tomato plants infected with PSTVd. Our findings reveal that PSTVd infection induces the accumulation of the selective autophagy receptor NBR1, potentially inhibiting autophagic flux. Pharmacological inhibition of TOR with AZD8055 mitigated PSTVd symptomatology by reducing viroid accumulation. Furthermore, TOR inhibition promoted the recovery of autophagic flux through NBR1 and primed the plant defence response, as evidenced by enhanced expression of both the defence-related genePR1bandS5H, a gene involved in the salicylic acid catabolism. These results suggest a novel role for TOR in regulating viroid-induced pathogenesis and highlight the potential of TOR inhibitors as tools for enhancing plant resistance against viroid infections.
Genetic, Natal, and Spatial Drivers of Social Phenotypes in Wild Great Tits
Authors: Satarkar Devi , Sepil Irem , Sheldon Ben C.
Published: July 2024

In social animals, group dynamics profoundly influence collective behaviours, vital in processes like information sharing and predator vigilance. Disentangling the causes of individual-level variation in social behaviours is crucial for understanding the evolution of sociality. This requires unravelling the genetic and environmental basis of these behaviours, which is challenging in uncontrolled wild populations. In this study, we partitioned genetic, developmental and spatial environmental variation in repeatable social network traits derived from foraging events using a multigenerational pedigree and extensive observational social data from a long-term monitored great tit population. Animal models indicated minimal narrow-sense heritability (2-3%) in group size choice, further reduced when spatial location was considered, which itself explains a substantial 30% of the observed variation. Individual gregariousness also had a small genetic component, with a low heritability estimate for degree (<5%). Centrality showed heritability up to 10% in one of three years sampled, whereas betweenness showed none, indicating modest genetic variation in individual sociability, but not group-switching tendencies. These findings suggest a small, albeit detectable, genetic influence on individual sociality, but pronounced spatial effects. Furthermore, our study highlights the importance of common environment effects (natal origin and brood identity), which essentially negated genetic effects when explicitly accounted for. In addition, we demonstrate that phenotypic resemblance can be a result of similarities beyond shared genes; spatial proximity at birth and natal environmental similarity explained up to 8% of individual sociability. Our results thus emphasise the role of non-genetic factors, particularly developmental and spatial variation, in shaping individual social behavioural tendencies.
Closing the gap in the clinical adoption of computational pathology: a standardized, open-source framework to integrate deep-learning algorithms into the laboratory information system
Authors: Angeloni Miriam , Rizzi Davide , Schoen Simon , Caputo Alessandro , Merolla Francesco , Hartmann Arndt , Ferrazzi Fulvia , Fraggetta Filippo
Published: July 2024

Digital pathology (DP) has revolutionized cancer diagnostics, allowing the development of deep-learning (DL) models supporting pathologists in their daily work and contributing to the improvement of patient care. However, the clinical adoption of such models remains challenging. Here we describe a proof-of-concept framework that, leveraging open-source DP software and Health Level 7 (HL7) standards, allows the integration of DL models in the clinical workflow.

Development and testing of the workflow were carried out in a fully digitized Italian pathology department. A Python-based server-client architecture was implemented to interconnect the anatomic pathology laboratory information system (AP-LIS) with an external artificial intelligence decision support system (AI-DSS) containing 16 pre-trained DL models through HL7 messaging. Open-source toolboxes for DL model deployment, including WSInfer and WSInfer-MIL, were used to run DL model inference. Visualization of model predictions as colored heatmaps was performed in QuPath.

As soon as a new slide is scanned, DL model inference is automatically run on the basis of the slide’s tissue type and staining. In addition, pathologists can initiate the analysis on-demand by selecting a specific DL model from the virtual slides tray. In both cases the AP-LIS transmits an HL7 message to the AI-DSS, which processes the message, runs DL model inference, and creates the appropriate type of colored heatmap on the basis of the employed classification model. The AI-DSS transmits model inference results to the AP-LIS, where pathologists can visualize the output in QuPath and/or directly from the virtual slides tray. The developed framework supports multiple DL toolboxes and it is thus suitable for a broad range of applications. In addition, this integration workflow is a key step to enable the future widespread adoption of DL models in pathology diagnostics.