bluuebunny/crossref_metadata_2025 huggingface dataset:
Reducing Emergency Department Hold Hours: A Hospital-wide Effort
Authors: McCormick Jill , Kinsinger Faith , Patel Ritika J. , Wicklund Grant , Roybal Deb
Published: February 2025

Patient throughput issues are of significant concern for U.S. hospitals and have serious implications for patient care quality and safety as well as hospital finances. In 2021, leaders of a community hospital commissioned a quality improvement team to address a bottleneck of patients in the emergency department (ED). The bottleneck was causing significant increases in the number of hours patients were held in the ED because of a lack of available inpatient beds. The team used the DMAIC improvement framework to analyze patient flow challenges across the hospital, design an evidence-based set of interventions, and measure improvements. Analysis revealed problems with communication breakdowns and workflow silos, discharge predictability, readiness of patients for discharge, timeliness of discharges, and lack of standardization in patient hand-offs and documentation processes. Addressing these issues resulted in patient throughput improvements including a reduction of greater than 75% in monthly ED hold hours after implementation.
A New Multifunction Oxygenator With a Dual-Chamber Gas Exchanger to Reduce Dependence on Oxygen Supply
Authors: Han Dong , Zhang Jiafeng , Shah Aakash , Griffith Bartley P. , Wu Zhongjun J.
Published: February 2025

Although extracorporeal membrane oxygenation (ECMO) systems have been used to provide temporary support for patients with severe respiratory or cardiac failure, they are often bedridden, in part because of their bulky size which relies solely on an unlimited source of wall oxygen. However, there is an unmet clinical need for ambulatory ECMO which necessitates downsizing the ECMO system. We sought to develop a new oxygenator to reduce the dependence on the oxygen supply source. The proposed oxygenator features a dual-chamber gas exchangers, with one chamber primarily responsible for carbon dioxide removal using ambient air and a subsequent chamber primarily responsible for oxygen transfer using pure oxygen. Computational fluid dynamics was used to analyze the blood flow field to avoid adverse stagnation and optimize gas exchange performance. Bovine blood was used for in vitro gas transfer test. This new oxygenator demonstrated the capability to provide adequate respiratory support (both carbon dioxide removal and oxygen transfer) to adult patients at blood rate of 4–6 L/min with an oxygen supply of only 2 L/min. The reduced use of oxygen with this new oxygenator may pave the way for the development of potable ECMO systems.
Irritable bowel syndrome, the gut microbiome, and diet
Authors: Yu Rosa Lu , Weber H. Christian
Published: February 2025

Purpose of review

To provide an update of recent studies exploring the role of the gut microbiota and diet in the pathogenesis and treatment of irritable bowel syndrome (IBS).

Recent findings

The human gut microbiome has been recognized as an important, active source of signaling molecules that explain in part the disorder of the gut brain interaction (DGBI) in IBS. Subsequent changes in the metabolome such as the production of short-chain fatty acids (SCFA) and serotonin are associated with IBS symptoms. Dietary components are recognized as important triggers of IBS symptoms and a diet low in fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) has been shown effective and safe, even when used long-term. Fecal microbiota transplantation (FMT) in IBS has not shown sustained and effective IBS symptom reduction in controlled clinical trials.

This update elucidates recent developments in IBS as it relates to clinical trial results targeting dietary and gut microbiota interventions. The gut microbiome is metabolically active and affects the bi-directional signaling of the gut-brain axis.
First-line anti-TNF agents, ustekinumab and vedolizumab perform similarly in Crohn’ disease, but not in ulcerative colitis
Authors: Supovec Eva , Hanžel Jurij , Novak Gregor , Manevski Damjan , Štabuc Borut , Drobne David
Published: February 2025

Background

Real-word comparisons between first-line biologicals in inflammatory bowel disease (IBD) are scarce.

Aims

The aim of this study is to compare drug persistence and patient reported outcome-2 (PRO-2) remission rates of first-line biological classes [anti-tumor necrosis factor (TNF) agents vs anti-integrin vedolizumab vs IL-12/23 inhibitor ustekinumab] in real life cohort.

Methods

Individual level data of 946 adults (588 Crohn’s disease and 358 ulcerative colitis) were retrieved from UR-CARE IBD platform. Adjusted drug survival curves using a pooled logistic model and PRO-2 remission rates for each class of biologicals were calculated and compared.

Results

In Crohn’s disease, no differences in drug survival were observed for anti-TNF agents vs vedolizumab vs ustekinumab as estimated survival with 95% confidence intervals were 0.81 (0.77–0.84) vs 0.89 (0.82–0.96) vs 0.88 (0.79–0.97) at year 1 and 0.52 (0.46–0.58) vs 0.58 (0.37–0.78) vs 0.58 (0.39–0.77) at year 4. In ulcerative colitis, however, anti-TNF agents had shorter drug survival than vedolizumab with estimated drug survival with 95% confidence intervals 0.60 (0.52–0.67) vs 0.76 (0.67–0.84) at year 1 and 0.37 (0.30–0.44) vs 0.50 (0.36–0.64) at year 4. No differences in PRO-2 remission rates were observed between drug classes in Crohn’s disease (P = 0.95), but more patients enjoyed PRO-2 remission in ulcerative colitis treated with anti-TNF agents compared to vedolizumab (94.8 vs 78.9%, P = 0.002).

Conclusion

Our real-world data suggest similar drug persistence and efficacy of first-line treatments with anti-TNF agents, vedolizumab and ustekinumab in Crohn’s disease. In ulcerative colitis, however, drug persistence was higher for vedolizumab compared to anti-TNF agents, but on the cost of lower PRO-2 remission rates.
Prosthetic Rehabilitation for Speech and Swallowing (PReSS): a novel, interdisciplinary approach to head and neck cancer survivorship
Authors: McMillan Holly , Montgomery Pattii , Cardoso Richard
Published: February 2025

Purpose of review

There are numerous physical, psychosocial, and functional morbidities following glossectomy, particularly impacting speech and swallowing. The lack of systematic rehabilitation programs, including a shortage of clinical rehabilitation and outcomes assessments, limited provider/resource access, and limited collaborative expertise within the interdisciplinary team, may contribute to the perceived hesitation regarding surgical intervention from providers and patients. Prosthetic rehabilitation involving intraoral devices may be beneficial to restore speech and swallowing function after head and neck cancer.

Recent findings

An interdisciplinary approach between speech pathologists and restorative dentists for designing and fabricating intraoral speech prostheses is presented. The Prosthetic Rehabilitation for Speech and Swallowing (PReSS) framework includes three distinct phases:

This publication outlines the interdisciplinary methodology for designing and fabricating intraoral prosthetics and offers a structured prosthetic program following head and neck cancer treatment. Adopting the PreSS framework may improve speech and swallowing outcomes, improving patients’ quality of life after head and neck cancer treatment.
Does Leadership Have to Have a Label?
Authors: Meier Adam
Published: February 2025

Transformational leadership has been the “gold standard” for nursing leaders. In reflection, the author poses a question about the challenges of today's nursing workforce and healthcare environment and offers a new way to allow nurse leaders some flexibility in style.
Integrating Complex Pain Concepts Into Prelicensure Nursing Education
Authors: Firestone Kari A. , Johnston Heidi , Portanova Jaclyn , Jones Kim Dupree
Published: February 2025

Background:

Unfolding case studies are an active learning strategy that help students integrate knowledge with practical experience, enhancing clinical judgment and easing their transition into professional practice.

Problem:

Chronic pain, a complex health issue, is often inadequately addressed in nursing curricula, leaving prelicensure nursing students unprepared to manage pain effectively in clinical practice, contributing to the academic-practice gap.

Approach:

Using an evidence matrix, faculty interviews, and syllabi analysis across 4 programs, gaps in chronic pain concepts were identified. A 4-term unfolding case study was developed to address these gaps, aligned with the American Association of College of Nursing Essentials and following a patient from acute to chronic pain transition.

Conclusions:

By incorporating evidence-based, active learning strategies like an unfolding case study for a complex concept such as chronic pain management scaffolded across a curriculum, nurse educators can better prepare future nurses for practice.
Reimbursement for Neuroma Surgery Over the Past Decade
Authors: Stearns Stephen A. , Raizman Noah M. , Raasveld Floris V. , Tereshenko Vlad , Gfrerer Lisa , Valerio Ian L. , Winograd Jonathan M. , Eberlin Kyle R.
Published: February 2025

Purpose

This study aimed to determine how Medicare physician reimbursements for operations related to symptomatic neuromas have changed over the past decade.

Methods

This retrospective review uses the Medicare Physician Fee Schedule Look-up Tool to access reimbursement rates for common peripheral nerve surgeries. Six CPT codes frequently used to bill for neuroma excision, burying in muscle, targeted muscle reinnervation (TMR), and regenerative peripheral nerve interface (RPNI) procedures were identified as representative of the peripheral nerve operations to treat symptomatic neuromas. Physician reimbursement rates were gathered from 2014 to 2024, with gross and inflation-adjusted changes in reimbursement calculated.

Results

For each included peripheral nerve procedure, there was a significant decrease in Medicare physician reimbursement both with and without inflation adjustments. CPT 64905 (for TMR) decreased 30%; CPT 64787 and 15769 (for intramuscular burying and RPNI) decreased 31% and 21%; and CPT 64784, 64782, and 64774 (for neuroma excision) decreased 28%, 26%, and 24%, respectively (all inflation-adjusted), with an average compound annual growth rate of −3.6%. For every 100 neuroma operations in 2014, surgeons in 2018 needed to perform an additional 5.6 to be reimbursed at equal levels. In 2024, surgeons need to perform an additional 27 operations for every 100 to be reimbursed equivalently as 5 years prior.

Conclusions

There has been a consistent decrease in physician reimbursement for procedures related to symptomatic neuromas, highlighting a larger trend in Medicare payments. Continued decline in reimbursement poses risk to these important treatment modalities, which could limit surgeons' ability to provide care to patients.
Seasonal differences in burn injuries and outcomes among adults and older adults at a Canadian provincial burn center
Authors: Hutter Maria Fernanda , Tedesco Diana Julia , Khalaf Fadi , Jeschke Marc G.
Published: February 2025

Background

The literature provides hints of seasonal influences on burn injury occurrence and outcomes in temperate climates. Still, data for geographic regions experiencing significant changes in climate throughout the year is scarce. Especially the influence of seasonal differences in burn incidence and outcomes for older adults (≥60 years old), a particularly vulnerable patient cohort with increased mortality and morbidity compared to adults (18-59 years old), has not been investigated so far. Since burns pose a significant public health concern, we aimed to understand seasonal burn injury admission patterns and outcomes to utilize them for targetable prevention measures and effective resource allocation.

Methods

This retrospective single-center cohort study examined data from adult burn patients (≥18 years) with reported %TBSA (Total Body Surface Area) treated between 2006 and 2020 at a provincial burn center in Ontario, Canada. Patients were stratified based on age group: adults (18-59 years) and older adults (≥60 years) Demographic data, comorbidities, and clinical outcomes were compared.

Results

A total of 2445 eligible patients were enrolled in this study. Most burn injuries occurred in Summer, in which the burn patient population was also significantly younger compared to Winter. Summer admissions showed a greater median %TBSA. In contrast, length of stay per %TBSA (LOS:TBSA) revealed a shorter hospitalization in Summer compared to Winter. However, mortality did not show differences across seasons.

Conclusion

Seasonal variations in the incidence and severity of burn injuries, along with associated fluctuations in LOS:TBSA, exist between age groups. This understanding can assist in tailoring burn prevention programs and aid in anticipating the types of burn injuries that may occur during specific times of the year to enhance patient care strategies.
Adjunctive Vasopressors and Short-Term Mortality in Adults with Septic Shock: A Systematic Review and Meta-Analysis
Authors: Bauer Seth R. , Wieruszewski Patrick M. , Bissell Turpin Brittany D. , Dugar Siddharth , Sacha Gretchen L. , Sato Ryota , Siuba Matthew T. , Schleicher Mary , Vachharajani Vidula , Falck-Ytter Yngve , Morgan Rebecca L.
Published: February 2025

Background

Adjunctive vasopressors are added to norepinephrine in one-third of adults with septic shock in the United States. However, effectiveness of this approach is unclear, and treatment recommendations are based on indirect evidence. We sought to synthesize the direct evidence for adjunctive vasopressor administration in adults with septic shock.

Methods

We searched MEDLINE, Embase, and Cochrane Central Register of Controlled Trials from inception to June 7, 2023. We included randomized clinical trials of adults with septic shock comparing adjunctive treatment with a vasopressin analogue, angiotensin II, methylene blue, hydroxocobalamin, or catecholamine analogue to standard care vasopressors. The primary outcome was short-term mortality (at or before 28-30 days or intensive care discharge). Secondary outcomes included kidney replacement therapy, digital/peripheral ischemia, and venous thromboembolism. Random-effects meta-analyses were conducted to derive risk ratios (RRs) and 95% CIs. The certainty of the evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation.

Results

Of 6763 records, 17 trials (3813 participants) were included. Compared with standard care, adjunctive vasopressor administration may reduce short-term mortality risk (RR, 0.92 [95% CI, 0.85 to 1.00], low certainty, 17 trials [18 participants]) and likely reduces kidney replacement therapy receipt (RR, 0.92 [95% CI, 0.84 to 1.01], moderate certainty, 8 trials [2408 participants]). Adjunctive vasopressor treatment may increase risk of digital/peripheral ischemia (RR, 2.44 [95% CI, 1.17 to 5.10], low certainty, 9 trials [2981 participants]) and venous thromboembolism (RR, 16.48 [95% CI, 0.96 to 283.17], low certainty, 1 trial [321 participants]). There was some evidence that the pooled estimate for short-term mortality was different (interaction P = 0.13) for trials adjudicated as low risk of bias (RR, 0.95 [95% CI, 0.87 to 1.05]) compared with trials adjudicated as some concerns or high risk of bias (RR, 0.82 [95% CI, 0.69 to 0.97]). The findings were robust to multiple sensitivity and subgroup analyses.

Conclusions

In adults with septic shock, adjunctive vasopressors may lower short-term death risk and likely lower kidney replacement therapy risk, but may increase risk of adverse effects. In the United States, adjunctive vasopressor use prevalence in septic shock is disconnected from the low evidence certainty for a favorable mortality-to-risk profile.

Registration

PROSPERO CRD42023427984
PTP1B and zonulin failed to predict the modification of muscle mass in critically ill patients with septic shock
Authors: Caroline Lemaitre , Zoé Demailly , Thomas Clavier , Christophe Girault , Gaëtan Béduneau , Dorothée Carpentier , Marchalot Antoine , Christine Bôle-Feysot , Steven Grange , Vincent Richard , Moïse Coëffier , Fabienne Tamion
Published: February 2025

Background

Proteolyse is one of the causes of loss of lean body mass, and depend of insulin. Proteintyrosine phosphatase 1B (PTP1B) and intestinal permeability (evaluated by zonulin) contribute of insulin metabolism. The objectives were to explore the relationship between PTP1B, Zonulin level and body composition during septic shock in humans.

Material and Methods

Prospective study including patients admitted to intensive care unit (ICU) for septic shock. Blood samples were collected on days 1 (D1) and 4 (D4) for study expression of PTPT1b (PCR) and zonulin. Muscle mass was evaluated by Fat-Free Mass (FFM) (by Bioelectrical impedance analysis) and rectum femoris cross-sectional area by ultrasound.

Results

We included 52 patients with a mean IGSII 53 [39-65], and a mortality in ICU of 32%. Between D1 and D4, aera of right quadriceps muscle (ARQ) and average of quadriceps muscles (AAQ) decreased (p = 0.002 and 0.009 respectively). We observed no modification in FFM. Median of PTP1b at D1 was 5.03 [2.36-10.96]. Median of plasmatic zonulin at D1 was 156.6 ng/ml [56.3-277.9]. We did not find any correlation between PTP1b, zonulin expression and muscle composition. The mortality rate was more important in patients with a low average quadriceps thickness (QT) or quadriceps area (QA) (p < 0.01), and tendency for patients who had an elevated zonulin in admission. By contrast, we did not observe significant associations between fat-free mass and PTP1B and mortality at D28.

Conclusion

We observed a trend of correlation between the whole blood PTPN1 gene expression at D1 and D4/D1 TLQ, because this is the only data which has a potential to address the relationship body mass change and proteolysis.

Keys words: Body composition, malnutrition, PTB1B, septic shock, Zonulin
Machine Learning and Shock Indices-Derived Score for Predicting Contrast-Induced Nephropathy in ACS Patients
Authors: Yavuz Yunus Emre , Tatar Sefa , Akıllı Hakan , Aslan Muzaffer , İçli Abdullah
Published: February 2025

Background

Contrast-induced nephropathy (CIN) is a serious complication following acute coronary syndrome (ACS), leading to increased morbidity and mortality. Machine learning (ML), combined with parameters such as shock indices, can potentially improve CIN risk prediction by analyzing complex variable interactions and creating accessible, clinically applicable models.

Methods

This retrospective case-control study included 719 ACS patients who underwent percutaneous coronary intervention (PCI). Patients were divided into two groups (CIN and non-CIN), and clinical, procedural, and hemodynamic parameters, including shock indices, were analyzed using machine learning algorithms. A new predictive model, CIN-Predict 5, was developed using the Gradient Boosting Machine (GBM) algorithm, incorporating clinically relevant and statistically significant variables. Correlations between model predictions and secondary outcomes, including in-hospital mortality and hospitalization duration, were evaluated.

Results

Among the variables used in the GBM algorithm, the Modified Shock Index emerged as the most significant predictor, with an importance score of 0.25. The CIN-Predict 5 model achieved an AUC of 0.87, outperforming the Mehran Risk Score (AUC = 0.75) for predicting CIN. The secondary outcomes showed that CIN-Predict 5 correlated significantly with in hospital mortality (r = 0.16, p < 0.001) and hospitalization duration (r = 0.20, p < 0.001).

Conclusions

The GBM-based model we developed, utilizing shock indices and derived through ML, provides a practical tool for early identification of high-risk CIN patients post-ACS, enabling timely preventive strategies and improving clinical decision-making.
Resuscitative Endovascular Balloon Occlusion of the Aorta: What You Need to Know
Authors: Shaw Joanna , Brenner Megan
Published: February 2025

Hemorrhage remains one of the leading causes of death from traumatic injury in both the civilian and military populations. Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a minimally invasive technique that can be used to treat hemorrhage in the critically ill. An alternative to maximally invasive methods such as resuscitative thoracotomy, REBOA is a temporizing measure to prevent exsanguination and allow for transition to definitive hemorrhage control. It is easily deployed by trained users and does not require surgical expertise to place. Its use has increased over the past decade with a growing body of literature that suggests it improves outcomes in select hemorrhagic trauma patients compared with patients who do not receive REBOA. REBOA has also been used for select nontraumatic cases. Judicious patient selection, knowing the technical aspects of placing REBOA, and clarity regarding its indications are key to maximize its efficacy as a mitigatory tool in hemorrhagic shock. This “What You Need To Know” review presents current evidence regarding use of REBOA for the acute care surgeon.

LEVEL OF EVIDENCE

Level V.
Functional imaging of time on task and habituation in passive exposure to faces with emotional expression
Authors: Labek Karin , Viviani Roberto
Published: February 2025

The amygdala responds to emotional stimuli but habituates at repeated presentation. Much less is known about time-on-task effects during exposure to emotional stimuli in the cortex. Here, we identified the neural substrates that show habituation or cortical decreased activity in a task of repeated passive exposure to faces with negative emotional expressions. We found that in the amygdala, habituation selectively involved the central nucleus and extended posteriorly in the hippocampal-amygdaloid region, consistently with reduced motivational and attentional effects of repeated stimulation. In the cortex, decreases in activity with time on task involved a network including the temporoparietal junction, the postsplenial region, and the ventromedial prefrontal cortex, mostly located at the transition from task activations to deactivations. These effects were analogous to those reported as encoding of social cognition information, suggesting a role in developing task-based representations of input content.
Artemisinin antagonizes cognitive disorder in hyperuricemia through glutamate receptor-interacting protein 1-suppressed pyroptosis
Authors: Chen Yanfang , Chen Shuangxi , Wang Huiqing , Cao Peng
Published: February 2025

The prevalence of hyperuricemia (HUA) is climbing worldwide and persistent elevation of serum uric acid impairs cognitive function. This study aimed to explore the mechanisms of Artemisinin (Art) antagonizing cognitive disorder in HUA by suppressing pyroptosis. A mouse model of HUA was established by intraperitoneal injection of 300 mg/kg potassium oxonate (PO) in C57BL/6 mice for 14 days. The mice were simultaneously treated with Art, an agonist of pyroptosis Polyphyllin VI (PPVI), or glutamate receptor-interacting protein 1 (GRIP1) knockdown lentiviral plasmid. After treatment, serum uric acid, IL-6, and TNF-ɑ levels were examined, as well as hippocampal IL-1β and IL-18 levels, and the cognitive function of mice was assessed by the Morris water maze test. Pathological changes in the CA1 of the hippocampus were observed. Cleave-caspase-1, GSDMD-N, and GRIP1 protein level in the hippocampus was quantified by western blot. After PO induction, the escape latency and the time spent in the target quadrant increased in mice, cell arrangement in CA1 hippocampus was loose and disorganized, with obvious inflammatory infiltration and serious damage being observed, and the mouse hippocampus had elevated cleaved-caspase-1, GSDMD-N, IL-1β, and IL-18. Art treatment reduced pyroptosis in the hippocampus and improved cognitive disorder in HUA mice. Administration of PPVI aggravated cognitive disorder in Art-treated HUA mice, and Art improved cognitive dysfunction in HUA mice by inhibiting pyroptosis through upregulation of GRIP1. Art blunts pyroptosis in the hippocampus of HUA mice suffering from cognitive disorder by upregulating GRIP1.
A finite set of content-free pointers in visual working memory: magnetoencephalography (MEG) evidence
Authors: Yu Xinchi , Lau Ellen
Published: February 2025

Human visual working memory (VWM) is known to be capacity-limited, but the nature of this limit continues to be debated. Recent work has proposed that VWM is supported by a finite (~3) set of content-free pointers, acting as stand-ins for individual objects and binding features together. According to this proposal, the pointers do not represent features within themselves, but rather bind features represented elsewhere together. The current study set out to test if neural hallmarks resembling these content-free pointers can be observed with magnetoencephalography (MEG). Based on two VWM delay-match-to-sample experiments (N = 20 each) examining memory for simple and complex objects, we report a sustained response in MEG over right posterior cortex whose magnitude tracks the core hypothesized properties of this content-free pointer system: load-dependent, capacity-limited, and content-free. These results provide novel evidence for a finite set of content-free pointers underlying VWM.
Reciprocal costs of infection and reproduction in
Drosophila melanogaster
Authors: Adhikari Kiran , Lazzaro Brian P.
Published: February 2025

Trade-offs occur when an organism has to allocate limited resources to multiple biological processes. How organisms allocate their resources and whether one trait gets priority over another is poorly understood. Prior work has shown that reproductive investment reduces the capacity of
Drosophila melanogaster
to mount an effective immune response against subsequent bacterial infection. However, it has not been tested whether the observed trade-off was unidirectional with reproductive fitness given primacy over immunity, or whether it might also occur in the reciprocal direction with an active prior immune response reducing reproductive output. In this work, we delivered bacterial infection to female
D. melanogaster
prior to mating and tested whether reproductive capacity became reduced. We found that infected females produced the same number of eggs as uninfected females, but the eggs from infected females exhibited lower survivorship to adulthood. Additionally, we found that mating destabilizes chronic bacterial infections, stimulating additional host death and increasing variance in pathogen burden. Together, our results suggest the cost of reproduction and infection in
Drosophila
females is reciprocal, regardless of the order in which they occur.
The effects of anisotropic dispersal on species coexistence in a metacommunity
Authors: Shinohara Naoto , Katsuhara Koki R.
Published: February 2025

Dispersal is a ubiquitous process occurring in any ecosystem, with a critical role in the regional coexistence of species that cannot coexist locally. However, previous studies have typically focused on a specific scenario where dispersal is isotropic, leaving the consequence of anisotropic, directionally skewed dispersal largely unexplored, despite its prevalence in natural ecosystems. In this study, we used simulations to study whether the anisotropy of dispersal promotes or hinders species coexistence in a metacommunity. We found that dispersal anisotropy plays a decisive role in species coexistence—with coexistence promoted when dispersal is more directed orthogonally to an environmental gradient, while it is less likely when dispersal is primarily parallel with the gradient. This occurred because dispersal directed orthogonally to the background environmental gradient transports individuals produced in ‘good’ habitats to other good habitats, creating conditions that favour several spatial coexistence mechanisms, such as spatial storage effects and fitness–density covariance. We conclude that the effect of anisotropic dispersal could be diverse, and therefore, it is necessary to consider the anisotropy and the distribution of environments for a better understanding of species coexistence in a metacommunity.
Wild fish use visual cues to recognize individual divers
Authors: Tomasek Maëlan , Soller Katinka , Jordan Alex
Published: February 2025

Many animal species have been shown to discriminate between individual humans in captive settings and may use a variety of cues to do so. Empirical evidence remains scarce for animals in the wild, however, particularly in aquatic contexts. For the first time, we investigated discrimination of individual humans by fish in the wild. We first trained two species of fish, saddled sea bream
Oblada melanura
and black sea bream
Spondyliosoma cantharus
, to follow a human diver to obtain a food reward. We then investigated whether they could discriminate between two human divers and follow the correct one in an operant-conditioning paradigm. We show that both species were able to quickly learn to discriminate between the two divers when they wore different diving gear. However, they showed no preference when both divers wore identical gear, suggesting that discrimination is based predominantly on visual cues from the dive gear. We discuss the implications of these results for ethical considerations and research practices.
Vaccine failure mode determines population-level impact of vaccination campaigns during epidemics
Authors: Lee Da In , Nande Anjalika , Anderson Thayer L. , Levy Michael Z. , Hill Alison L.
Published: February 2025

Vaccines are a crucial tool for controlling infectious diseases, yet rarely offer perfect protection. ‘Vaccine efficacy’ describes a population-level effect measured in clinical trials, but mathematical models used to evaluate the impact of vaccination campaigns require specifying how vaccines fail at the individual level, which is often impossible to measure. Does 90% efficacy imply perfect protection in 90% of people and no protection in 10% (‘all-or-nothing’) or that the per-exposure risk is reduced by 90% in all vaccinated individuals (‘leaky’) or somewhere in between? Here, we systematically investigate the role of vaccine failure mode in controlling ongoing epidemics. We find that the difference in population-level impact between all-or-nothing and leaky vaccines can be substantial when
R
0
is higher, vaccines efficacy is intermediate, and vaccines slow but cannot curtail an outbreak. Comparing COVID-19 pandemic phases, we show times when model predictions would have been most sensitive to assumptions about vaccine failure mode. When determining the optimal risk group to prioritize for limited vaccines, we find that modelling a leaky vaccine as all-or-nothing (or vice versa) can change the recommended target group. Overall, we conclude that models of vaccination campaigns should include uncertainty about vaccine failure mode in their design and interpretation.
Aortic stretch and recoil create wave-pumping effect: the second heart in the systemic circulation
Authors: Aghilinejad Arian , Bilgi Coskun , Geng Haojie , Pahlevan Niema M.
Published: February 2025

Wave propagation in the heart tube is key to establishing an early pumping mechanism, as explained by impedance pump theory in zebrafish. Though initially proposed for embryonic blood circulation, the role of impedance-like behaviour in the mature cardiovascular system remains unclear. This study focuses on the understudied physiological mechanism of longitudinal displacement in the adult aorta caused by the long-axis motion of the heart. Using magnetic resonance imaging on 159 individuals, we compared aortic displacement profiles between a control group and those with heart failure, revealing a significant difference in aortic stretch between the two groups. Building on this clinical evidence, we conducted
in vitro
experiments to isolate the effects of longitudinal aortic wave pumping by eliminating the pumping action of the heart. We identified three biomechanical properties of stretch-related longitudinal wave pumping that exhibit characteristics like impedance pump: (i) a nonlinear flow–frequency relationship, (ii) bidirectional flow, and (iii) the potential for both positive and negative flow at a fixed frequency, contingent upon the aorta’s wave speed dictating the wave state. Our results demonstrate for the first time that this mechanism generates a significant flow, potentially providing a supplementary pumping mechanism for the heart.
The human HELQ helicase and XRN2 exoribonuclease cooperate in R-loop resolution
Authors: Pan J. M. , Betts H. , Cubbon A. , He L. , Bolt E. L. , Soultanas P.
Published: February 2025

The human HELQ helicase is a superfamily 2, 3′-5 helicase homologous to POLQ and RNA helicases of the Ski2-like subfamily. It is involved in diverse aspects of DNA repair and is an emerging prognosis biomarker and novel drug target for cancer therapy. HELQ interacts with RPA through its inherently disordered N-HELQ domain and hence is recruited to RPA-bound DNA substrates. Our study reveals a novel role for HELQ in R-loop resolution. We show in cells and
in vitro
that HELQ is recruited by RPA at R-loops, which are then resolved if HELQ is catalytically active as an ATPase/helicase. Furthermore, we identify a functional interaction of HELQ with XRN2, a nuclear 5′ to 3′ exoribonuclease, which we suggest coordinates R-loop unwinding by HELQ with RNA digestion by XRN2. Collectively, we assign a new biological function for HELQ in genome stability in metazoans through its involvement with XRN2 in R-loop metabolism.
The histone deacetylase inhibitor Scriptaid targets G-quadruplexes
Authors: Sanchez-Martin Victoria , Ruzic Dusan , Tello-Lopez Maria J. , Ortiz-Morales Andrea , Murciano-Calles Javier , Soriano Miguel , Nikolic Katarina , Garcia-Salcedo Jose Antonio
Published: February 2025

Scriptaid is a chemical compound with anti-tumoural effects due to its role as a histone deacetylase inhibitor. Despite sharing part of the chemical structure with other ligands of G-quadruplexes (G4s), the interaction of Scriptaid with G4s has not been explored before. We synthesized Scriptaid and screened its cytotoxic activity in cellular models of colorectal cancer (CRC). We extensively evaluated its biological activity by cell cycle, immunofluorescence, qRT-PCR and Western blot experiments. To identify the G4 targets of Scriptaid, we conducted a panel of binding assays. Here, we show that Scriptaid induced cytotoxicity, cell cycle arrest and nucleolar stress in CRC cells. Moreover, Scriptaid impaired RNA polymerase I (Pol I) transcription, stabilized G4s and caused DNA damage. Finally, we disclose that these effects were attributable to the binding of Scriptaid to G4s in ribosomal DNA. In conclusion, our work reveals that a primary impact of Scriptaid on human cells is the interaction with G4s.
Proximal partners of the organellar N-terminal acetyltransferase NAA60: insights into Golgi structure and transmembrane protein topology
Authors: Tanco Sebastian , Jonckheere Veronique , Tharkeshwar Arun Kumar , Bogaert Annelies , Gevaert Kris , Annaert Wim , Van Damme Petra
Published: February 2025

Biotin identification (BioID) is an interactomics approach that utilizes proximity labelling to map the local interactome or proxeome of proteins within a cell. This study applies BioID to investigate proteins proximal to NAA60 (N-alpha-acetyltransferase 60), an N-terminal acetyltransferase (NAT) of pathological significance in human disease, characterized by its unique Golgi localization. NAA60 is known to N-terminally acetylate transmembrane proteins that present their N-terminus on the cytosolic face of the membrane, and its involvement in maintaining Golgi structure has previously been established. Using a stable cell-line expressing an NAA60-BirA* fusion protein, we isolated biotinylated proteins through streptavidin affinity purification. Mass spectrometry analysis revealed over 100 proximal partners of NAA60, enriched in proteins localized on the
trans
-side of the Golgi apparatus. High-confidence proximity interactors included golgins and GRASP proteins, essential for Golgi integrity. Considering the transmembrane nature of NAA60, the identification of biotinylated peptides inferred the topology of transmembrane protein interactors within the secretory pathway. Subsequent suborganellar localization analysis revealed a more prominent
medial
/
trans
-Golgi localization of NAA60. Our findings underscore the role of NAA60 and its interactors in maintaining Golgi structural integrity and highlight the effectiveness of BioID in generating critical protein topology data, invaluable for enhancing the prediction of protein topology within cellular compartments.
High-density lipoprotein cholesterol: how studying the ‘good cholesterol’ could improve cardiovascular health
Authors: Diaz Lucy , Bielczyk-Maczynska Ewa
Published: February 2025

High cholesterol levels are associated with an increased risk of cardiovascular disease, specifically atherosclerosis, a leading cause of death worldwide. Atherosclerosis occurs when cholesterol and fat build up in plaques along blood vessel walls, restricting blood flow and preventing nutrients and oxygen from diffusing in and out of the bloodstream. High-density lipoprotein cholesterol (HDL) particles prevent the build-up of such plaques, removing excess cholesterol from the peripheral tissues and delivering it to the liver, where it can be removed from the body. This pathway is known as reverse cholesterol transport (RCT). Because HDL plays a key role in preventing plaque buildup, understanding how this molecule and RCT function in the body could help us develop much-needed new atherosclerosis therapies and prevention strategies. However, HDL metabolism is complex, and research on HDL has been less favoured than research investigating a much better-understood molecule, low-density lipoprotein cholesterol, as a treatment target. More specifically, the receptors involved in the process of taking up HDL within the liver and their relationships to one another, along with the mechanism of whole, or holoparticle uptake of HDL remain to be clarified. In this review, we discuss several outstanding mysteries in HDL metabolism, consider why previous clinical trials to improve cardiovascular health by modulating HDL levels have been unsuccessful and argue that understanding HDL metabolism is essential for crafting interventions to reduce cardiovascular disease risk.
Projected speaker numbers and dormancy risks of Canada’s Indigenous languages
Authors: Boissonneault Michaël , Tallman Adam , Gast Volker , Greenhill Simon J.
Published: February 2025

UNESCO launched the International Decade of Indigenous Languages in 2022 to draw attention to the impending loss of nearly half of the world’s linguistic diversity. However, how the speaker numbers and dormancy risks of these languages will evolve remains largely unexplored. Here, we use Canadian census data and probabilistic population projection to estimate changes in speaker numbers and dormancy risks of 27 Indigenous languages. Our model suggests that speaker numbers could, over the period 2001–2101, decline by more than 90% in 16 languages and that dormancy risks could surpass 50% among five. Since the declines are greater among already less commonly spoken languages, just nine languages could account for more than 99% of all Canadian Indigenous language speakers in 2101. Finally, dormancy risks tend to be higher among isolates and within specific language families, providing additional evidence about the uneven nature of language endangerment worldwide. Our approach further illustrates the magnitude of the crisis in linguistic diversity and suggests that demographic projection could be a useful tool in assessing the vitality of the world’s languages.
The predictive outfielder: a critical test across gravities
Authors: Aguado Borja , López-Moliner Joan
Published: February 2025

Intercepting moving targets is a widespread challenge across many species. In humans, heuristics that use optic variables have excelled in guiding interception, relying on a closed-loop system to couple optic variables directly with direction of locomotion. This contrasts with models that explicitly recover final positions from initial trajectory conditions. However, comparing these different approaches using empirical data is challenging, as they often predict similar locomotion trajectories. We present a model based on optic variables that continuously updates predictions on the landing position in the three-dimensional scene and remaining flight time based on the outfielder’s real-time movements. A distinct feature is the model’s adaptability to different gravitational accelerations, making its predictions inherently tailored to specific environments. By actively integrating gravity, our model produces trajectory predictions that can be validated against actual paths. To compare our model with previous ones, we conducted experiments within virtual reality, strategically varying simulated gravity and physical size. The variation in gravity resulted in qualitatively distinct predictions between heuristics based solely on optic variables and our model, which incorporates gravity. The empirical trajectories, kinematic patterns and timing responses aligned well with our model’s predictions, emphasizing the importance of including environmental constants.
Behavioural repertoires in moving crowds: an observational approach
Authors: Sieben Anna , Postmes Tom
Published: February 2025

The wide variety of behaviour found in crowds is a challenge for current models of crowd movement behaviour. To aid the development of a new generation of models, this paper develops a systematic observational approach based on social psychological knowledge about how humans recognize and use social meaning and structures. To develop this approach, we studied the movement behaviour of participants in a pedestrian crowd experiment, more specifically in four experimental runs (
n
= 351) of crowd situations, videotaped from a top-view perspective. In the experiments, large groups of around 80−90 imagined being on the way to a concert. There was no instruction for how to behave except that participants’ motivation to arrive at the gate first was varied through instructions (low/high). Through a qualitative, iterative process of systematic observation a complete list of behavioural repertoires (an ethogram) was collected. Behaviours were performed by either individuals, small interactive groups or large action groups. The observational dataset was enriched with pedestrian trajectory data, used to create heatmaps for density and speed, as well as time–distance plots. The analysis reveals that participants show many, sometimes rapid, changes both between movement repertoires and between the social unit they are engaged in.
If you blink at me, I’ll blink back. Domestic dogs’ feedback to conspecific visual cues
Authors: Canori Chiara , Travain Tiziano , Pedretti Giulia , Fontani Rachele , Valsecchi Paola
Published: February 2025

Blinking, along with other facial expressions, has been suggested to play a role in dogs’ intra- and interspecific communication, however the feedback this signal elicits from the audience is still poorly studied. In this study, we investigated the behavioural and physiological responses of 54 domestic dogs to videos of conspecifics performing blink. Based on existing literature, we hypothesized that dogs would show a higher rate of blinking when exposed to blink than to another facial expression (nose lick) and to an attentive still-looking face (control). Results showed that dogs blinked more during the blink video compared to the nose lick (NL) video, suggesting a mimicry phenomenon and implying a possible role of blinking in dogs’ communication. Cardiac analyses showed increased heart rate variability values during the video sessions independently to the type of facial signal projected, suggesting that the stimuli were not perceived as stressful. The present results open the door to future investigation of blink synchronization, as this aspect was not directly addressed in the present study. Future research should also explore the effects of eye blink and NL in modulating intraspecific social interactions.
A marine predator relies on both social cues and frequently updated memory to search for prey
Authors: Collet Julien , Thiebault Andréa , Bonnet-Lebrun Anne-Sophie , Tremblay Yann , Carpenter-Kling Tegan , Keys Danielle , Pistorius Pierre
Published: February 2025

Finding scattered resources is a challenge for marine predators, their search strategies shaping in turn their response to global changes. Three types of search strategies are generally considered: random opportunistic search, reliance on conspicuous social cues or long-term individual fidelity to predictably productive areas. More complex strategies, namely intermediate, composite and/or those varying across time and environmental conditions are likely to prevail but are rarely explored. We investigated memory strategies in Cape gannets, a marine predator heavily relying on social cues, and closely related to the northern gannet which shows long-term individual foraging fidelity. Repeat GPS tracks within seasons revealed that two different individuals leaving the colony more than 3 days apart showed random chances to forage in a similar direction, whereas within-individuals, birds persisted in a same direction for longer timescales, reaching random levels only after 10 days, or 9 consecutive trips. This strategy of transient individual preferences within a breeding season was observed in most individuals every year. These results suggest a consistent and complex search strategy mixing social cues and private information updated every few days. Our simple approach can readily be applied to other central place foragers to better understand the evolutionary ecology of search strategies.
Rapid and wash-free anti-drug antibody assay enabled by the complementary nanoluciferase biosensor
Authors: Sun Ruoxuan , Qian Mark G. , Zhang Xiaobin
Published: February 2025

Biotherapeutics have demonstrated remarkable therapeutic efficacy across a wide range of diseases; however, their clinical application is often hindered by the development of anti-drug antibodies (ADAs). Traditionally, ADA monitoring has relied on ligand-binding assays (LBAs) such as enzyme-linked immunosorbent assays (ELISA) or electrochemiluminescence assays (ECLIA). Although effective, these methods require multiple washing and incubation steps, extending data generation time to several hours or even days. In contrast, homogeneous immunoassays offer a promising alternative due to their “mix-and-read” feature, which significantly reduces operational complexity, time, and cost compared to conventional LBAs. In this study, we explored the feasibility of rapid ADA detection using a wash-free homogeneous assay based on the split nanoluciferase (SplitNluc) biosensor system. Through case studies involving diverse therapeutic modalities including antibody-drug conjugates (ADC), Fc-fusion protein, Fc-less multidomain biotherapeutics (MDB), and single-domain antibody (SdAb), we demonstrated that the SplitNluc platform is a versatile and efficient tool for robust and rapid ADA monitoring. This approach not only streamlines the detection process but also holds potential for broader applications in biotherapeutic development and clinical monitoring.