Holliday junctions (HJs) are key intermediates in homologous recombination, and their branch migration influences how recombination intermediates are positioned and processed. Although structural studies have shown that HJs interconvert between open and stacked-X conformations, and the stacked-X state has long been proposed to inhibit migration, it remains unclear whether such pausing creates a substantial kinetic barrier to long-range spontaneous branch migration. Here, we develop a magnetic-tweezer single-molecule assay that tracks spontaneous HJ migration over extended distances ($\sim 290$ bp) immediately after junction formation. We find that migration is discontinuous, alternating between active movement and long-lived pauses lasting seconds to tens of seconds. Focusing on pauses of at least 1 s, we show that Mg$^{2+}$ strongly increases both pause duration and pause frequency, whereas higher temperature and applied tension suppress long-lived pausing. Under high Mg$^{2+}$, low temperature, and low force, these pauses dominate total migration time and reduce effective migration several fold, establishing them as a major kinetic barrier. In addition, nucleoid-associated protein HU increases long-pause frequency and pause occupancy under conditions where intrinsic pausing is weak. Together, these results show that spontaneous HJ migration is governed by a tunable long-lived paused state consistent with a stacked-X-like migration-inhibitory conformation.
We investigated sex differences in the production of pauses in autistic (pre-)adolescents in two conversational contexts: a monologue and an interactive discussion. This study included 107 French-speaking participants (Mage = 12.35 years), 49 autistic (22 females, 27 males) and 58 nonautistic (30 females, 28 males). Speech was elicited from two tasks: a get-to-know conversation and a narrative task. We analyzed the production of filled "uh" and "um" pauses as well as the production of unusually long silent pauses (> 700 ms). Autistic participants produced more silent pauses than nonautistic participants, but no significant group differences were found for filled pauses. Filled pauses occurred more frequently in the get-to-know than in the narratives, which underscores their pragmatic functions. No significant effect of sex was found. Autism diagnosis and conversational context, but not sex, influenced pause productions. Our results also highlight the importance of cross-linguistic studies, including in autism research, to avoid the overgeneralization of findings from English-speaking populations. https://doi.org/10.23641/asha.32078268.
Hummingbirds hover, enabling them to serve as exclusive pollinators for many plant groups with which they have coevolved. They combine bird muscle power with insect flight skills to hover and maneuver in any direction. This study investigates an under-explored aspect of their hovering flight: many species exhibit an alternative gait, in which they flap their wings discontinuously, including momentary pauses sporadically interspersed between short series of wingbeats, which collectively generate a pattern we denote as 'intermittent hovering'. These brief pauses have not been characterized in hummingbirds but may play aerodynamic, energetic, and/or signaling roles. To detect and measure intermittent hovering, we present a high-throughput method to quantify these irregular wingbeat pauses using computer vision and signal analysis. High-speed videos of 11 species collected by recording free-living hummingbirds allowed us to track and analyze the pauses during hovering. The proposed algorithm has a precision of 74%, accurately detecting flapping pauses and thus intermittent hovering. Most of the misclassification errors were false positives: when very still hovering hummingbirds were continuously moving their wings, but some of the consecutive frames were similar enough that the algorithm classified them as a brief pause. These false positives, however, are easily discarded upon quick visual inspection, and the algorithm had only 19 false negatives across all videos, actually detecting intermittent hovering if it was present. This method is a step forward in creating tools that help researchers analyze complex behavioral patterns. Our study confirms the feasibility of reliably detecting intermittent hovering, contributing to our understanding of hummingbird flight dynamics.
Schizophrenia (SZ) disrupts language in ways that may be universal across languages. This study investigated whether linguistic anomalies previously observed in SZ also occur in Turkish, a morphologically rich and agglutinative language. We hypothesised that SZ patients would differ from healthy controls (HCs) across multiple linguistic domains, including features typically sensitive to cross-linguistic variation. Speech characteristics of 50 native Turkish-speaking SZ patients were compared with 50 HCs matched for age, sex, length of education, and handedness. Speech data were collected in 15-minute interviews. The interview recordings were transcribed and analysed for various lexical, syntactic, and phonological measures using CLAN, and compared for discourse measures using fastText word embedding models. The number of words produced per minute, mean length of utterance, average word frequency, the number of filled pauses, discourse coherence, and question-response similarity were lower in the patient group than in the control group. The content word-function word ratio, sentence prediction loss, type-token ratio, number of silent pauses, and silent pauses-to-total speech ratio were higher in the patient group than in the control group. Specific clinical and sociodemographic variables were identified as predictors of speech abnormalities in patients. The hypothesis was confirmed. Turkish-speaking SZ patients displayed speech patterns similar to those reported in other language groups, including language-sensitive variables. This supports the idea of universal linguistic disruptions in SZ. The findings are particularly valuable given the scarcity of research on Turkish, a low-resource and typologically distinct language.
The substantia nigra pars reticulata (SNr) functions as the principal inhibitory output of the basal ganglia, with the timing of its spikes critically controlling downstream disinhibition required for movement initiation. The external globus pallidus (GPe) and D1-expressing medium spiny neurons (D1-MSNs) in the striatum provide GABAergic inputs to the SNr that differ in their amplitude and kinetic properties. How these inputs interact with the intrinsic membrane currents that determine SNr firing is only partially understood. Using optogenetics, computational modeling, and electrophysiology in acute mouse brain slices, 47 animals of either sex were used for measurements, and we found an unexpected interaction between GABAergic inputs and hyperpolarization-activated currents (Ih) that tunes inhibitory efficacy in a pathway-specific manner. GPe inputs evoke fast, large IPSCs that transiently suppress SNr firing within a narrow window but whose rapid decay enables depolarization from Ih to restore firing after only a brief pause. In contrast, the slower decay kinetics of striatal IPSCs enables more sustained inhibition that counters the depolarizing drive from Ih to produce longer pauses, despite their lower conductance amplitudes. Pharmacological blockade of Ih with ZD7288 eliminated the rapid recovery of firing after GPe inhibition and equalized the inhibitory efficacy between GPe and striatal pathways. These findings establish an important interplay between synaptic kinetics and intrinsic membrane conductances in establishing pathway-specific inhibitory balance in the basal ganglia.Significant statement Our study reveals that inhibitory pathways to the substantia nigra pars reticulata are differentially shaped by the interplay between synaptic kinetics and intrinsic membrane conductances. Using optogenetics, electrophysiology, and modeling, we showed that fast-decaying GABAergic inputs from the external globus pallidus are rapidly overcome by Ih, producing only brief pauses in SNr firing, whereas slower striatal inputs generate longer-lasting inhibition. Blocking Ih abolishes this difference, demonstrating that intrinsic currents tune inhibitory efficacy in a pathway-specific manner. These results identify a biophysical mechanism that helps set the balance of basal ganglia output essential for movement control.
Fluent speech production remains largely preserved across adulthood, yet subtle disruptions such as pauses, repetitions, and revisions become more common with age. These disfluencies may reflect underlying cognitive and neural changes that accompany aging, particularly in executive function (EF) and large-scale brain network organization. In this study, we examined whether EF and resting-state functional connectivity (RSFC) independently or jointly explained age-related differences in naturalistic speech disfluencies in an adult lifespan sample (n = 252, ages 20-81 years). RSFC was used to assess network segregation within three systems implicated in language and cognitive control: language network, default mode network (DMN), and multiple demand (MD) network. These task-independent connectivity patterns provide insight into how the brain's functional architecture impacts speech production and its age-related vulnerabilities. Our findings indicate that age was associated with increased rates of specific disfluency subtypes, such as unfilled pauses, repetitions, and revisions, as well as lower EF and lower language, MD, and DMN network segregation. Although increasing age was associated with lower EF, EF performance did not predict disfluencies or mediate their age-related increase. In contrast, higher DMN segregation predicted lower overall disfluencies, repetitions, and revisions. Age moderated the relationship between DMN segregation and repetitions, with a significant association only in younger and middle-aged adults, suggesting weaker brain-behavior relationships at older ages. DMN segregation also partially mediated the relationship between age and revisions. These findings suggest that while EF relates to planning-related disruptions, changes in functional brain organization may more directly contribute to age-related increases in self-monitoring disfluencies.
Mixed methods research combines the depth of qualitative inquiry with the breadth of quantitative measurement to gain a more comprehensive understanding of complex phenomena. Spiral approaches have been applied within mixed method research as forms of iterative integration and synthesis. Despite its potential, the operationalization of spiral approaches remains conceptual and nebulous, limiting its broader application. This descriptive methodological paper presents spiral comparison as a replicable method for study design and synthesis, contextualized within a convergent mixed methods-grounded theory study exploring motivation for physical activity among adults receiving care from a Federally Qualified Health Center.Prior application of spiraling in mixed methods designs is presented, including the within sequential explanatory designs and the double helix model. Diverging from these models, our approach emphasizes cyclical integration over structural pairing, culminating in a narrowing of insights toward theoretical clarity. Spiral comparison builds upon constant comparison by integrating both qualitative and quantitative findings cyclically throughout data collection and analysis, rather than after independent analysis is complete.Within the example study, quantitative and qualitative data were collected concurrently, and analysis began during data collection. Spiral comparison pauses were implemented to assess preliminary findings and emergent patterns. Pauses informed pivots to data collection, theoretical understanding, and guided theoretical sampling. The spiral comparison approach enabled the identification of key incongruences and prompted updates to sampling and refinement of analytic focus. These methodological developments contributed directly to the derivation of a grounded theory model describing motivation for physical activity in an underserved population.Joint displays were created and updated in real time to visually present and synthesize findings. Transparency was enhanced by joint displays which also facilitated metainference generation and theory development. The spiral comparison method demonstrated its value in navigating complexity, uncovering deeper meaning, and supporting methodological rigor.We conclude by advocating for the broader application of spiral comparison in health sciences and other mixed methods research contexts. By demystifying the spiral approach and offering clear procedural guidance, this study supports its adoption in future research aiming for holistic and patient-centered insights.
Cognitive maps of the environment are initially encoded in a fragile form susceptible to interference, but they can stabilize over time-a process called "consolidation". This study investigated whether consolidation is a gradual or an all-or-none process. In the main condition, participants formed first a map of environment A, then a map of environment B, and then returned to A (sequence: A1 -> B -> A2). Performance increased from A1 to A2, but this increase was smaller than in a control condition where B was replaced by a pause filled with unrelated activities (sequence: A1 -> pause -> A2). Adding a pause after A1 in the main condition (sequence: A1 -> pause -> B -> A2) had no substantiable effect on performance. In contrast, adding a replica of A1 (sequence: A1 -> AR -> B -> A2) improved performance so that it no longer differed significantly from the control condition. This pattern of findings is consistent with the view that (1) cognitive maps consolidate gradually rather than abruptly, and (2) consolidation proceeds during task learning but not during pauses filled with other activities.
Hazard perception is a crucial skill for drivers and is typically measured using computer-based hazard perception tests. In these tests, drivers identify potential hazards in video clips recorded from the driver's perspective. Recently, researchers have also focused on another driver attribute called "hazard prediction." In hazard prediction tests, each scenario pauses just before a potentially dangerous event, and drivers must predict the subsequent events. Urban bus rapid transit (BRT) systems in Iran operate on dedicated routes that present specific hazards, such as sudden pedestrian crossings, motorcycle traffic, and emergency vehicles. Therefore, investigating the hazard perception and prediction abilities of BRT drivers can yield valuable insights to improve safety and reduce accidents. This study was conducted in Tehran, Iran, involving 187 urban BRT drivers. Hazard perception and prediction tests were designed, and demographic as well as cognitive questionnaires were administered to assess driver characteristics. The data were analyzed using SmartPLS software and structural equation modeling. The final structural equation model for hazard perception indicated that social cognition, planning, and inhibitory control were the most influential factors. For hazard prediction, sustained attention, cognitive flexibility, inhibitory control, decision-making, and memory emerged as the most significant variables. The results of this research can inform the training, testing, and evaluation of urban BRT drivers.
This study investigates the lived experiences of menopause among Chinese women residing in Greater China (Hong Kong and mainland China). Specifically, it focuses on menopausal stigma, a focal theme identified by previous research on menopause. Existing public outreach and health campaigns in Western and Chinese contexts to date assume the universality of menopausal stigma and focus on de-stigmatizing this life stage. In this paper, we draw on theme-oriented discourse analysis and 46 interviews with Chinese women to examine their actual experiences of menopausal stigma in relation to their self-perceptions (self-stigma) and their social environment (public stigma). Based on the analysis of our data, we demonstrate that menopausal stigma is less pervasive and more implicit in the analysed Chinese contexts, with a general societal shift towards a greater acceptance and normalization of menopause. Women also express a preference for traditional Chinese medicine and cultural practices of care. Residual stigma, however, still exists, and manifests discursively through contextual factors (topic focus, preference of informal settings) and interactional features (vague language, hedging, pauses). Overall, our analysis challenges the universality of the phenomenon of menopausal stigma and foregrounds the importance of culturally- and context-specific frameworks of menopause for public outreach and health campaigns. Our study lends support to observational methodologies being most suitable for investigating the intra- and inter-personal dimensions of stigma. In particular, a discourse analytic enquiry provides a nuanced understanding of women's lived experiences and reveals the subtleties of underlying societal attitudes and ideologies.
To evaluate whether an institutional shift from anticoagulation with heparin to bivalirudin in Impella 5.5 patients altered bleeding or thrombotic rates, transfusion dependency, or device biocompatibility. All patients supported by an Impella 5.5 between August 2022 and December 2024 were reviewed retrospectively. Heparin was used before December 2023, at which point the switch was made to bivalirudin. Groups were defined by anticoagulant initiated by postimplantation day 2, and patients with crossover or anticoagulation pauses for >2 days were excluded from the laboratory analyses. Baseline characteristics, anticoagulation details, complications, and clinical outcomes were compared between the heparin and bivalirudin groups. Biocompatibility was assessed via laboratory values recorded over the first 14 days of Impella support or until device explantation in patients supported for <14 days. Among the 168 patients, 83 (49%) received heparin and 85 (51%) received bivalirudin. Baseline characteristics were similar in the 2 groups (P > .05), as were rates of thrombotic events (13% vs 14%; P = .871), total bleeding events (37% vs 30%; P = .275), and transfusion requirements (57% vs 51%; P = .433). However, bivalirudin patients demonstrated significantly faster rates of platelet recovery and lactate dehydrogenase reduction after Impella implantation (all P < .05), had fewer insertion site bleeds that required reoperation (10% vs 1%; P = .015), and were more often within their partial thromboplastin time goal (on 24% vs 41% of device-supported days; P ≤ .001). Systemic anticoagulation with bivalirudin in Impella 5.5 patients is associated with clinically meaningful improvements in postoperative thrombocytopenia and biocompatibility, with easier management, fewer insertion site bleeds, and more time within the target anticoagulation range.
Exercise induced hypoalgesia (EIH) is characterized by an acute reduction in pain perception following exercise. However, lack of knowledge exists regarding the effects of long duration exercise on EIH. This study aims to explore (1) the effect of a 120 min exercise on EIH in trained male cyclists, and (2) whether the potentially observed EIH results differ between local loaded and unloaded central landmarks. In a randomized controlled crossover design, 20 trained male cyclists conducted a bicycle ergometer session of 120 min at 70 % of the individual anaerobic threshold (IAT) and a control session in addition to a pre-experimental session (including medical anamnesis, incremental exercise test, IAT determination) with pauses of ≥2 days in between the respective visits. Heart rate (bpm), lactate concentrations (mmol/l), and rate of perceived exertion (RPE; 6-20) were documented. Pre and post, pain sensitivity was measured employing pressure pain thresholds (PPT [N/cm2]) at local muscular (rectus femoris, tibialis anterior), local articular (knee, ankle), and central landmarks (sternum, forehead). Exercise resulted in an average heart rate of 141.2 ± 9.4 bpm, an average lactate concentration of 1.6 ± 0.4 mmol/l, and RPE scores of 14.9 ± 2.9. Regarding PPT, no 'time' × 'session' interaction effects were observed for local muscular (p=0.588), local articular (p=0.588), or central landmarks (p=0.910), with these PPT (N/cm2) values observed: local muscular (exercise: pre=81.0 ± 19.5, post=83.0 ± 18.4, relative change: 4.5 ± 16.6 %; control: pre=85.1 ± 22.9, post=85.3 ± 22.5, relative change: 0.7 ± 10.8 %), local articular (exercise: pre=81.9 ± 21.0, post=80.8 ± 21.5, relative change: -0.7 ± 12.2 %; control: pre=81.7 ± 20.9, post=79.2 ± 23.3, relative change: -3.2 ± 12.8 %), and central (exercise: pre=47.9 ± 13.7, post=45.9 ± 11.7, relative change: -1.1 ± 19.8 %; control: pre=48.8 ± 13.0, post=47.1 ± 13.5, relative change: -3.3 ± 16.1 %). Findings suggest that long duration exercise of a standardized moderate intensity may not be effective to induce EIH in trained male cyclists, while also no hyperalgesia is observed. These results are not different between loaded and unloaded body parts. SK/AE 221026 (University of Wuppertal, Germany).
Endotracheal suctioning is a routine procedure in the pediatric ICU (PICU) and can be performed via open or closed systems. Closed-system suctioning has benefits for pressure maintenance in the ventilatory system and oxygen supply during the technique but is less effective. The association of an expiratory pause in closed-system suctioning is an alternative technique. We sought to evaluate the volume of suctioned secretions, respiratory mechanics, and hemodynamic parameters during closed endotracheal suctioning with expiratory pause, compared with conventional closed suctioning. Randomized crossover pilot trial with infants receiving invasive mechanical ventilation >24 h, with neuromuscular blocker, without cough reflex, randomized to define the order of suctioning techniques (T1-technique 1 conventional suctioning without expiratory pause; T2-technique 2: with expiratory pause), performed with a 2-h interval. Evaluated hemodynamic parameters (heart rate, blood pressure, and peripheral arterial oxygen saturation), respiratory mechanics (static and dynamic compliance, inspiratory and expiratory resistance, driving pressure), and suctioning secretion were weighed on a precision balance. Shapiro-Wilk test for normally distributed variables analysis and generalized estimating equation for effect analysis. Ten infants were included with a median age of 2 months (1.0-3.7). The amount of secretions from the technique with expiratory pause was significantly higher compared with conventional suctioning (mean 1.4 g vs 1.1 g; P < .001). Treatment effect was observed in the analysis of driving pressure (P < .001) and inspiratory resistance (P = .02), with an increase in these variables after suctioning with expiratory pause. There were no significant differences in hemodynamic variables. The closed-system suctioning with expiratory pause was more effective in secretion removal compared with conventional closed suctioning. However, driving pressure and inspiratory resistance increased after suctioning with an expiratory pause.
Formal thought disorder (FTD), a hallmark of schizophrenia spectrum disorders, manifests as incoherent speech and poses challenges for clinical assessment. Traditional clinical rating scales, though validated, are resource-intensive and lack scalability. Automated speech recognition (ASR) allows for objective quantification of linguistic and temporal features of speech, offering scalable alternatives. Furthermore, ASR-derived utterance timestamps provide access to pause dynamics, which are thought to reflect the cognitive processes underlying speech production. Yet, their added value beyond semantic measures remains insufficiently explored. In this study, we evaluated a scalable multimodal framework that integrates pause features with semantic coherence metrics across three datasets: naturalistic self-recorded diaries (AVH, n = 140 participants), structured picture descriptions (TOPSY, n = 72 participants), and dream narratives (PsyCL, n = 43 participants). Pause-related features were evaluated alongside established coherence measures using support vector regression (SVR) to predict clinical FTD scores. Models using pause features alone robustly predict manually rated FTD severity consistently across datasets. Integrating pause features with semantic coherence metrics enhanced predictive performance compared to coherence-only models, with late fusion yielding the most robust and consistent gains in all three datasets. On average across datasets, Spearman correlation increased from ρ = 0.413 for semantic-only models to ρ = 0.455 with late fusion. The performance gains from semantic and pause features integration held consistently across all contexts, though the nature of the most informative pause patterns was dataset-dependent. These findings suggest that both pause dynamics and semantic coherence reflect complementary aspects of thought disorganization. Our integration framework provides a scalable approach for refining the assessment of disorganized speech to advance automated speech analysis in psychosis.
The sound of speech reflects the speaker's mood in a way that may enable objective measurement of depression from speech audio recordings. As previous studies relied on volunteers without a diagnosis or selected subsets of acoustic features, it is unknown which acoustic features measure clinically relevant depression. We examined a comprehensive set of 77 system, source, spectral, and prosodic features of speech in 239 adults, including 147 with major depressive disorder, who spoke following neutral, positive, and negative prompts. We randomly divided the participants into an analysis set of 176 and a test set of 63 individuals. In the training set, we quantified the relationships between acoustic features and depression severity on the Montgomery Åsberg Depression Rating Scale (MADRS). We built XGBoost machine learning models to differentiate depression severity levels (none, mild, moderate, severe) and validated them in the unseen test set. Multiple acoustic features discriminated depression severity levels with prosodic features contributing the most information. Speech energy velocity, intensity variation, voiced rate, pause duration (prosodic features) and the third formant variance (a system feature) predicted depression severity consistently across prompts. Intensity, energy, pause duration, and harmonic difference contributed the most to XGBoost models that discriminated severity levels in the test set. The analysis is limited to speech in English. Acoustic, in particular prosodic, features can discriminate clinically relevant levels of depression among diagnosed patients. The robustness of these predictors across emotional contexts suggests a potential for application in a variety of settings.
The Hawaiian phoneme inventory includes a consonant ('okina) typically described as glottal stop. Recent studies have found that 'okina is rarely produced with full glottal closure utterance-medially, and is instead produced as a period of creaky phonation. This study investigated the acoustic correlates of utterance-initial 'okina following a pause. Although visible creaky phonation did not occur for utterance-initial 'okina, several reliable acoustic correlates were found during the first vowels of utterances that started with 'okina. Vowels preceded by 'okina had higher fundamental frequency, more abrupt onsets of acoustic energy, greater acoustic energy both in the fundamental frequency and across all frequency ranges, lower harmonics-to-noise ratios, and higher jitter than vowels that started without a preceding 'okina. Linear discriminant analyses of the data showed that these acoustic correlates were able to correctly categorize ∼75% of productions. Although no concurrent articulatory data were collected, arguments are provided to suggest that 'okina is regularly produced as full glottal closure utterance-initially in Hawaiian, possibly because of effects of prosodic strengthening. We believe the present study is the first to establish a relationship between utterance-initial glottal stop and these acoustic effects on the following vowel.
Zimbabwe is highly dependent on United States Government (USG) funding for the HIV Response, where 42% of the HIV expenditures in 2020 were financed by the USG and in 2023, PEPFAR invested more than $200 million to support HIV programmes. In late January 2025, the USG issued a "Stop Work Order," suspending funding for international aid and development during a 90-day review period and this was expected to have a significant negative impact on the Zimbabwean healthcare system therefore an epidemiological assessment was conducted to assess the impact of the stop work order. To assess the impact on incidence and mortality, an epidemiological assessment using the Avenir Health Goals model simulated five scenarios ranging from temporary pauses to the indefinite withdrawal of PEPFAR and 11% reduction in the Global Fund funding support. The stopping funding specified in the waiver plus 11% reduction in the Global Fund funding results in 74% (11,000) additional new HIV infections. The 90-day stop-work order will result in 35% (6,000) additional new HIV infections in 2025. The stopping of PEPFAR direct funding will result in additional 7,000 new HIV infections in 2025. Stopping all PEPFAR direct funding will add 35,000, 90-days pause will add 31,000, while stopping support to HIV prevention programs will add 22,000 additional new HIV infections through 2030. Stopping all PEPFAR direct funding will result in more than 13% increase in AIDS-related deaths with additional 107,000 deaths through 2030. The 90 days pause will reduce adult treatment coverage by 10% from 95% to 85% in 2025, while stopping direct PEPFAR funding will result in a reduction in adult ART coverage by 40% to 55% in 2025. These disruptions pose a significant threat to Zimbabwe's ability to achieve epidemic control and reach the 2030 target of ending AIDS as a public health threat.
Living tissues strengthen under repeated mechanical loading, yet replicating such adaptive growth in synthetic materials remains a formidable challenge. Here, we report a protein-based hydrogel that undergoes mechanochemically induced self-growth, autonomously reinforcing its baseline mechanical properties under applied stress. This strategy harnesses the copper-storage protein Csp1, whose force-regulated unfolding releases Cu(I) that catalyzes in situ azide-alkyne cycloaddition, generating secondary crosslinks under mechanical load. Upon unloading, Csp1 refolds and re-sequesters Cu(I), halting catalysis and restoring growth capacity. This mechano-catalytic feedback loop enables stress- and time-dependent self-reinforcement within a closed system, without external monomer supply. The hydrogel exhibits programmable mechanical memory via leveraging Cu(I) homeostasis in cyclic growth-pause-growth transitions. By coupling force-dependent protein conformational dynamics with catalytic activity, this strategy establishes a generalizable mechanochemical framework for designing self-adapting biomaterials whose structure and function evolve under mechanical stimulation.
Accurate preoperative imaging is essential in advanced epithelial ovarian cancer, where complete cytoreduction remains the strongest prognostic factor. This study evaluates the CT PAUSE score-a structured, domain-based reporting tool-for its utility in surgical planning and multi-disciplinary team (MDT) decision-making. In this prospective cross-sectional study between September 2022 to February 2024, 124 patients with FIGO stage III/IV ovarian cancer underwent 175 contrast-enhanced CT scans. PAUSE components-Peritoneal Cancer Index (PCI), Ascites/abdominal wall disease, Unfavourable sites, Small bowel/mesenteric disease, and Extra-peritoneal metastases-were prospectively scored during evaluation. Interobserver agreement was assessed in a subset of 30 cases. MDT triage using PAUSE resulted in a complete cytoreduction rate of 89.3%. A simplified nomogram based on upper abdominal disease volume showed discriminatory ability (area under the curve (AUC) [95% CI] = 0.820 [0.740-0.880]) and could be an alternative to the full radiological PCI-based nomogram (AUC) [95% CI] = 0.763 [0.677-0.835]), in busy clinical settings. Interobserver agreement was substantial for both nomogram scores, with higher reliability observed for the score derived from the upper abdominal disease-based nomogram (intraclass correlation coefficient (ICC) [95% CI] = 0.710 [0.582-0.825] versus 0.627 [0.460-0.778]; p < 0.001). CT PAUSE provides a structured approach to radiological reporting and may support more consistent MDT discussions and surgical triage in advanced ovarian cancer. Its performance in this cohort might suggest potential for integration into clinical workflows, pending further validation. There was no funding source for this study.
Understanding the respiratory patterns of marine mammals on land can provide insight into their respiration and breath-hold diving physiology at sea. In this study, we analyzed the respiratory patterns of southern elephant seals (Mirounga leonina) resting on land, emphasizing ontogenetic variations. We observed 478 elephant seals at Península Valdés, Argentina, and recorded 16,626 respiratory cycles through direct observation and video analysis to evaluate differences in breathing phases: inspiration (INSP), post-inspiratory pause (PIP), expiration (EXP), and post-expiratory apnea (PEA). All seals displayed episodic breathing patterns, with the PIP phase significantly longer (4.3 ± 6.67 s) compared to INSP and EXP (1.5 ± 1.30 s and 1.2 ± 1.1 s, respectively). We found respiratory cycles were longer and frequencies lower in older seals, corresponding to allometric scaling with body size and physiological maturity. PEAs were infrequent, representing only 1.6% of cycles, but their occurrence and durations increased with age, possibly consistent with greater oxygen storage capacity. Additionally, we found ground temperature influenced respiratory phases, particularly shortening the EXP and INSP duration at higher temperatures, indicating a potential thermoregulatory adaptation. State of wakefulness also influenced PEA occurrence, with a higher probability of occurrence during a presumably asleep state. Our findings contribute to understanding the physiological adaptations enabling the aquatic lifestyle of elephant seals and underscore substantial developmental changes in respiratory control during terrestrial resting periods.