bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract Sa403: Chest Compression Metrics During Adult In-Hospital Cardiopulmonary Resuscitation: A GWTG-Resuscitation Study
Authors: O'Halloran Amanda , Morgan Ryan , Alvey Jessica , Reeder Ron , Patterson Elizabeth , Raymond Tia , Perman Sarah , Edelson Dana , Wolfe Heather , Nadkarni Vinay , Berg Robert , Abella Benjamin , Sutton Robert
Published: November 2024

Background:
CPR quality is an important modifiable component of cardiac arrest care. Current chest compression (CC) guidelines were primarily generated from out-of-hospital arrest data. However, they are applied to cardiac arrests in all contexts, including in-hospital.

Aims:
We aimed to: 1) quantitatively describe in-hospital cardiac arrest (IHCA) CC metrics; 2) determine the association of current AHA guideline-recommended CC metrics with IHCA outcomes; and 3) discover new CC targets using IHCA data and quantify their association with outcomes. We hypothesized that existing CC targets (rate 100-120 compressions per minute [cpm], depth 50-60 mm, CCF>80%) would be associated with improved outcomes.

Methods:
Retrospective cohort using the AHA GWTG-Resuscitation adult IHCA registry. Events in 2015-2022 lasting ≥1 min with recorded CC metrics were included. To discover alternative CC targets, we utilized a combination of cubic splines, ROC curves, and clinician judgment. Multivariable logistic regression evaluated the association between exposures (guideline-recommended depth [50-60 mm], rate [100-120 cpm], CCF [>80%]; novel targets for depth, rate, CCF) and outcomes (primary: survival to discharge; secondary: survival with favorable neurological outcome).

Results:
Of 587,588 IHCAs, 3391 events at 42 sites were included (rate: n=3380; depth: n=2892; CCF: n=2698). Median age was 65 years [IQR 54, 73]. Median rate was 112 cpm (IQR 105, 120); depth 61 mm (IQR 53.3, 68.6); and CCF 90% (IQR 82%, 95%). There was no association between current guideline-recommended CC targets and survival to discharge (rate: aOR 1.08 [95CI 0.88, 1.32], p=0.46; depth: aOR 0.88 [95CI 0.71, 1.08], p=0.22; CCF: aOR 0.79 [95CI 0.62, 1.01], p=0.058). In our spline/ROC curve analysis, we identified alternative targets of rate 100-110 cpm, depth 40-50 mm, and CCF>95%, which were associated with higher odds of survival to discharge (rate: aOR 1.32 [95CI 1.10, 1.58], p<0.01; depth: aOR 1.41 [95CI 1.07, 1.86], p=0.015; CCF: aOR 2.08 [95CI 1.67, 2.60], p<0.01) and survival with favorable neurological outcome (rate: aOR 1.38 [95CI 1.13, 1.69], p<0.01; depth: aOR 1.52 [95CI 1.14, 2.05], p<0.01; CCF: aOR 2.14 [95CI 1.66, 2.75], p<0.01).

Conclusions:
In this adult IHCA study, contrary to our hypothesis, existing guideline-recommended CC targets were not associated with outcomes. Alternative targets derived from GWTG-R (rate 100-110 cpm; depth 40-50 mm; CCF>95%) were associated with improved outcomes.
Abstract Sa505: Cerebral Oxygen Saturation Measurement Using Near-Infrared Spectroscopy During In-Hospital Cardiac Arrest Predicts Early Outcome
Authors: Putowski Mateusz , Dudzikowska Magdalena , Siudak Zbigniew
Published: November 2024

Introduction:
The effectiveness of cardiopulmonary resuscitation is dependent on maintaining optimal cerebral perfusion. NIRS provides a non-invasive method of monitoring cerebral oxygen saturation (rSO2), providing real-time information on the quality of resuscitation. Dynamics of rSO2 changes in the peri-resuscitation period and depending on the drugs administered have not yet been fully investigated.

Hypothesis:
It was assumed that continuous monitoring of rSO2 using NIRS during CPR can serve as an indicator of resuscitation quality and outcome. Moreover, a positive correlation between rSO2 and EtCO2 was assumed.

Goals:
The aim of the study was to assess the dynamics of rSO2 changes during CPR and in the period up to 24 hours after successful resuscitation. Moreover, the relationship between rSO2 and EtCO2 levels and ROSC was determined, as well as the influence of adrenaline and NaHCO3 supply on rSO2 values.

Methods:
A prospective observational study was performed at the University Hospital in Krakow (Poland). The study included 104 consecutive patients who experienced IHCA. The rSO2 and EtCO2 levels were monitored (using Masimo Open Connect™ MOC-9™). CPR was performed by the Early Response Team. Once ROSC was obtained rSO2 and EtCO2 monitoring were continued for 24 hours or until cardiac arrest resumed. Patients were divided into three groups: no ROSC, ROSC with survival < 30 days, ROSC with survival ≥ 30 days.

Results:
ROSC was achieved in 54 patients and survival was ≥30 days in 16 patients. It was found that rSO2 values were statistically significantly higher during the entire CPR process in patients with ROSC compared to patients without ROSC (p<0.001). See Figure 1. A positive correlation was obtained between EtCO2 and rSO2 in the ROSC group. There were no significant changes in rSo2 values after the administration of adrenaline and NaHCO3 (p=0.604).

Conclusions:
Monitoring rSO2 during CPR can be a valuable prognostic tool. Higher rSO2 values correlate positively with the achievement of ROSC, demonstrating the effectiveness of real-time NIRS measurements as an indicator of effective cerebral perfusion. The average rSO2 values after adrenaline administration remained at a similar level in all groups. Cerebral oxygen saturation remains a more stable measurement than EtCO2.
Abstract Sa506: Early Serial Somatosensory Evoked Potentials Can Assess Brain Injury Severity and Recovery in Swine Cardiac Arrest Models
Authors: Harding Laura , Mergos Joshua , Tiba Mohamad , Cramer Traci , Greer Nicholas , stacey william , Sandroni Claudio , Sanderson Thomas , Neumar Robert , Hsu Cindy
Published: November 2024

Introduction:
Bilateral absent cortical N20 somatosensory evoked potentials (SSEPs) at 12 and 24 hours after return of spontaneous circulation (ROSC) can predict poor neurologic outcome in cardiac arrest patients. However, it remains unknown if early SSEPs can be used to assess the efficacy of neuroprotective therapies after cardiac arrest. We hypothesized that the rate of SSEP recovery during the first 24 hours after ROSC can differentiate brain injury severity.

Methods:
Eighteen Yorkshire swine (50-60 kg) were subjected to 5 (VF-5) or 10 minutes (VF-10) of ventricular fibrillation followed by advanced cardiac life support until ROSC. Sham animals were included to control for the effects of sedatives and instrumentation. Bilateral median nerves were stimulated with 35 mA at the forepaws. Cortical signal amplitudes were collected for 1 hour before cardiac arrest (baseline), for the first 4 hours after ROSC, and at 6, 12, 18, and 24 hours after ROSC for 15 minutes at each time point. Two-way ANOVAs were performed to determine inter- and intra-group differences using GraphPad Prism.

Results:
VF-5 (n= 9) and VF-10 (n=9) animals showed similar and significant N20 suppression from baseline during the first 6 hours after ROSC compared to sham animals (n = 4;
Table 1
,
Figure 1
), but both recovered during the first 24 hours after ROSC. VF-10 animals showed trends toward slower N20 recovery compared to VF-5 animals. VF-5 animals demonstrated mean (SD) N20 recovery to 97.1 (33.5)% of baseline by 24 hours after ROSC, whereas VF-10 animals (n= 9) had mean (SD) N20 recovery of 63.9 (28.7)% of baseline by 24 hours after ROSC. Sham animals (n=4) demonstrated the known attenuating effect of Propofol on N20 amplitude to a mean (SD) of 68.9 (15.4)% of baseline by 24 hours after ROSC.

Conclusions:
Our study demonstrates the feasibility of using serial N20 cortical SSEPs to assess brain function recovery and potentially quantify brain injury severity during the first 24 hours after ROSC in swine cardiac arrest models. Future studies are needed to better understand the impact of prolonged sedation on N20 amplitude and correlate the rate of N20 recovery with blood-based biomarkers and histological findings to confirm the construct validity of early SSEPs in our swine cardiac arrest models.
Abstract Sa703: Investigating Racial Disparities in Out-of-Hospital Cardiac Arrest Interventions in Salt Lake City, Utah, USA
Authors: Awad Emad , Druck Jeff , Johnson Michael , Hopkins Christy , Awad Ahmed Z , Al Kurdi Dilan , Youngquist Scott
Published: November 2024

Aims:
The primary objective of this study was to investigate ethnic disparities in out-of-hospital cardiac arrest (OHCA) interventions, specifically the administration of epinephrine and ant arrythmias. The secondary objective was to explore the association with the provision of bystander CPR (CPR) and the application of Automated External Defibrillator (AED).

Methods:
This was a retrospective analysis of data from the Salt Lake City Fire Department from 2010 to 2023. The study included adults 18 years or older who experienced OHCA and were treated by EMS. Ethnicity was categorized as Whites, Blacks, Hispanics, Asians, and others. Multivariable regression analysis was used to examine the association between ethnicity and the specified outcomes.

Results:
Unadjusted analyses revealed no significant differences across ethnic groups in epinephrine and antiarrhythmic medication administration and bystander CPR. However, significant ethnic disparities were observed in AED use: the Asian population had the highest rate (21.8%), while the Black population had the lowest (6.5%). The multivariable analysis found no significant association between ethnicity and any OHCA interventions examined in this study.

Conclusions:
Our multivariable analysis did not reveal any statistically significant association between ethnicity and various OHCA interventions, including epinephrine administration, antiarrhythmic medication use, bystander CPR, and AED intervention in Salt Lake City. These findings suggest that regional differences in ethnic disparities in OHCA may vary across locations, emphasizing the need for further research into disparities in other regions and the impact of factors such as socioeconomic status and neighborhood conditions.
Abstract Sa706: Sex Differences in ROSC and Survival from Out of Hospital Cardiac Arrest
Authors: Gwo Pam Pam , Burguera-Couce Eric , Nichols Julie , Piktel Joseph , Laurita Kenneth , Wilson Lance
Published: November 2024

Background:
Determining factors predicting return of spontaneous circulation (ROSC) and survival after out of hospital cardiac arrest (OHCA) are a high priority for guiding clinical decision making and understanding differences in patient outcomes. Although sex differences in OHCA outcomes have been described, there are inconsistent reports, and mechanisms underlying these differences remain unclear.

Aim:
To determine whether sex differences and arrest factors are associated with ROSC and survival after OHCA.

Hypothesis:
Sex differences in both ROSC and survival are associated with differences in both arrest characteristics and care delivery.

Methods:
Single site observational study of consecutive adult emergency medical services (EMS) patients with OHCA at a large tertiary care center between 1/1/2018-3/31/2024. EMS reports, continuous EMS ECG recordings and electronic health records were analyzed to identify the presence ROSC and determine demographics, arrest characteristics, and survival. Statistical significance was determined using Chi-square and logistic regression (LR) analyses.

Results:
344 (71%) patients had ROSC and 139 patients (29%) had no ROSC. Patients with ROSC vs. no ROSC were similar regarding age, race, and ethnicity. Patients with ROSC were more likely to be female (p<0.003), and female patients with ROSC were more likely to have both a primary arrest rhythm of VT/VF and asystole (p <0.05), rearrest (p<0.013), and had a longer time from arrest to ROSC (34 vs. 25 min, p<0.1). Interestingly, in a LR model, female sex was associated with greater 6-month survival (OR: 3.3, 1.6-6.5, p<0.003). There were no sex differences in patients receiving post-arrest cardiac catheterization or targeted temperature management.

Conclusion:
Despite generally worse arrest characteristics, female sex was associated with increased ROSC and survival. Given this, and similar delivery of post-arrest care, these data suggest that in this cohort, sex differences, rather than care delivery, may underlie differences in outcome. Whether additional disparities in arrest and post-arrest care contribute will be important to determine.
Abstract Sa808: Validation of a Modified Pediatric Sequential Organ Failure Assessment Score Following Cardiac Arrest in Children with Cardiac Disease
Authors: Zeida Haar Lucas , Prakash Rithika , Foster Sierra , Li Xilong , Bhaskar Priya , Lasa Javier , Raman Lakshmi , Yu Priscilla
Published: November 2024

Introduction:
The Pediatric Sequential Organ Failure Assessment (PSOFA) is a severity of illness score that has not been validated in children after IHCA.

Hypothesis:
A modified PSOFA (mPSOFA) score, adjusted for post-cardiac arrest care with additional adjustments if ECMO is utilized, measured after pediatric IHCA in a cardiac intensive care unit (CICU) is associated with survival to hospital discharge (SHD).

Methods:
This was a retrospective cohort study of IHCA events in children admitted to a single-center pediatric CICU from 9/2016 to 4/2023. Patients were grouped into those who utilized ECMO (including ECPR) and those who did not after ROC. PSOFA was modified for all patients by removing the neurologic score. For days that ECMO was utilized, patients were assigned the maximum cardiovascular and respiratory scores. Total mPSOFA was scored from 0 to 20 with higher scores indicating greater organ dysfunction. Mean mPSOFA scores were calculated daily for 28 days after ROC, or until hospital discharge or death, if they came first. Univariate and multivariable logistic regression models were used to assess the association between mean mPSOFA scores and SHD. A secondary outcome was SHD with favorable neurologic outcome (FNO), defined by Pediatric Cerebral Performance Category (PCPC) discharge score of 1 to 3, or no change from admission.

Results:
Of 102 index events, overall SHD was 60.8% (N=62) and SHD w/FNO was 55.9% (N=57). There were 59 patients in the ECMO subgroup. Compared to non-survivors, survivors had lower CPR duration (p=<0.01), ECPR use (p=0.01), and mean mPSOFA scores (3.95±2.32 vs 6.95±4.45, p=0.02). In univariate analysis, increased mean mPSOFA scores were associated with decreased SHD (OR 0.85, 95% CI 0.73-0.98, p=0.03) and SHD w/FNO (OR 0.85, 95% CI 0.74-0.99, p=0.04) in the ECMO subgroup, but only decreased SHD (OR 0.58, 95% CI 0.35-0.96, p=0.03) in patients not requiring ECMO. On multivariable analysis controlling for CPR duration and ECPR use, increased mPSOFA scores were associated with decreased SHD (OR 0.79, 95% CI 0.66-0.95, p=0.01) and SHD w/FNO (OR 0.79, 95% CI 0.66-0.96, p=0.02) for ECMO patients, but were not associated with any measured outcomes for patients not requiring ECMO.

Conclusion:
This retrospective study of children admitted to a single-center CICU demonstrates that increased mean mPSOFA scores captured for 28 days after IHCA are associated with decreased SHD for children utilizing ECMO during or after cardiac arrest.
Abstract Su101: Mesenchymal Stem Cell-Derived Extracellular Vesicles Mitigate Lipopolysaccharide Activation of Porcine Peripheral Blood Mononuclear Cells
Authors: Rolland Tyler , Zahra Sumbule , Cucinotta Daniel , Weil Brian
Published: November 2024

Objective:
Systemic inflammation is a well-established component of post-cardiac arrest syndrome (PCAS), a condition responsible for significant morbidity and mortality in patients who achieve return of spontaneous circulation (ROSC) following sudden cardiac arrest. Immune cell activation is pivotal in PCAS pathophysiology and commonly presents ~12hr post-ROSC with endotoxemia (“sterile sepsis”) where lipopolysaccharide (LPS) is present in systemic circulation. Given the paucity of available interventions to inhibit LPS-induced immune activation in the context of PCAS, we investigated the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) to modulate the inflammatory response of porcine peripheral blood mononuclear cells (PBMCs) activated by LPS in vitro.

Methods:
Porcine bone marrow-derived MSCs (P2) were cultured for 5 days and serum-starved for 3 days to collect MSC-EVs. These EVs were isolated from conditioned media using size exclusion chromatography and ultracentrifugation, then characterized by nanoparticle tracking analysis (ZetaView) and ExoCheck. Naïve PBMCs from healthy swine were cultured for 1 week before stimulation with either basal media or LPS (5ug/mL). MSC-EVs were added to activated PBMCs (2.5e8–2e9 EVs/well) and inflammatory surface marker expression (flow cytometry), inflammatory cytokine transcripts (qPCR) and release (ELISA), and reactive oxygen/nitrogen species (ROS/RNS) production were assessed 24 hours later.

Results:
LPS-stimulated PBMC populations exhibited altered surface marker expression consistent with enrichment of inflammatory granulocytes (CD172+CD163-), macrophages (CD14+CD163+), and adhesion molecules (CD172+) compared to basal media (all p<0.05). Addition of MSC-EVs significantly reduced the number of all inflammatory cell populations, with the most prominent effects achieved at the highest EV dose (2e9 EVs/well). Likewise, MSC-EVs significantly attenuated LPS-activated PBMC expression and secretion of TNFα and IL-6 (Figure 1) and decreased ROS/RNS production (Figure 2) in a dose-dependent manner.

Conclusion:
MSC-EVs attenuate LPS-induced activation of PBMCs in a dose-dependent manner, as determined by reductions in pro-inflammatory surface marker expression, inflammatory cytokine gene expression and secretion, and ROS/RNS production. These findings indicate that MSC-EVs or MSCs alone, may be a viable therapeutic approach to modulate LPS-mediated immune activation in PCAS.
Prognostic Significance and Associations of Neural Network–Derived Electrocardiographic Features
Authors: Sau Arunashis , Ribeiro Antônio H. , McGurk Kathryn A. , Pastika Libor , Bajaj Nikesh , Gurnani Mehak , Sieliwonczyk Ewa , Patlatzoglou Konstantinos , Ardissino Maddalena , Chen Jun Yu , Wu Huiyi , Shi Xili , Hnatkova Katerina , Zheng Sean L. , Britton Annie , Shipley Martin , Andršová Irena , Novotný Tomáš , Sabino Ester C. , Giatti Luana , Barreto Sandhi M. , Waks Jonathan W. , Kramer Daniel B. , Mandic Danilo , Peters Nicholas S. , O’Regan Declan P. , Malik Marek , Ware James S. , Ribeiro Antonio Luiz P. , Ng Fu Siong
Published: November 2024

BACKGROUND:

Subtle, prognostically important ECG features may not be apparent to physicians. In the course of supervised machine learning, thousands of ECG features are identified. These are not limited to conventional ECG parameters and morphology. We aimed to investigate whether neural network–derived ECG features could be used to predict future cardiovascular disease and mortality and have phenotypic and genotypic associations.

METHODS:

We extracted 5120 neural network–derived ECG features from an artificial intelligence–enabled ECG model trained for 6 simple diagnoses and applied unsupervised machine learning to identify 3 phenogroups. Using the identified phenogroups, we externally validated our findings in 5 diverse cohorts from the United States, Brazil, and the United Kingdom. Data were collected between 2000 and 2023.

RESULTS:

In total, 1 808 584 patients were included in this study. In the derivation cohort, the 3 phenogroups had significantly different mortality profiles. After adjusting for known covariates, phenogroup B had a 20% increase in long-term mortality compared with phenogroup A (hazard ratio, 1.20 [95% CI, 1.17–1.23];
P
<0.0001; phenogroup A mortality, 2.2%; phenogroup B mortality, 6.1%). In univariate analyses, we found phenogroup B had a significantly greater risk of mortality in all cohorts (log-rank
P
<0.01 in all 5 cohorts). Phenome-wide association study showed phenogroup B had a higher rate of future atrial fibrillation (odds ratio, 2.89;
P
<0.00001), ventricular tachycardia (odds ratio, 2.00;
P
<0.00001), ischemic heart disease (odds ratio, 1.44;
P
<0.00001), and cardiomyopathy (odds ratio, 2.04;
P
<0.00001). A single-trait genome-wide association study yielded 4 loci.
SCN10A
,
SCN5A
, and
CAV1
have roles in cardiac conduction and arrhythmia.
ARHGAP24
does not have a clear cardiac role and may be a novel target.

CONCLUSIONS:

Neural network–derived ECG features can be used to predict all-cause mortality and future cardiovascular diseases. We have identified biologically plausible and novel phenotypic and genotypic associations that describe mechanisms for the increased risk identified.
Return and Circular Migration Motives of Nordic and Baltic Citizens during the Covid-19 Pandemic and Diaspora Engagement
Authors: Kļaviņš Didzis , Birka Ieva , Stučka Malvīne
Published: November 2024

The contribution of this article is to collect and evaluate developed-country citizen-migration motives during the first year of the Covid-19 pandemic (March 2020–March 2021) by concentrating on return and circular migration to the Nordic and Baltic countries. The focus is on trying to understand who returned and why, and if these individuals were likely to stay or engage in further circular migration. In our exploratory study, we engaged with prevailing migration theories to analyse our unique dataset, to ascertain how well existing scholarship might account for and predict migration during a crisis situation. The study makes a valuable contribution to the ongoing discussion on the effect of Covid-19 on migration patterns, especially of highly qualified migrants, and calls for further scholarly investigation into the impact of emotions, social relations and obligations on return and circular migration motivations. This study also reveals how governments with established diaspora policies and initiatives that promote return migration engaged with the returning citizens.
The Impact of Digital Transformation on Enterprise Supply Chain Performance and Precision Management
Authors: Yang Lei , Liu Xianfeng , Liu Xuanhuang
Published: November 2024

In the pursuit of investigating the intricate interplay among enterprise digital transformation, supply chain performance, and precision management within the context of the era of big data, this research undertakes an empirical inquiry employing a structured questionnaire survey. This research commences by scrutinizing the impact of digital transformation on enterprise supply chain (ESC) performance, elucidating the strategic application of precision management in the digital transformation process, and subsequently offers comprehensive elucidations encompassing digital transformation, ESC performance, and precision management from diverse analytical perspectives. Subsequently, an array of research hypotheses is postulated and systematically substantiated through rigorous data analysis. Notably, the outcomes of the experimentation attest to the robustness of the questionnaire designed for this research, manifesting Cronbach’s α coefficients that consistently surpass the threshold of 0.8 across all dimensions. Moreover, the Kaiser-Meyer-Olkin (KMO) values, surpassing 0.82, further endorse the instrument’s reliability and validity, rendering it eminently suitable for experimental deployment. Subsequently, in the correlation analysis, a statistically significant relationship is discerned between the dual dimensions of digital transformation and the dual facets of ESC performance and precision management, ultimately affirming the validity of hypotheses H1a, H1b, H2a, H2b, H3a, H3b, H4a, and H4b. In the regression analysis, the coefficients of determination for the two regression models are 0.478 and 0.557, further confirming the hypotheses proposed in this research. The conclusion suggests that digital transformation is an evolving process, and enterprises should adopt a stance of continuous improvement and innovation. Regular assessments of the effectiveness of digital transformation should be conducted, with adjustments and improvements made based on feedback results. Therefore, this research provides valuable insights into the analysis of the relationship between digital transformation and ESC and precision management.
Assessing Biodiversity Loss and the Challenge of Implementing Nature Conservation Laws in Africa
Authors: Ogunniyi Daniel , Azeta Angela
Published: November 2024

Despite multilateral global efforts to improve biodiversity conservation, the African biodiversity range is increasingly facing existential threats. The Red List of Threatened Species (RLTS) adopted by the International Union for the Conservation of Nature (IUCN) to protect relevant species is not effectively implemented in many African countries. In this study, we identify the legal mechanisms to protect biodiversity at regional and national levels, focusing specifically on Liberia and Nigeria. We also identify the specific drivers of biodiversity loss in sub-Saharan Africa as a framework for formulating context-specific laws. The study highlights the importance of prioritising legislative action reflecting the IUCN’s red list of threatened species and the need to develop local solutions to more contextual challenges. The added relevance of creating specialised agencies to address the crisis of biodiversity loss is also discussed.
The Hengduan Mountains’ Subsidiary ranges impacted the geographic distribution patterns of bats
Authors: Liu Wei , Li Jing , He Jingying , Xu Guanbing , Wang Yanmei , Yang Yaping , Song Yiwen , Zhao Liming , Bu Yanzhen , Niu Hongxing
Published: November 2024

The role of the Hengduan Mountains in biodiversity distribution is well-documented, but the impact of its subsidiary ranges on species distribution and evolution remains unclear. This study examined the Stoliczka’s Asian Trident Bat (Aselliscus stoliczkanus) to assess how Pleistocene climatic changes and the uplift of these ranges influenced its distribution and evolution. Using species distribution models, morphometric data, and molecular genetic analysis, we identified shifts in the bat’s distribution under different climatic scenarios and evaluated its morphological and genetic differentiation. We found a significant correlation between the bat’s distribution and warmest quarter precipitation, with habitat suitability fluctuating in response to climatic changes. The subsidiary ranges facilitated morphological and genetic differentiation among bat populations and acted as barriers to dispersal. These findings underscore the critical role of the Hengduan Mountains’ subsidiary ranges in shaping bat distribution and evolution, providing new insights into the effects of geological changes on small mammals in the region.
From Enemy in Real Life to dramatis persona
Authors: Sasso Ludovica
Published: November 2024

The dispute between Poggio Bracciolini and Lorenzo Valla (1452–1453) was the intellectual contest par excellence of the Italian Quattrocento, and the scholarly confrontation among them stood out especially in the first two orationes in Vallam of the ‘Florentine’, and in the first Antidotum in Pogium of the Roman. In these examples, an intense mutual criticism of the opponent’s linguistic skills, grammatical method, and teaching of Latin appears. This contribution focuses on the subsequent development of the dispute, i.e., on Poggio’s oratio tertia and quarta in Vallam and Valla’s Apologus. In these cases, the mutual metamorphosis of the opponent from a real enemy to a dramatis persona (as character of a ‘tale’) will be investigated. With this literary mechanism, the conventional norms of the invectiva are transformed into a different approach characterised by a sort of theatrical performance, with an higher content of fantasy, literary freedom, and humour.
The Dangers of Demagogues and Democratic Revolution: on Aristotle’s Education of the Serious
Authors: Leonardo Kenneth Andrew Andres
Published: November 2024

This article concerns the dangers of demagogues in democracies described in the Politics and the edifying purposes of Aristotle’s ethical works in relation to the politically ambitious student. The translation of σπουδαῖος as serious is key to understanding the connection between these works. Although similar arguments appear elsewhere in his Corpus, Aristotle’s arguments in the Great Ethics are unique because the audience is warned about the dangers of political rule and is ultimately led away from the pursuit of it. Aristotle appears to specifically lead this class of politically ambitious students toward a serious pursuit of virtue, justice, and prudence with a final view to both friendship and citizenship. This emphasis is significant because an ‘individual who is serious-about-rule’ (σπουδάρχης) is excessively eager for office. Furthermore, ‘those serious-about-rule’ are dangerous when they act as demagogues, and this is one cause of revolutions in democracies.
Feeling One’s Way: Emotion and Medieval Literature
Authors: Lynch Andrew
Published: November 2024

This afterword sums up and responds to the articles in the special issue. It notes the variety in representations of the textual self and its constitution through emotion across medieval Northern Europe; representations which nevertheless depend on an imagined body. It also calls attention to the development of ideas of subjectivity and interiority and the ways in which literary experimentation drives social change, ending with a plea to reconsider the association of the medieval period with violence.
Captive Books, Captive Teachers. Spoils of the Long Turkish Wars in 17th-century Vienna
Authors: Petrolini Chiara
Published: November 2024

This article follows the journey of Turkish, Arabic, and Persian manuscripts – seized as spoils of war during the Long Turkish Wars – from the battlefields to the library collections of a Protestant baron and a Catholic librarian in Vienna. It examines ownership records and marginalia, shedding light on how these ‘oriental’ texts were decoded and sometimes misinterpreted by a diverse group of non-Ottoman actors, including soldiers, bibliophiles, and scholars. It contributes to understanding the reading habits of Ottoman soldiers, enabling comparisons with those of their Christian counterparts. In addition, this article follows the story of Dervīş İbrāhīm, a Muslim prisoner of war, who worked for Sebastian Tengnagel. Interweaving objects, books, and people, it underscores the entangled threads of violence and knowledge in a period marked by profound religious and social change.
Anomalous Hawaiian Sea Level Pressure Is Key to Initiate the North Pacific Meridional Mode
Authors: Wang Yiming , Bao Ming
Published: November 2024

The spring North Pacific meridional mode (NPMM) has a significant impact on the development of the following El Niño–Southern Oscillation (ENSO). Thus, understanding the source of the NPMM is of great importance for predicting the subsequent ENSO. The prevailing explanation for the formation of the spring NPMM is associated with the North Pacific Oscillation (NPO) during the preceding winter. Using observational data and phase 6 of the Coupled Model Intercomparison Project (CMIP6) outputs, this study clarifies that the anomalous sea level pressure (SLP) over the Hawaiian region from January to March (JFM), rather than the NPO, is key to initiate the spring NPMM. Analysis of the JFM SLP anomalies related to the spring NPMM reveals that the greater standard deviation of SLP anomalies at higher latitudes amplifies the impact of extratropical atmospheric variability on the formation of the spring NPMM. The key role of the Hawaiian SLP anomalies is further supported by their ability to initiate the spring NPMM independently of the NPO, whereas the NPO cannot. The Hawaiian SLP anomalies can also initiate the spring NPMM independently of the wintertime central Pacific ENSO which is NPMM’s another possible source. The results of the CMIP6 outputs demonstrate that the impact of the JFM Hawaiian anomalies on the spring NPMM is consistent with the observation, whereas the impact of the JFM NPO is inconsistent. Not all the JFM SLP anomalies associated with the spring NPMM exhibit the NPO-like pattern in these models.

Significance Statement

The North Pacific meridional mode (NPMM) is the leading mode of ocean–atmosphere variability over the tropical and subtropical North Pacific after removing the concurrent ENSO, which is most significant in boreal spring. Previous studies mainly assume that the spring NPMM formation is associated with the North Pacific Oscillation (NPO) during the preceding winter. This study elucidates that the anomalous sea level pressure (SLP) over the Hawaiian region, rather than the NPO, is key to initiate the spring NPMM. The greater standard deviation of SLP anomalies at higher latitudes is responsible for the emergence of the NPO-like pattern. These results can enhance our understanding of the extent to which the NPMM is affected by extratropical atmospheric variability.
Zonal and directional variations in tensile properties of bovine articular cartilage with special reference to strain rate variation
Authors: Verteramo A. , Seedhom B.B.
Published: November 2024

The aims of this study were: (i) to investigate the variation in the tensile properties of articular cartilage with depth through cartilage thickness and fibre orientation; (ii) to determine the effect of strain rate on tensile properties of articular cartilage.

Materials and method: All experimental work was performed on cartilage specimens taken from two bovine knee joints. Osteochondral plugs 12 mm in diameter were harvested with a special reamer from the femur and the tibial plateaux of each knee. Slices (0.2 mm thick), of articular cartilage were cut from the plug with a microtome. The predominant orientation of the collagen fibres on the cartilage surface was determined using the pinpricking technique. Each specimen used for the tensile test was cut, so as to produce a dumbbell shape, with a gauge length of 6 mm. Uniaxial tensile tests were performed on each specimen in order to determine the tensile Young's modulus, and ultimate tensile strength (UTS). In this investigation, these tensile tests were carried out at different strain rate: 1, 20, 50 and 70%/sec.

Results: As regards the zonal properties, it was found that tensile stiffness was greater in the superficial layer than in deep layer. However, a few specimens from the deep layer displayed similar or greater stiffness compared to the superficial layer. With respect to the directional properties, the specimens oriented parallel to the predominant alignment of collagen, were stiffer than those, which were perpendicular to it in each layer. However, only the results regarding the deep layer can be considered statistically significant. In regard to the variation of modulus with the strain‐rate, the results showed that there is no significant increase of the modulus with increasing strain rate from 20 to 50% per second. However, at 70% per second, articular cartilage stiffness considerably increased by up to one order of magnitude greater than that determined at lower strain rates in both the superficial and deep layer. Moreover, the UTS of cartilage specimens tested at 70% per second showed a significant rise, reaching values of four to five times that of those measured at 1, 20 or 50% per second.

Conclusion: The steep increases in both the stiffness and ultimate tensile strength of cartilage at high strain rates point to the existence in cartilage of a mechanism for its protection from damage by stresses arising in trauma, which are usually applied at high rates. This mechanism needs to be elucidated. The reduced anisotropy found in the present study pointed out that collagen is likely to be less organized in bovine cartilage than in the human and therefore, a study of its ultra‐structure would be appropriate.
Macroscale modeling of cartilage: mixture theory versus homogenization
Authors: Moyne Christian , Murad Márcio A.
Published: November 2024

The equations governing the electro‐chemo‐hydro‐mechanical processes in cartilage are derived using the periodic homogenization technique. First the equations at the microscale are recalled. Then the homogenization technique is applied to propagate the physics to the macroscale. The results of this work and of the thermodynamical approach used by various authors are finally compared.
Uniaxial tensile testing of canine annulus fibrosus tissue under changing salt concentrations
Authors: Huyghe J.M. , Drost M.R.
Published: November 2024

Recent modelling efforts in the field of mechanics of the intervertebral disc, demonstrate that the deformation properties of intervertebral disc tissue are intimately linked to compositional changes. This paper presents uniaxial tensile relaxation experiments of canine annulus fibrosus tissue under stepwise changes of external salt concentration.
Passage in monolayer influences the response of chondrocytes to dynamic compression
Authors: Wiseman Mike , Bader Dan L. , Reisler Tom , Lee David A.
Published: November 2024

This study tests the hypothesis that expansion by passage in monolayer influences the response of isolated articular chondrocytes to dynamic compression. Chondrocytes, isolated from bovine articular cartilage, were seeded in monolayer and passaged 4 times (P1–4). For assessment of chondrocytic and fibroblastic phenotype, freshly isolated and passaged cells were seeded on glass coverslips or in 2% alginate beads and cultured for 7 days in DMEM + 10% FCS. Samples were assayed for DNA and GAG content and stained for collagen types I and II. In separate experiments, freshly isolated or passaged chondrocytes were seeded at 10×106 cells.ml−1 in 4% cylindrical agarose constructs and subjected to 15% dynamic compressive strain at 1 Hz for 24 hours. [3H]‐thymidine incorporation, SO4 incorporation and nitrite release were analysed. Immediately following isolation (P0), chondrocytes seeded in alginate expressed high levels of type II collagen, but did not stain for type I collagen. Following repeat passage the cells expressed enhanced levels of type I collagen, with an associated reduction in type II collagen staining. These data indicate a modulation to a fibroblastic phenotype during monolayer expansion which was not rapidly reversed by culture in a 3D hydrogel. Dynamic compression down‐regulated SO4 incorporation at P0, but did not affect [3H]‐thymidine incorporation. By contrast the incorporation of both SO4 and [3H]‐thymidine was enhanced by dynamic compression at both P1 and to a lesser extent P2. SO4 and [3H]‐thymidine incorporation were inhibited at P3 and P4. Nitrite release was down‐regulated by dynamic compression at all passages. These data demonstrate a clear modulation in the response of bovine articular chondrocytes to dynamic compression following passage in monolayer.
The influence of oxygen and hydrostatic pressure on articular chondrocytes and adherent bone marrow cells in vitro
Authors: Scherer Katrin , Schünke Michael , Sellckau Roland , Hassenpflug Joachim , Kurz Bodo
Published: November 2024

Tissue engineering of articular cartilage from chondrocytes or stem cells is considered to be a potential aspect in the treatment of cartilage defects. In order to optimize culture conditions the influence of low oxygen tension (5%) – single or in combination with intermittent hydrostatic pressure (HP: 30/2 min on/off loading; 0.2 MPa) – on the biosynthetic activity (sulfate and proline incorporation) of human osteoarthritic chondrocytes cultured on collagen I/III membranes was investigated. Additionally, chondrogenesis from high density or monolayer cultures of bovine adherent bone marrow cells (aBMC) with and without chondrogenic medium supplements (CM) was analyzed by RT‐PCR (mRNA expression of aggrecan and collagen type II). We could show that low oxygen tension increases significantly the biosynthesis of collagen I/III membrane‐associated chondrocytes and even higher under co‐stimulation with HP. While there is no chondrogenesis in monolayer cultures, CM induces expression of cartilage matrix molecules in high density cultures of aBMC which is even increased under the influence of low oxygen tension. Both, low oxygen tension and HP without CM are alone not sufficient stimuli for chondrogenesis. It can be concluded that low oxygen tension and HP might be useful tools in cartilage tissue engineering and that these physico‐chemical factors promote but do not induce chondrogenesis under the given conditions.
Modulation of collagen synthesis in normal and osteoarthritic cartilage
Authors: Gouttenoire Jérôme , Valcourt Ulrich , Ronzière Marie‐Claire , Aubert‐Foucher Elisabeth , Mallein‐Gerin Frédéric , Herbage Daniel
Published: November 2024

In osteoarthritic cartilage, chondrocytes are able to present heterogeneous cellular reactions with expression and synthesis of the (pro)collagen types characteristic of prechondrocytes (type IIA), hypertrophic chondrocytes (type X), as well as differentiated (types IIB, IX, XI, VI) and dedifferentiated (types I, III) chondrocytes. The expression of type IIA procollagen in human osteoarthritic cartilage support the assumption that OA chondrocytes reverse their phenotype towards a chondroprogenitor phenotype. Recently, we have shown that dedifferentiation of mouse chondrocytes induced by subculture was associated with the alternative splicing of type II procollagen pre‐mRNA with a switch from the IIB to the IIA form. In this context, we demonstrated that BMP‐2 favours expression of type IIB whereas TGF‐β1 potentiates expression of type IIA induced by subculture. These data reveal the specific capability of BMP‐2 to reverse the program of chondrocyte dedifferentiation. This interesting feature needs to be tested with human chondrocytes since cell amplification is required for the currently used autologous chondrocyte transplantation.
ATP in the mechanotransduction pathway of normal human chondrocytes
Authors: Millward‐Sadler S.J. , Wright M.O. , Flatman P.W. , Salter D.M.
Published: November 2024

Extracellular nucleotides have been shown to have diverse effects on chondrocyte function, generally acting via P2 purinoceptors. We have previously shown that mechanical stimulation at 0.33 Hz of normal human chondrocyte cultures causes cellular hyperpolarisation, while chondrocytes derived from osteoarthritic (OA) cartilage depolarise. Experiments have been undertaken to establish whether ATP is involved in the response of the chondrocyte to mechanical stimulation.

Chondrocytes, isolated from normal and OA cartilage obtained, with consent, from human knee joints following surgery, were cultured in non‐confluent monolayer. Cells were mechanically stimulated at 0.33 Hz for 20 minutes at 37°C in the presence or absence of inhibitors of ATP signalling, or were stimulated by the addition of exogenous ATP or derivatives, and electrophysiological measurements recorded. Samples of medium bathing the cells were collected before and after mechanical stimulation, and the concentration of ATP in the cell medium was measured. Total RNA was extracted from cultured chondrocytes, reverse‐transcribed and used for RT‐PCR with primers specific for P2Y2 purinoceptors.

ATP, UTP 2‐methylthioadenosine and αβ‐methylene adenosine 5′‐triphosphate all induced a hyperpolarisation response in normal human articular chondrocytes. No significant change was observed in the membrane potentials of chondrocytes isolated from OA cartilage following the addition of these nucleotides to the medium. In normal chondrocytes, the hyperpolarisation induced by ATP was blocked by the presence of apamin, indicating the involvement of small‐conductance calcium‐activated potassium channels. Following mechanical stimulation of normal chondrocytes, an increase was observed in ATP concentration in the cell culture medium bathing the cells. The presence within the culture medium of suramin or pyridoxal‐phosphate‐6‐azophenyl‐2′,4′‐disulphonic acid (PPADS) prior to and during the period of mechanical stimulation abolished the hyperpolarisation response in normal chondrocytes. The presence of mRNA for P2Y2 purinoceptors was demonstrated in both normal and OA chondrocytes by RT‐PCR.

These results suggest that ATP has a role in the response of normal chondrocytes to mechanical stimulation, via P2Y2 purinoceptors. This response appears to be different in chondrocytes derived from OA cartilage, and may be important in the progression of this disease.
Functional tissue engineering of chondral and osteochondral constructs
Authors: Lima Eric G. , Mauck Robert L. , Han Shelley H. , Park Seonghun , Ng Kenneth W. , Ateshian Gerard A. , Hung Clark T.
Published: November 2024

Due to the prevalence of osteoarthritis (OA) and damage to articular cartilage, coupled with the poor intrinsic healing capacity of this avascular connective tissue, there is a great demand for an articular cartilage substitute. As the bearing material of diarthrodial joints, articular cartilage has remarkable functional properties that have been difficult to reproduce in tissue‐engineered constructs. We have previously demonstrated that by using a functional tissue engineering approach that incorporates mechanical loading into the long‐term culture environment, one can enhance the development of mechanical properties in chondrocyte‐seeded agarose constructs. As these gel constructs begin to achieve material properties similar to that of the native tissue, however, new challenges arise, including integration of the construct with the underlying native bone. To address this issue, we have developed a technique for producing gel constructs integrated into an underlying bony substrate. These osteochondral constructs develop cartilage‐like extracellular matrix and material properties over time in free swelling culture. In this study, as a preliminary to loading such osteochondral constructs, finite element modeling (FEM) was used to predict the spatial and temporal stress, strain, and fluid flow fields within constructs subjected to dynamic deformational loading. The results of these models suggest that while chondral (“gel alone”) constructs see a largely homogenous field of mechanical signals, osteochondral (“gel bone”) constructs see a largely inhomogeneous distribution of mechanical signals. Such inhomogeneity in the mechanical environment may aid in the development of inhomogeneity in the engineered osteochondral constructs. Together with experimental observations, we anticipate that such modeling efforts will provide direction for our efforts aimed at the optimization of applied physical forces for the functional tissue engineering of an osteochondral articular cartilage substitute.
Organ printing: Fiction or science
Authors: Jakab Karoly , Neagu Adrian , Mironov Vladimir , Forgacs Gabor
Published: November 2024

Aggregates of living cells (i.e. model tissue fragments) under appropriate conditions fuse like liquid drops. According to Steinberg's differential adhesion hypothesis (DAH), this may be understood by assuming that cells are motile and tissues made of such cells possess an effective surface tension. Here we show that based on these properties three‐dimensional cellular structures of prescribed shape can be constructed by a novel method: cell aggregate printing. Spherical aggregates of similar size made of cells with known adhesive properties were prepared. Aggregates were embedded into biocompatible gels. When the cellular and gel properties, as well as the symmetry of the initial configuration were appropriately adjusted the contiguous aggregates fused into ring‐like organ structures. To elucidate the driving force and optimal conditions for this pattern formation, Monte Carlo simulations based on a DAH motivated model were performed. The simulations reproduced the experimentally observed cellular arrangements and revealed that the control parameter of pattern evolution is the gel‐tissue interfacial tension, an experimentally accessible parameter.