bluuebunny/crossref_metadata_2025 huggingface dataset:
Little Killers or Victims of the System? Soviet Schoolchildren in Campaigns for the Extermination of Ground Squirrels
Authors: Perga Tetiana Yuriivna
Published: February 2025

This article examines the role of Soviet children in ground squirrels’ extermination campaigns in the 1930s–1950s, influenced by state propaganda. It contextualizes the practice of using children in pest control efforts as part of a wider Soviet agricultural modernization, where nature was perceived as an adversary to be subdued. The article examines Soviet debates on the messages children’s literature about nature should convey and explores how these practices shaped values such as kindness, compassion, and cruelty. It also addresses the ethical implications of child labor, the normalization of violence against nature, and the impact of these experiences on children’s moral development.
Sacrificial Lambs and Rallying Cries: The Politics of Adult Education at the University of Manitoba, 1907–1949
Authors: McLean Scott
Published: February 2025

This article narrates the engagement of the University of Manitoba in two waves of the extension movement that shaped adult education work at universities across North America: one rooted in the delivery of public lectures and another rooted in the “Wisconsin idea” of serving citizens and the state. In contrast to developments at provincial universities to the west and east, extension work at the University of Manitoba was not institutionalized until 1949. The article analyzes the politics of adult education at the University of Manitoba, arguing that extension work was treated at different times as a sacrificial lamb and as a rallying cry by university administrators in relations with the provincial government. It analyzes economic and institutional factors that explain why the politics of adult education were so different in Manitoba than in nearby provinces. It offers insight for those interested in adult education programs delivered through universities beyond Canada.
The Cost of Caregiving: The Disproportionate and Invisible Impact of COVID-19 on Women
Authors: Sanders Jane Elizabeth , Carrothers Emily , Gamble Olivia , Neeb Derek , Arundel M.K.
Published: February 2025

The COVID-19 pandemic had a global impact, altering how society and those within it function. While these changes affected almost everyone, there is evidence that women were disproportionately impacted. This reflexive thematic analysis included data gathered from parents, social work students, university faculty, and school board professionals (n = 113) from 2020 to 2023. We explored the experiences of female-identified parents and caregivers during COVID-19. The findings underscore the intense but often invisible burden that women, specifically mothers and caregivers, experienced throughout the pandemic. We found that women experienced acute stress in the realms of paid and unpaid labour, childcare, children's academics, and family mental health. Implications include a call to acknowledge this disproportionate impact and its consequences for gender equity, a recognition of the ongoing impact of COVID-19 on children, youth, families, and women, a recognition of the invisible labour that often falls upon women, and the implementation of critical methodologies in social work education and research to foster the use of such approaches within the field.
Leveling the Playing Field: Opportunities for School Recess to Promote Wellness and Reduce Disparities in Elementary School Children
Authors: Konduru Divya , Lowrey Kerri M. , Hager Erin R.
Published: February 2025

Background: School recess provides several benefits to elementary school students, including physical, emotional, and social health benefits. Despite these benefits, there is a growing shift toward reducing or reallocating recess time in school. Furthermore, not all students have equitable access to recess and its benefits due to disparities in recess policies and implementation by socioeconomic status of the communities served by the school and academic or behavioral conduct of individual students. Conclusions: Strong state-level legislation requiring recess for all elementary schools and for all elementary school children is necessary to ensure equitable access to recess and its benefits.
The impact of a ninth-century Jewish physician on North African and European medical culture: Isaac al-Israelī
Authors: Yıldız Firdevs
Published: February 2025

Isaac al-Israelī (died early ninth century AD) was a Jewish physician. He is known for writing important works in many different fields such as medicine, philosophy, pharmacology, botany, and Jewish theology. He was a court physician as the chief physician during the rule of the Aghlebids and Fatimids in North Africa. He ensured the systematization and institutionalization of the first medical school established in Qayrawān under the name of Bayt al-Hikma. Israelī was considered an authority in the field of medicine in Qayrawān and is known for his major works in this field. Many of his works were translated into Latin, Hebrew, English and Spanish over time and were first translated into Latin by Constantinus Africanus (died 1082 AD) in 1082. Thanks to these translations, Israel's medical works reached Europe via Sicily and were used as textbooks in the medical school of Salerno (The Schola Medica Salernitana). Moreover, his works continued to be taught with interest in many European universities until the 17th century.

In this study, the contributions of a Jewish scholar who continued his medical career in the Islamic development of medicine in North Africa, and in the establishment of a medical school there.
How responsible leadership affects employees’ turnover intention in China: A psychological contract perspective
Authors: Han Zhiyong , Wang Dan , Cheng Yu , Shao Wei
Published: February 2025

Background

The current high rate of employee turnover has become a key factor affecting organizational stability and core competitiveness, which requires organizational leaders to work with a higher sense of responsibility. Although several studies have confirmed that responsible leadership (RL) negatively affects employees’ turnover intention, the specific mechanism of this effect has not been fully elucidated.

Objective

On the basis of the discrepancy model of psychological contract violation (PCV) and substitutes for leadership theory, this study aims to examine the indirect impact of RL on employees’ turnover intention through employees’ PCV and the moderating effect of organizational identification.

Method

We collected a sample of 389 employees from Chinese companies and used SPSS and Amos for confirmatory factor analysis (CFA), correlation analysis, and hypothesis testing.

Results

The findings show that RL can reduce employees’ turnover intention directly and by influencing employees’ PCV. Organizational identification negatively moderates the negative effect of RL on PCV and weakens the mediating effect of PCV in the relationship between RL and subordinates’ turnover intention.

Conclusion

This study reveals the intrinsic mechanism by which RL impacts employees’ turnover intention, providing theoretical support and practical experience for managers to set a learning example for employees and effectively suppress their turnover intention.
School Safety: A Critical Issue for School Administrators
Authors: Dolph David A. , Holland Daniel
Published: February 2025

This article discusses a variety of aspects related to safety in K-12 schools.
The Relationship Between Students’ Mathematical Abilities in Algebraic Equations and Their Physics Examination Performance
Authors: Paskali Jonathan , Tarmo Albert
Published: February 2025

This study investigated the impact of students’ mathematical abilities in algebraic equations on their performance in physics on the Form Four Mock Examination. In this mixed-method study, 160 students’ mathematics and physics scores from high- and low-performing schools in Tanzania's Tabora region were analyzed using logistic regression. It was found that students who scored high on algebraic equations-based questions were more likely to perform well on physics problems requiring algebraic application. We concluded that students’ coincidentally low performance in secondary mathematics and physics is partly due to a lack of necessary mathematics skills required to solve physics problems. This implies that improving mathematics learning is essential for enhancing physics performance.
Proximity, Perceived Costs and Benefits, and Public Support for Indian Gaming
Authors: Boehmke Frederick J. , Branton Regina , Witmer Richard C.
Published: February 2025

The introduction of Indian gaming has offered a new path for economic development, allowing gaming nations to achieve greater self-sufficiency. The benefits of gaming have also extended beyond the boundary of Indian nations as adjacent communities benefit from the demand created by Indian casinos. As Indian gaming expands, it is important to consider how the public perceives this form of Native American economic development. Herein, we examine public sentiment regarding Indian gaming using original survey data. Of particular interest is the effect of living near tribal gaming on the perceived costs and benefits and support for Indian gaming. To measure the effect of such exposure, we utilize a maximum likelihood estimator that allows simultaneous estimation of the effect of such exposure and the shape of the distance decay function that governs the measure of exposure itself. Our findings indicate exposure affects respondents’ perceptions of the benefits of Indian gaming for tribes, but not overall support for Indian gaming.
Semi-analytical solutions of the three-dimensional size-dependent thermoelastic contact of the microstructured materials under a hot indenter
Authors: Wang Yuxing , Li Jialing , Wang Ling , Hu Chi , Shen Huoming , Liu Juan
Published: February 2025

This paper reports a novel model for solving size-dependent three-dimensional thermoelastic contact behavior. The model accounts for the effects of local bending in microstructured materials and the interface heat flux on size-dependent thermoelastic contact behavior. Analytical expressions for the material response under unit heat flux and unit force have been derived within the framework of higher-order thermoelastic continuum theory. A semi-analytical contact model is established based on the conjugate gradient method and discrete convolution fast Fourier transform, which incorporates thermo-mechanical coupling effects at the contact interface and has no restrictions on the geometry of the contact surfaces. Based on the developed model, detailed parametric analyses have been conducted with two typical indenter shapes, spherical indenter and flat-ended cylindrical indenter, to discuss the combined effects of thermal expansion, size dependence, and material properties on microscale thermoelastic contact behavior.
Utilization and perception of generative artificial intelligence by medical students in residency applications
Authors: Smith Blake , Ramadoss Tanya , D’Amario Vanessa , Shoja Mohammadali M , Rajput Vijay , Cervantes Jorge
Published: February 2025

After completing medical school in the United States, most students apply to residency programs to progress in their training. The residency application process contains numerous writing sections, including the personal statement, curriculum vitae, and “impactful experiences” section. This study’s purpose is to investigate the perception of third and fourth-year medical students on generative artificial intelligence (GenAI) and its influence on the residency application process. We developed a 13-question survey using the REDCap application to explore participants’ educational background, year in school, preferred medical specialty, and perception of current or potential use of GenAI within residency applications. More than half of the responders have already used or plan to use GenAI for assistance in developing their personal statements for their applications. A considerable percentage (43.3%) will use GenAI to edit/modify a draft of the personal statement. More than half of survey participants believe that in the future, GenAI may alter the significance program directors place on letters of recommendation (LORs) in their selection criteria for deciding who to interview and select. Our survey results indicate that a number of students are either using or are receptive to the idea of using GenAI to draft or refine certain components of their residency application, such as the personal statement and impactful experiences section. As the application of GenAI expands, in-person interactions in the evaluation of candidates may become increasingly critical, and although personal statements and LORs are currently significant components of the residency application, their future roles remain a question.
Clear commitments and signals of support: The inclusion of Finnish parties’ electoral pledges in coalition agreements
Authors: Ylisalo Juha , Nieminen Sakari , Makkonen Kimmo
Published: February 2025

Multiparty governments often draft extensive coalition agreements to enforce policy compromises made at the government formation stage. Given that such agreements have important policy consequences, parties have strong incentives to ensure that their key objectives are included. This study addresses the inclusion of parties’ specific electoral pledges in the coalition agreements of three Finnish governments, based on over 1000 pledges. The results show that pledges falling into issue areas that were salient to parties’ campaigns were relatively likely to be included, especially if the level of salience was approximately the same to the other government parties as well. In contrast, the probability of inclusion was lower where a party had made more pledges in an issue area. The analysis suggests that a notable share of government parties’ pledges never became part of coalition agreements, but the pledges that were included reflected the most salient campaign themes.
Brain-penetrant histone deacetylase inhibitor RG2833 improves spatial memory in females of an Alzheimer's disease rat model
Authors: Ndukwe Kelechi , Serrano Peter A , Rockwell Patricia , Xie Lei , Figueiredo-Pereira Maria E
Published: February 2025

Background

Nearly two-thirds of Alzheimer's disease (AD) patients are women. Therapeutics for women are critical to lowering their elevated risk of developing this major cause of adult dementia. Moreover, targeting epigenetic processes such as histone acetylation that regulate multiple cellular pathways is advantageous given the multifactorial nature of AD. Histone acetylation takes part in memory consolidation, and its disruption is linked to AD.

Objective

Determine whether the investigational drug RG2833 has repurposing potential for AD. RG2833 is a histone deacetylase HDAC1/3 inhibitor that is orally bioavailable and permeates the blood-brain-barrier.

Methods

RG2833 effects were determined on cognition, transcriptome, and AD-like pathology in 11-month TgF344-AD female and male rats. Treatment started early in the course of pathology when therapeutic intervention is predicted to be most effective.

Results

RG2833-treatment of 11-month TgF344-AD rats: (1) Significantly improved hippocampal-dependent spatial memory in females but not males. (2) Upregulated expression of immediate early genes, such as Arc, Egr1 and c-Fos, and other genes involved in synaptic plasticity and memory consolidation in females. Remarkably, out of 17,168 genes analyzed for each sex, no significant changes in gene expression were detected in males at p < 0.05, false discovery rate <0.05, and fold-change equal or > 1.5. (3) Failed to improve amyloid beta accumulation and microgliosis in female and male TgF344-AD rats.

Conclusions

Our study highlights the potential of histone-modifying therapeutics such as RG2833 to improve cognitive behavior and drive the expression of immediate early, synaptic plasticity and memory consolidation genes, especially in female AD patients.
Evaluating the feasibility of a community-adapted multi-domain intervention for dementia prevention in older adults
Authors: Kuroda Yujiro , Fujita Kosuke , Sugimoto Taiki , Uchida Kazuaki , Yokoyama Yoko , Shimazu Taichi , Saito Junko , Arai Hidenori , Sakurai Takashi
Published: February 2025

Background

Dementia impacts individuals, families, and society, necessitating effective prevention strategies.

Objective

To evaluate the feasibility of a community-adapted multi-domain intervention for dementia prevention among older adults in Obu City, Japan and how uncertainties in implementing definitive trials can be reduced.

Methods

A 12-month one-arm intervention trial was conducted with 80 community-dwelling older adults aged 65–86 years from two district regions. The multi-domain intervention included physical exercise, nutrition guidance, cognitive training, social participation, and vascular risk management. The primary outcome was the continuation rate, defined as the proportion of participants attending >60% of classes from the initial assessment to 6 months. Secondary outcomes, such as fidelity, acceptability, and appropriateness, were assessed through qualitative and quantitative evaluations. Additionally, health outcomes, including cognitive function and overall lifestyle, were evaluated.

Results

The study achieved continuation rates of 75% and 76% at 6 and 12 months, respectively, indicating high feasibility. Participants showed high program acceptability (average acceptance score, 4.4 of 5). Fidelity was high regarding content coverage and duration, although the frequency and coverage varied between study sites. Cognitive function remained stable; food-diversity status improved significantly over the study period, though the absence of a control group limits causal interpretation of these changes.

Conclusions

The community-adapted multi-domain intervention for dementia prevention demonstrated high feasibility and acceptability among older adults. Our findings can help reduce uncertainties and support planning future definitive trials to evaluate the effectiveness of community-based dementia-prevention programs.
Genetic and biomarker disclosure process in a memory and aging study
Authors: Mayan Inbal , Roth Heidi , Ghosh Dhrubajyoti , Whitson Heather E , Johnson Kim G
Published: February 2025

Despite growing awareness that disclosing biomarker results to research participants is aligned with ethical principles of researcher-participant partnership, there are currently no widely adopted guidelines for this disclosure in Alzheimer's disease research. We developed a process and tools to deliver biomarker and genetic results to 65 participants of The Memory and Aging Study of the Duke-UNC Alzheimer's Disease Research Center (ADRC). Survey responses of 46 participants were analyzed. We show high participant satisfaction and lower anxiety levels after receiving the results. The developed process and materials provide a template for standardized Alzheimer's disease biomarker result delivery in the research setting.
Sentient dignity and the plausible inclusion of animals
Authors: Perry Matthew Wray
Published: February 2025

Dignity often serves as the cornerstone for a justification of rights. However, it has been criticised for its exclusion of nonhuman animals and many human individuals: dignity is traditionally grounded in a capacity that some but not all humans and animals possess, e.g. rationality. To successfully overcome this problem of exclusion, this article argues that we should adopt an account of sentient dignity, i.e. an account of dignity based on sentience alone. The article thus makes three contributions. First, it demonstrates that the basis of dignity has yet to receive a plausible justification. To illustrate this, it outlines the problem of exclusion, and it exposes three problems with a prominent solution offered by Pablo Gilabert. According to Gilabert's view, dignity should be based on several valuable capacities including rationality, sentience and cooperation, among others. However, basing dignity on several capacities (i) risks over-inflating the scope of dignity, (ii) struggles to account for internal complexity, and (iii) produces problematic moral distinctions. Second, the article argues that sentient dignity overcomes these three problems whilst being plausibly inclusive. Finally, it contends that an account of sentient dignity vindicates the non-redundancy of dignity, renders sociopolitical discourse philosophically coherent, and harnesses dignity's potential strategic value.
Individualized career planning intelligent teaching system for college students based on adaptive artificial intelligence
Authors: Huang Yujing
Published: February 2025

This paper discusses importance and application prospects of the personalized intelligent teaching system for college students’ career planning based on adaptive artificial intelligence. The system uses deep learning and natural language processing technology to accurately analyze students, and combines big data analysis and cloud computing technology to provide customized career planning services. The system can not only help students better understand themselves and the market, but also provide rich educational resources and personalized guidance to improve scientificity and effectiveness of career planning. The emergence of this system provides strong support for students’ career development, and also opens up a new path for the innovation and development of career education. Experiments show that the students’ job satisfaction and job-seeking success rate of the system designed in this paper are 90% and 85%, respectively, which are significantly higher than 70% and 65% of the traditional method. The system plays an important role in connecting students, schools and enterprises, and can effectively promote further development of career education.
Beyond the surface: A case study about nevus sebaceous removal for cosmetic concerns
Authors: Lewis Joshua , Singh Jatinder P , Nicanord Ernst J
Published: February 2025

Nevus sebaceous, a benign scalp birthmark, typically presents without immediate health concerns but may require removal as it becomes bothersome with age. Symptoms are typically cosmetic, lacking pain or bleeding. Clinical presentation varies with age, initially appearing as a smooth, hairless yellowish patch, later evolving into an elevated lesion after the onset of puberty. We report a case of a 25-year-old female with nevus sebaceous. Despite its benign nature, the patient opted for excision due to cosmetic concerns and the potential for malignancy. Surgical removal was successful without complications. This case underscores the importance of early diagnosis and intervention to alleviate discomfort and potential malignancy. While rare, malignant transformation can occur, emphasizing the need for vigilant monitoring and timely surgical intervention, particularly during pre-puberty stages. Treatment should prioritize removal to prevent malignant progression and address cosmetic concerns. Further research is needed to refine management strategies for nevus sebaceous.
Black Undergraduate Flourishing: Contributions of Racial Centrality and Religiosity
Authors: Hope Meredith O. , Goodwill Janelle R. , Williams Nia , Brittian Loyd Aerika
Published: February 2025

Flourishing has emerged as an important concept in human thriving. Yet, limited research has examined flourishing among Black emerging adults. Ethnic and racial identity (ERI) and religiosity are critical cultural strengths that promote positive outcomes for Black emerging adults. However, their unique and concurrent contributions to flourishing remain understudied. Data from 591 African American, Black Caribbean, and Continental African Christian undergraduates in the 2020-2021 Healthy Minds Study tested hypothesized links between one domain of ERI (i.e., centrality), religiosity, and flourishing. We probed for within-group differences. Linear regression results revealed that higher levels of ERI centrality and frequency of religious social participation were positively associated with flourishing for the full sample. Ethnicity did not moderate the ERI centrality-flourishing link. Stratified model results suggest that these relationships were only significant for African Americans. Our findings underscore the importance of studying positive outcomes in Black emerging adults and probing for within-group heterogeneity.
Barriers to dental providers’ use of a clinical decision support tool for pain management following tooth extractions
Authors: Mitchell Shannon Gwin , Gryczynski Jan , Worley Donald C. , Asche Stephen E. , Truitt Anjali R. , Rindal D. Brad
Published: February 2025

Background

De-implementing non-effective or even harmful practices in healthcare is sometimes necessary, as has been the case with opioid prescribing in dentistry over the past decade. One approach to practice transformation is to deploy clinical decision support (CDS) tools. This qualitative study examined barriers to CDS use as part of a cluster randomized trial that aimed to decrease opioid prescribing for pain management following tooth extractions across a large dental practice.

Method

Twenty dental providers who took part in the larger randomized trial were purposively selected to complete a semi-structured qualitative interview. Participants represented a broad range in terms of years of practice, dental specialization, and CDS use patterns. Interviews were conducted via Zoom, audio recorded, transcribed, and analyzed using a content analysis approach in ATLAS.ti following participation in the cluster randomized trial.

Results

Reasons for not using the CDS fell generally into two broad categories: unintentional (i.e., forgetting to use the CDS) and intentional. Providers who forgot to use the CDS after training and implementation either were not sure where to look for the alert on the screen or did not remember to look for it because its use was never incorporated into their workflow. Reasons for deciding not to use the CDS included feeling that it slowed down their workflow, thinking that the information it provided would not be useful, and not trusting the functionality of the system.

Conclusions

There were numerous, interdependent human, organizational, and technological factors that influenced the intentionally and unintentionally low CDS use rates observed in the study. Findings highlight issues to be aware of and address in future implementation efforts that utilize CDS.

Trial registration

Clinicaltrials.gov NCT03584789.
Left Atrium Strain as a Diagnostic Measure for Diastolic Dysfunction: A Systematic Review and Meta-Analysis
Authors: Mahmoodi Zohreh , Naderi Nasim , Taghavi Sepideh , Rashki Ghalenoo Sara
Published: February 2025

Objective:

The aim of this meta-analysis was to evaluate if left atrial strain (LAS) can be utilized as a reliable diagnostic indicator for the existence and severity of diastolic dysfunction (DD).

Materials and Methods:

A careful search was conducted of PubMed, Embase, and Scopus databases for published research up to August 30, 2022. Two independent researchers independently reviewed all studies using the inclusion criteria and extracted the data in a data extraction file. Any inconsistencies were settled by consensus or discussion with a third author. The meta-analysis was carried out using a statistical program.

Results:

A total of seven articles consisting of 2106 patients were included. The pooled sensitivity and specificity of LAS in diagnosing DD were 78% (95% confidence interval [CI] = 69%–86%) and 76% (95% CI = 72%–79%). The corresponding positive likelihood ratio was 3.3 (95% CI = 2.5–4.1), and the negative likelihood ratio was 0.27 (95% CI = 0.18–0.43).

Conclusion:

The LAS, independent from left atrium (LA) size/volume, demonstrated a good sensitivity and specificity, in DD evaluation and might be a relevant metric to be considered in suspected patient cases.
Formation of amorphous molybdenum sulfide in abiotic and biotic sulfidic conditions: A comparative study on molybdenum sequestration mechanisms
Authors: Phillips Rachel F. , Leng Weinan , Singerling Sheryl A. , Desmau Morgane , Xu Jie
Published: February 2025

Concentrations of sedimentary molybdenum (Mo) have been used as a proxy for palaeoceanographic redox conditions based on the distinctive behaviour of Mo under oxic versus euxinic (i.e., anoxic and sulfidic) conditions. However, the mechanisms that govern Mo sequestration in various euxinic settings are not fully resolved. It has previously been proposed that sulfate-reducing bacteria (SRB), the main drivers and regulators of euxinic conditions, can actively take up and reduce Mo intracellularly and passively induce Fe-independent Mo complexation and reduction at their cell surfaces. However, uncertainties remain regarding the underlying interactions and relative contributions of these proposed biotic Mo sequestration pathways. In this study, systematic experiments were carried out to examine the interactions among Mo(VI) species (MoO42- or MoS42-), ferrous iron (Fe2+) and SRB with a focus on combinations of conditions that lead to reductive Mo precipitation. The speciation of aqueous Mo and composition, structure, oxidation states and bonding environment of precipitated Mo-sulfides were analysed using UV-vis spectrophotometry (UV-vis), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and synchrotron-based X-ray absorption spectroscopy (XAS). Results indicate that SRB does not directly reduce Mo but, rather, plays a passive role in mediating Mo sequestration by providing sulfide and potential nucleation sites at their reactive cell surfaces for precipitation. However, even in the presence of SRB cells, Fe2+ was required for Mo precipitation in all conditions tested. By identifying the limiting (and non-limiting) factors in the Mo reduction and sequestration process, this study provides significant new insights for interpreting Mo palaeoredox proxies.
Post Transplant Cyclophosphamide as GvHD Prophylaxis in Patients Receiving Mismatched Unrelated HCT: the PHYLOS trial.
Authors: Raiola Annamaria , Bruno Benedetto , Risitano Antonio Maria , Mosna Federico , Cavattoni Irene Maria , Onida Francesco , Saporiti Giorgia Natascia , Patriarca Francesca , Battista Marta Lisa , Pavone Vincenzo , Mele Anna , Chiusolo Patrizia , Sica Simona , Loteta Barbara , di Grazia Carmen , Carella Angelo Michele , Salvatore Dalila , Morello Enrico , Leoni Alessandro , Giaccone Luisa , Bernasconi Paolo , Terruzzi Elisabetta , Mordini Nicola , Borghero Carlo , Zallio Francesco , Luppi Mario , Grassi Anna , Olivieri Attilio , Piras Eugenia , Sacchi Nicoletta , Ciccone Giovannino , Castiglione Anna , Degrandi Eliana , Angelucci Emanuele , Martino Massimo , Bonifazi Francesca
Published: February 2025

Post-transplant high-dose cyclophosphamide (PTCy) is effective in overcoming the negative impact of HLA disparity in the haploidentical setting. In the light of these results, we investigated the efficacy and safety of PTCy, with a calcineurine inhibitor and mycophenolate mofetil, in improving clinical outcomes of haematopoietic cell transplantation (HCT) from mismatched unrelated donor (MMUD) in patients with acute myeloid malignancies by reducing aGvHD incidence and severity. A prospective single arm, phase II study (PHYLOS - NCT03270748) was conducted by the Italian GITMO. The primary objective was the cumulative incidence (CI) of grade II-IV aGvHD. Conditioning regimen for all patients was busulfan (total dose 12.8mg/kg) and fludarabine (total dose 160mg/m2). The ethical committees of the participating centers approved the study (EURODRACT 2017-003530-85). Seventy-seven consecutive patients (AML: 64; MDS: 13) were enrolled at 26 Italian transplant centers (January 2020-November 2022). Median age was 53 years (range 19-65). The 100-day cumulative incidence (CI) of grade II-IV aGvHD was 18.2% (95%CI: 10.6-27.6) and 6.5% (95%CI: 3.1-15.1) for grade III-IV. Seventy-one patients (92%) had full-donor chimerism with complete neutrophil engraftment by day +30.One-year CI of chronic GvHD (cGvHD) was 13.4% (95%CI: 6.9-22.1). One-year CI of non-relapse mortality was 9.1% (95%CI: 4.0-16.9), and the relapse rate was 23.8% (95%CI: 14.9-33.9). One-year overall survival and graft-relapse-free survival were 78.6.% (95%CI: 67.4-86.3) and 55.3% (95%CI: 43.4-65.7), respectively. Our study in a homogeneous patient cohort suggests that PTCy leads to a low rate of aGvHD and improves clinical outcomes of MMUD transplantation.
Pilot feasibility study to determine the utility of direct access and quantitative magnetic resonance cholangiopancreatography (MRCP) in the assessment of suspected acute biliary or ductal gallstone presentations
Authors: Novak Alex , Acharya Anita , Beer Sally , Espinosa Alexis , Smith Giles Bond , Saga Cyrene , Andrews Jane , Bailey Adam , Soonawalla Zahir , Bungay Helen , Pavlides Michael
Published: February 2025

Background

Patients with suspected acute gallstone disease typically undergo abdominal ultrasound. MRCP is often used for patients with abnormal LFTs, potentially making ultrasound unnecessary for this group. Despite high inter-reader variability in MRCP interpretation, new AI technologies may automate and standardize detection and measurement.

Method

Patients with suspected acute gallstone disease and abnormal liver function tests were randomized into two diagnostic pathways, direct MRCP and standard care. Admission data, healthcare resource use, and clinical outcomes were recorded. National Health Service national 20/21 tariffs were used to calculate and compare healthcare costs. MRCP scans were subsequently analysed using MRCP + software (Perspectum Ltd).

Results

27 participants were enrolled over 12 months, 15 to direct MRCP and 11 to standard care. One patient was excluded from analysis. Mean patient time to diagnostic report and mean per patient associated direct medical cost and mean cost to diagnosis for the direct MRCP and standard of care group was 2.53 days, £449.54, and £647 respectively for the direct MRCP group and 4.18 days costing £742.06 and £896 for standard care. MRCP + analysis of 11 scans showed significant differences between the groups in terms of gallbladder volume (80.2mm3 gallstone present versus 30.1mm3 without, p = 0.018 and cystic duct median width (4.6 mm gallstone present versus 2.7 mm without, p = 0.042).

Conclusions

Direct MRCP may be a feasible and potentially cost-effective diagnostic strategy for patients with suspected acute gallstone disease and deranged LFTs. Automated measurement of MRCP parameters shows promise in detecting obstruction. Larger trials are warranted to assess this potential.

Clinical trial number

This study is registered with ClinicalTrials.gov (NCT03709030). Registration date: October 17, 2018.
Sickness absence among privately employed white-collar workers during the COVID-19 pandemic; a prospective cohort study
Authors: Farrants Kristin , Müller Mira , Alexanderson Kristina
Published: February 2025

Background

The COVID-19 pandemic brought with it several changes, both regarding infection with COVID-19 itself as well as measures to combat the spread of infection, that might have affected sickness absence (SA) patterns. The aim was to explore whether incidence and length of SA changed between 2019, 2020, and 2021, as well as to determine factors associated with SA due to COVID-19 or COVID-like diagnoses among privately employed white-collar workers.

Methods

A cohort of all privately employed white-collar workers in 2018 in Sweden (n = 1 347 778; 47% women) was followed prospectively during 2019, 2020, and 2021 using linked nationwide register data. We calculated numbers and proportions of people with incident SA (in SA spells > 14 days) due to COVID-19, COVID-like diagnoses (certain respiratory, infectious, and symptom-based diagnoses used in the beginning of the pandemic for suspected COVID-19), and all other SA, respectively, and mean number of SA days with somatic and mental diagnoses. Logistic regression was used to determine odds ratios (OR) and 95% confidence intervals for associations between prior diagnosis-specific SA, sociodemographic and work-related factors and incident SA due to COVID-19 or COVID-like diagnoses.

Results

In 2020, 0.6% of the women and 0.3% of the men had incident SA due to COVID-19. For SA with COVID-like diagnoses, the corresponding proportions were 1.2% and 0.5%. The proportion of people with all other SA was stable across the years, at 8.1–8.4% for women and 3.7–3.9% for men. The mean number of SA days per person increased each year for somatic diagnoses but for mental diagnoses it decreased from 2019 to 2020 and increased to 2021 among women and men. Factors associated most strongly with incident SA due to COVID-19 or COVID-like diagnoses were low income (adjusted OR-range 1.36–5.67 compared to the highest income group) and prior SA due to COVID-like diagnoses (OR-range 4.67–5.31 compared to those with no such prior SA).

Conclusions

A small proportion of privately-employed white-collar workers had incident SA spells > 14 days due to COVID-19 or COVID-like diagnoses. The factors associated with SA due to COVID-19 were similar to factors associated with SA due to other diagnoses in previous studies.
Gp350-targeted CAR-T therapy in EBV-positive Burkitt lymphoma: pre-clinical development of gp350 CAR-T
Authors: Wang Jiajia , Wang Huiping , Ding Yangyang , Cao Nengneng , Nan Fengya , Wu Fan , Li Cong , Liang Xue , Xiao Meng , Guo Jinjing , Gao Zhimai , Yan Li , Zhou Tielin , Li Yanli , Zhai Zhimin
Published: February 2025

Background

Epstein-Barr virus (EBV) is an oncovirus belonging to the herpesvirus family, associated with the pathogenesis of multiple malignancies, particularly Burkitt lymphoma (BL). The virus remains latent in host cells and plays a critical role in tumor progression through various mechanisms. A key glycoprotein, gp350, expressed during the lytic phase of EBV, is instrumental in viral entry into B cells and presents a unique antigenic target, making it a promising candidate for immunotherapeutic approaches, such as chimeric antigen receptor T-cell (CAR-T) therapy.

Methods

In this study, we engineered CAR-T cells targeted against the gp350 glycoprotein and assessed their therapeutic potential through a series of in vitro and in vivo experiments. The efficacy of the gp350-CAR-T cells was evaluated by comparing their cytotoxic effects against both EBV-positive and -negative tumor cell lines. We utilized a xenograft model of Burkitt lymphoma to monitor the impact of gp350-CAR-T cell administration on tumor progression and overall survival.

Results

The engineered gp350-CAR-T cells demonstrated potent cytotoxicity specifically against EBV-positive tumor cell lines. In our in vivo xenograft model, administration of gp350-CAR-T cells resulted in significant inhibition of tumor growth, highlighting their capability to effectively target and eliminate EBV-positive lymphomas. This selectivity underscores the potential of utilizing gp350 as a specific target for immunotherapy.

Conclusion

Our findings advocate for the clinical application of gp350-directed CAR-T therapy as a prospective treatment strategy for patients with relapsed or refractory EBV-positive tumors. Given the encouraging preclinical results, further research is warranted to optimize CAR-T cell production processes and extend the potential of this therapy to other EBV-associated malignancies, paving the way for improved outcomes in affected patient populations.
Prognostic accuracy of point-of-care ultrasound in patients with pulseless electrical activity: a systematic review and meta-analysis
Authors: Jian Shang-Jun Zhang , Cheng Tzu-Heng , Yen Chieh-Ching
Published: February 2025

Background

The prognosis for pulseless electrical activity (PEA) is typically poor; however, patients with cardiac activity observed on point-of-care ultrasound (POCUS) tend to have better outcomes compared to those without. This systematic review and meta-analysis were conducted to assess the prognostic accuracy of cardiac activity detected by POCUS in predicting resuscitation outcomes in patients experiencing PEA.

Methods

A comprehensive literature search was conducted in PubMed, Embase, and the Cochrane Central Register of Controlled Trials to identify relevant studies. The pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio, and the area under the summary receiver operating characteristic curve (SROC) were calculated using the bivariate model.

Results

Eighteen studies comprising 1202 patients were included in the meta-analysis. Cardiac activity observed on POCUS demonstrated a pooled sensitivity of 0.86 (95% CI 0.67–0.95) and specificity of 0.64 (95% CI 0.51–0.75) for predicting return of spontaneous circulation, a pooled sensitivity of 0.89 (95% CI 0.80–0.94) and specificity of 0.73 (95% CI 0.63–0.81) for survival to admission (SHA), and a pooled sensitivity of 0.79 (95% CI 0.58–0.91) and specificity of 0.58 (95% CI 0.47–0.68) for survival to discharge. The highest area under the SROC, 0.89 (95% CI 0.86–0.92), was observed for SHA.

Conclusions

Our study suggests that POCUS may serve as a vital component of a multimodal approach for early termination of resuscitation.
Comparative evaluation and performance of large language models on expert level critical care questions: a benchmark study
Authors: Workum Jessica D. , Volkers Bas W. S. , van de Sande Davy , Arora Sumesh , Goeijenbier Marco , Gommers Diederik , van Genderen Michel E.
Published: February 2025

Background

Large language models (LLMs) show increasing potential for their use in healthcare for administrative support and clinical decision making. However, reports on their performance in critical care medicine is lacking.

Methods

This study evaluated five LLMs (GPT-4o, GPT-4o-mini, GPT-3.5-turbo, Mistral Large 2407 and Llama 3.1 70B) on 1181 multiple choice questions (MCQs) from the gotheextramile.com database, a comprehensive database of critical care questions at European Diploma in Intensive Care examination level. Their performance was compared to random guessing and 350 human physicians on a 77-MCQ practice test. Metrics included accuracy, consistency, and domain-specific performance. Costs, as a proxy for energy consumption, were also analyzed.

Results

GPT-4o achieved the highest accuracy at 93.3%, followed by Llama 3.1 70B (87.5%), Mistral Large 2407 (87.9%), GPT-4o-mini (83.0%), and GPT-3.5-turbo (72.7%). Random guessing yielded 41.5% (p < 0.001). On the practice test, all models surpassed human physicians, scoring 89.0%, 80.9%, 84.4%, 80.3%, and 66.5%, respectively, compared to 42.7% for random guessing (p < 0.001) and 61.9% for the human physicians. However, in contrast to the other evaluated LLMs (p < 0.001), GPT-3.5-turbo’s performance did not significantly outperform physicians (p = 0.196). Despite high overall consistency, all models gave consistently incorrect answers. The most expensive model was GPT-4o, costing over 25 times more than the least expensive model, GPT-4o-mini.

Conclusions

LLMs exhibit exceptional accuracy and consistency, with four outperforming human physicians on a European-level practice exam. GPT-4o led in performance but raised concerns about energy consumption. Despite their potential in critical care, all models produced consistently incorrect answers, highlighting the need for more thorough and ongoing evaluations to guide responsible implementation in clinical settings.
Proteomic profiling of human plasma and intervertebral disc tissue reveals matrisomal, but not plasma, biomarkers of disc degeneration
Authors: Dube Christabel Thembela , Gilbert Hamish T. J. , Rabbitte Niamh , Baird Pauline , Patel Sonal , Herrera Jeremy A. , Baricevic-Jones Ivona , Unwin Richard D. , Chan Danny , Gnanalingham Kanna , Hoyland Judith A. , Richardson Stephen M.
Published: February 2025

Background

Intervertebral disc (IVD) degeneration is a common cause of low back pain, and the most symptomatic patients with neural compression need surgical intervention to relieve symptoms. Current techniques used to diagnose IVD degeneration, such as magnetic resonance imaging (MRI), do not detect changes in the tissue extracellular matrix (ECM) as degeneration progresses. Improved techniques, such as a combination of tissue and blood biomarkers, are needed to monitor the progression of IVD degeneration for more effective treatment plans.

Methods

To identify tissue and blood biomarkers associated with degeneration progression, we histologically graded 35 adult human degenerate IVD tissues and matched plasma from the individuals into two groups: mild degenerate and severe degenerate. Mass spectrometry was utilised to characterise proteomic differences in tissue and plasma between the two groups. Top differentially distributed proteins were further validated using immunohistochemistry and qRT-PCR. Additionally, correlational analyses were conducted to define similarities and differences between tissue and plasma protein changes in individuals with mild and severe IVD degeneration.

Results

Our data revealed that the abundance of 31 proteins was significantly increased in severe degenerated IVD tissues compared to mild. Functional analyses showed that more than 40% of these proteins were matrisome-related, indicating differences in ECM protein composition between severe and mild degenerate IVD tissues. We confirmed adipocyte enhancer-binding protein 1 (AEBP1) as one of the most significantly enriched core matrisome genes and proteins as degeneration progressed. Compared to others, AEBP1 protein levels best distinguished between mild and severe degenerated IVD tissues with an area under the curve score of 0.768 (95% CI: 0.60–0.93). However, we found that protein changes from associated plasma exhibited a weak relationship with histological grading and AEBP1 tissue levels. Given that systemic plasma changes are complex, a larger sample cohort may be required to identify patterns in blood relating to IVD degeneration progression.

Conclusions

In this study, we have identified AEBP1 as a tissue marker for monitoring the severity of disc degeneration in humans. Further work to link alterations in tissue AEBP1 levels to changes in blood-related proteins will be beneficial for detailed monitoring of IVD degeneration thereby enabling more personalised treatment approaches.
Asthma
Authors: O’Keefe Andrew , Connors Lori , Ling Ling , Kim Harold
Published: February 2025

Asthma is one of the most common respiratory disorders in Canada, however, many Canadians with asthma remain poorly controlled. In most patients, control can be achieved through appropriate therapy, including: inhaled corticosteroids (ICS), combination ICS/long-acting beta2-agonists (LABA), “triple therapy” with ICS/LABA/long-acting muscarinic receptor antagonist (LAMA), and biologic therapies. The medical management of severe asthma, in particular, has changed dramatically with the incorporation of biologics in asthma treatment plans. Allergen-specific immunotherapy represents a potentially disease-modifying therapy for many patients with asthma; it must only be prescribed by physicians with appropriate training in allergy. Other essential components of asthma management include: regular monitoring of asthma control and risk of exacerbations; patient education and written asthma action plans; assessing barriers to treatment and adherence to therapy; adequate management of comorbidities (e.g., allergic rhinitis) and reviewing inhaler device technique. This article provides a review of current literature and guidelines for the appropriate diagnosis and management of asthma in adults and children.