bluuebunny/crossref_metadata_2025 huggingface dataset:
Role of Inclusive Entrepreneurship Educators: An Actor Network Theory Perspective
Authors: Eid Niveen , Akella Devi
Published: December 2024

This paper integrates our autoethnographic narratives as entrepreneurship educators affiliated with higher education institutions located in different parts of the world with the theoretical concepts of Actor-Network Theory (ANT). We provide insights on how educators’ identities are constructed and how these identities can inspire curriculum and pedagogical interventions that transform marginalized entrepreneurship students into inclusive entrepreneurs, capable of handling political oppression, racial and ethnic discrimination, stress, and the inequities existing within society. Empirical analysis utilizing Callon’s model of translation comprising of four phases: problematization; interessement, enrollment, and mobilization, reveals that educators enact four roles encompassing: (1) Critical Educators; (2) Devil’s Advocates; ( 3) Critical Investigators; and ( 4) Pedagogy Shapers while engaging with their respective academic networks. The identities of educators are not distinct nor isolated outcomes. Instead, their epistemological, ontological, pedagogical, and axiological underpinnings are shaped by the networks with which they engage with over the duration of their career spans. The educators enact roles which possess the power to remedy existing inadequacies within the existing entrepreneurship curriculum making it more pluralistic, pragmatic, and comprehensive.
Effectiveness of Yoga and Physical Exercises on Emotional and Behavioral Problems and Academic Performance Among Indian Adolescents: A Randomized Trial
Authors: Pandey Mangesh , Dwivedi Krishna , Behera Narayan
Published: December 2024

Emotional and behavioral issues in adolescents pose significant obstacles to psychological well-being and academic achievement, potentially leading to severe mental health conditions. The escalating prevalence of these behavioral challenges can adversely affect a nation’s educational, economic, and social health. This study aims to find appropriate solutions to behavioral problems and academic underperformance in adolescents through a two-arm randomized trial. It involves 200 students from distinct locations in India. Intervention encompasses integrated practices of yoga and physical exercises independently. Incorporation of ancient learning principles introduces a novel facet to the intervention protocol for educational and developmental purposes. Participants were evenly distributed across yoga and physical exercise groups. Preintervention and postintervention are evaluated through Strength and Difficulty Questionnaire alongside assessment of academic score of students. Findings exhibit a noteworthy transition among yoga group participants for behavioral problems from clinical risk status to normalized levels. Examination of the correlation between academic performance with various emotional and behavioral problems underscored the detrimental impact of these issues on scholastic attainment. Notably, the influence of yoga surpassed that of physical exercise in enhancing academic performance and mitigating emotional problems, conduct issues, hyperactivity, peer-related challenges, and overall strength and difficulty symptoms. The results suggest that the school-based interventions involving moderate to vigorous physical activity may be considered as a strategy to address adolescent mental health concerns and to enhance academic outcomes. It is further suggested that the policymakers and health professionals can explore such activities as an option to address the growing prevalence of mental health disorders.
Health Literacy and Patient Compliance: Implications for Public Health Interventions from a COVID-19 Study
Authors: Menifield Charles E. , Damas Kasny , Chen Tong , Hudson Shawna , Van Ryzin Gregg , Song Miyeon , Hill Diane , Harris-Neal Nikeysha , Alsbrook Ketlen
Published: December 2024

A wealth of research has documented the detrimental consequences of health illiteracy and its impact on a multitude of health-related issues. Scholars across various disciplines have consistently shown that individuals with higher educational attainment, those born in the United States, and those with greater English proficiency, are more likely to exhibit higher levels of health literacy. However, the extent to which these individuals adhere to established health guidelines remains an understudied area. Therefore, we analyzed data from one of the largest cities impacted by COVID-19 in the United States, to determine whether traditional predictors of high health literacy levels translated into higher levels of vaccination intentions and vaccination doses, to protect themselves and their communities from COVID-19 related illness and death. The results indicated that individuals with high health literacy levels do not necessarily exhibit higher levels of compliance, thus challenging conventional wisdom.
Visual and refractive outcomes of trocar-assisted intrascleral three-piece intraocular lens fixation
Authors: Pellegrini Marco , Adamo Ginevra , Nardella Michele , Sarti Laura , Talli Pietro Maria , Nasini Francesco , Mura Marco
Published: December 2024

Purpose

To report the visual and refractive outcomes of trocar-assisted sutureless intrascleral three-piece intraocular lens (IOL) fixation, and to compare the accuracy of different IOL power formulas in this setting.

Methods

Twenty eyes of 20 patients who underwent trocar-assisted sutureless three-piece IOL scleral fixation were included. Two trocar-cannula systems were placed at 3 and 9 o’clock position creating 2.5 mm scleral tunnels. The haptics of a three-piece IOL were grasped with serrated retinal forceps, externalized through the scleral tunnels and fixed by making a flange. Prediction error (PE) was calculated as the actual postoperative spherical equivalent (SE) refraction minus the SE predicted refraction. The predicted SE was calculated using the Barret Universal II, Emmetropia Verifying Optical (EVO), Hoffer Q, Holladay 1, Holladay II, and SRK/T.

Results

At 6 months after surgery, corrected distance visual acuity improved from 0.66 ± 0.36 to 0.17 ± 0.13 logMAR ( p < .001). The lowest median absolute PE was obtained by the Barrett formula (0.73D), followed by the EVO (0.81D), Holladay 1 (0.94D), SRK/T (0.98D), Hoffer Q (1.05D) and Haigis (1.64D) formulas. The highest percentage of eyes within ±1.00 D were obtained with the Barrett (60.0%), and EVO (55.0%) formulas.

Conclusion

Although trocar-assisted intrascleral three-piece IOL fixation yields good visual results, the predictability of refractive outcomes is lower than in standard cataract surgery. All formulas showed a slight tendency towards a hyperopic refractive surprise.
From adversarialism to antagonism: Challenges to the norms of the broadcast news accountability interview in an age of conflict
Authors: Montgomery Martin
Published: December 2024

The accountability interview in which a public figure is held to account for their statements or actions is a well-established armature in the delivery of broadcast news. In its broadcast canonical form it relies on questioning as an instrument for addressing issues of knowledge, responsibility, and the rightness of actions of those with public standing. However, shifts in questioning techniques have accelerated a movement towards argument in the context of the broadcast accountability interview and a corresponding loosening of its interview structure. Indeed, there are signs of a growing tendency for the interview framework itself to be questioned by interviewees. This article examines what is at stake in these changes and asks if the accountability interview in an era of heightened conflict remains fit for purpose or is facing a kind of legitimation crisis.
Structure and improved corrosion properties of MAO coating on Mg-5Gd-1Zn-0.4Zr formed under various current densities
Authors: Tian Leiyu , Peng Zixuan , Wang Yan , Geng Xue , Dong Qiangsheng , Zhang Xiaobo
Published: December 2024

To investigate the structure and corrosion properties of micro-arc oxidation (MAO) coating on Mg-5Gd-1Zn-0.4Zr (GZ51K) alloys for biomedical application, the alloy was MAO-treated using silicate electrolyte system under current density of 400, 600 and 800 mA/cm2 respectively. The microstructure, surface analysis and corrosion resistance of samples were evaluated by scanning electron microscopy, energy-dispersive X-ray spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy, potentiodynamic polarisation, electrochemical impedance spectroscopy in SBF solution. The results indicate that the main phases of the MAO coatings were MgO, Mg2SiO4 and MgF2. With the increase of MAO current density, the thickness of the MAO coating decreased from 16.5 to 10.4 μm. When MAO current density is 400 mA/cm2, the specimen shows the best corrosion resistance with a four-order-of-magnitude decrease on Icorr ((1.95 ± 0.01) × 10−10 A/cm2), a four-order-of-magnitude increase on RP((7.67 ± 0.02) × 107 Ω cm2). Even though the thickness of the MAO coatings obtained with 600 and 800 mA/cm2 are very close, the corrosion resistance of the coating prepared under 800 mA/cm2 is better than that under 600 mA/cm2. Generally, MAO treatment can greatly slow down corrosion rate of the GZ51K alloy and keep uniform corrosion mode which is desirable for biodegradable implant applications.
Animal-assisted intervention services across UK intensive care units: A national service evaluation
Authors: Wright Sam , McAree Holly , Hosey Megan , Tantam Kate , Connolly Bronwen
Published: December 2024

Background:

Animal-assisted interventions (AAI) can provide psychological support to critical care patients during their intensive care unit (ICU) admission. However, there are currently no data on AAI services across UK ICUs. The current study therefore aims to (i) determine how many ICUs in the UK offer services, (ii) characterise available services and (iii) explore and review local documentation for service oversight.

Methods:

A service evaluation comprising two parts; a national survey of UK ICU’s, analysed using descriptive statistics, and review of local service oversight documents, analysed using a framework approach.

Results:

Responses from 74 sites (/242, 30.6%) were included in survey analysis. AAI services were present at 32 sites (/74, 43.2%), of which 30 offered animal-assisted activity services alone and 2 offered both animal-assisted activity and animal-assisted therapy services. Animal-assisted activity services were typically delivered on a weekly basis, lasting 30–60 min and with dogs the sole animal employed. Concern over infection prevention and control was the most common barrier to service provision, as well as a lack of supporting evidence. Sixteen sites provided 27 oversight documents for analysis, that highlighted unique and shared responsibilities between critical care staff and animal therapy handlers, including aspects of administration, welfare and infection control.

Conclusion:

From a small sample, AAI services were available in less than half of ICUs. Empirical value of interventions is countered by current lack of definitive evidence of effectiveness, which should be addressed before wider implementation of AAI services and the associated resource requirements, is undertaken.
Influence of palmar plate injury on outcomes of zone 2 flexor tendon repair
Authors: Akyurek Mustafa , Hafiz Gunes , Sayan Mihrican
Published: December 2024

This study investigates the impact of proximal interphalangeal joint palmar plate injury on outcomes of flexor tendon repair in zone 2, excluding cases with fractures or dislocations. A retrospective review of 47 digits in 45 patients treated between 2014 and 2022 was conducted, analysing surgical notes, ultrasound images and patient photographs. The palmar plate was injured in 17 digits and intact in 30. Outcomes were assessed using the Strickland criteria for active range of movement 6 months postoperatively. Our analysis revealed that palmar plate injuries significantly affect flexor tendon repair outcomes, with a normal palmar plate increasing the likelihood of excellent recovery by 18 times. Although previous studies indicate no consensus on the impact of flexor digitorum superficialis repair, our findings emphasize the importance of palmar plate integrity. Nerve injury and flexor digitorum superficialis repair did not show significant effects on recovery in this cohort. Our study provides valuable insights into the importance of the injury to the palmar plate.

Level of evidence: III
Plain Language Summary of Publication: Does crushing vibegron 75 mg tablet affect its safety or the amount of vibegron in the body over time in healthy adults?
Authors: King Jennifer , Tuders Nancy , Varano Susann , Owens-Grillo Janet
Published: December 2024

What is this summary about?

This is a plain language summary of an article published in the journal Clinical Pharmacology in Drug Development. It is about a study of a medicine called vibegron. Vibegron is approved by the US Food and Drug Administration (also called the FDA) to treat overactive bladder, also known as OAB.

It may be easier for people with swallowing issues to take a pill by crushing it and mixing it with applesauce instead of swallowing it whole. Researchers did this study to find out if vibegron could be safely crushed and mixed with applesauce. Participants took vibegron that was either crushed or intact, and researchers compared how much vibegron made it into the bloodstream over time. The researchers asked whether people who took crushed vibegron had more unwanted medical events (called adverse events) than people who took vibegron as an intact pill.

What were the results?

Crushed vibegron tablets did not change in applesauce for 4 h at room temperature. Just over half of the participants (53%) said that the taste was not different than expected. The amount of vibegron in blood over time was similar between those who took crushed vibegron and those who took intact vibegron. The most common adverse events were headache, constipation, and nausea. No participant experienced a serious adverse event during the study, meaning that no adverse events required hospital care or caused permanent damage or disability. Adverse events that might be related to vibegron occurred in seven participants (23%) after they took crushed vibegron and six participants (20%) after they took the intact pill.

What do the results mean?

The results of this study show that vibegron can be crushed and taken with applesauce without increases in adverse events compared to taking the intact pill. Crushed vibegron did not change in applesauce and the amount of vibegron in blood over time was similar when vibegron was crushed in applesauce or taken whole. This means that people may take vibegron as a crushed or intact pill for overactive bladder. This may be particularly important for people with difficulty swallowing.

Who should read this article?

This article is for people with overactive bladder symptoms who have a hard time swallowing pills. It may also be helpful for their families and care partners, and for health care professionals who care for people with overactive bladder.

Where can I find the original article on which this summary is based?

The original article is called “Pharmacokinetics and Safety of Vibegron 75 mg Administered as an Intact or Crushed Tablet in Healthy Adults.” You can read the original article published in Clinical Pharmacology in Drug Development at this link:

•  https://accp1.onlinelibrary.wiley.com/doi/10.1002/cpdd.1169
Possible sinoatrial node dysfunction in a 6-month-old domestic shorthair cat
Authors: Hillen Florence , Locquet Laurent
Published: December 2024

Case summary

A 6-month-old male entire domestic shorthair cat was presented to the ophthalmology department for nasolacrimal duct cannulation and flushing, and castration under general anaesthesia. On pre-anaesthetic assessment, the cat had a heart rate of 90 beats/min (bpm). Clinical examination was unremarkable, although the cat appeared stressed. The echocardiogram was within normal limits. An ambulatory electrocardiogram (ECG) monitor was fitted overnight, and analysis of the ECG revealed a sinus rhythm with a lower than normal heart rate. The mean 1 min rate was 98 bpm. There was a slower than normal sinus rhythm and frequent ventricular escape beats. Differential diagnoses included increased vagal tone and sinoatrial node dysfunction (SND). The latter was suspected as the cat demonstrated signs of stress although an atropine response test was not performed.

Relevant and novel information

SND is relatively common in dogs but extremely rare in cats. To the authors’ knowledge, there is only one affected cat mentioned in the literature. In both dogs and humans, most cases described are in middle-aged and elderly patients. Although the condition is recognised in human infants and fetuses, it has not been reported in dogs under 2 years of age. This case is unusual because SND was suspected in an immature cat. On analysis of the ECG, the heart rate was considerably lower than those previously reported in hospitalised cats; however, findings on physical examination were subtle, highlighting the importance of pre-anaesthetic examination in identifying unexpected abnormalities.
How Reliable is the Assessment of Fusion Status Following ACDF Using Dynamic Flexion-Extension Radiographs?
Authors: Martin Christopher T. , Yoon Sangwook Tim , Alluri Ram Kiran , Benzel Edward C. , Bono Chris M. , Cho Samuel K. , Chou Dean , Chen Xiaolong , Cheung Jason P.Y. , Cabrera Juan P. , Ćorluka Stipe , Demetriades Andreas K. , Gary Matthew F. , Ghogawala Zoher , Hamouda Waeel , Han Inbo , Hauri Dimitri , Hsieh Patrick C. , Jain Amit , Kim Jun S. , Le Hai V. , Louie Philip K. , Luo Zhuojing , Meisel Hans-Jörg , Muthu Sathish , Ryu Dal-Sung , Sansur Charles A. , Schoenfeld Andrew J. , Scaramuzzo Laura , Schroeder Gregory D. , Rajasekaran Shanmuganathan , Sotiris Veranis , Vadalà Gianluca , Vergroesen Pieter-Paul A. , Wang Jeffrey C. , Wu Yabin , Riew K. Daniel ,   AO Spine Knowledge Forum Degenerative
Published: December 2024

Study Design

Reliability study.

Objectives

The radiographic diagnosis of non-union is not standardized. Prior authors have suggested using a cutoff of <1 mm interspinous process motion (ISPM) on flexion-extension radiographs, but the ability of practicing surgeons to make these measurements reliably is not clear.

Methods

29 practicing spine surgeons measured ISPM on 19 levels of ACDF from 9 patients. Surgeons relied on these measurements to report on fusion status. Inter-observer correlation co-efficients (ICC), standard error (SEM) and the minimum detectable difference (MD) of these measurements were calculated. We screened for clerical errors by checking measurements more than one standard deviation from the group mean.

Results

The ICC for ISPM was .76 (.64; .88) with a SEM of 1 mm and a MD of 2.76 mm. Agreement on fusion status was moderate, with an ICC of .6 (.44; .76). After screening for and removing clerical errors, the ICC improved to .82 (.71; .91), SEM improved to .83 mm, and MD improved to 2.29 mm. Six reviewers had an ICC >.9. The ICC from these high performing reviewers was .94 (.9; .97), SEM was .45 mm, and MD was 1.26 mm.

Conclusions

The MD of 2.29 mm in our study group was not precise enough to support a cutoff of <1 mm ISPM as the sole measurement technique in screening for non-union after ACDF, and there was only moderate agreement amongst surgeons on fusion status based on dynamic radiographs. More stringent techniques are necessary to avoid mis-diagnosing non-union in clinical studies. Future studies should consider auditing measurements to identify clerical errors.
Peripheral defects precede neuromuscular pathology in the Smn2B/− mouse model of spinal muscular atrophy
Authors: Reilly Aoife , Beauvais Ariane , Al-Aarg Majd , Yaworski Rebecca , Sutton Emma R. , Thebault Simon , Kothary Rashmi
Published: December 2024

Background:

Spinal Muscular Atrophy (SMA) is an inherited neurodegenerative disease caused by the loss or mutation of the survival motor neuron 1 (SMN1) gene. Though classically regarded as a motor neuron disorder, reports are increasingly describing the involvement of non-neuronal organs in SMA. The Smn2B/− mouse is a model of SMA that displays a peripheral phenotype including metabolic defects.

Objective:

Here, we characterized several neuronal and non-neuronal defects in the Smn2B/− mouse throughout development to better understand the progression of the disease and the relationship between tissue defects.

Methods:

We collected tissues from mutant Smn2B/− mice and Smn2B/+ littermate controls at several timepoints and evaluated spinal cord motor neuron loss, neuromuscular junction pathology, muscle fiber size, liver steatosis, and pancreatic islet cell composition. Blood glucose and plasma neurofilament light chain (NfL) were also measured.

Results:

Smn2B/− mice displayed several peripheral defects prior to motor neuron loss and showed early elevations in neurofilament light chain (NfL) protein.

Conclusions:

This work provides an important framework for guiding future research with this mouse model and demonstrates that the liver may be an early target in the development of SMA.
Purpose in Life in Parkinson’s Disease: Its Relationships with Well-Being, Psychological Distress and Motor Function
Authors: Vescovelli Francesca , Sarti Daniele , Ruini Chiara
Published: December 2024

Objectives: To examine the role of purpose in life in a sample of patients with Parkinson’s disease and its correlations with well-being, quality of life, psychological distress, and motor function; and to compare patients reporting higher versus lower levels of purpose in life. Method: 59 patients completed the Purpose in Life subscale Scales and other questionnaires concerning quality of life, personal well-being, and psychological distress. Their motor function was assessed with the Short Physical Performance Battery. They were divided into (1) High purpose in life individuals—HPIL—( n = 23); (2) Low purpose in life individuals—LPIL—( n = 36). Bivariate correlations between questionnaires and ANOVA between-group were calculated. Results: Purpose in life was significantly and positively correlated to well-being, quality of life and motor function, and negatively to psychological distress. After controlling for age, gender, marital status, years from diagnosis and dopamine medication, HPIL individuals reported significantly higher levels of well-being, quality of life, better physical functioning and lower distress. Discussion: Purpose in life is strongly associated with mental well-being and motor function in patients with Parkinson’s disease. These findings suggested the importance of developing interventions to promote purpose in life also in this population.
Predictors of Late Antenatal Care Initiation: A Multicentre Cross-Sectional Study in Ghana
Authors: Gbene Jonathan , Takase Mohammed Augustine , Ayangba Valentine , Azumah Abanga Williams , Hamza Anwar Sadat , Alechana Justina Atogichiga , Dzantor Edem Kojo , Tarkang Elvis E.
Published: December 2024

Background

Despite free maternal healthcare, about 50% of pregnant women in Ghana initiate their antenatal clinic (ANC) late.

Aim

This study aimed to identify the factors that contribute to the late initiation of ANC among pregnant women in the Jasikan District, Ghana.

Method

A cross-sectional study was conducted between December 2021 and May 2022 in multiple health facilities. Multistage sampling was employed to select 352 pregnant women attending ANC in selected health facilities. A structured questionnaire was used to collect the data. The data was analyzed using Stata version 14.0. Descriptive statistics was used to describe the study variables and multivariable logistic regression models were performed to determine the predictors of late ANC initiation at p < .05 and 95% confidence interval (CI).

Results

Approximately 45.7% of the participants initiated ANC late. Age less than 20 years, older age groups (40–49 [odds ratio (OR): 18.0, 95%CI: 3.68–88.0, p < .001]; 30–39 [OR: 6.4, 95%CI: 1.76–22.87, p = .005] and 20–29 [OR: 4.6, 95%CI: 1.30–15.98, p = .018]) were associated with late initiation of ANC. Having a higher number of children (4 [OR: 2.8, 95%CI: 1.36–5.79, p = .005] and 3 [OR: 2.5, 95%CI: 1.33–4.58, p = .004]) were predictors of late ANC initiation as compared to having one child. Women who sought for advice from women leaders (OR: 3.5, 95%CI: 1.18–10.12, p = .02) were about three (3) times more likely to initiate ANC late as compared to those who sought for advice from friends. Women who felt poorly received at ANC (OR: 7.7, 95%CI: 2.188–27.078, p = .001) were about eight (8) times more likely to initiate ANC late as compared to those who felt well received. Again, those who spent over six (6) hours during ANC visits (OR: 18.4, 95%CI: 4.246–79.734, p < .001) had an 18 times higher risk of initiating ANC late relative to those who spent less than 3 h.

Conclusion

The study findings highlight the need for interventions that addresses the social and cultural factors, negative perceptions of ANC, and long waiting times at health facilities to improve early initiation of ANC. Such interventions can assume health education and promotion to address the sociocultural and unfavorable perceptions toward ANC. The sector ministry and the health facilities may consider expanding ANC service centers to reduce long waiting times.
Relocating the imaginary nation through nature: The performance politics of Arbor Day in postwar Taiwan
Authors: Kao Yu-Ting , Wang Chih-Hung
Published: December 2024

This article examines the transformation of Arbor Day in postwar Taiwan, focusing on how it has been used to relocate the imaginary nation—shifting from associations with mainland China toward alignment with the island-based regime in Taiwan. Using the framework of performance politics, we analyze how Arbor Day serves as a contested arena where various social actors—ranging from the central government and local authorities to civil society—compete to reassemble the mise-en-scène of nature. We argue that performative acts from these different sectors collectively distance Arbor Day from its early reliance on the mainland-oriented Founding Father narrative, redirecting attention toward localized concerns such as urban greening, environmental conservation, and urban governance. In this process, a “relocated” nation gradually emerges as the imagined setting of Arbor Day, reflecting Taiwan's shifting national identity. While Arbor Day continues to express nationalism, what changes over time is the scale of the nation these performances seek to address at different historical moments and for various purposes.
Fixing crisis, transforming landscapes: Social, spatial, ecological, and racial fixes in New Deal South Carolina
Authors: Vickers Morgan P.
Published: December 2024

This article examines the spatial, social, ecological, and racial fixes of the Santee-Cooper Project, a New Deal hydroelectric project constructed between 1938 and 1942 that inundated the homes of 901 Black, Indigenous, and poor White families in central South Carolina. Drawing upon Ruth Wilson Gilmore’s concept of crisis, and Clyde Woods and David Harvey’s notion of the (socio-)spatial fix, the research underscores how the New Deal attempted to address economic, political, and racial crises by implementing a series of fixes aimed at stabilizing economic markets while reshaping ecological and racial landscapes. This article reveals how the New Deal reconfigured Black geographies and ecologies, displacing communities and ecosystems in the name of progress. By scrutinizing local administrative practices and broader regional consequences, the article highlights the far-reaching impacts of state-initiated development amid crises of racial capitalism. The analysis concludes with an attention to the Green New Deal, pushing back against the fixity inherent in the original public works program, and advocating for a nuanced approach to repair in the face of environmental crises. By reassessing the historical significance of the New Deal and the missteps made in the face of early 20th-century crises, this research informs debates on socio-environmental justice and equitable development, offering guidance for navigating crises in the modern era.
Multiple life-threatening complications in a patient who received lung transplantation due to cystic fibrosis and their management
Authors: Kececi Ozgur Gizem , Ozdil Ali , Korkmaz Pervin , Akcam Tevfik İlker
Published: December 2024

Cystic fibrosis patients may be considered for lung transplantation. Although these patients may experience more successful outcomes and survival rates compared to others, various complications can arise. In particular, infectious complications and septic deaths may be more prevalent in cystic fibrosis patients compared to other lung transplant indications. Considering all these factors, recognizing and managing complications that may arise during the postoperative period in this patient group are of critical importance. In this article, multiple life-threatening complications occurring in the post-transplant period in a patient who underwent lung transplantation due to cystic fibrosis are chronologically presented, and their management is discussed.
Development and Validation of the Blastic Plasmacytoid Dendritic Cell Neoplasm Prognostic Score
Authors: Haddad Philip A , Gaddam Shiva Jashwanth , Gupta Ankita
Published: December 2024

Background

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an uncommon and highly aggressive hematologic malignancy primarily characterized by its frequent involvement of the skin and potential to rapidly progress to systemic disease. Initially misclassified under various categories, such as blastic NK-cell lymphoma, and later as a subset of acute myeloid leukemia (AML), BPDCN has now been distinctly recognized as a unique myeloid neoplasm. Despite recent advancements in understanding its pathogenesis and clinical behavior, the prognosis of BPDCN remains poor and highly variable among patients. Accurate prognostic tools are crucial for improving patient management and outcomes. This study focuses on developing and validating a clinical prognostic score for BPDCN, aiming to stratify patients better based on their risk and guide therapeutic decision-making.

Methods

Using a constructed BPDCN database of 273 cases, we analyzed demographics and clinicopathologic factors. Of these, 218 cases had complete survival and outcomes data. Cox proportional-hazards models and Log-rank tests were used to identify factors impacting overall survival (OS). Factors with significant impact on OS were scored based on their hazard ratios. A validation cohort of 106 BPDCN-confirmed cases was used to test the score. Subsequently, both cohorts were combined and split into adult and pediatric cohorts for further testing and validation across age groups.

Results

The median OS for the initial, validation, adult, and pediatric cohorts were 16, 15, 12, and 60 months, respectively. The following dichotomous variables significantly impacted OS: Age > 60 (10 vs. 30 months), lymphadenopathy (14 vs. 42 months), bone marrow involvement (14 vs. NR months), splenomegaly (10 vs. 16 months), disseminated skin disease (13 vs. NR months). Variables were assigned points: 1 point for each variable, except age > 60, splenomegaly, and disseminated skin disease, which were given 2 points due to their high hazard ratios. The risk model categorized patients into low (0-2 points), intermediate (3-4 points), and high-risk (5-8 points) groups. Median OS for these groups were NR, 24, and 10 months, respectively (p < 0.0001). The BPS similarly identified 3 risk groups in the validation cohort(38 vs. 13 vs. 9 months, p = 0.0001), adult cohort (22 vs. 13 vs. 9 months, p < 0.0001), and pediatric cohort(NR vs. 36 vs. 9 months, p = 0.002).

Conclusion

The BPDCN prognostic score (BPS) is a promising tool that effectively stratifies patients into 3 distinct risk categories with significant differences in overall survival. This score was validated in multiple cohorts, including adult and pediatric groups, but requires prospective validation for further confirmation.
Super-Enhancer-Associated Long Noncoding RNA Lnc-SPI1U Participates in PU.1 Feedback Regulation By Interacting with HNRNPH1 and Hnrnpf
Authors: Ma Xuefei , Sun Weifen , Li Yilu , Tan Yun , Wang Xuefeng , Wang Kankan
Published: December 2024

Super-enhancers (SEs) are essential regulatory elements that orchestrate the precise transcriptional regulation of cell-type- and state-specific-gene expression during hematopoietic differentiation. The role of SEs on the regulation of long noncoding RNAs (lncRNAs) during myeloid differentiation remains poorly understood. In this study, we illustrated the landscape of SE-associated lncRNAs in acute promyelocytic leukemia (APL) by integrating 20 datasets of H3K27Ac ChIP-seq and 379 datasets of RNA-seq from the TCGA and Beat AML databases. We identified 44 lncRNAs that are located in close proximity to SEs, which may play a pivotal role in the pathogenesis APL. Among these, we designated the lncRNA RP11-750H9.5, which is found upstream of the SE region of the SPI1 gene encoding key hematopoietic transcription factor PU.1, as lnc-SPI1U. Our data found that lnc-SPI1U was involved in the regulatory loop of PU.1 during all-trans retinoic acid (ATRA)-induced differentiation. The lnc-SPI1U transcript and its genomic locus functionally play distinct roles in SPI1 gene expression. lnc-SPI1U inhibited cell differentiation and apoptosis while promoting cell proliferation during ATRA-induced myeloid differentiation. This effect was mediated by destabilizing SPI1 mRNA in concert with HNRNPH1 and HNRNPF interactions. Conversely, the genomic deletion at the lnc-SPI1U locus diminished SPI1 activation. Further analysis of transcriptional regulation illustrated that PU.1 induced the expression of lnc-SPI1U by binding to its promoter and enhancer regions, and the induction of lnc-SPI1U by ATRA was dependent on PU.1. These findings suggest that lnc-SPI1U might function as a “brake” to modulate PU.1 level and participate in PU.1 feedback regulation, thereby accurately fine-tuning the expression of PU.1 at the optimal level for myeloid differentiation. However, the PML/RARα fusion protein, characteristic of APL, disrupted the lnc-SPI1U-SPI1 regulatory circuit by hijacking the lnc-SPI1U genomic region, leading to the inhibition of SPI1 activation. Our findings emphasize the significant role of SE-associated lncRNAs, such as lnc-SPI1U, in the gene regulatory networks involved in hematopoietic differentiation.
Development of a Machine Learning-Based Risk Score for Predicting Atrial Fibrillation in Treatment-Naive CLL Patients Initiating BTK Inhibitor Therapy
Authors: Tadmor Tamar , Melamed Guy , Alapi Hilel , Gazit Sivan , Patalon Tal , Rokach Lior
Published: December 2024

Background: One of the limiting toxicities of BTKi therapy is the development of atrial fibrillation (AF), with an incidence of 3% to 16%.

Aim: To identify patients with chronic lymphocytic leukemia (CLL) who are at high risk of developing AF, using a machine learning approach.

Methods: The CLL cohort was based on data obtained from electronic medical records from Maccabi, the second-largest healthcare organization in Israel. We evaluated more than 100 variables to develop the scoring schema. The optimal scoring model was determined using the code available at https://github.com/ustunb/risk-slim, implemented in Python 3.5 and CPLEX 12.6.

Results: A total of 3964 patients with a CLL diagnosis were available in the database. 208 patients started a BTKi during the study period, 16 of whom developed AF during follow-up. In addition to well-established factors (age, sex, and hypertension) that are used in many existing AF scores that were developed for the general population, the algorithm detected other factors that were associated with a high risk for AF, in particular: type of BTKi used, low eGFR (<30 mL/min/1.73m2), elevated absolute monocytes (>1100/µL), elevated CRP, elevated CK, and elevated B2MG (>2.5 mg/L). Based on the total score, we identified 3 main AF risk groups as following: low (0-6), intermediate (7-11) and high (≥12). The median AFS were 28 and 56 months for the high-risk and intermediate-risk groups, respectively, and was not reached for the low-risk group. The difference between the groups was statistically significant (P=0.0013).

The proposed scoring model reached a C-index of 0.744+/-0.082 and it outperformed the score ranking of Shanafelt et al that obtained a C-index of 0.626+/-0.138 on the same data. The improvement was found to be statistically significant (P=0.024).

Conclusion: Our novel score has a high concordance index to predict the development of AF in patients with CLL treated with BTKi.
Loss of IRF2BP2 Drives an Actionable IL-1β/IL-1R Signaling Loop in DLBCL
Authors: Tabatabai Areya , Klein Sebastian , Höfmann Svenja , Zhou Tanja , Theiss Felix , Flümann Ruth , Möllmann Michael , Hartnack Maximilian , Kesper Stefanie , Arora Aastha , Knittel Gero , Reinhardt Hans Christian
Published: December 2024

Diffuse large B cell lymphoma (DLBCL) is a highly heterogeneous disease and is the most common lymphoid malignancy in adults (Swerdlow et al., 2016, Alizadeh et al., 2000). It is traditionally divided into two subtypes based on the cell-of-origin: Activated B cell-like (ABC) DLBCL and germinal center B cell-like (GCB) DLBCL (Alizadeh et al., 2000). DLBCL can be further subdivided into clusters A53, ST2, N1, BN2, EZB, and MCD based on the mutational profiles of the tumors (Schmitz et al., 2018, Wright et al., 2020). While cure rates of ~65% are achievable in DLBCL patients with frontline combination chemo-immune therapy (e.g. R-CHOP), treating relapsed or refractory disease remains a challenge, particularly in ABC-DLBCL and MCD patients (Pfreundschuh et al., 2011, Tilly et al., 2015, Schmitz et al., 2018).

Interferon regulatory factor 2 binding protein 2 (IRF2BP2) is a transcriptional repressor that is frequently mutated in MCD patients, with many of these mutations predicted to be loss-of-function (Schmitz et al., 2018). Besides human DLBCL tumors, in previously published MCD mouse models, which harbor a B cell-specific loss of Prdm1, expression of mutant Myd88p.L252P, overexpression of BCL2, and in some cases expression of a Cd79b ITAM mutation, Irf2bp2 is also one of the most frequently co-mutated genes (Knittel et al., 2016, Flümann et al., 2023, Flümann et al., 2024). However, the role of IRF2BP2 in lymphoma biology and as a potential tumor suppressor gene in DLBCL has not been investigated.

To understand the role of IRF2BP2 in the germinal center reaction, we analyzed the B cell compartment of autochthonous mice which harbor a B cell specific knockout of Irf2bp2 at a premalignant age. We observed a dramatic decrease in germinal center B cells in Irf2bp2 knockout mice compared to controls, as well as a higher relative memory B cell output and reduced class switch recombination. This preliminary dataset suggests that Irf2bp2 may play a role in the dynamics of the germinal center reaction and B cell differentiation.

Moreover, we show that CRISPR/Cas9-mediated loss of IRF2BP2 in human ABC-DLBCL cell lines leads to increased proliferation and NF-KB signaling, compared to IRF2BP2-proficient cells. Additionally, we find that IRF2BP2 knockout ABC-DLBCL cells express higher interleukin-1 beta (IL1β) and are sensitive to anti-IL1β inhibition both in vitro and in vivo, while IRF2BP2-proficient cells remain insensitive. Furthermore, murine lymphoma cell lines derived from MCD mouse models, which harbor a spontaneous Irf2bp2 mutation are also sensitive to anti-IL1β inhibition in vitro and retain sensitivity over several weeks. Our findings suggest that IL1β is the primary mediator of increased NF-KB signaling upon IRF2BP2 perturbation and anti-IL1β therapy could be a potential treatment strategy for IRF2BP2-mutant patients.
Retrospective Comparison of Survival and Risk Stratification By Quantitative RT-PCR Monitoring in Newly Diagnosed Pediatric Acute Myeloid Leukemia with RUNX1::RUNX1T1 Fusion Treated with AML-CAMS-2009 and AML-CAMS-2016
Authors: Zhang Luyang , Guo Ye , Yang Wenyu , Chen Xiaojuan , Chen Yumei , Zhang Li , Zou Yao , Zhu Xiaofan , Ruan Min
Published: December 2024

Objective: The study is intended to compare the clinical outcomes of pediatric patients with AML with RUNX1::RUNX1T1 fusion treated with the AML-CAMS-2009 and AML-CAMS-2016 regimens, as well as to explore early molecular thresholds with prognostic advice. Methods: The study retrospectively analyzed the clinical data of 146 pediatric patients newly diagnosed with AML with RUNX1::RUNX1T1 fusion who received treatment with AML-CAMS-2009 (n = 74) or AML-CAMS-2016 (n = 72) regimens in a single center. Patients on protocol 2009 were followed until December 31, 2020, with a median follow-up of 66 (1-135) months; patients on protocol 2016 were followed until November 30, 2022, with a median follow-up of 43.5 (1-82) months. Results: There was a trend toward improved overall survival with the 2016 regimen in comparison to the 2009 regimen (87.3±4.5% vs. 73.9±5.5%, P = 0.060). At remission following one course of induction chemotherapy, a ≥3 log reduction in RUNX1::RUNX1T1 transcripts in BM had a significant influence on RFS (93.3±6.4% vs. 63.4±8.9%, P = 0.013) and OS (100.0% vs. 69.3±8.6%, P = 0.013) in patients treated with regimen 2009. Compared to the 2009 regimen, the 2016 regimen improved the prognosis of patients with a ＜3 log reduction in RUNX1::RUNX1T1 transcripts, although the difference was not statistically significant (P = 0.162). Nevertheless, with the 2016 regimen, the worse survival of patients with a ＜ 3 log reduction in fusion gene by induction chemotherapy was not statistically significant (＜3 log vs. ≥3 log reduction: RFS 67.7±8.4% vs.91.3±5.9%, P=0.051; OS 83.8±7.4% vs. 100%, P=0.059). Fusion genes detected by quantitative real-time PCR of less than 0.4%, 0.2%, and 0.01% after induction chemotherapy, consolidation 1, and consolidation 2, respectively, significantly affected RFS in patients, both in 2009 and 2016 protocols (P＜0.050). Significant improvements in RFS and OS were seen in patients who achieved two or more detections of the above targeted quantification of fusion genes (P＜0.005). Conclusion: 1. The 2016 regimen did not result in a decrease in the overall prognosis, despite the fact that it reduced the intensity of therapy. 2. The extent of molecular remission following one course of induction chemotherapy has a substantial impact on the long-term prognosis. 3. Regardless of the regimen, integrating the response to the first three courses of chemotherapy provides prognostic significance.
Medicaid Expansion and Cancer-Specific Survival Among Individuals with Acute Lymphoblastic Leukemia
Authors: Akinyemi Oluwasegun Austine , Abobarin-Aofolaju Olufunmilayo , Adeoye Tayo , Abodunrin Faith , Adubi Oreoluwa , Ikugbayigbe Seun , Odusanya Eunice , Fasokun Mojisola , Michael Miriam , Hughes Kakra
Published: December 2024

INTRODUCTION

Medicaid expansion under the Affordable Care Act (ACA) has aimed to improve healthcare access and outcomes for low-income individuals across the United States. Acute Lymphoblastic Leukemia (ALL), a rapidly progressing hematological malignancy, demands timely and comprehensive medical intervention to optimize patient survival rates. Despite advancements in treatment, disparities in cancer-specific survival persist (CSS), particularly among socioeconomically disadvantaged populations.

OBJECTIVE

This study investigates the impact of Medicaid expansion on CSS among individuals diagnosed with ALL, aiming to explore the extent to which increased healthcare access through Medicaid expansion may influence survival outcomes in this vulnerable patient population.

METHODOLOGY

We utilized the Surveillance, Epidemiology, and End Results (SEER) cancer registry to examine the impact of Medicaid expansion on CSS among individuals diagnosed with ALL. A difference-in-difference analysis (DID) was conducted to evaluate the effect of the policy on survival outcomes. Texas, a state that has not implemented Medicaid expansion, was compared with California, which adopted the policy in 2014. The analysis adjusted for significant covariates including age, sex, race/ethnicity, socioeconomic status, and treatment modalities. By comparing pre- and post-expansion periods in these two states, we aimed to isolate the impact of Medicaid expansion on CSS in ALL patients.

RESULT

Among 22,303 patients, 60.0% were in California (13,384), while 40.0% were in Texas (8,919). The pre-ACA period included 14,129 patients (62.0% in California and 38.0% in Texas), and 8,174 patients were in the post-ACA period (56.6% in California and 43.4% in Texas). In the post-ACA implementation period, there was a 23.5% reduction in the hazard of deaths (HR=0.77, 95% CI 0.70-0.85). Medicaid expansion significantly improved cancer-specific survival among individuals with ALL across different race/ethnicity and income levels (DID=-0.69, 95% CI -1.18 to -0.19). The most significant improvements were observed among minority groups: Blacks (DID=-0.80, 95% CI -1.39 to -0.21) and Hispanics (DID=-0.72, 95% CI -1.35 to -0.22), as well as individuals with lower income levels (DID=-0.66, 95% CI -1.14 to -0.18).

CONCLUSION

The implementation of the ACA and its Medicaid expansion component led to a substantial improvement in cancer-specific survival among individuals with acute lymphoblastic leukemia in California compared to non-expansion Texas.
Analysis of the Nervous System Adverse Events Associated with Blinatumomab: A Real-World Study Using the FDA Adverse Event Reporting System Database
Authors: Gao Wen , Lu Yaxiao , Wang Xianhuo , Zhang Huilai
Published: December 2024

Background: Nervous system toxicity (NST) is one of the most frequent and dangerous side effects of blinatumomab, which is the world's first bispecific antibody drug targeting both CD19 and CD3. Current clinical trial data do not fully reflect the real-world situation. Therefore, this study evaluated the NST of blinatumomab therapy using the United States Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).

Methods: Data were retrieved from FAERS for the period from October 1, 2014 to September 30, 2023. The reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence interval progressive neural network (BCPNN), and multi-item gamma Poisson shrinker (MGPS) algorithms were used for data mining. The time to onset (TTO) and clinical outcomes due to blinatumomab-associated NST were assessed.

Results: In the FAERS database, 5,962 adverse reaction case reports primarily implicating blinatumomab were extracted. Male individuals accounted for the highest proportion (2,396 cases, 40.19%) of patients, patients aged 18-45 years old were the most prevalent (1,205 cases, 20.21%), and the majority of reports originated from the United States (3,494 cases, 58.60%), with the highest number of cases reported in 2021 (844 cases, 14.16%). Employing the ROR, PRR, BCPNN, and MGPS methods collectively identified 43 signals of nervous system adverse reactions. Among these adverse reactions, neurotoxicity, neurological symptoms, agnosia, intention tremor, and immune effector cell-associated neurotoxicity syndrome had the highest ROR values. For the neurological events, the median TTO was 3 days, with a range from 1 to 17 days. The highest fatality rate for neurological events was observed in increased intracranial pressure disorders, which also had the highest co-occurrence rate with cytokine release syndrome (CRS) at 36%.

Conclusions: Most NST (79%) did not overlap with cytokine release syndrome.The presence of CRS led to a higher fatality rate in patients experiencing neurological toxicities. In clinical practice, thorough medication evaluation should be conducted prior to administering blinatumomab, especially for high-risk patients with pre-existing neurological conditions.

Keywords: Blinatumomab, Nervous system toxicity, Pharmacovigilance, FDA Adverse Event Reporting System (FAERS)