bluuebunny/crossref_metadata_2025 huggingface dataset:
A variational principle in flexo-electromagnetism with an application to electromagnetic wave generation from flexoelectric plates
Authors: Duan Biwen , Zhu Feng , Zhao Zinan , Pan Ernian , Qu Yilin
Published: January 2025

Electromagnetic (EM) waves are the primary information carriers for modern communication devices, enabling the rapid transmission and reception of data. The excitation of EM waves through electromechanical couplings, such as the piezoelectric effect in non-centrosymmetric materials, was systematically studied by Mindlin. In contrast, this paper investigates the excitation of EM waves induced by flexoelectricity in dielectric plates, a mechanism applicable to all materials. By incorporating strain gradient, flexoelectric, and EM effects, we extend Hamilton’s principle to derive the governing equations and corresponding boundary/continuity conditions for flexo-electromagnetism. Using this newly developed theoretical framework, we analyze the vibration and EM radiation behavior of an infinite flexoelectric plate in simple thickness modes. Unlike piezoelectric mechanisms, our study reveals that EM waves can be effectively excited by thickness-shear (associated with u1) and thickness-twist (associated with u2) modes, while the thickness-stretch (associated with u3) mode fails to generate EM radiation. Numerical results demonstrate that a flexoelectric plate with thickness-shear modes can excite significant electric and magnetic fields, with observable radiation power. For example, under a strain of 10-5 in a plate of 40 µm thickness, the radiated power reaches approximately 41 W/m2, above the power density of mobile communication base stations in China (<40 W/m2). This provides the telecommunication industry with novel insights into the design of nanomechanical magnetoelectric antennas.
A comprehensive review on advancements in water-lubricated bearings: Surface texture, tribological performance, and thermal effects
Authors: Ohdar Sumit Kumar , Behera Suraj Kumar
Published: January 2025

This review paper digs into the multidimensional aspects of water-lubricated bearings, emphasizing surface texture, tribological performance, and thermal effects. It looks closely at water-lubricated bearings, widely recognized as accessible and eco-friendly. In particular, the impact of surface texture on wear, friction, and overall performance are investigated. The tribological properties are analyzed to comprehend the link between bearing surfaces and lubricating water, accentuating friction, and wear reduction advancements. The review also explores the different materials used in water-lubricated bearings, assessing their chemical and mechanical attributes to determine the optimal superior composite for better performance and long-lasting. To apprehend the effects of temperature changes on performance and material integrity, the thermal behavior of these bearings is also meticulously inspected. This comprehensive review attempts to clearly understand the contemporary state of affairs and potential future directions in developing exceptional-performance water-lubricated bearings.
Tapping into teacher feedback in digital storytelling: Learning outcomes, emotions, and perceptions
Authors: Purnomo Cynthia Ayu , Chen Hsieh-Jun
Published: January 2025

With the existing research gap regarding the validation of the effects of teacher feedback, the relatively limited exploration of the correlation between teacher feedback and speaking performance, and the inadequate examination of emotions, this study endeavored to investigate the efficacy of teacher feedback in digital storytelling among learners of English as a foreign language (EFL). Emphasis is placed on speaking performance, emotions, perceptions among high and low achievers, and teacher reflections. Employing a mixed-methods approach, the research design incorporated data from pre-/post-tests of digital storytelling, student responses to an emotion questionnaire, student perceptions of teacher feedback, and teacher reflections on feedback practices. The findings demonstrated that teacher feedback not only significantly impacted students’ speaking performances throughout the digital storytelling process but also played a key role in regulating their emotions. Both high and low achievers exhibited predominantly positive emotions during digital storytelling and creation. However, high achievers demonstrated greater sensitivity to competitive pressures, contributing to slight differences in emotional experiences between the two groups. Furthermore, low achievers displayed a greater desire for feedback and derived more substantial benefits, particularly in the areas of image selection and arrangement. Based on teacher reflections, feedback types were focused on adjusting chosen storybooks (including storyline development and image/illustration design), establishing fulfillment criteria, ensuring equitable distribution of work and presentation within each group, and addressing pronunciation concerns.
Family carers and the provision of person-centred dementia care for activities of daily living
Authors: Carparelli Chiara , Oyebode Jan R , Riley Gerard A
Published: January 2025

Care provided by family members is not always consistent with the principles of person-centred dementia care (PCDC) and interventions to improve the quality of care are needed. A good foundation for the development of such interventions is provided by an understanding of how good and poor care practices are manifested in everyday care, and of the challenges to providing good quality care. Thirty people providing care to a spouse or partner with dementia were interviewed, and asked to describe examples of the care they provided for activities of daily living and the challenges to providing good quality care. Framework analysis was used to guide and interpret the interviews. Interpretation was guided by the VIPS conceptualisation of PCDC which incorporates the principles of Valuing, Individual, Perspective, and Social. The quality of care varied, and examples of good and poor care practices are described. The principles of PCDC were sometimes in conflict with one another and with other considerations, such as personal safety and the wellbeing of the carer. Participants were often faced with challenging decisions in which they had to weigh up these different issues. To be credible, guidance for carers need to reflect the complexity of the issues they face.
Does the “National Civilized City” increase land revenue? An empirical inquiry into China’s Prefecture-level cities
Authors: Wu Weijia , Liu Weixing
Published: January 2025

With the continuous development of urbanization in China, land revenue has become one of the main sources of revenue for local governments and played a significant role in economic development. Existing research has discussed the causes of land revenue or land finance from multiple perspectives. However, little is known about how political incentives such as top-down evaluations and commendations of city branding affect local land income. Based on the quasi experiment of obtaining the branding title of “National Civilized City,” this study employs staggered difference-in-differences to analyze the impact of the “National Civilized City” on local land revenue. Meanwhile, using a series of empirical analyses to ensure the robustness of the results. The empirical findings indicate that obtaining the “National Civilized City” branding will significantly increase local land revenue. The “National Civilized City” branding’s influence on land revenue will be moderated by real estate investment and social consumption. Specifically, when the amount of real estate investment and social consumption is higher, it will significantly enhance the impact of “National Civilized City” on local land revenue; when the real estate investment and social consumption at low level, it will significantly reduce the impact of “National Civilized City” on local land revenue.
Combining Action Research With Design Science as a Qualitative Research Methodology. An Application to Service (Operations) Management Research
Authors: Castro Valeria de , Martín-Peña María Luz , Martínez Esperanza Marcos , Salgado Maricela
Published: January 2025

Services currently represent most of the present economic activity. Research methodologies that allow organisations to solve their service operations-related problems while facilitating the design and creation of new artefacts with which to support the complex reality that services represent are required. Action Research (AR) is a methodology that has proved to be effective in organisations by solving real problems. This methodology can be enriched with others that provide practical and usable solutions. This paper presents Design Science Action Research (DSAR), a methodology that combines AR and Design Service Research (DSR) and examines its usefulness for Service (Operation) Management research by supporting the development of new artefacts acting in the real context of organisations. DSAR has been applied in a case study concerning a service company that is addressing the transformation of its service design and delivery processes. We contribute to the literature on AR and DSR with a new methodology resulting from the combination of both approaches that can be used in order to conduct SOM research. We provide step-by-step guidance on its application and discuss the main advantages of using this combination in a real case.
Territoriality and the politics of ancestrality: Meaning, scope, and depth of Indigenous struggles in the North of Chile
Authors: Cornejo Puschner Sascha Miguel
Published: January 2025

This article explores the complex interplay between territory, culture, politics, and livelihoods through the ancestral land claims of the Indigenous Aymara community of Chumiza in northern Chile. The Aymara community's struggle for meaning, life, and identity is deeply rooted in a historical context in which the question of territory is inherently cultural, political, and economic. For the Aymara people, the concepts of territory and environment are not just abstract notions but deeply intertwined with their historical awareness, cultural traditions, and their profound relationship with the land. Understanding how land and territory are defined, planned, and regulated is therefore crucial to comprehending their production through state policies and institutional frameworks. These diverse interpretations and definitions, shaped by the state, international law, and Indigenous communities, often clash. The Aymara community's territorial reclamation reconfigures these legal, political, and symbolic dimensions to re-establish territory as a distinct entity, underpinned by a specific historical connection between a people and their land, encapsulated in the notion of ancestrality.
Successful use of gadolinium contrast medium for flow-diverter stent placement in a patient with hypersensitivity to iodinated contrast: A case report
Authors: Saito Shoji , Hasegawa Hitoshi , Takahashi Hayate , Ichinohe Mamoru , Seto Hiroki , Mizuta Ryosuke , Kawabe Keita , Sano Masakazu , Oishi Makoto
Published: January 2025

Gadolinium contrast medium can serve as an alternative to iodinated contrast medium when the latter is unsuitable. In this report, we describe a case of a carotid–ophthalmic aneurysm in which angiograms were obtained using gadolinium contrast medium for flow-diverter stent placement due to the patient’s history of bronchial asthma and hypersensitivity reactions to iodinated contrast medium. To enhance the visibility of gadolinium contrast medium, which typically provides lower contrast compared to iodinated contrast medium, we employed a contrast-enhancing and noise-reducing protocol on our image-guided therapy system. We performed catheterization and established working angles guided by a roadmap based on previous magnetic resonance angiography, the position of which was adjusted using cone-beam computed tomography performed before the intervention. This approach helped reduce the amount of contrast medium required. The procedure was successful and did not induce hypersensitivity reactions, morbidity, or mortality. Thus, the efficacy of the contrast-enhancing imaging protocol and the magnetic resonance angiography-based roadmap was confirmed. Measures must be taken to address gadolinium contrast medium-specific adverse events, limitations on the amount of contrast medium used, and the issue of low-contrast angiograms.
Definitions of Hemodynamic Instability Related to Renal Replacement Therapy in Critically Ill Patients: A Systematic Review Protocol
Authors: Wang Jean Zhuo , Sikora Lindsey , Farrell Peter , Hiremath Swapnil , Clark Edward G.
Published: January 2025

Background:

Hemodynamic instability related to renal replacement therapy (HIRRT) is a common complication affecting critically ill patients that require renal replacement therapy (RRT). There is currently no consensus regarding the definition of HIRRT in critically ill patients. In this context, the impacts of HIRRT on clinical outcomes such as mortality or renal recovery in critically ill patients are unclear.

Objective:

The primary objective of this proposed systematic review is to evaluate the association between HIRRT and clinical outcomes, as reported within randomized control trials in the literature. The secondary objective of this systematic review is to compare rates of HIRRT, according to various definitions used by randomized controlled trials, across different RRT modalities used to treat critically ill patients, with the goal of paving the way toward a common definition of HIRRT for future research.

Design:

Systematic review and meta-analysis

Measurements:

The rates of HIRRT, mortality, and renal recovery will be reported according to each definition of HIRRT

Patients:

Critically-ill adults with acute kidney injury admitted to intensive care units

Methods:

The search strategy will be developed to identify articles in Medline, MEDLINE In-Process, EMBASE, and Cochrane CENTRAL Registry. We will include randomized control trials examining renal replacement therapy in critically ill patients. This will include intermittent hemodialysis (iHD), all forms of prolonged intermittent RRT (PIRRT), and continuous renal replacement therapy (CRRT). Only articles that report a definition of HIRRT and the rates of HIRRT will be included in our analysis. Two reviewers will independently screen all articles for inclusion and exclusion. Data extraction and quality assessment will be also performed in duplicate. All disagreements will be resolved through discussion or a third reviewer.

Limitations:

The heterogeneity in the definitions of HIRRT and outcome reporting may limit the ability to perform meta-analysis and perform comparisons in the rates of HIRRT between RRT modalities.

Conclusions:

This systematic review aims to assess the association between HIRRT and important clinical outcomes. In doing so, we will identify definitions of HIRRT within the current literature and the rates of HIRRT associated with these definitions. HIRRT can result in early discontinuation of dialysis, organ injury from hypoperfusion, and may negatively impact mortality and renal recovery in critically ill patients. This systematic review will synthesize the impact and frequency of HIRRT reported in the literature and, in doing so, may help determine the extent to which common definitions of HIRRT might be recommended for standardized use in future research related to HIRRT.

Systematic Review Registration:

PROSPERO registration number: CRD42023396550.
Consumer opinion on the use of machine learning in healthcare settings: A qualitative systematic review
Authors: Stephens Jacqueline H , Northcott Celine , Poirier Brianna F , Lewis Trent
Published: January 2025

Introduction

Given the increasing number of artificial intelligence and machine learning (AI/ML) tools in healthcare, we aimed to gain an understanding of consumer perspectives on the use of AI/ML tools for healthcare diagnostics.

Methods

We conducted a qualitative systematic review, following established standardized methods, of the existing literature indexed in the following databases up to 4 April 2022: OVID MEDLINE, OVID EMBASE, Scopus and Web of Science.

Results

Fourteen studies were identified as appropriate for inclusion in the meta-synthesis and systematic review. Most studies ( n = 12) were conducted in high-income countries, with data extracted from both mixed methods (42.9%) and qualitative (57.1%) studies. The meta-synthesis identified four overarching themes across the included studies: (1) Trust, fear, and uncertainty; (2) Data privacy and ML governance; (3) Impact on healthcare delivery and access; and (4) Consumers want to be engaged.

Conclusion

The current evidence demonstrates consumers’ understandings of AI/ML for medical diagnosis are complex. Consumers express a complex combination of both hesitancy and support towards AI/ML in healthcare diagnosis. Importantly, their views of the use of AI/ML in medical diagnosis are influenced by the perceived trustworthiness of their healthcare providers who use these AI/ML tools. Consumers recognize the potential for AI/ML tools to improve diagnostic accuracy, efficiency and access, and express a strong interest to be engaged in the development and implementation process of AI/ML into routine healthcare.
Impact of digital device utilization on public health surveillance to enhance city resilience during the public health emergency response: A case study of SARS-CoV-2 response in Thailand (2020–2023)
Authors: Chutarong Watcharaporn , Thammalikhit Roongaroon , Kraiklang Rungwasun , Sawangwong Anurak , Saechang Orachorn , Guo Yuqian , Zhang Weiwen
Published: January 2025

Objective

This study aims to examine the impact of digital devices on public health surveillance, the impact of public health surveillance on resilient cities, and the impact of digital devices on resilient cities.

Methods

Questionnaires were issued to residents of Thailand during the severe acute respiratory syndrome coronavirus 2 response (2020–2023). In total, 1025 valid responses were recorded from Thai nationals and expatriates. Exploratory factor analysis, confirmatory factor analysis, and structural equation modeling were used to assess the model through IBM SPSS 23 and AMOS 23.

Results

Digital devices have a strong positive direct effect on public health surveillance ( β = 0.73, p ≤ .001), public health surveillance has a strong positive direct effect on resilient cities ( β = 0.79, p ≤ .001), and digital devices have a low positive direct and a moderate indirect effect on resilient cities ( β = 0.13, p ≤ .001, and β = 0.58, p ≤ .001, respectively). The use of digital devices in data collection, analysis, and dissemination, positively impacted public health surveillance, considering five dimensions: medical and vaccine, individual, health care, epidemiological, and disease. Meanwhile, using digital devices in public health surveillance positively impacted the resilience of cities, considering three dimensions: socioeconomic, institutional, and living. The causal relationship model of the digital device utilization on public health surveillance enhancing the resilience of the cities met all the necessary criteria: X2/ df = 2.802, comparative fit index = 0.953, goodness of fit index = 0.901, normed fit index = 0.935, Tucker–Lewis index = 0.935, root mean square of approximation = 0.048, and root of mean square residual = 0.043. This indicates the model fits the empirical data.

Conclusion

Digital devices are vital tools in collecting, analyzing, and disseminating public health surveillance-related data during the public health emergency. This, in turn, can improve medical and vaccine, individual, health care, epidemiological, and disease surveillance, and also enhance cities’ socioeconomic, institutional, and living resilience.
The causal effect of Internet use on rural middle-aged and older adults’ depression: A propensity score matching analysis
Authors: Ma Junqi
Published: January 2025

Objective

Depression among older adults is increasingly becoming a global public health issue. Along with the rapid development of digital information technology, the Internet has profoundly changed the lifestyle of older adults. However, few studies have focused on the mental health of rural middle-aged and older adult populations, and this study aims to explore the impact of Internet use on depressive symptoms among rural middle-aged and older adults.

Methods

Our study is based on 10,946 Chinese rural participants aged 45 and above in the 2018 China Health and Retirement Longitudinal Study (CHARLS). Depression is measured by a 10-item Centre for Epidemiologic Studies (CES-D10), and multiple linear regression and the propensity score matching (PSM) method are used to examine the effect of Internet use on depression in Chinese rural middle-aged and older adults.

Results

Internet use significantly reduced depression in rural middle-aged and older adults. The mechanism was that Internet use improved mental health by improving social interaction and enhancing social support. Furthermore, desk computer, laptop computer, and cellphone use were all significantly associated with lower depression scores compared to non-Internet users. And the more the content of Internet use, the significantly lower the level of depression in rural middle-aged and older adults. Heterogeneity analysis showed that Internet use reduced depression more pronounced in the groups of males, those in elementary and secondary education, low-medium income, and aged under 75.

Conclusion

The paper confirms that Internet use significantly reduces depression, with social interaction and social support playing a mediating role. The results of the study show that strengthening rural Internet infrastructure can promote healthy aging in rural areas.
The Training of Rhythm Skills and Executive Function: A Systematic Review
Authors: Ahokas J. Riikka , Saarikallio Suvi , Welch Graham , Goswami Usha , Parviainen Tiina
Published: January 2025

Objective

The focus of this study is on rhythm-elicited movement and its impacts on executive function. The main aim of this review was to identify previous, controlled intervention research on this topic, and to study the effectiveness of the included research interventions. We hypothesized we would find research supporting the alleged positive impact of rhythm training on cognition.

Methods

Systematic literature searches were performed in Web of Science (WoS), PubMed, Education Resources Information Center (ERIC), and APA PsycArticles and PsycInfo databases from 2000 to May 2022. The selected studies were evaluated for methodological quality using the modified Downs and Black checklist.

Results

The eligibility criteria of this review identified populations from preschool to old age and included research interventions that could be defined as “training music rhythm skills”. Only studies with active control training using executive function (EF) measures, published between 2000 and 2022, peer reviewed, and written in English were included. From the initial result of a total of 15,677 identified records, 10 research reports met the eligibility criteria and were included in the final synthesis of this systematic review. The mean methodological quality score of these records was 24.7 out of 28 on the Downs and Black checklist. Five of the included studies provided statistically significant results in regard to our hypothesis.

Conclusion

During our targeted review period of 2025–2022, there is a fundamental paucity of studies aiming at testing the benefits of rhythm training on EF.
Relationship Between Personality Traits and Emotional Impacts of the COVID-19 Pandemic on Canadian Emerging Adults
Authors: Moore Mackenzie , Yunus Fakir Md , Thompson Kara , Keough Matthew , Krank Marvin , Conrod Patricia J. , Stewart Sherry H.
Published: January 2025

We assessed whether traits from the four-factor vulnerability model for substance misuse are associated with the content of emotional descriptions given by Canadian university students of the impact of the COVID-19 pandemic on their lives. Personality traits were measured in 1185 first- and second-year undergraduates (mean age = 19.11 years; 79% female). Written responses to “Tell us about how the COVID-19 pandemic is impacting your life” were coded using Linguistic Inquiry and Word Count software. Negative binomial analyses were run to examine links between traits and emotion word types used in responses. Anxiety sensitivity was associated with increased use of anxiety words; hopelessness was associated with increased use of negative emotion and sadness words, and decreased use of positive emotion words; and impulsivity was associated with increased use of anger words. Findings have implications for personality-tailored interventions for students vulnerable to distress resulting from highly stressful situations such as pandemics.
Investigating Inpatient Acceptance of a Unique Telemedicine Service Trialled in the Acute Ward in Rural Australia
Authors: Reid Carol Joy , Church Catherine
Published: January 2025

This study investigated inpatient acceptance of a unique telemedicine clinical service piloted from December 2022 to June 2025 in 3 rural acute wards in Victoria, Australia. The use of virtual care was complementary to the visiting general practitioner (GP) model common in rural hospitals. The qualitative study employed 3 researcher-designed questions: Did you feel safe using the virtual healthcare doctor?; Did you feel the care you experienced was as it should be? And; If you were offered virtual care again, would you use it? Participants ( n = 38) were predominantly over 65 years (95%). Findings describe safe care as being able to understand the virtual doctor, be listened to, and ask questions. Participants affirmed that the care experienced was helpful due to prompt in-hospital clinical interventions organized by the virtual weekend coverage. Most were first-time users of virtual care and recognized that rural doctors need a break. Barriers to acceptance of the service were concerns about the loss of in-person visits with their local doctor and that virtual care could replace local GPs.
Earth at 1.5 degrees warming: How vulnerable is Antarctica?
Authors: Fricker Helen Amanda , Freer Bryony Isabella Diana , Galton-Fenzi Benjamin Keith , Walker Catherine Colello
Published: January 2025

The Antarctic Ice Sheet is integral to Earth's climate system, influencing global energy and water cycles, and ecosystems. Enough ice is stored in regions most vulnerable to rapid retreat to cause sea levels to rise by ∼15 m if they completely melted, making their stability a key concern. As global temperatures approach and look to surpass 1.5°C (Box 1) above pre-industrial levels, Antarctic ice loss is accelerating, with the potential to trigger significant climatic shifts. Yet, the complex processes governing its stability in a warming climate remain insufficiently understood, limiting society's preparedness. Given the accelerating rate of ice loss and its profound implications, urgent and coordinated efforts to reduce uncertainties around future Antarctic ice changes are essential for policymakers and society, as the resulting melt will have global consequences, especially for coastal areas already facing rising flood risks.
Measurable residual disease and posttransplantation gilteritinib maintenance for patients with FLT3-ITD-mutated AML
Authors: Levis Mark J. , Hamadani Mehdi , Logan Brent R. , Jones Richard J. , Singh Anurag K , Litzow Mark R , Wingard John R. , Papadopoulos Esperanza B. , Perl Alexander E. , Soiffer Robert J. , Ustun Celalettin , Ueda Oshima Masumi , Uy Geoffrey L , Waller Edmund K. , Vasu Sumithira , Solh Melhem M , Mishra Asmita , Muffly Lori , Kim Hee-Je , Stelljes Matthias , Najima Yuho , Onozawa Masahiro , Thomson Kirsty J , Nagler Arnon , Wei Andrew H , Marcucci Guido , Chen Caroline , Hasabou Nahla , Rosales Matt , Hill Jason E. , Gill Stanley C. , Nuthethi Rishita , King Denise , Mendizabal Adam M , Devine Steven M. , Horowitz Mary M , Chen Yi-Bin
Published: January 2025

BMT CTN 1506 ("MORPHO"; NCT02997202) was a randomized phase 3 study of gilteritinib compared to placebo as maintenance therapy after hematopoietic stem cell transplantation (HCT) for patients with FLT3-ITD-mutated acute myeloid leukemia (AML). A key secondary endpoint was to determine the impact on survival of pre- and/or post-HCT measurable residual disease (MRD), as determined using a highly sensitive assay for FLT3-ITD mutations. Generally, gilteritinib maintenance therapy was associated with improved relapse-free survival (RFS) for participants with detectable peri-HCT MRD, whereas no benefit was evident for those lacking detectable MRD. We conducted a post-hoc analysis of the data and found that the level of MRD detected with this approach correlated remarkably with RFS and relapse risk, and that MRD detectable at any level negatively impacted RFS. In the placebo arm, 42.2% of participants with detectable FLT3-ITD MRD relapsed compared to 13.4% of those without detectable MRD. We found that 14.8% of participants had multiple FLT3-ITD clones detected as MRD and had worse survival irrespective of treatment arm. Finally, we examined the kinetics of FLT3-ITD clonal relapse or eradication and found that participants on the placebo arm with detectable MRD relapsed rapidly after HCT, often within a few weeks. MRD-positive participants on the gilteritinib arm relapsed either with FLT3 wild type clones (as assessed by capillary electrophoresis), after cessation of gilteritinib with persistent MRD, or on progression of multi-clonal disease. These data demonstrate the potential of using FLT3-ITD MRD to guide therapy with gilteritinib for this subtype of AML.
Selenoprotein-Mediated Redox Regulation Shapes the Cell Fate of HSCs and Mature Lineages
Authors: Aoyama Yumi , Yamazaki Hiromi , Nishimua Koutarou , Nomura Masaki , Shigehiro Tsukasa , Suzuki Takafumi , Zang Weijia , Tatara Yota , Ito Hiromi , Hayashi Yasutaka , Koike Yui , Fukumoto Miki , Tanaka Atsushi , Zhang Yifan , Saika Wataru , Hasegawa Chihiro , Kasai Shuya , Kong Yingyi , Minakuchi Yohei , Itoh Ken , Yamamoto Masayuki , Toyokuni Shinya , Toyoda Atsushi , Ikawa Tomokatsu , Takaori-Kondo Akifumi , Inoue Daichi
Published: January 2025

The maintenance of cellular redox balance is crucial for cell survival and homeostasis and is disrupted with aging. Selenoproteins, comprising essential antioxidant enzymes, raise intriguing questions about their involvement in hematopoietic aging and potential reversibility. Motivated by our observation of mRNA downregulation of key antioxidant selenoproteins in aged human hematopoietic stem cells (HSCs) and previous findings of increased lipid peroxidation in aged hematopoiesis, we employed tRNASec gene (Trsp) knockout (KO) mouse model to simulate disrupted selenoprotein synthesis. This revealed insights into the protective roles of selenoproteins in preserving HSC stemness and B-lineage maturation, despite negligible effects on myeloid cells. Notably, Trsp KO exhibited B lymphocytopenia and reduced HSCs' self-renewal capacity, recapitulating certain aspects of aged phenotypes, along with the upregulation of aging-related genes in both HSCs and pre-B cells. While Trsp KO activated an antioxidant response transcription factor NRF2, we delineated a lineage-dependent phenotype driven by lipid peroxidation, which was exacerbated with aging yet ameliorated by ferroptosis inhibitors such as vitamin E. Interestingly, the myeloid genes were ectopically expressed in pre-B cells of Trsp KO mice, and KO pro-B/pre-B cells displayed differentiation potential toward functional CD11b+ fraction in the transplant model, suggesting that disrupted selenoprotein synthesis induces the potential of B-to-myeloid switch. Given the similarities between the KO model and aged wild-type mice, including ferroptosis vulnerability, impaired HSC self-renewal and B-lineage maturation, and characteristic lineage switch, our findings underscore the critical role of selenoprotein-mediated redox regulation in maintaining balanced hematopoiesis and suggest the preventive potential of selenoproteins against aging-related alterations.
Dual ASXL1 and CSF3R mutations drive myeloid biased stem cell expansion and enhance neutrophil differentiation
Authors: Darmusey Lucie , Bagley Anna J , Nguyen Thai T , Carlson Hanqian L , Blaylock Hunter , Shrestha Shawn B , Pang Amara , Tauchmann Samantha , Taylor Sarah C , Foley Amy C , Niño Katia E , Pietras Eric M , Braun Theodore P , Maxson Julia E.
Published: January 2025

Mutations in the epigenetic regulator Additional Sex Combs-Like 1 (ASXL1) are frequently observed in chronic neutrophilic leukemia (CNL). CNL is a myeloproliferative neoplasm (MPN) driven by activating mutations in the Colony Stimulating Factor 3 Receptor (CSF3R), which cause excessive neutrophil production. Despite the high rates of co-occurrence, the interplay between ASXL1 and CSF3R mutations in hematopoiesis and leukemia remains poorly understood. Here, we present a new mouse model with both Asxl1Y588X and Csf3rT621I mutations, which recapitulates features of human MPNs. Csf3r-mutant mice exhibit an age-associated depletion of hematopoietic stem cells, which is tempered by adding of Asxl1Y588X. This combination of mutations causes an expansion of myeloid-biased long-term hematopoietic stem cells. As the mice age, they develop neutrophilia, but leukemia is rare, suggesting additional mutations may be required for transformation. Using models of myeloid differentiation, we find that Asxl1 truncation enhances CSF3RT618I-driven neutrophil differentiation, activating inflammatory pathways associated with mature myeloid cell production. Moreover, cells with both mutations have increased H3K4me1 at neutrophil-associated enhancers. Mutant ASXL1 is known to decrease the genome-wide abundance of the repressive histone mark H2AK119ub. While we see the expected decrease in H2AK119ub in Asxl1-mutant cells, this effect is reversed when CSF3R is also mutated, suggesting a complex interplay between these mutations in regulating chromatin dynamics during hematopoiesis. Our findings highlight context-dependent effects of ASXL1 mutation in myeloid disorders and provide insights into the mechanisms underlying neutrophil differentiation in ASXL1 and CSF3R dual mutant MPN.
Pre-treatment Pulmonary Function Testing Has Limited Utility In B-cell Lymphoma Treated with CD19 CAR T-cells
Authors: Sdayoor Inbal , Shouval Roni , Fried Shalev , Marcus Ronit , Danylesko Ivetta , Yerushalmi Ronit , Shem-Tov Noga , Itzhaki Orit , Jacoby Elad , Kedmi Meirav , Nagler Arnon , Shimoni Avichai , Segel Michael J , Avigdor Abraham
Published: January 2025

Pulmonary function tests (PFT) are recommended for hematopoietic cell transplantation (HCT) evaluation. However, their prognostic value in chimeric antigen receptor T-cell (CAR-T) therapy remains unclear. We assessed the predictive significance of PFTs and pulmonary comorbidity classifications, per the Hematopoietic Cell Transplantation-Comorbidity Index (HCT-CI), in B-cell lymphoma patients undergoing autologous CD19-CAR-T therapy. Single-center retrospective analysis encompassing 192 patients with relapsed/refractory (R/R) B-cell lymphoma, treated with commercial and point-of-care CD19-directed CAR-T therapy. Pre-therapy PFT were conducted, and patients were stratified into 3 HCT-CI-based pulmonary comorbidity grades, utilizing forced expiratory volume in 1 second (FEV1) and single-breath diffusing capacity for carbon monoxide (DLCO). Outcomes and toxicities were evaluated using univariate and multivariable Cox regression, logistic regression, Kaplan-Meier method, and spline models. Pulmonary comorbidity measures were not correlated with overall response rates or immune-toxicities, including cytokine release syndrome grade>2 and immune effector cell-associated neurotoxicity grade>2. Categorical FEV1, DLCO, and pulmonary comorbidity level did not correlate with overall survival (p=0.3, p=0.4, p=0.6, respectively) or progression free survival (PFS) (p=0.058, p>0.9, p=0.2, respectively). FEV1 as continuous measure was associated with reduced PFS in a multivariable model (HR 0.87 [95% CI 0.78-0.96], p=0.007). Spline modeling demonstrated a linear correlation between FEV1 and PFS. Categorical FEV1, DLCO, and pulmonary comorbidity level failed to predict therapy efficacy or toxicity. FEV1 as continuous measure was the sole PFT measure associated with PFS, independent of OS or severe toxicities.
Causal models and prediction in cell line perturbation experiments
Authors: Long James P. , Yang Yumeng , Shimizu Shohei , Pham Thong , Do Kim-Anh
Published: January 2025

In cell line perturbation experiments, a collection of cells is perturbed with external agents and responses such as protein expression measured. Due to cost constraints, only a small fraction of all possible perturbations can be tested in vitro. This has led to the development of computational models that can predict cellular responses to perturbations in silico. A central challenge for these models is to predict the effect of new, previously untested perturbations that were not used in the training data. Here we propose causal structural equations for modeling how perturbations effect cells. From this model, we derive two estimators for predicting responses: a Linear Regression (LR) estimator and a causal structure learning estimator that we term Causal Structure Regression (CSR). The CSR estimator requires more assumptions than LR, but can predict the effects of drugs that were not applied in the training data. Next we present Cellbox, a recently proposed system of ordinary differential equations (ODEs) based model that obtained the best prediction performance on a Melanoma cell line perturbation data set (Yuan et al. in Cell Syst 12:128–140, 2021). We derive analytic results that show a close connection between CSR and Cellbox, providing a new causal interpretation for the Cellbox model. We compare LR and CSR/Cellbox in simulations, highlighting the strengths and weaknesses of the two approaches. Finally we compare the performance of LR and CSR/Cellbox on the benchmark Melanoma data set. We find that the LR model has comparable or slightly better performance than Cellbox.
Intranasal racemic ketamine maintenance therapy for patients with treatment-resistant depression: a naturalistic feasibility study
Authors: Halpape Katelyn , Pashovitz Raelle , Wanson Annabelle , Hooper Monika , Peters Evyn M.
Published: January 2025

Background

Ketamine is a promising therapy for treatment-resistant depression due to its rapid onset, although benefits are often transitory, with patients needing maintenance therapy to prevent relapse. Most data supporting ketamine for treatment-resistant depression refers to the intravenous route of administration, leaving alternative routes lacking in data, especially as maintenance regimens. Moreover, the safety of ketamine maintenance therapy is poorly defined. This report aims to describe and evaluate a novel hospital-to-outpatient intranasal racemic ketamine maintenance therapy program.

Methods

This was an observational program evaluation study. Participants were adult inpatients with treatment-resistant depression who had been successfully treated with intranasal racemic ketamine in hospital and were being referred for outpatient maintenance therapy with an intranasal racemic ketamine spray, administered at a specialized community treatment centre. Effectiveness was assessed with the Self-Report Quick Inventory of Depressive Symptomatology, the Quality of Life Scale, and the Clinical Global Impression-Improvement scale.

Results

Five patients were enrolled, completing up to 14 treatment sessions over 192 days. The mean dose administered throughout treatment was 220 mg (100 to 400 mg). All patients had decreased (or stable) depressive symptoms and increased (or stable) quality of life. There were no serious adverse events or discontinuations due to adverse effects. Reported adverse effects included anxiety and nausea. Slight blood pressure increases were seen during treatment, none of which required intervention.

Conclusions

Intranasal racemic ketamine maintenance therapy for treatment-resistant depression appeared to be feasible and well tolerated, although effectiveness conclusions cannot be drawn from this small pilot study. Further investigations regarding the safety and effectiveness of intranasal ketamine maintenance therapy are warranted.
Practice of self-medication to manage oral health issues in a community setting of Nepal
Authors: Shrestha Ashish , Bhagat Tarakant , Agrawal Santosh Kumari , Gautam Ujwal , Joshi Naresh Prasad
Published: January 2025

Background

Self-medication has been defined as the practice of self-diagnosis and medication use without seeking professional healthcare advice. Its prevalence for alleviating dental problems in Nepali communities has not been explored. This study was conducted to assess self-medication for oral health problems in a community setting in Nepal.

Methods

A community-based cross-sectional study was conducted in two conveniently selected wards of Baraha Municipality of Sunsari district in August 2021 using a pre-validated questionnaire in the Nepali language. The prevalence of self-medication for oral health problems was assessed. The chi-square and Mann-Whitney U tests were used to check its association with demographic variables.

Results

The prevalence of self-medication was found to be 43.3%. The most common health problem leading to self-medication was toothache (78.5%). Around half of the respondents (55.1%) replied achieving temporary relief after its use while around a quarter (25.1%) thought that self-medication was effective in taking care of their problems. Three-quarters of the respondents (75.7%) knew that they had to visit a dentist if their problems persisted. The annual family income was significantly associated with the practice of self-medication for oral health problems. (p = 0.013)

Conclusion

Self-medication was found to be frequently utilized by the people of Baraha municipality with almost every second person with oral health problems reporting using it to solve their problems. This phenomenon is disproportionately seen in those with lower economic status.

Clinical trial number

Not applicable.
A hyperspectral open-source imager (HOSI)
Authors: Troscianko Jolyon
Published: January 2025

Background

The spatial and spectral properties of the light environment underpin many aspects of animal behaviour, ecology and evolution, and quantifying this information is crucial in fields ranging from optical physics, agriculture/plant sciences, human psychophysics, food science, architecture and materials sciences. The escalating threat of artificial light at night (ALAN) presents unique challenges for measuring the visual impact of light pollution, requiring measurement at low light levels across the human-visible and ultraviolet ranges, across all viewing angles, and often with high within-scene contrast.

Results

Here, I present a hyperspectral open-source imager (HOSI), an innovative and low-cost solution for collecting full-field hyperspectral data. The system uses a Hamamatsu C12880MA micro spectrometer to take single-point measurements, together with a motorised gimbal for spatial control. The hardware uses off-the-shelf components and 3D printed parts, costing around £350 in total. The system can run directly from a computer or smartphone with a graphical user interface, making it highly portable and user-friendly. The HOSI system can take panoramic hyperspectral images that meet the difficult requirements of ALAN research, sensitive to low light around 0.001 cd.m−2, across 320–880 nm range with spectral resolution of ~ 9 nm (FWHM) and spatial resolution of ~ 2 cycles per degree. The independent exposure of each pixel also allows for an extremely wide dynamic range that can encompass typical natural and artificially illuminated scenes, with sample night-time scans achieving full-spectrum peak-to-peak dynamic ranges of > 50,000:1.

Conclusions

This system’s adaptability, cost-effectiveness and open-source nature position it as a valuable tool for researchers investigating the complex relationships between light, environment, behaviour, ecology and biodiversity, with further potential uses in many other fields.
Dystonia caused by ANO3 variants is due to attenuated Ca2+ influx by ORAI1
Authors: Ousingsawat Jiraporn , Talbi Khaoula , Gómez-Martín Hilario , Koy Anne , Fernández-Jaén Alberto , Tekgül Hasan , Serdaroğlu Esra , Ortigoza-Escobar Juan Darío , Schreiber Rainer , Kunzelmann Karl
Published: January 2025

Background

Dystonia is a common neurological hyperkinetic movement disorder that can be caused by mutations in anoctamin 3 (ANO3, TMEM16C), a phospholipid scramblase and ion channel. We previously reported patients that were heterozygous for the ANO3 variants S651N, V561L, A599D and S651N, which cause dystonia by unknown mechanisms.

Methods

We applied electrophysiology, Ca2+ measurements and cell biological methods to analyze the molecular mechanisms that lead to aberrant intracellular Ca2+ signals and defective activation of K+ channels in patients heterozygous for the ANO3 variants.

Results

Upon expression, emptying of the endoplasmic reticulum Ca2+ store (store release) and particularly store-operated Ca2+ entry (SOCE) were strongly inhibited, leading to impaired activation of KCa3.1 (KCNN) K+ channels, but not of Na+-activated K+ channels (KNa; SLO2). The data provide evidence for a strongly impaired expression of store-operated ORAI1 Ca2+ influx channels in the plasma membrane of cells expressing ANO3 variants.

Conclusions

Dysregulated Ca2+ signaling by ANO3 variants may impair the activation of K+ channels in striatal neurons of the brain, thereby causing dystonia. Furthermore, the data provide a first indication of a possible regulation of protein expression in the plasma membrane by ANO3, as has been described for other anoctamins.
Clinical efficacy and hemodynamic effects of levosimendan in cardiac surgery patients after surgery
Authors: Zhao Meiling , Hou Yunfeng , Yuan Meng , Ma Shuang , Yue Yifeng
Published: January 2025

Objective

To investigate the therapeutic effect of levosimendan on hemodynamics in patients undergoing major cardiac surgery and presenting with acute postoperative heart failure.

Methods

The subjects of the study were 160 patients with severe cardiac conditions who underwent surgery and had acute heart failure. Eighty cases each were assigned to the research and control groups using a random number table. Document the general patient data for each of the two groups; compare the clinical outcomes of the two groups. The hemodynamic states of the two groups were compared both before and after therapy. 48 h after surgery, echocardiography was performed in both groups to determine cardiac function. 48 h after surgery, N-terminal pro-brain B-type natriuretic peptide (NT-Pro-BNP) levels were compared between the two groups.

Results

The overall effective rate was significantly higher in the research group (92.5%) compared to the control group (76.25%, P < 0.05). Post-treatment, the research group demonstrated a significant reduction in CVP (9.25 ± 2.11 cmH2O vs. 11.36 ± 3.08 cmH2O, P < 0.001), heart rate (100.30 ± 8.69 bpm vs. 105.74 ± 7.69 bpm, P < 0.001), and lactic acid levels (1.68 ± 0.59 mmol/L vs. 2.69 ± 0.55 mmol/L, P < 0.001). The research group also showed improvements in SBP (117.23 ± 8.74 mmHg vs. 113.25 ± 7.55 mmHg, P = 0.002) and urine output (4.21 ± 1.76 mL/kg/h vs. 3.65 ± 1.23 mL/kg/h, P = 0.021). Cardiac function indicators 48 h after surgery indicated a higher LVEF (55.21 ± 8.04% vs. 47.18 ± 6.60%, P < 0.001) and lower LVEDVi and LVESVi in the research group (P < 0.001 for both). NT-Pro-BNP levels were significantly lower in the research group (6010.19 ± 1208.52 pg/mL vs. 9663.21 ± 2391.34 pg/mL, P < 0.001). The incidence of complications was lower in the research group (5% vs. 22.5%, P = 0.001).

Conclusion

Cardiac surgery patients are prone to complications with acute heart failure after surgery. Treatment with levosimendan can significantly improve clinical efficacy and reduce complications. It can also effectively improve patients' cardiac function and promote hemodynamic stability.