bluuebunny/crossref_metadata_2025 huggingface dataset:
Receipt and Timeliness of Mental Health Assessment, Treatment, and Acute Services Following Foster Care Entry
Authors: Swanson Ann S. , Font Sarah A.
Published: February 2025

Children often enter foster care (FC) with mental health (MH) concerns. Failure or delay in initiating treatment may result in overreliance on acute MH services. This report leverages 2010–2019 linked administrative child welfare and healthcare claims data for 13,562 Wisconsin children entering FC at ages 3–16 years to describe patterns of MH services during FC and examine how MH service use varies by demographic characteristics and maltreatment, FC, and MH histories. Two-thirds of children received MH assessment or treatment during FC, of whom 61% initiated services within 3 months of entry. Younger age, kinship care, and absence of MH history were negatively associated with onset of assessment and treatment. One in 7 children used acute MH services, with higher rates for Black children, adolescents, and youth in non-family settings. Timely MH assessment and treatment is important for foster children’s wellbeing, but current guidelines may lack accountability and monitoring mechanisms.
On the representation of fourth- and higher-order anisotropic elasticity tensors in generalized continuum models
Authors: d’Agostino Marco Valerio , Martin Robert J , Lewintan Peter , Bernardini Davide , Danescu Alexandre , Neff Patrizio
Published: February 2025

The classification of all fourth-order anisotropic tensor classes for classical linear elasticity is well known. In this article, we review the related problem of explicitly computing the dimension and the expressions of the elements belonging to these classes, and we extend this computation to fourth-order elasticity tensors acting on non-symmetric matrices. These tensors naturally appear in generalized continuum models. Based on tensor symmetrization, we provide the most general forms of these tensors for orthotropic, transversely isotropic, cubic, and isotropic materials. We present a self-contained discussion and provide detailed calculations for simple examples.
Irrigation Water Allocation for Enhanced Productivity and Economic Gain of Haricot Bean (Phaseolus vulgaris): A Study in Semi-arid Region of Ethiopia
Authors: Negash Tatek Wondimu , Tefera Abera Tesfaye , Ashami Bikila Gebeyehu , Gurms Dinku Aynalem , Worku Tigist , Tezera Ketema , Bayisa Gobena Dirirsa
Published: February 2025

This study aimed to evaluate the impact of varying irrigation levels on haricot bean yield and its related attributes. The experiment was conducted with five irrigation treatments: 60%, 80%, 100%, 120%, and 140% Manageable Allowed Depletion (MAD). The results revealed that the 80% MAD treatment produced the highest haricot bean yields, with 25.03, 26.07, and 23.46 qt/ha in 2016, 2017, and 2018, respectively, with no significant difference from the 100% MAD treatment. The lowest yields per hectare were observed under the 140% MAD treatment, with yields of 18.05, 18.6, and 15.45 qt/ha respectively, across the same years. The average maximum yield across all 3 years was 24.84 qt/ha for the 80% MAD treatment, whereas the minimum was 17.36 qt/ha for the 140% MAD treatment. Water productivity was lowest at 4.32 kg/mm for the 60% and 140% MAD treatments, while the highest values were recorded at 6.09 and 6.07 kg/mm for the 100% and 80% MAD treatments, respectively. Economically, the 80% MAD treatment yielded the highest economic gain of 30,193.1 birr/ha. Therefore, based on these findings, applying 80% MAD under furrow irrigation is recommended for optimal haricot bean production in the semi-arid regions of Ethiopia and similar environments.
Prevalence of Preoperative Anxiety and Associated Factors Among Surgical Patients: Systematic Review and Meta-Analysis in Ethiopia
Authors: Lami Magarsa , Negash Abraham , Dereje Jerman , Hiko Ahmed , Mesfin Sinetibeb , Gebreyesus Arsema , Belama Nano , Ahmed Omer Nesredin , Balis Bikila , Jibro Usmael
Published: February 2025

Background:

Preoperative anxiety is commonly characterized as a feeling of tension, apprehension, nervousness, distressing fear, and emotional discomfort preceding surgery. Different studies across the countries indicated an inconsistent prevalence of preoperative anxiety and its associated factors. Therefore, this study aimed to determine the pooled prevalence of preoperative anxiety and associated factors among surgical patients in Ethiopia.

Methods:

In this study, all observational study designs conducted in Ethiopia were included while studies that did not report our main outcome of interest or did not meet the quality criteria by Joanna Briggs Institute (JBI) critical appraisal techniques were excluded. Electronic databases (PubMed, SCOPUS, Web of Science Core Collection, CAB Abstract, EMBASE, and CINHAL (EBSCO)), Google Scholar, and lists of references were used to search works of literature in Ethiopia. STATA version 17 was used for analysis, and the odds ratios of the outcome variable were determined using the random-effects model. Computing values assessed heterogeneity among the studies for I2 and P-values. Also, sensitivity analysis and funnel plot were done to assess the stability of pooled values to outliers and publication bias respectively.

Results:

A total of 10 studies were included with a total of 3054 participants. The pooled prevalence of preoperative anxiety among surgical patients in Ethiopia was 60% (95% CI: 55-66, P < .001, I2 = 90.00%). The overall prevalence among non-obstetric patients was 59% (95% CI: 53-66) while among obstetric 66% (95% CI: 62-69). Fear of complication (AOR = 2.32, 95% CI: 1.23, 3.41, P = .62, I2 = 0.00%), postoperative pain (AOR = 1.92, 95% CI: 1.29, 2.56, P = .37, I2 = 0.00%), and fear of death (AOR = 2.27, 95% CI: 1.53, 3.00, P = .70, I2 = 0.00%) were significantly associated with preoperative anxiety.

Conclusion:

This study revealed a high pooled prevalence of preoperative anxiety among surgical patients in Ethiopia. The findings showed that fear of complication, postoperative pain, and fear of death were significantly associated with preoperative anxiety. This implies that a multidisciplinary approach involving various healthcare professionals is essential to optimize patient care and outcomes by addressing postoperative pain through pain management, counselling on fear of death, and complications to reduce the level of preoperative anxiety.
Perceived Entrapment, Goal Adjustment and Goal Ambivalence as Predictors for Suicide Ideation in High-Risk Prisoners
Authors: Miller Rachael , Huddy Vyv , Forrester Andrew , Cabourne Jarrod
Published: February 2025

The integrated motivational-volitional (IMV) model of suicide presents a pathway between perceived entrapment to the development of suicide ideation. This cross-sectional, questionnaire-based study used a sample of 106 male high-risk prisoners, to explore the predictive power of entrapment and goal factors linked to self-regulation (goal adjustment and ambivalence about personal goals) for suicide ideation. A logistic hierarchical regression showed that four factors: goal re-engagement, goal disengagement, goal ambivalence and internal entrapment, as a set, were able to predict any current suicide ideation over and above established risk factors (depression, social support, rumination and history of suicidal behaviour), [Formula: see text](8) = 45.90, p < 0.001. As internal entrapment (odds ratio = 1.16) increased, this contributed significantly to the likelihood of current suicide ideation. This adds to findings that level of internal entrapment is an important factor in understanding the presence of suicide ideation and that this may also be applicable in prisoners. Interestingly, against the direction of hypotheses, higher willingness to engage with new goals (OR = 1.21) and lower historic suicide risk (OR = 0.87), also significantly contributed to the likelihood of current suicide ideation. Findings are discussed in relation to existing literature and with consideration of this specialist participant group.
International QEEG Certification Board Guideline Minimum Technical Requirements for Performing Clinical Quantitative Electroencephalography
Authors: Collura Tom , Cantor David , Chartier Dan , Crago Robert , Hartzoge Allison , Hurd Merlyn , Kerson Cynthia , Lubar Joel , Nash John , Prichep Leslie S. , Surmeli Tanju , Thompson Tiff , Tracy Mary , Turner Robert
Published: February 2025

Quantitative electroencephalogram (QEEG) is a technology which has grown exponentially since the foundational publication by in Science in 1997, introducing the use of age-regressed metrics to quantify characteristics of the EEG signal, enhancing the clinical utility of EEG in neuropsychiatry. Essential to the validity and reliability of QEEG metrics is standardization of multi-channel EEG data acquisition which follows the standards set forth by the American Clinical Neurophysiology Society including accurate management of artifact and facilitation of proper visual inspection of EEG paroxysmal events both of which are expanded in this guideline. Additional requirements on the selection of EEG, quality reporting, and submission of the EEG to spectral, statistical, and topographic analysis are proposed. While there are thousands of features that can be mathematically derived using QEEG, there are common features that have been most recognized and most validated in clinical use and these along with other mathematical tools, such as low resolution electromagnetic tomographic analyses (LORETA) and classifier functions, are reviewed and cautions are noted. The efficacy of QEEG in these applications depends strongly on the quality of the acquired EEG, and the correctness of subsequent inspection, selection, and processing. These recommendations which are described in the following sections as minimum standards for the use of QEEG are supported by the International QEEG Certification Board (IQCB).
Disrupting bodegas: Automation, appropriation, and the branding of urban authenticity
Authors: Fernández Arlene C.
Published: February 2025

In September of 2017, two former Google employees announced the launch of a start-up in the U.S. called Bodega, a human-less convenience kiosk designed with machine learning capabilities that was named after small, neighborhood brick-and-mortar convenience stores in New York City. Using a textual analysis approach, this article explores the critical discourse that emerged on social media, blogs, and online news outlets in the aftermath the start-up's launch. It suggests that the narrative constructed about bodegas in urban communities reified a brand of multicultural urban authenticity and immigrant determination and grit. The branding of bodegas distances them from the very communities they historically served and obscures the complex realities of labor, precarity, and gentrification in New York City.
Antibacterial and Antidiarrheal Activities of the Combined Extracts of Houttuynia cordata Thunb. and Portulaca oleracea L. Against Enterotoxigenic Escherichia coli
Authors: Cheng Haoran , Wang Xiaoxia , Jiang Yuanyuan , Xu Zhihong , Zhang Zhizhou , Wang Long , Yang Ruiwu , Liao Jinqiu , Zhang Li
Published: February 2025

Background/Purpose: As traditional Chinese medicinal herbs are known for their heat-clearing and detoxifying properties, Houttuynia cordata Thunb. and Portulaca oleracea L. are considered safer alternatives to antibiotics. As a compound preparation, they have better efficacy than a single medicine and have multi-target antibacterial activity. However, there is still a gap in the research on the antibacterial and antidiarrheal mechanism of the combination of Houttuynia cordata Thunb. and Portulaca oleracea L. against enterotoxigenic Escherichia coli, thus we studied the antimicrobial and antidiarrheal activities of the combination of ethanol extract and essential oil from Houttuynia cordata Thunb. (HEE and HEO) and ethanol extract from Portulaca oleracea L. (PEE) against enterotoxigenic Escherichia coli. Materials and methods: The combination (CB-HHP) of HEE, HEO, and PEE was detected, and the anti- E. coli activity was determined to study its antibacterial mechanism, and an anti-diarrhea experiment was carried out in mice. Results: The results showed that the combination (CB-HHP) of HEE, HEO, and PEE had a synergistic effect on Escherichia coli, and affected the integrity of the cell membrane by increasing the permeability of cell wall and cell membrane. In vitro, CB-HHP treatment significantly inhibited the formation of E. coli bacterial biofilm. In vivo, gavaging with CB-HHP could significantly relieve the weight loss and diarrhea rate and protect the duodenal villi of mice infected by E. coli, as well as increasing the concentration of immunoglobulin (Ig) G, IgM, and IgA in serum. Conclusion: The CB-HHP demonstrated remarkable antibacterial activity, antidiarrheal activity, and intestinal protective function, with the potential to be used as plant-derived food additives.
The Pruritus Mediator Recombinant Mucunain Induced Apoptosis Through Caspase 8 Signaling Pathway in the Skin Epithelial Cells
Authors: Wang Zhen , Wu Fanghui , Yin Yifeng , Song Yunyang , Liu Yanli
Published: February 2025

Background

Mucunain, a cysteine protease extracted from the spicules of cowhage, can induce intense itching as a pruritus mediator independent of histamine. It is well known that erythema, edema and vesicles on skin may occur immediately following contact with Mucunain. A recent study has demonstrated that Mucunain may trigger pruritus and inflammation on the left or right groin of each Maltese–Beagle atopic dog. The aim of this study was to investigate the cytotoxic effect of Mucunain on a cocultured skin epithelial cell model in vitro.

Methods

Functional recombination Mucunain (rtMucunain) were obtained following induction, purification, and renaturation. Human keratinocytes and dermal fibroblasts were cocultured to construct a cocultured cell model skin epithelium cell model. The growth inhibition was measured using an MTS test. Microscopy was used to observe morphological alterations in cell architecture. The DCFH-DA assay was used to evaluate reactive oxygen species production, the cells death type was identified using a Flow cytometry assay, and the pro-inflammatory cytokines IL-6 and −8 were detected using an ELISA assay. The ability to form an apoptosis network was investigated by a Western blot assay to assess apoptosis-related protein expression.

Results

Following purification and renaturation, rtMucunain was obtained with a yield of up to 50 mg/L. In the cocultured skin epithelial cells treated with rtMucunain, cell growth was inhibited in a dose- and time-dependent manner, with doses of 2.5 µM or higher resulting in significant cytotoxicity. Morphological analysis revealed increased cell dispersion and abnormal morphology, particularly following prolonged exposure. Levels of reactive oxygen species were elevated, indicating oxidative stress. Flow cytometry and Western-blot data demonstrated that the cells underwent apoptosis, with extrinsic apoptosis pathways (NF-κB and Caspase-8) being activated by rtMucunain. Furthermore, treatment with rtMucunain markedly enhanced levels of IL-6 and IL-8, suggesting a robust pro-inflammatory response.

Conclusion

rtMucunain showed a strong inflammation and apoptosis effect in a cocultured skin epithelium cell model. This effect may be due to the activated Caspase 8 signaling pathway, on which NF-κB might play an important role. It was the first time to clarify the cytotoxic effect of rtMucunain on the skin epithelial cell model, and the comprehensive understanding the damaged mechanisms of rtMucunain on normal skin cells can provide a data basis for the skin irritated experiment of rtMucunain and its analogues.
Cognitive Simulation Using Mental Rehearsal for Procedural Learning in Medical Students: A Narrative Review
Authors: Le Khang Duy Ricky
Published: February 2025

Mental rehearsal, defined as the deliberate cognitive rehearsal of tasks without action, is an emerging approach to procedural skills learning in healthcare education. In particular, mental rehearsal has been associated with durable improvement of complex skills in various fields such as aviation, high performance sports and surgery. Despite this, mental rehearsal-based practices in healthcare are challenged with mainly informal and highly heterogeneous practice. Given this, the efficacy of mental rehearsal in medical education remains poorly characterised. Furthermore, there is currently no evidence-based approach to integrating mental rehearsal in the medical curriculum, nor frameworks to guide development of mental rehearsal skills for students. This narrative review explores mental rehearsal in medical education and evaluates the current principles of mental rehearsal and how these can be applied to improve procedural skills learning for medical students.
Rural Solid Waste Management: Experiences from Bihar
Authors: Katewa Yogendra , Gautam Rajendra Singh , Pradhan Sambit
Published: February 2025

The pace of solid waste generation in rural areas of India has been indiscriminately increasing with the change in lifestyle and inclination towards consumer-oriented societies. The lack of solid waste management in rural areas drastically affects the overall health of the communities and ecology. The article highlights the management perspective of waste management, the impacts of community engagement and the process to be followed to plan, execute and sustain solid waste management projects for sustainable outcomes. The article is an outcome of field-based experiences from an action research project piloted in rural areas of Bihar. It was evident that various tools of community engagement, consultation with stakeholders, establishing feedback mechanisms, quality of services and motivation of sanitation workers are the building blocks of successful waste management projects.
Electrochemical machining with identical polarity of tool and workpiece: A feasibility study
Authors: Rajakumaran Maran , Dvivedi Akshay
Published: February 2025

The prevailing belief is that anodic dissolution in electrochemical machining occurs only when the tool and workpiece are connected to a D.C. power supply’s negative and positive terminals. However, the present work challenges this convention by exploring alternative possibilities for achieving anodic dissolution. Two new configurations are investigated, in which both the tool and workpiece are connected to the same polarity, either both positive or both negative. Numerical and experimental studies were conducted to support these claims. In contrast to the existing convention, the effect of equal polarity was analyzed by examining the machined hole diameter and using light-emitting diode.
Harnessing amino acid pathways to influence myeloid cell function in tumor immunity
Authors: Pan Jiongli , Lin Yi , Liu Xinyuan , Zhang Xiaozhen , Liang Tingbo , Bai Xueli
Published: February 2025

Amino acids are pivotal regulators of immune cell metabolism, signaling pathways, and gene expression. In myeloid cells, these processes underlie their functional plasticity, enabling shifts between pro-inflammatory, anti-inflammatory, pro-tumor, and anti-tumor activities. Within the tumor microenvironment, amino acid metabolism plays a crucial role in mediating the immunosuppressive functions of myeloid cells, contributing to tumor progression. This review delves into the mechanisms by which specific amino acids—glutamine, serine, arginine, and tryptophan—regulate myeloid cell function and polarization. Furthermore, we explore the therapeutic potential of targeting amino acid metabolism to enhance anti-tumor immunity, offering insights into novel strategies for cancer treatment.
A combined comfort and safety-based approach to assess the performance of advanced driver assistance functions
Authors: Gulino Michelangelo-Santo , Vichi Giulio , Cecchetto Federica , Di Lillo Luigi , Vangi Dario
Published: February 2025

Advanced Driver Assistance Systems (ADAS) play a fundamental role in improving the driving experience by enhancing both comfort and safety. Currently, there is a lack of objective methods to quantify ADAS performance comprehensively, especially in different emergency conditions such as avoidable and inevitable collision states.

This study introduces a framework for evaluating ADAS performance in any condition of potential interaction between two or more vehicles. For impacts that are avoidable by the system’s intervention, assessments are based on comfort using vehicle acceleration (ISO 2631) and safety considering the minimum distance achieved between vehicles (clearance). In cases where the impact is inevitable, the performance indicator focuses on the injury risk for vehicle occupants associated with the collision and resulting from the ADAS intervention. To illustrate the application of this methodology, two case studies are presented, involving vehicles equipped and not equipped with ADAS. These cases respectively represent a real impact extracted from an in-depth accident database and a consumer program test for an Adaptive Cruise Control (ACC) function.

By analyzing the behavior of autonomous steering and braking functions in a simulation environment as ADAS parameters are varied (i.e., the time between consecutive scans of the scenario by sensors and the time for full actuation of drive-by-wire systems), it becomes possible to compare performances of different types of intervention logic. This approach not only facilitates the identification of the performance of potentially available ADAS functions (as ACC) but also helps in highlighting the best logic applicable in a specific conflict. The retrieved information has the potential to indicate margins for improvement of ADAS already on the market, and simultaneously guide the development of next-generation ADAS with an increasing focus on autonomous driving and enhanced user technology acceptance.
CellMAP: an open-source software tool to batch-process cell topography and stiffness maps collected with an atomic force microscope
Authors: Allard Antoine , Liboz Maxime , Crépin Raphaël , Labdi Sid , Maciejak Olek , Malo Michel , Campillo Clément , Lamour Guillaume
Published: February 2025

Atomic force microscopy (AFM) is the gold-standard technique to simultaneously map the morphology and viscoelastic properties of living cells. Although existing software tools, both open-source and from AFM manufacturers, can analyze cells individually, there is a growing need for fast and accessible codes to compile data from multiple cells into a single dataset. To address this, we present CellMAP, a user-friendly software tool that streamlines the batch-processing of AFM-derived topography and stiffness maps of living cells. Our analysis pipeline includes but is not limited to: flattening of the underlying substrate surface, filtering of outlier values, measurement of the cell surface and volume, and measurement of height and stiffness distributions. CellMAP can also generate a composite cell that reflects the height and stiffness properties of an entire cell population.
Exploration of pulse wave analysis under reactive hyperemia and close to an arteriovenous fistula: a comparative analysis
Authors: Busch Veit , Müller Sandra , Streis Joachim , Westhoff Timm H. , Felderhoff Thomas , Seibert Felix S. , Reuter Stefan , Mueller Niklas
Published: February 2025

Background

Analyzing novel pulse wave parameters, we aimed to study specific changes in pulse waveform under high flow conditions in three collectives (i.e., healthy individuals and two collectives of patients with kidney disease and different levels of comorbidities): First, under reactive hyperemia in order to assess endothelial function. Second, close to an ateriovenous fistula in order to assess fistula function.

Methods

Subjects underwent local peripheral tonometric pulse wave analysis with the SphygmoCor® device and duplex sonography to assess flow velocity (peak Vmax and diastolic Vdiast) under physiological conditions. Corresponding measurements were then performed under reactive hyperemia and at fistula arms. The area under the curve and the mean slope between the systolic peak and the end of systole of pulse waves and duplex flow velocities were analysed as parameter differences under high flow and physiological conditions (∆A2 and ∆m2, ∆Vmax and ∆Vdiast). In addition, the augmentation index was evaluated (only) under physiological conditions. The Wilcoxon test was used to assess parameter differences and linear correlation was performed.

Results

A total of 108 subjects were evaluated (23 healthy and 85 with fistula in two distinct collectives n = 39/45, measurements under reactive hyperemia in 62 individuals). Significant increments in the novel pulse parameters were observed under reactive hyperemia and near a fistula and were found to correlate with corresponding changes in flow velocity (reactive hyperemia: ∆A2 and ∆m2/Vmax r = 0.347, p = 0.006 and r = 0.374, p = 0.003; fistula: ∆A2/∆Vmax r = 0.315, p = 0.003, no significant correlation for ∆m2/Vmax). Consistent with their different vascular status and endothelial function, changes in pulse wave parameters during reactive hyperemia were significantly different in patients and healthy subjects. Both high flow conditions induced similar changes in the pulse waveform and a delay of the systolic peak in all three collectives. The augmentation index was different in the three collectives and correlated with the increase of the novel parameters and the peak flow velocity under reactive hyperemia: ∆A2 r = 0.445, p < 0.001, ∆m2 r = 0.338, p = 0.007, ∆Vmax r = 0.460.

Conclusion

Detection of changes in pulse waveform under high flow conditions is potentially a new clinical application to characterize endothelial function and the functional status of ateriovenous fistulas.
Regional differences in triage decisions affect hospital mortality among frail COVID-19 patients in the COvid MEdicaTion study
Authors: Minnema Julia , Sablerolles Roos , van Kempen Janneke , van der Kuy Hugo , Polinder-Bos Harmke , van de Loo Bob , Versmissen Jorie , Haaksma Miriam L. , Lafeber Melvin , Faes Miriam C. ,   on behalf of the COMET research team^
Published: February 2025

Objectives

The scarcity of intensive care unit (ICU) beds during the COVID-19 pandemic has led to a large number of national and international guidelines for the triage of ICU admission. Regional variation in medical decision making might affect ICU triage decisions. We investigate whether regional differences in ICU admission, as surrogate for triage decisions, affect in-hospital mortality in COVID-19 patients.

Methods

The COMET study is a multicenter, observational cohort study, including adult patients hospitalized for COVID-19 between March 2020– July 2020. Patients’ characteristics, prescribed medication, clinical characteristics, and CFS were collected. Patients from 11 European countries were included and these countries were categorized into two regions: north and south. The effects of region on ICU admission and in-hospital mortality were assessed using logistic regression analyses stratified for frailty.

Results

Frail patients had a higher risk for ICU admission in southern compared to northern countries (OR: 1.64; 95%CI: 1.10–2.46), whereas fit patients had a similar risk for ICU admission in southern compared to northern countries (OR: 0.75; 95%CI: 0.55–1.01). There was no difference in in-hospital mortality between northern and southern countries for fit and frail patients (respectively OR: 0.82; 95% CI 0.52–1.29, and OR: 1.11; 95% CI: 0.74–1.66).

Conclusion

Our study shows that, despite variation in rates of ICU admission between northern and southern countries for frail patients, no difference in in-hospital mortality was observed. This might help optimize prioritization of resources in a pandemic setting while offering options for palliative care instead of ICU admission.
Assessment of sleep problems in patients with Kawasaki disease: a survey-based study
Authors: Tharwat Samar , Nassar Mohammed Kamal
Published: February 2025

Introduction

Kawasaki disease (KD) is a rare systemic inflammatory disease that primarily affects children under the age of five. It is now recognized as the most prevalent cause of acquired heart diseases in children in developed countries.

Objectives

The aim of this study was to evaluate sleep disturbances in patients with KD and identify their prevalence and associations.

Methods

This cross-sectional analytic survey-based study was carried out on 262 participants (130 KD patients and 132 age- and sex-matched healthy controls). Participants were invited via social media groups. Sociodemographic data, clinical characteristics and therapeutic data of KD patients were collected. To identify the presence of sleep disturbances, all participants completed Children’s Sleep Habits Questionnaire (CSHQ).

Results

The median age for KD patients was 6 years, and 51.5% of them were female, the median age at disease onset was 2.5 years, and the median disease duration was 3 years. The sleep scores of patients with KD were significantly higher than those of the control group (55.72 ± 11.97 vs. 49.45 ± 8.54, p < 0.001). The total duration of sleep did not exhibit any statistically significant difference between patients with KD and healthy controls (p = 0.399). KD patients exhibited significantly elevated scores in sleep onset delay, sleep duration, night wakings, parasomnias, and sleep-disordered breathing (p < 0.001). Additionally, they showed marginally higher scores in daytime sleepiness (p = 0.059). Younger age of KD patients was associated with higher rates of bedtime resistance (p < 0.001) and sleep anxiety (p = 0.005). Younger age at KD onset was associated significantly with higher rates of bedtime resistance (p = 0.009), sleep anxiety (p = 0.038), night wakings (p = 0.017), and worse sleep quality (p = 0.033). KD Patients who exhibited lethargy, and received corticosteroid medication had significantly higher sleep scores than those who did not.

Conclusion

Patients with KD experience higher sleep disturbance than their healthy counterparts. Young age, early disease onset, lethargy and corticosteroid administration are linked to poor sleep quality.
Barriers and facilitators to detection and treatment of obstructive sleep apnoea syndrome in people with severe mental illnesses, qualitative interview study and referrer survey
Authors: Faulkner Sophie , Firth Joseph , Shiers David , Kalucy Megan
Published: February 2025

Obstructive sleep apnoea syndrome (OSAS) is a relatively common condition. It has a range of negative health and quality of life implications, but there are established tests to detect it, and recommended treatment pathways which have been well tested. OSAS is prevalent in people with severe mental illness (SMI), and research suggests it is under-detected in this group. This study aimed to examine and explore barriers and facilitators to the detection and treatment of OSAS in people with severe mental illnesses. Staff and patients with a range of relevant experiences were interviewed, and a large scale survey of potential OSAS referrers was conducted. Interviews were analysed thematically, survey responses were summarised descriptively, and results are presented together for comparison and enhanced interpretation. The results highlight a lack of awareness of OSAS outside of specialist sleep services, resulting in poor detection and treatment of OSAS in people with SMI. Comorbidities, symptoms and circumstances of this group may make the presence of OSAS less obvious, and can make diagnosis and adapting to treatment more difficult, but also emphasise the benefits of successful continuous positive airway pressure (CPAP) treatment in this group. The challenges of adapting to CPAP were described and acknowledged, but the impact of successful CPAP was for some life changing. The harm of delayed diagnosis was perceived as unjust. We recommend increased screening for OSAS in people with SMI, supported by increased education and training about OSAS in staff who work with people with severe mental illnesses, and increased awareness in service users and carers.
Single-nucleotide polymorphisms in dizygotic twin ovine fetuses are associated with discordant responses to antenatal steroid therapy
Authors: Fee Erin L. , Usuda Haruo , Carter Sean W. D. , Ikeda Hideyuki , Takahashi Tsukasa , Takahashi Yuki , Kumagai Yusaku , Clarke Michael W. , Ireland Demelza J. , Newnham John P. , Saito Masatoshi , Illanes Sebastian E. , Sesurajan Binny Priya , Shen Liang , Choolani Mahesh A. , Oguz Gokce , Ramasamy Adaikalavan , Ritchie Sara , Ritchie Andrew , Jobe Alan H. , Kemp Matthew W.
Published: February 2025

Background

Antenatal steroid (ANS) therapy is given to women at risk of preterm delivery to accelerate fetal lung maturation. However, the benefit of ANS therapy is variable and how maternal and fetal factors contribute to this observed variability is unknown. We aimed to test the degree of concordance in preterm lung function, and correlate this with genomic, transcriptomic, and pharmacokinetic variables in preterm dizygotic twin ovine fetuses.

Methods

Thirty-one date-mated ewes carrying twin fetuses at 123 ± 1 days’ gestation received maternal intramuscular injections of either (i) 1 × 0.25 mg/kg betamethasone phosphate and acetate (CS1, n = 11 twin pairs) or (ii) 2 × 0.25 mg/kg betamethasone phosphate and acetate, 24 h apart (CS2, n = 10 twin pairs) or (iii) 2 × saline, 24 h apart (negative control, n = 10 twin pairs). Fetuses were surgically delivered 24 h after their final treatment and ventilated for 30 min.

Results

ANS-exposed female fetuses had lower arterial partial pressure of carbon dioxide (PaCO2) values than male fetuses (76.5 ± 38.0 vs. 97.2 ± 42.5 mmHg), although the observed difference was not statistically significant (p = 0.1). Only 52% of ANS-treated twins were concordant for lung maturation responses. There was no difference in fetal lung tissue or plasma steroid concentrations within or between twin pairs. Genomic analysis identified 13 single-nucleotide polymorphisms (SNPs) statistically associated with ANS-responsiveness, including in the proto-oncogene MET and the transcription activator STAT1.

Conclusions

Twin fetal responses and ANS tissue levels were comparable with those from singleton fetuses in earlier studies. Twin ovine fetuses thus benefit from ANS in a similar manner to singleton fetuses, and a larger dose of betamethasone is not required. Assuming no difference in input from the placental or maternal compartments, fetal lung responses to ANS therapy in dizygotic twin preterm lambs are dependent on the fetus itself. These data suggest a potential heritable role in determining ANS responsiveness.
The Data Artifacts Glossary: a community-based repository for bias on health datasets
Authors: Gameiro Rodrigo R. , Woite Naira Link , Sauer Christopher M. , Hao Sicheng , Fernandes Chrystinne Oliveira , Premo Anna E. , Teixeira Alice Rangel , Resli Isabelle , Wong An-Kwok Ian , Celi Leo Anthony
Published: February 2025

Background

The deployment of Artificial Intelligence (AI) in healthcare has the potential to transform patient care through improved diagnostics, personalized treatment plans, and more efficient resource management. However, the effectiveness and fairness of AI are critically dependent on the data it learns from. Biased datasets can lead to AI outputs that perpetuate disparities, particularly affecting social minorities and marginalized groups.

Objective

This paper introduces the “Data Artifacts Glossary”, a dynamic, open-source framework designed to systematically document and update potential biases in healthcare datasets. The aim is to provide a comprehensive tool that enhances the transparency and accuracy of AI applications in healthcare and contributes to understanding and addressing health inequities.

Methods

Utilizing a methodology inspired by the Delphi method, a diverse team of experts conducted iterative rounds of discussions and literature reviews. The team synthesized insights to develop a comprehensive list of bias categories and designed the glossary’s structure. The Data Artifacts Glossary was piloted using the MIMIC-IV dataset to validate its utility and structure.

Results

The Data Artifacts Glossary adopts a collaborative approach modeled on successful open-source projects like Linux and Python. Hosted on GitHub, it utilizes robust version control and collaborative features, allowing stakeholders from diverse backgrounds to contribute. Through a rigorous peer review process managed by community members, the glossary ensures the continual refinement and accuracy of its contents. The implementation of the Data Artifacts Glossary with the MIMIC-IV dataset illustrates its utility. It categorizes biases, and facilitates their identification and understanding.

Conclusion

The Data Artifacts Glossary serves as a vital resource for enhancing the integrity of AI applications in healthcare by providing a mechanism to recognize and mitigate dataset biases before they impact AI outputs. It not only aids in avoiding bias in model development but also contributes to understanding and addressing the root causes of health disparities.
Antimicrobial and antiproliferative activity of biosynthesized manganese nanocomposite with amide derivative originated by endophytic Aspergillus terreus
Authors: El-Gazzar Nashwa , Farouk Reem , Diab Nervana S. , Rabie Gamal , Sitohy Basel
Published: February 2025

Background

Scientists have faced difficulties in synthesizing natural substances with potent biological activity from cost-effective sources. Endophytic fungi metabolites with nanoparticles have been utilized to develop a friendly, suitable procedure to address this problem and ameliorate the average amount of antioxidant, antimicrobial, and anticancer materials. Therefore, this study utilized endophytic fungi as a source of the natural extract with biosynthesized manganese nanoparticles (MnNPs) in the form of nanocomposites.

Methods

Thirty endophytic fungi were isolated and were assessed for their antioxidant activity by 1, 1-Diphenyl-2-picrylhydrazyl (DPPH) and antimicrobial activity. The most potent isolate was identified utilizing 18S rRNA and was applied to purify and separate their natural antimicrobial products by Flash column chromatography. In addition, the most potent product was identified based on instrumental analysis through Nuclear magnetic resonance (NMR), Fourier-transform infrared (FTIR), and Gas chromatography-mass spectrometry (GC.MS). The purified product was combined with biosynthsesized manganese nanoparticles (MnNPs) for the production of nanocomposite (MnNCs). Later on, the physicochemical features of MnNPs and its MnNCs were examined and then they were assessed for determination their biological activities.

Results

The most potent isolate was identified as Aspergillus terreus with accession number OR243300. The antioxidant and antimicrobial product produced by the strain A. terreus was identified as an amide derivative consisting of 3-(2-Hydroxy-4,4-dimethyl-6-oxo-1-cyclohexen-1-yl)-4-oxopentanoic acid (HDOCOX) with the chemical formula C13H18O5. Furthermore, purified HDOCOX, MnNPs and Mn-HDOCOX-NPs nanocomposite (MnNCs) showed significant antimicrobial effectiveness. The minimum inhibitory concentrations (MICs) determined for MnNCs were 10 µg/mL against C. albicans and E.coli. Furthermore, MnNCs were reduced hepatocellular carcinoma viability.

Conclusion

The use of HDOCOX, either alone or in combination with MnNPs, is a potential candidate for inhibiting pathogenic microbes and the development of an anticancer drug pipeline.
Cross-protection against homo and heterologous influenza viruses via intranasal administration of an HA chimeric multiepitope nanoparticle vaccine
Authors: Zhao Yongqiang , Liu Jia , Peng Chun , Guo Shuangshuang , Wang Bo , Chen Longping , Wang Yating , Tang Haiwen , Liu Liming , Pan Qi , Li Shiren , Wang Jingyu , Yang Dongni , Du Enqi
Published: February 2025

Background

Influenza A viruses (IAVs) cause seasonal influenza epidemics and pose significant threats to public health. However, seasonal influenza vaccines often elicit strain-specific immune responses and confer little protection against mismatched strains. There is an urgent need to develop universal influenza vaccines against emerging and potentially re-emerging influenza virus infections. Multiepitope vaccines combining multiple conserved epitopes can induce more robust and broader immune responses and provide a potential solution.

Results

Here, we demonstrated that an HA chimeric multiepitope nanoparticle vaccine, delivered intranasally conferred broad protection against challenges with various influenza viruses in mice. The nanoparticle vaccine co-expresses the ectodomain of haemagglutinin (H), three repeated highly conserved ectodomains of matrix protein 2 (M), and the M-cell-targeting ligand Co4B (C) in a baculovirus-insect cell system. These elements (C, H and M) were presented on the surface of self-assembling ferritin (f) in tandem to generate a nanoparticle denoted as CHM-f. Intranasal vaccination with CHM-f nanoparticles elicited robust humoral and cellular immune responses, conferring complete protection against a variety of IAVs, including the A/PR8/34 H1N1 strain, the swine flu H3N2 strain, the avian flu H5N8 strain, and H9N2. When CHM-f nanoparticles adjuvanted with CpG IAMA-002, the weight loss protective effect, cellular immune responses and mucosal IgA responses were significantly augmented. Compared with controls, mice immunized with CHM-f nanoparticles with or without CpG IAMA-002 showed significant reductions in weight loss, lung viral titres and pathological changes.

Conclusions

These results suggest that CHM-f nanoparticle with or without CpG IAMA-002 is a promising candidate as a universal influenza vaccine.

Graphical Abstract
“Lost in translation?” Animal research in the era of precision medicine
Authors: Frühwein Hamideh , Paul Norbert W.
Published: February 2025

Preclinical animal research has long been a cornerstone in evaluating the efficacy, toxicity, and safety of potential drug treatments before they proceed to human clinical trials. However, given the intricate nature of human physiology and the complexities of diseases such as cancer, this paper critically examines the role of animal experimentation in translational research, both from epistemological and ethical viewpoints. We argue that the ethical obligation to protect animals extends beyond their instrumental value for human benefit; it is rooted in the intrinsic value of their well-being. Consequently, we advocate for a paradigm shift in medical research: the adoption of new approach methodologies (NAMs) not merely as supplementary tools but as complete replacements for animal use in medical studies. In this context, replacement emerges as the key principle—an imperative that should be prioritized over all other considerations.
A missense variant in the SOX5 gene (c.221C > T) is associated with intellectual disability
Authors: Yang Xiujuan , Gan Zhongzhi , Guo Xiaoling , Huang Xiang , Liu Juan , Zheng Yingchun , Zhou Xiaoqiang , Lian Jingli , Liu Yue , Yang Tingting , Li Chao , Chen Fenying , He Fei , Xu Xiangmin , Zhou Yasi , Liu Qian , Yang Xingkun , Xiong Fu
Published: February 2025

Objectives

The SOX5 gene has been identified as the pathogenic gene responsible for Lamb-Shaffer syndrome. In this study, we examined the SOX5 variant (c.221C > T, p.Thr74Met) within a Chinese family presenting with intellectual disability and evaluated the functional implications of SOX5 by in vitro experiment.

Materials and methods

The family underwent a clinical assessment of intellectual development, which included precise clinical exome sequencing to identify causative genetic variants. The potential deleterious effects and pathogenicity of the variant were predicted using bioinformatics tools such as Mutation Taster, PROVEAN, and SIFT. Additionally, protein stability was evaluated using I-Mutant, and 3D protein structures were modeled with I-TASSER. Western blots and QPCR were employed to assess gene expression and protein stability. Flow cytometry was utilized to compare the cell cycle dynamics between wild-type and mutant cells.

Results

A previously identified missense variant (c.221C > T) in the SOX5 gene was determined to be the underlying cause of intellectual disability in a Chinese family. Functional assays demonstrated that mutant cells exhibited increased levels of SOX5 mRNA and protein relative to wild-type cells, accompanied by enhanced protein stability. Additionally, the mutant SOX5 protein was found to alter the cell cycle and downregulate the mRNA expression levels of the ACAN, AXIN2, SOX9, and PDGFRA genes.

Conclusions

We confirmed that the SOX5 p.Thr74Met variant is associated with intellectual disability in a second-generation Chinese family. This mutant protein potentially exhibits increased stability, influences the cell cycle, and downregulates genes related to bone and neural functions.
EGFR inhibition augments the therapeutic efficacy of the NAT10 inhibitor Remodelin in Colorectal cancer
Authors: Zheng Yongbin , Song Dan , Guo Ming , Wang Chenhong , Ma Mingzhen , Tao Gongcai , Liu Licui , He Xiaobo , Cao Fengyu , Luo Dan , Zhao Qingchuan , Xia Zhongyuan , An Yanxin
Published: February 2025

Background

Colorectal cancer (CRC) is the second leading cause of cancer-related death worldwide, and treatment options for advanced CRC are limited. The regulatory mechanisms of aberrant NAT10-mediated N4-acetylcytidine (ac4C) modifications in cancer progression remains poorly understood. Consequently, an integrated transcriptomic analysis is necessary to fully elucidate the role of NAT10-mediated ac4C modifications in CRC progression.

Methods

NAT10 expression levels were analyzed in CRC samples and compared with those in corresponding normal tissues. The potential mechanisms of NAT10 in CRC were investigated using RNA sequencing, RNA immunoprecipitation sequencing, and acetylated RNA immunoprecipitation sequencing. Additional in vivo and in vitro experiments, including CCK-8 assays, colony formation and mouse xenograft models, were conducted to explore the biological role of NAT10-mediated ac4C modifications. We also evaluated and optimized a potential treatment strategy targeting NAT10.

Results

We found that NAT10 is highly expressed in CRC samples and plays a pro-oncogenic role. NAT10 knockdown led to PI3K-AKT pathway inactivation, thereby inhibiting CRC progression. However, treatment with the NAT10 inhibitor Remodelin induced only a limited and reversible growth arrest in CRC cells. Further epigenetic and transcriptomic analysis revealed that NAT10 enhances the stability of ERRFI1 mRNA by binding to its coding sequence region in an ac4C-dependent manner. NAT10 knockdown decreased ERRFI1 expression, which subsequently activated the EGFR pathway and counteracted the inhibitory effects on CRC. Based on these findings, we demonstrated that dual inhibition of NAT10 and EGFR using Remodelin and the EGFR-specific monoclonal antibody cetuximab resulted in improved therapeutic efficacy compared to either drug alone. Moreover, we observed that 5-Fluorouracil promoted the interaction between NAT10 and UBR5, which increased the ubiquitin-mediated degradation of NAT10, leading to ERRFI1 downregulation and EGFR reactivation. Triple therapy with Remodelin, cetuximab, and 5-Fluorouracil enhanced tumor regression in xenograft mouse models of CRC with wild-type KRAS, NRAS and BRAF.

Conclusions

Our study elucidated the mechanism underlying 5-Fu-induced NAT10 downregulation, revealing that NAT10 inhibition destabilizes ERRFI1 mRNA through ac4C modifications, subsequently resulting in EGFR reactivation. A triple therapy regimen of Remodelin, cetuximab, and 5-Fu showed potential as a treatment strategy for CRC with wild-type KRAS, NRAS and BRAF.