bluuebunny/crossref_metadata_2025 huggingface dataset:
Study on the strategy for improving the accuracy of aerodynamic simulation based on digital wind tunnel
Authors: Duan Menghua , Feng Jinyang , Huang Shunqiao , Huang Tao , Zhang Qiang , Wang Qingyang , Xu Lei
Published: February 2025

With the rapid development of the new energy vehicle industry, automakers are paying more attention to aerodynamics and are increasingly demanding efficient and high-precision simulation development methods. In this paper, a digital wind tunnel model was established based on the full-scale aerodynamic acoustics wind tunnel of China Automotive Engineering Research Institute (CAERI). Comparisons were conducted wit the physical wind tunnel regarding the boundary layer thickness, pressure gradient, and turbulence intensity for the empty wind tunnel, pressure distribution on vehicle surfaces, and total pressure distribution in the wake and around the tire. The mesh adaptation technology and modified turbulence model were adopted to compute and compare three types of extended DrivAer model, namely Sedan, Fastback, and Estate, under multiple working conditions. The research shows that the mesh adaptation strategy significantly improves the efficiency and robustness of flow field calculation, reducing 21.0% of the computational time as compared to the Box mesh strategy. The k – ω turbulence model is more consistent with the wind tunnel test results in calculating the drag and lift coefficients of vehicles than the k – ε model, and can be widely used for various types of vehicles with a calculation error of less than 2%.
Functional activity and mobility: A new technology-aided program to support people with intellectual and visual disabilities
Authors: Lancioni Giulio E , Alberti Gloria , Pezzuoli Francesco , Olivieri Alessandro , Singh Nirbhay N , O’Reilly Mark F , Sigafoos Jeff , Desideri Lorenzo
Published: February 2025

Background

People with intellectual disability and severe visual impairment or blindness tend to have low levels of functional activity engagement and low levels of mobility/ambulation.

Objective

The study assessed a new technology-aided program to support four adults with intellectual disability and blindness in their activity and mobility engagement.

Methods

The program was implemented following single-case research methodology. The activity consisted of completing object kits. The objects needed for the kits were distributed over a relatively large space and the participants moved around that space to collect them and distribute them in the kits. The program (a) was based on the use of a smartphone, tags with radio frequency identification codes, and a tag reader linked to the smartphone, and (b) ensured that the participants would receive physical support, verbal instructions, and preferred stimulation.

Results

During the baseline phase (without the program), the participants were unable to engage in activity and mobility. During the intervention (using the program), all participants managed to engage in activity and mobility correctly completing the object kits available during the sessions.

Conclusions

The results suggest that the program might be useful to support activity and mobility in people like the participants of this study.
Molecular Characterization of Vascular Transformation of Lymph Node Sinuses via Oncomine Comprehensive Assay
Authors: Hegazy Shaymaa , Naous Rana
Published: February 2025

Vascular transformation of lymph node sinuses (VTSs) is defined as phenotypic transformation of the lymph node sinusoidal lining from lymphatic to vascular endothelium. The pathogenesis of VTS remains unclear. Thus far, VTS has not been characterized at the molecular level. Herein, we shed some light on VTS pathogenesis while providing a detailed description of its clinical, histopathologic, immunophenotypic, and molecular features. Our specimens involved 2 women and 3 men, aged 36 to 66 years (mean 49 years old). The lymph nodes were in the right inguinal ( n = 2), left axillary ( n = 1), right renal perihilar ( n = 1), and left external iliac ( n = 1) regions. The lesions ranged from 0.5 cm to 1.5 cm (mean 0.9 cm). All 5 specimens showed no recurrences on follow-up. Three specimens exhibited a spindle cell subtype, 1 specimen showed a mixed subtype, and another specimen displayed solid subtype. Immunohistochemically, VTS demonstrated variable staining for CD31, CD34, ERG, D2-40, and SMA. Next-generation sequencing revealed mutations in ataxia-telangiectasia mutated (Tier I/II) and NBN (variants of uncertain significance [VUSs]) genes in 1 specimen, while mutations in POLE (VUS), FANCI (VUS), ARID1A (VUS), ERBB4 (VUS), and MSH6 (VUS) genes were seen in 3 other specimens. The VUS genomic alterations were regarded as germline mutations given their variant allele frequency approaching 50%. In conclusion, most genomic alterations in VTS are germline VUS with rare pathogenic Tier I/II mutation detected in 1 specimen. Based on our case series, it is appropriate to consider VTS as a nonneoplastic process until more data exist.
Treatment effects of cladribine tablets on data-driven patterns of regional grey matter atrophy in multiple sclerosis
Authors: Barrantes-Cepas Mar , Noteboom Samantha , Colato Elisa , Battaglini Marco , Sormani Maria Pia , De Stefano Nicola , Steenwijk Martijn D , Koubiyr Ismail , Schoonheim Menno M
Published: February 2025

Background:

Treatment with cladribine tablets (CladT) in relapsing–remitting multiple sclerosis (RRMS) reduced global grey matter (GM) atrophy, but the effects on regional GM are unknown.

Objectives:

This study aimed to investigate the effect of CladT compared with placebo on magnetic resonance imaging (MRI)-derived patterns of GM atrophy.

Methods:

We used MRI and clinical data from the CLARITY study, including 393 people with RRMS (CladT (3.5 mg/kg), n = 200 or placebo, n = 193) at baseline, 24, 48 and 96 weeks after treatment initiation. SynthSeg-derived volume changes and GM atrophy patterns derived from source-based morphometry were analysed for group differences over time and associations with disability using mixed-effect models.

Results:

Deep GM (β = −0.03, p < 0.01), thalamus (β = −0.04, p < 0.01) and the brainstem–thalamus pattern (β = −0.03, p < 0.05) showed higher reduction in the placebo compared with treated group. These regions showed no effect during a predefined pseudo-atrophy period, where global volume loss was worse in the treatment group. Between W24 and W96, Expanded Disability Status Scale (EDSS) scores were associated with lower deep GM volume (β = −0.16, p = 0.001), thalamic volume (β = −0.16, p < 0.001), and the brainstem–thalamus pattern (β = −0.12, p < 0.05).

Conclusion:

CladT are associated with clinically relevant and slower neurodegeneration in RRMS. Strongest effects were seen in deep GM, thalamus, and brainstem, underlining the importance of regional MRI measures for assessing treatment effects.
A general framework for random effects models for binary, ordinal, count type and continuous dependent variables
Authors: Tutz Gerhard
Published: February 2025

A general random effects model is proposed that allows for continuous as well as discrete distributions of the responses. Responses can be unrestricted continuous, bounded continuous, binary, ordered categorical or given in the form of counts. The distribution of the responses is not restricted to exponential families, which is a severe restriction in generalized mixed models. Generalized mixed models use fixed distributions for responses, for example the Poisson distribution in count data, which has the disadvantage of not accounting for overdispersion. By using a response function and a threshold function, the proposed mixed threshold model can account for a variety of alternative distributions that often show better fits than fixed distributions used within the generalized linear model framework. A particular strength of the model is that it provides a tool for joint modelling, responses may be of different types, some can be discrete, others continuous.
‘You’re trying to juggle everything’: Understanding the consequences of emotional labour for senior probation officers in England and Wales
Authors: Westaby Chalen , Ainslie Sam , Fowler Andrew , Phillips Jake
Published: February 2025

Much academic research has explored what it means to be a practitioner in the criminal justice system and a small body of research explores the roles and experiences of leaders. However, very little research has sought to understand the critical role of line managers in supporting frontline practitioners and activating the policy goals of an organisation situated – as they are – in the middle of an institution's chain of command. Good line management can improve worker well-being, organisational commitment and job satisfaction. In doing so, line managers perform high levels of emotional labour which – in turn – creates potentially adverse impacts on their own well-being. This article explores how line managers in probation – Senior Probation Officers – experience and cope with the consequences of having to perform emotional labour. We present the analysis of qualitative data gathered with 26 Senior Probation Officer (SPOs) and 2 senior managers across England and Wales exploring the effects of performing emotional labour and toxin handling. We also identify how they cope with these consequences through formal and informal sources of support such as ‘communities of coping’. We conclude by considering what our findings say about the interplay between individual and organisational factors and how the ways in which probation managers are asked by the organisation to use their emotions is detrimental to the well-being of SPOs and the organisation more broadly. We offer ways the Probation Service can refocus organisational priorities and goals to ameliorate the emotional toll felt by SPOs and benefit the organisation as a whole.
Binary Barriers: Avatar Creation and Play for Nonbinary Video Game Players
Authors: Smith Xan
Published: February 2025

Virtual spaces and video games offer a unique opportunity for nonbinary and gender-diverse users to embody and express a gender that is congruent with their identity. The aim of this study was to better understand character creation, avatar identification, and virtual gender expression for nonbinary players, who's gender does not typically align with traditional male/female binary avatar options. Twenty-five nonbinary video game players participated in exploratory semistructured interviews. A grounded theory approach was used to thematically analyze the transcribed data. Nonbinary players use avatars to explore and experience nonbinary gender expressions. When nonbinary gender options are not available, players describe methods for circumventing in-game features and norms. Participants express negative experiences due to gender choice constraints. Lastly, participants suggest features that would allow for a gender expression that is congruent to their own gender. These findings have important implications for improving the wellbeing of nonbinary and gender-diverse players.
Positional roles, match outcomes, and location: Understanding performance dynamics in second division soccer
Authors: Revesz Laszlo , Stengl Violet , Kadar Laszlo , Rado Daniel , Safar Sandor , Csaki Istvan
Published: February 2025

The aim of this study was to uncover how different positional roles, match outcomes and match location impacts psychomotor performance, which was investigated among Hungarian soccer players. The sample consisted of 201 players, who were tracked across 38 matches by using GPS devices. Metrics, such as distance covered, high intensity running among others were observed. Results based on ANOVA tests and independent samples t-tests showed several significant values.

According to our findings, central midfielders accounted for the greatest endurance, while wide midfielders excelled in high-speed activities during match play. Furthermore, players tended to cover more distance and perform higher intensity running during lost matches. In terms of explosive actions, they were more prevalent during matches that were played abroad. Interestingly, home-field advantage did not show a significant result in locomotor variables, yet a higher count of explosive actions was recorded during away matches.

Positional roles have a significant impact on player performance, with central midfielders and wide midfielders showing different activity profiles. Match results are closely related to physical effort, with losing matches requiring more effort. Contrary to conventional views, the home field advantage is not reflected in locomotor variables, although increased explosive actions in away matches suggest adaptive behavior. These results may inform training and match preparation strategies, emphasizing the endurance of central midfielders and the high intensity actions of wide midfielders.
Differentiating idiopathic Parkinson’s disease from multiple system atrophy-P using brain MRI-based radiomics: a multicenter study
Authors: Huang Yin-Hui , Yang Mei-Li , Li Yuan-Zhe , Chen Ya-Fang , Cai Chi , Huang Jing , Wang Yi , Li Tie-Qiang , Ye Qin-Yong
Published: February 2025

Background:

Differentiating idiopathic Parkinson’s disease (IPD) from multiple system atrophy-parkinsonian type (MSA-P) is essential for optimizing patient care and prognosis, given the differences in disease progression and treatment response.

Objectives:

This study aimed to develop and evaluate a radiomics-based model using magnetic resonance imaging (MRI)-derived features to distinguish IPD from MSA-P.

Design:

A multicenter retrospective study.

Methods:

A multicenter retrospective study was conducted with 287 patients (186 IPD and 101 MSA-P) who underwent brain MRI. Radiomic features were extracted from T1-weighted imaging and T2-weighted imaging sequences, and various machine learning classifiers were applied, including logistic regression, support vector machine (SVM), ExtraTrees, extreme gradient boosting, and Light Gradient Boosting Machine. Model performance was assessed using area under the curve (AUC), accuracy, sensitivity, and specificity. A nomogram combining clinical and radiomic features was also evaluated.

Results:

The SVM model, selected as the base for the Rad-signature, achieved the best diagnostic performance, with AUCs of 0.885 and 0.900 in the training and testing cohorts, respectively. The Rad-signature significantly outperformed clinical-only models in distinguishing IPD from MSA-P. The nomogram incorporating radiomic and clinical features yielded the highest diagnostic accuracy (AUC = 0.973 and 0.963 for training and testing cohorts, respectively) and balanced sensitivity and specificity. Decision curve analysis confirmed the nomogram’s clinical utility.

Conclusion:

Radiomics-based MRI analysis offers a powerful tool for distinguishing IPD from MSA-P, enhancing diagnostic accuracy, and aiding personalized treatment planning. Integrating radiomic and clinical data may improve diagnostic workflows in clinical practice.
Is Overweight Protective Against Fracture Occurrence? Age and Site-Dependent Different Association Between Body Mass Index and the Incidence of Hip and Vertebral Fractures
Authors: Bae Kunhyung , Han Sangsoo , Han Kyoungdo , Park Jiwon , Hong Jae-Young , Choi Sung Hoon
Published: February 2025

Study Design

Retrospective observational study.

Objective

To investigate the effects of body mass index (BMI), age, and sex on the occurrence of hip and vertebral fractures in the South Korean population.

Methods

We enrolled participants who underwent routine health screenings conducted by the Korean National Health Insurance Service in 2009 and followed up from 2010 to 2018. Cox proportional analyses assessed the hazard ratios for hip and vertebral fractures compared to individuals with a normal BMI.

Results

A total of 2,515,078 individuals were included in this analysis, the mean age was 53.8 years, and 50.1% were men. Low BMI emerged as a risk factor for both hip and vertebral fractures, with a stronger association observed for hip fractures ( P < 0.01). Hip fracture incidence decreased with increasing BMI in all patients. However, compared to the normal BMI group, the incidence of vertebral fractures in patients under 65 years was 10.4%, 12.8%, and 24.1% higher in the underweight, obese I, and obese II groups, respectively ( P < 0.001) and that of women, 4.4%, 4.1%, 9%, and 13.4% higher in the underweight, overweight, obese I, and obese II groups, respectively ( P < 0.001).

Conclusions

Our findings showed that regardless of sex and age, higher BMI consistently correlates with a lower risk of hip fractures. However, elevated BMI may increase the risk of vertebral fractures in women and those under 65 years. This study underscores the complexity of the relationship between BMI and fracture risks, highlighting the necessity for specific guidelines to mitigate fracture risks across diverse populations.
Menstrual migraine prevalence and features in women with endometriosis: A common disabling comorbidity
Authors: Merki-Feld Gabriele S , Neumeier Maria S , Dietrich Hanna , Niggli Angela , Leeners Brigitte , Schankin Christoph J. , Andreas Gantenbein , Sandor Peter
Published: February 2025

Introduction:

Endometriosis is a highly prevalent disabling comorbidity of women with migraine. The aim of the current study was to identify menstrual migraine prevalence and features in women with endometriosis.

Methods:

This observational study included data from patients visiting our outpatient clinic from 2015 to 2021. Information was collected from charts and through structured phone interviews. Patients with surgically confirmed endometriosis and migraine were included.

Results:

A total of 92 from 344 endometriosis patients suffered from migraine and a subset of 35 from menstrual migraine (MM). From the subset of women with MM 42.9% reported to have auras. Groups did not differ with regard to rASRM stage. Women with MM reported significantly more pain days/month at present and 5 years ago and more often a MIDAS Grade 4 ( p < 0.01). Both groups had less migraine attacks/month now, compared with monthly attacks 5 years ago. All women experienced endometriosis surgery in this interval. There was a trend towards more severe dysmenorrhoea with onset at menarche and towards higher use of analgesics for menstrual pain during the bleeding in the MM group. Less deliveries were noted in the group with MM.

Conclusion:

In women with similar endometriosis stages MM is associated with a higher migraine frequency, more dysmenorrhoea days and a higher burden of disease. Future studies are needed to better understand a potential influence of menstrual migraine on the number of deliveries. Our findings suggest, that close collaboration of neurologists with gynaecologists and shared treatment decisions might be of advantage for patients with the comorbidity.
Is there a role for hypnosis in palliative care?
Authors: Vayne-Bossert Petra , Hardy Janet
Published: February 2025

Hypnosis has gained popular interest over the last few decades and has become increasingly subject to research study. Evidence of benefit in the palliative care setting is largely lacking, but it has been shown to have a favourable impact on psychological symptoms, especially anxiety, as well as chronic pain conditions. As a personalised approach, hypnotherapy is an excellent example of individual-centred care. Moreover, in the absence of significant adverse effects, it offers great promise as a complementary therapy.
Aberrant single-cell phenotype and clinical implications of genotypically defined polyclonal plasma cells in myeloma
Authors: Da Viá Matteo Claudio , Lazzaroni Francesca , Matera Antonio , Marella Alessio , Maeda Akihiro , De Magistris Claudio , Pettine Loredana , Solimando Antonio Giovanni , Desantis Vanessa , Peretti Giuseppe M , Mangiavini Laura , Giorgino Riccardo , Fabris Sonia , Pioggia Stefania , Marchetti Alfredo , Barbieri Marzia , Lonati Silvia , Cattaneo Alessandra , Tornese Marta , Scopetti Margherita , Calvi Emanuele , Latifinavid Nayyer , Castellano Giancarlo , Torricelli Federica , Neri Antonino , Fokkema Cathelijne , Cupedo Tom , Lionetti Marta , Passamonti Francesco , Bolli Niccolò
Published: February 2025

Multiple Myeloma is driven by clonal plasma cell (cPC)-intrinsic factors and changes in the tumorigenic microenvironment (TME). To investigate if residual polyclonal PCs (pPCs) are disrupted, single-cell (sc) RNAseq and sc B-cell receptor analysis were applied in a cohort of 46 samples with PC dyscrasias and 21 healthy donors (HDs). Out of n=234,789 PCs, 64,432 were genotypically identified as pPCs with frequencies decreasing over different disease stages, from 23.66% in monoclonal gammopathy of undetermined significance (MGUS) to 3.23% in MMs (p=0.00012). Both cPCs and pPCs had a comparable expression of typical lineage markers (i.e. CD38, CD138), while others were more variable (CD27, ITGB7). Only cPCs overexpressed oncogenes (e.g. CCND1/2, NSD2), but CCND3 was often expressed in pPCs. BCMA was expressed on both p- and cPCs, while GPRC5D was mostly upregulated in cPCs with implications for on-target, off-tumor activity of targeted immunotherapies. In comparison with HDs, pPCs from patients showed upregulated autophagy and disrupted interaction with TME. Importantly, interferon related pathways where significantly enriched in pPCs from patients vs HDs (p-adjusted < 0.05) showing an inflamed phenotype affecting genotypically normal PCs. Function of pPCs was consequently impacted and correlated with immunoparesis, driven by disrupted cellular interactions with TME. Leveraging our scRNAseq data, we derived a "healthy PC signature" that could be applied to bulk transcriptomics from the CoMMpass dataset and predicted significantly better PFS and OS (log rank p < 0.05 for both). Our findings show that genotypic, single-cell identification of pPCs in PC dyscrasias has relevant pathogenic and clinical implications.
Synergistic antitumor effect of combined EZH2 and DOT1L inhibition in B-cell lymphoma
Authors: Nguyen Van T. M. , Namba Hiroe , Porter Hayley , Shlyueva Daria , Lopez Ernesto , Melcher Alan , Béguelin Wendy , Melnick Ari M. , Helin Kristian
Published: February 2025

Despite the approval of several new treatments for patients with B-cell lymphoma, there is still a large unmet need. Diffuse large B-cell lymphoma (DLBCL) and Follicular lymphoma (FLs) are the two most common B-cell lymphoma subtypes, accounting for approximately 50% of all cases. EZH2 heterozygous gain-of-function somatic driver mutations are frequently found in Germinal Center B cell (GCB) DLBCLs and FLs. An EZH2 inhibitor has shown durable responses in patients with relapsed or refractory FL, however a considerable fraction of the patients did not show an objective response. To identify alternative therapeutic strategies, we performed CRISPR/Cas9 knockout screens in B-cell lymphoma cells treated with or without an EZH2 inhibitor. This led to the identification of the histone methyltransferase DOT1L as a potential therapeutic target. Specifically, we showed that an EZH2 inhibitor synergizes with a DOT1L inhibitor in a panel of B-cell lymphoma cell lines, regardless of EZH2 mutation status. Mechanistically, we demonstrated that the two inhibitors cooperatively suppress DOT1L-regulated cell cycle genes, up-regulate genes involved in interferon signaling including antigen presenting genes and ultimately drive B cell differentiation by de-repressing EZH2-regulated plasma cell signature genes. Furthermore, we demonstrated the effectiveness of this epigenetic combination strategy in a xenograft model, which resulted in significant abrogation of tumor growth. Together, our studies provide pre-clinical proof-of-concept for an epigenetic combination therapy to overcome resistance and improve durability of response for the treatment of B-cell lymphoma, warranting clinical investigation and illustrating an important convergent role of EZH2 and DOT1L in B cell lymphomagenesis.
Targeting the DNA Damage Response through TBL1X in Mantle Cell Lymphoma
Authors: Pray Betsy , Baiocchi Ethan James , Leon Sydney , Barta Brian , Koirala Shirsha , Tsyba Liudmyla , Hinterschied Claire , Carvajal-Moreno Jessika , Hout Ian , Nishat Shamama , Jindal Udita , Jain Neeraj , Singh Satishkumar , Sehgal Lalit , Chan Wing Keung , Hanel Walter , Yalowich Jack , Baiocchi Robert A. , Alinari Lapo
Published: February 2025

Mantle cell lymphoma (MCL) is an incurable B-cell lymphoma characterized by significant genomic instability. MCL patients who progress on targeted therapies have a short survival; thus, novel therapeutic strategies are urgently needed. Overexpression of transducin β-like protein 1 X-linked (TBL1X) has been documented in several types of cancer and associated with poor prognosis. TBL1X is a critical regulator of multiple oncogenic networks; however, its function in MCL has not been explored. Our data show that, unlike normal B cells, MCL cells express abundant levels of TBL1X and that genetic knockdown of TBL1X and treatment with tegavivint (Iterion), a first-in-class small molecule targeting TBL1X, promote MCL cell death in vitro and in vivo. Moreover, TBL1X controls the stability of key MCL oncogenic drivers, cyclin D1 and RAD51, and targeting TBL1X results in significant DNA damage, cell cycle arrest, and ultimately cell death. Combining tegavivint with PARP-1/2 inhibitor talazoparib results in synergistic MCL cell death in vitro, and in vivo this combination significantly prolonging the survival of an MCL PDX. Together, our results define the role of TBL1X in maintaining genomic stability in MCL and establish targeting TBL1X as a novel therapeutic strategy for patients with this incurable disease.
Instantaneous dose rate as a crucial factor in reducing mortality and normal tissue toxicities in murine total-body irradiation: a comparative study of dose rate combinations
Authors: Zhu Hongyu , Liu Shihua , Qiu Jiaqi , Hu Ankang , Zhou Wanyi , Wang Jian , Gu Weihang , Zhu Yinuo , Zha Hao , Xiang Rong , Li Junli , Qiu Rui , Zhao Chong , Huang Peng , Deng Xiaowu
Published: February 2025

Purpose

The ultra-high dose rate (UHDR) radiation shows promise in eradicating tumors while reducing normal tissue toxicities. However, the biological outcomes of UHDR are influenced by various factors, particularly the mean dose rate and instantaneous dose rate. Additionally, the UHDR response at large field sizes is lacking. This study aimed to explore the impact of different dose rate combinations on gastrointestinal biological outcomes following total-body irradiations (TBI) and to examine the involved molecular signaling pathways.

Method

Female C57BL6/J mice received 10 Gy TBI using three modes: ultra-high mean and ultra-high instantaneous dose rate irradiation (HH mode), low mean and ultra-high instantaneous dose rate irradiation (LH mode), and low mean and low instantaneous dose rate irradiation (LL mode). Mice were euthanized at 3 h and 48 h post irradiation to assess acute normal tissue damage and perform transcriptome sequencing. Furthermore, a subset of mice was monitored for 30 days to evaluate survival.

Results

We found that when the instantaneous dose rate is sufficiently high (> 105 Gy/s), both ultra-high or low mean dose rate irradiation reduced mice mortality, myelosuppression, DNA damage, and cell apoptosis. The survival probabilities 30 days after 10 Gy TBI were 4/7, 4/6, and 0/6 in the HH, LH, and LL groups, respectively. Myelosuppression was lower at 3 h and 48 h post HH and LH irradiations than LL irradiation. The better regulated inflammatory response was evident at 48 h post HH and LH irradiation compared to LL irradiation. Additionally, DNA damages and cell apoptosis in the intestinal tissue were significantly reduced after HH and LH irradiations compared to LL irradiation. Transcriptome sequencing of intestinal tissues revealed that HH irradiation activated immune response pathways and suppressed mitochondrial related pathways compared to LL irradiation.

Conclusion

Our findings underscore the pivotal role of instantaneous dose rate in reducing radiation damages. When the instantaneous dose rate is sufficiently high (> 105 Gy/s), both ultra-high or low mean dose rate irradiation (HH and LH mode) reduced mice mortality, myelosuppression, DNA damage, and cell apoptosis. Understanding these dose rate effects and biological responses are crucial for optimizing radiotherapy strategies and exploring the potential benefits of UHDR irradiation.
Social isolation induces sexually aggressive behaviour in male Wistar rats
Authors: Ngala Mbiydzenyuy Elvis , Hemmings Sian Megan Joanna , Womersley Jacqueline Samantha , Shabangu Thando W. , Qulu-Appiah Lihle
Published: February 2025

Background

Sexual violence, a pervasive global issue, significantly impacts individuals and societies, necessitating a deeper understanding of its underlying biological mechanisms. This study aimed to elucidate the role of stress-induced dysregulation of the hypothalamus-pituitary-adrenocortical axis in sexual aggression in male Wistar rats. Employing a sexual aggression paradigm, we investigated the effects of social isolation on aggression, anxiety-like behaviour, and neurochemistry in virgin adult male Wistar rats.

Results

The results showed that social isolation significantly escalated aggressive behaviours and induced anxiety-like responses in male rats. The sexual aggression test revealed that socially isolated males exhibited heightened aggression towards non-receptive females. Neurochemical analyses indicated significant alterations in key markers, such as corticotrophin-releasing hormone, oxytocin, and arginine vasopressin, correlating with the observed behavioural changes. Gene expression analyses revealed significant findings, particularly in the expression of the oxytocin receptor (OXTR) and vasopressin receptor 1 A (AVPR1A) genes. Social isolation and the duration of aggressive behaviour prior to the sexual aggression test significantly influenced OXTR expression in the hippocampus and AVPR1A expression in both the prefrontal cortex and hippocampus, highlighting the complex interplay between environmental stressors, neurochemical responses, and gene expression in the manifestation of sexual aggression behaviour.

Conclusions

This study underscores the critical impact of stress and social isolation on sexual aggression, providing valuable insights into possible neurobiological underpinnings of sexual violence. Understanding these mechanisms is crucial for developing effective interventions to mitigate the consequences of sexual aggression.
Point-of-care ultrasound training among anesthesiology residency programs in the United States
Authors: Edwards Jordon , Ahn Daniel , Alcaraz Daniel , Chiles Collin , Khuu Tina , Soni Nilam J. , Goyal Varun , Manohar Crystal
Published: February 2025

Background

Point-of-care ultrasound (POCUS) use has become ubiquitous in the field of anesthesiology. However, POCUS training curriculum in anesthesiology residencies vary widely. We performed a survey study to better understand the structure of existing POCUS training and identify barriers to instituting a POCUS curriculum for anesthesiology trainees.
Real-world analysis of the efficacy and safety of nusinersen in pediatric patients with spinal muscular atrophy
Authors: Li Wenjing , Zhang Qin , Miao Hongjun , Xu Jin
Published: February 2025

Background

Spinal muscular atrophy (SMA) is a rare neurodegenerative disease that significantly affects multiple systems in children. Nusinersen, the first approved treatment for SMA, enhances SMN protein production by targeting the RNA splicing site of the SMN2 gene, thus improving motor function. However, the high cost of nusinersen treatment raises concerns about its economic feasibility.

Methods

This study retrospectively analyzed clinical data of 42 pediatric SMA patients treated with nusinersen from January 2022 to October 2024 at our hospital. We assessed the efficacy, safety, and economic impact of nusinersen in different SMA types. Motor function was evaluated using the CHOP-INTEND, HINE-2, HFMSE, and RULM scales. Safety was assessed based on adverse reactions and events, and economic evaluation considered total treatment costs and average cost per injection.

Results

Nusinersen significantly improved motor function in SMA patients, especially in type I patients, who showed notable increases in CHOP-INTEND and HINE-2 scores. The RULM score had the highest increase among type II patients, while improvements were relatively lower in type III patients. Regarding safety, the incidence of adverse events was 40.48%, with fever being the most common adverse reaction, occurring in 36.36% of cases. Economic analysis indicated that the total treatment cost was highest for type III patients, though the cost differences among types were not statistically significant (P > 0.05).

Conclusion

Nusinersen demonstrated significant clinical efficacy and favorable safety in pediatric SMA patients, with improved economic feasibility after insurance coverage. Our findings support early SMA screening and presymptomatic nusinersen administration to maximize therapeutic benefits. Further multicenter, large-sample, long-term follow-up studies are warranted to validate and expand upon these findings.
Retraction Note: The oncogenic Golgi phosphoprotein 3 like overexpression is associated with cisplatin resistance in ovarian carcinoma and activating the NF-κB signaling pathway
Authors: He Shanyang , Niu Gang , Shang Jianhong , Deng Yalan , Wan Zhiyong , Zhang Cai , You Zeshan , Shen Hongwei
Published: February 2025

This article has been retracted. Please see the Retraction Notice for more detail: https://doi.org/10.1186/s13046-017-0607-0.
Genome-wide CRISPR guide RNA design and specificity analysis with GuideScan2
Authors: Schmidt Henri , Zhang Minsi , Chakarov Dimitar , Bansal Vineet , Mourelatos Haralambos , Sánchez-Rivera Francisco J. , Lowe Scott W. , Ventura Andrea , Leslie Christina S. , Pritykin Yuri
Published: February 2025

We present GuideScan2 for memory-efficient, parallelizable construction of high-specificity CRISPR guide RNA (gRNA) databases and user-friendly design and analysis of individual gRNAs and gRNA libraries for targeting coding and non-coding regions in custom genomes. GuideScan2 analysis identifies widespread confounding effects of low-specificity gRNAs in published CRISPR screens and enables construction of a gRNA library that reduces off-target effects in a gene essentiality screen. GuideScan2 also enables the design and experimental validation of allele-specific gRNAs in a hybrid mouse genome. GuideScan2 will facilitate CRISPR experiments across a wide range of applications.
A qualitative study exploring participants’ experiences of the SCOPE2 trial: chemoradiotherapy dose escalation in oesophageal cancer
Authors: Holland-Hart Daniella , Longo Mirella , Bridges Sarah , Nixon Lisette , Hawkins Maria , Crosby Tom , Nelson Annmarie
Published: February 2025

Introduction

This qualitative study explored patients’ experiences and perceptions of the SCOPE2 trial. The trial studied radiotherapy dose escalation in patients with inoperable oesophageal cancer treated with definitive chemo-radiation. SCOPE2 embedded a phase II trial for patients with a poor early response using positron emission tomography (PET) scans.

Methods

This longitudinal interview study took place between 2017 and 2021. Patients eligible for chemoradiotherapy were recruited from five clinical sites in the UK. Participants were invited to participate in three semi-structured interviews across four different time points: baseline (before treatment) and at 2–3 months, 3–6 months or 6 months + after baseline. This paper focuses on recruitment to the trial, practical management, the impact of COVID-19 and reflections of being on the trial. Real-time reporting to the trial team was used to inform potential improvements to trial conduct and recruitment. The interviews were thematically analysed.

Results

Ten participants were interviewed in 16 longitudinal interviews. There were five female and five male interview participants; three participants were accompanied by companions during their interviews. Recruitment to the trial and qualitative study was challenging. Motivations for joining the trial included altruism, potentially receiving better care and monitoring and the opportunity to improve their quality of life. Participants required adequate time to consider information and regular updates regarding trial and treatment process. Participants felt that their trial experience was minimally impacted by COVID-19, although some delays to treatment were reported.

Conclusion

Increased opportunities for patients to discuss and receive appropriate and timely information from trial staff and third sector partners could enhance patients’ understanding of future trials, treatments and procedures. Slow recruitment to the trial and qualitative study was further impeded by the COVID-19 pandemic and future trials would benefit from a more fully integrated approach to qualitative recruitment.

Clinical trial registration

ClinicalTrials.gov: NCT02741856 registered on 12 April 2016; ISRCTN: 9,712,546 registered on 26 October 2016.
A proinflammatory response and polarized differentiation of stromal elements characterizes the murine myeloma bone marrow niche
Authors: Ghamlouch Hussein , Gagler Dylan C. , Blaney Patrick , Boyle Eileen M. , Wang Yubao , Avigan Jason , Choi Jinyoung , Landgren Ola , Tsirigos Aristotelis , Maura Francesco , Morgan Gareth J. , Davies Faith E.
Published: February 2025

Background

The bone marrow (BM) niche contains non-hematopoietic elements including mesenchymal stromal cells (MSC) and bone marrow endothelial cells (BMEC) which provide mechanical support, and control hematopoietic cell growth and differentiation. Although it is known that multiple myeloma (MM) cells interact closely with the BM microenvironment, little is known about the impact of MM on non-hematopoietic niche-forming cells.

Methods

To address the role of the niche in MM pathogenesis, we utilized the 5TGM1 murine model. During the asymptomatic precursor stage of the model, we isolated the rare non-hematopoietic cells and performed single cell RNA sequencing. Using in-silico methods we characterized the individual cellular components of the niche, their relative abundance and differentiation state before and after exposure to MM cells as well as their intercellular interactions.

Results

MM engraftment increased the abundance of MSC-lineage cells, BMECs and enhanced endothelial to mesenchymal transition. An inflammatory and oxidative stress signal was identified together with polarization of MSC differentiation away from osteocyte formation towards adipocytes which provide growth factors that are known to support MM expansion. BMEC differentiation was polarized towards sinusoidal endothelial cells with a pro-angiogenic/pro-inflammatory phenotype.

Conclusions

MM cells impact the BM niche by generating a pro-inflammatory microenvironment with MSC differentiation being changed to generate cell subsets that favor MM growth and survival. In order to induce remission and improve long-term outcome for MM patients these inflammatory and oxidative stress signals need to be reduced and normal niche differentiation trajectories restored.
Overcoming barriers to implementation of patient engagement in clinical trials: feasibility testing of an embedded study
Authors: Castonguay Geneviève , Bédard Sylvain , Dubois Anick , Lessard Émilie , Rivard Léna , Rouly Ghislaine , Boivin Antoine
Published: February 2025

Background

Patient engagement is attracting considerable interest as a potential strategy to improve the conduct of clinical trials, with evidence of significant improvement in research participant recruitment. However, impact on the retention and adherence of clinical trial participants requires further studies. Embedded studies are specific research designs where a secondary study is “embedded” into a larger host study. We aimed to investigate the feasibility of embedding a study of patient partnership in research, within an ongoing multi-center clinical trial on drug treatment.

Methods

We developed and embedded a patient engagement intervention (embedded study) into a phase 3 randomized clinical drug trial (host study). The patient engagement intervention consisted of discussions between host study participants and a patient partner, to improve research participants’ experience and retention in the clinical trial. We carried out individual semi-structured interviews with patient partners and other research team members involved in the development and implementation of the embedded study, as well as an analysis of project documents. Data were analyzed using qualitative thematic analysis.

Results

Factors impacting feasibility and lessons learned for future embedded studies on engagement science were identified. Barriers that curtailed the implementation of patient engagement into an ongoing clinical trial included: the late integration of the embedded study into the host clinical trial, different visions of patient partnership and its potential benefits, differences in communication style and preferences, a lack of fit between the specific needs of the host study and the proposed engagement model, and an overall sense of burden. Integrating patient partners into the host clinical trial was seen as potentially beneficial in improving the experience of participants in the host clinical trial through experience sharing, providing support for the consent process, and improving knowledge transfer.

Conclusions

This feasibility study offers insights into how contextual factors and decisions made during the design phase can impact the implementation of patient engagement studies embedded in a clinical trial. Findings suggest that knowledge of the clinical trial context (e.g., organizational, administrative, regulatory, ethics) and early collaboration among embedded study and host study teams before initiation of both studies are key conditions for success.
Detection of thrombus in a venous air trap chamber using ultrasound imaging: a case report
Authors: Ito Yoshiaki , Tanaka Toshiyuki
Published: February 2025

Background

During hemodialysis, the formation of thrombi inside the venous air trap chamber is associated with high venous pressure. Direct observation inside the venous air trap chamber involves invasive procedures and risks affecting the closed-circuit system. Methods for non-invasive observation inside venous air trap chambers have not yet been generalized.

Case presentation

A thrombus was identified in the filter inside a venous air trap chamber during emergency hemodialysis performed on a man in his 60s with acute renal dysfunction. During subsequent hemodialysis sessions, we regularly monitored the venous air trap chamber using ultrasound imaging and employed colour Doppler to identify the thrombus. Images were also captured that revealed signs of anomalies.

Conclusions

Ultrasound imaging allows non-invasive observation of the interior of a venous air trap chamber. Employing this non-invasive method poses less risk to patients and can potentially be applicable to continuous renal replacement therapy in circuit configurations that use chambers.
Improving power distribution networks with dwarf mongoose optimization for improved photovoltaic incorporation in rural-urban settings
Authors: Chen Guo , Honggang JIA , Jian Zeng , Zhiqi Zhang , Xingxing Zhou
Published: February 2025

This paper aimed to assess new connotations and characteristics of power distribution networks in new situations like integrating photovoltaic (PV) systems. Power system emission reduction is an ongoing subject of discourse, and solar energy production using PV is gaining popularity. Centralized and unidirectional systems, nevertheless, provide difficulties. An investigation is expected to comprehend the network’s design and PV integration capacity’s (PV-IC’s) responsiveness to subsequent generations.With an emphasis on low and medium-voltage networks, the paper presents a unique dwarf mongoose optimization (DMO)approachfor developing efficient network configurations. It analyzes the effect of network configuration on PV-IC.This study is experimented with MATLAB/Simulink platform based on the DMO technique. Different PV system numbers and peak powers, together with alternate providing substations, have been modeled for a certain set of load locations. The load time series computed shows rural-urban zones, and the proposed DMO is implemented on several topological generations. The computed results indicate that network topologies must be changed to accommodate raised solar energy production and PV-IC, with rural regions attaining up to 8.2 kW using TF (+). Our proposed DMO approach surpassed alternatives, with rural regions having a higher PV-based load of 190 kW compared to 120 kW in urban areas. Voltage control tactics, like RPC and Curt, benefit up to 55% of rural customers versus 15% in urban areas. Policy changes for household PV incorporation may be needed to maximize solar energy use.
Black psychiatrists’ experience of discrimination and related behaviours in the workplace: UK survey
Authors: Hombo Jade , Owusu-Mensah Lovita , Orrell Martin , Kwentoh Mona-Lisa
Published: February 2025

Aims and method

In the UK, Black doctors experience higher levels of discrimination, bullying and harassment compared with other doctors. This study aims to explore the impact of this on perceived well-being and mental health. A UK survey of 109 Black psychiatrists asked about racism, othering, microaggressions, bullying and harassment, plus any links to career progression or mental well-being.

Results

Sixty-three survey participants (57.8%) had faced workplace microaggressions, 44 (40.4%) had experienced workplace bullying and 41 (37.6%) had faced workplace harassment. Forty-seven (43.1%) participants reported a detrimental impact on their mental health, with 35 (32.1%) considering quitting and 24 (22%) reporting a poorer work performance.

Clinical implications

These experiences are unacceptable and can be traumatic. The impact of racism and discrimination can also undermine effective service delivery. Barriers to reporting can prolong mistreatment and deter professional aspirations among Black psychiatrists. Collective action is needed to drastically improve the workplace environment, including the widespread institutional adoption of an anti-discriminatory stance.
Effects of Lorentz symmetry violation on a spin-1/2 neutral particle in a doubly anharmonic potential
Authors: Oliveira A. S. , Okada Kim , Belich Humberto
Published: February 2025

We investigate the quantum dynamics of a spin-1/2 neutral particle under the effects of Lorentzsymmetry violation, characterized by a fixed time-like background vector and azimuthal electricfields added to the potential of a pure quartic oscillator. These effects, induced by the backgroundvector that defines a preferred spacetime direction, modify the dynamics of the spin-1/2 neutralparticle and give rise to a doubly anharmonic oscillator-like potential. The main challenge is to findanalytical solutions to the Schr¨odinger equation, considering that this nonlinear potential modelsrealistic quantum physics scenarios. Finally, we obtain bound-state solutions in the nonrelativisticlimit for the Schr¨odinger-Pauli equation of a spin-1/2 neutral particle. An interesting quantumeffect is observed: the constant associated with the pure quartic oscillator term is quantized,meaning it depends on the system’s quantum numbers.