bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Age-Based Nomogram as the Best Predictor for Long-Term Overall Survival in Head and Neck Mucosa-Associated Lymphoid Tissue Lymphoma
Authors: Fan Chaoxin , Jiang Aimin , Zhao Rui , Chen Miaomiao
Published: February 2025

Objectives

Head and neck mucosa-associated lymphoid tissue (MALT) lymphoma, a rare subtype of non-Hodgkin lymphoma, has received limited attention regarding its prognosis. This study aimed to illuminate the clinical characteristics and identify prognostic factors for head and neck MALT lymphoma, intending to develop an accessible tool for clinicians to predict long-term survival probabilities and inform therapeutic strategies.

Methods

This multicentre retrospective study enrolled 424 head and neck MALT lymphoma patients from the Surveillance, Epidemiology, and End Results Program (SEER) database. Least absolute shrinkage and selection operator (LASSO)-Cox regression analysis identified independent prognostic factors for overall survival (OS), leading to the development of an age-based nomogram predicting OS probabilities at 5, 10, and 15 years. Evaluation included time-dependent receiver operating curve (ROC), calibration curves, and decision curve analysis.

Results

Multivariate Cox analysis highlighted age exceeding 65 years [hazards ratio (HR): 2.97, 95% confidence interval (CI): 1.94-4.57; P < 0.001] and unmarried status (HR: 1.58, 95% CI: 1.07-2.33, P = 0.023) as significantly associated with shorter OS, while black race correlated with longer OS (HR: 0.25, 95% CI: 0.09-0.69, P = 0.007). The age-based nomogram, integrating these factors, demonstrated efficacy in predicting 5-year [area under the curve (AUC): 0.640] and 10-year OS (AUC: 0.705), with an impressive AUC of 0.842 for the 15-year OS probability in the training cohort. Decision curve analysis affirmed the nomogram’s clinical utility, surpassing individual factors. Consistent results were observed in validation cohorts.

Conclusion

Our study provides crucial insights into head and neck MALT lymphoma, filling gaps in understanding its clinical landscape. The validated age-based nomogram serves as a practical tool for clinicians, offering enhanced prognostic precision and guiding personalized treatment strategies in this understudied lymphoma subtype.
Formability improvement and mechanism analysis of fiber metal laminates under extra normal stress
Authors: Chen Yizhe , Huo Jiachen , Wang Zhuoqun , Wang Hui , Hua Lin
Published: February 2025

Fiber metal laminates (FMLs) are advanced super-hybrid sandwich materials. They have been increasingly used in the aerospace industry. However, the low formability of heterogeneous FMLs in the traditional forming process restricts its large-scale application. This paper proposed the idea of introducing extra normal stresses to improve the formability of FMLs by using flexible die forming. The carbon fiber reinforced aluminum alloy laminates (CARALL) were prepared. A flexible die forming finite element model was established, and a platform was constructed to investigate the effects of laminate layup structures and the flexible die hardness. The mechanism of formability improvement was analyzed. The results indicate that the formability of the FMLs is better compared with the carbon fiber sheets. The formability can be increased significantly with a larger flexible die hardness. The 3 + 2 type laminate showed the highest improvement in formability and ultimate limit states per unit thickness. It is formed by alternately stacking three layers of aluminum alloy and two layers of carbon fiber reinforced plastics (CFRP). The specific order of layers is AL/CFRP/AL/CFRP/AL. The matrix type of CFRP is thermosetting epoxy resin. The maximum improvement in formability and the load limit per unit thickness of the 3 + 2 type layup structures were 28.8% and 4.94 N/mm, respectively. The mechanism of formability improvement was analyzed. The mechanism analysis showed that the additional normal stresses through a flexible die forming reduced the spherical tensor of stress. The additional normal stresses can promote damage closure during plastic deformation. It also improved the material’s Lode parameter, increasing the formability. This study demonstrates that flexible die forming helps enhance the deformation capacity of laminates and is a potential method for preparing high-performance, high-plasticity super-hybrid material components.
Utilizing multimodal ultrasonography in conjunction with serum Ki-67 and HER2 tests for breast cancer detection and prognosis
Authors: Liu Lei , Zong Xiao-Jian , Wu Jie , Li Jing-Jing , Yuan Ping , Cao Jian
Published: February 2025

Objective

To examine the diagnostic and prognostic value of multimodal ultrasound and serum human epidermal growth factor receptor 2 (HER2) and Ki-67 antigen (Ki-67) testing for breast cancer.

Methods

We enrolled 65 patients with breast cancer admitted to the Tianjin Fourth Centre Hospital between March 2018 and March 2019 as the study group, while the control group consisted of 65 patients with benign breast nodules admitted during the same time period. All cases underwent ultrasound elastography (UE), contrast-enhanced ultrasonography (CEUS), serum examination, and Ki-67 and HER2 testing to determine the differences in multimodal ultrasound parameters and biomarkers, respectively, between the two groups and their relationship to the pathological features of breast cancer; ROC curves were generated to determine the accuracy of the combined examination in predicting breast cancer prognosis.

Results

The study group had significantly higher UE score and CEUS-PI, significantly lower time to peak (TTP) and mean transit time (MTT) levels than the control group ( P < 0.001), and significantly higher serum HER2 and tumor tissue Ki-67 expression ( P < 0.05).

Conclusion

It is possible to improve the breast cancer diagnosis rate by using multimodal ultrasound in conjunction with serum Ki-67 and HER2 testing.
Examining the lifespan of red blood cells in individuals with systemic lupus erythematosus
Authors: Tian Pan , Luo Feng-Lan , Chen Ai-Zhen , Yuan Yue-Xing , Yu Lian
Published: February 2025

Objective

The objective of this study is to examine the lifespan of red blood cells (RBCs) in individuals with systemic lupus erythematosus (SLE), explore the factors influencing this lifespan, and assess its significance in clinical contexts.

Methods

The experimental group comprised of 182 patients with SLE, while the control group consisted of 90 healthy participants. By using a non-invasive breath test, we measured the RBC lifespan in both groups. Subsequently, we conducted a comparative analysis of general clinical data and laboratory findings to explore the correlation between RBC lifespan in patients with SLE and various parameters associated with RBC characteristics, inflammatory markers, and immunological indicators. Furthermore, we examined the impact of COVID-19 infection on RBC lifespan among patients with SLE and assessed the diagnostic efficacy of RBC lifespan.

Results

RBC lifespan was notably reduced in the SLE group in comparison to the healthy control group ( P = 0.002). A positive correlation was observed between RBC lifespan and hemoglobin (HB), complement 3, and complement 4, whereas a negative correlation was noted with IgG, erythrocyte sedimentation rate (ESR), C-reactive protein, and anti-dsDNA levels (all P < 0.05). Noteworthy independent contributors to the reduction in RBC lifespan among patients with SLE included disease activity and presence of anemia. While RBC lifespan remained unchanged in the control group before and after COVID-19 infection ( P > 0.05), a reduction in RBC lifespan post-COVID-19 infection was observed among patients with SLE ( P < 0.05). Also, RBC lifespan was notably shorter during the active disease phase of SLE compared to the stable phase, with post-COVID-19 active patients with SLE exhibiting even shorter RBC lifespan compared to the pre-COVID-19 active group (all P < 0.05). An optimal cutoff for the prediction of anemia in patients with SLE on the day of assessment was determined to be 93.5 days (AUC 0.792, P < 0.05).

Conclusion

Patients with SLE exhibited shorter RBC lifespan in contrast to the healthy population, which is notably linked with levels of inflammatory and immune markers, as well as the incidence of COVID-19 infection. This discovery holds crucial significance for both the diagnosis of anemia and the comprehension of its underlying pathogenic mechanisms within the context of SLE.
Veiled conspiracism: Particularities and convergence in the styles and functions of conspiracy-related communication across digital platforms
Authors: Buehling Kilian , Zhang Xixuan , Heft Annett
Published: February 2025

Digital communication venues are essential infrastructures for anti-democratic actors to spread harmful content such as conspiracy theories. Capitalizing on platform affordances, they leverage conspiracy theories to mainstream their political views in broader public discourse. We compared the word choice, language style, and communicative function of conspiracy-related content to understand its platform-dependent differences and convergence. Our cases are the conspiracy theories of the New World Order and Great Replacement, which we analyzed on 4chan/pol/, Twitter, and seven alternative US news media longitudinally from 2011 to 2021. The conspiracy-related texts were comparatively analyzed using a multi-method approach of computational and quantitative text analyses. Our results show that conspiracy narrations are increasingly present in all venues. While language differs vastly between platforms, we observed a style convergence between Twitter and 4chan. The results show how more coded language veils the spread of racist and antisemitic content beyond the so-called dark platforms.
Leaking panic as policy: Bordering, scaling, and forming in Austrian distributive politics
Authors: Streinzer Andreas
Published: February 2025

The article argues for a theoretical vocabulary to analyse how processes of demarcation and exclusion can be accompanied by a language of sharing. The article analyses how neo-nationalist and white supremacist exclusions in Austria were often justified by political panics about ‘leaking’. Leaking panic is a trope in which presumably hideous Others siphon resources from an imagined ‘us’, used for proposing targeted attacks at ‘them’ to secure warm and communal sharing among that imagined ‘us’. I bring this observation to a discussion of recent work in economic anthropology on sharing and its promise for transnational distribution. To theorise how imaginaries of sharing rest on constructions of the community of sharing and distribution, I propose to add bordering, scaling, and forming as auxiliary concepts. I take these theoretical instruments to investigate the cutting of welfare benefits for the children of transnational labourers in the name of ‘fairness for Austrian families’ and the protection of private foundations to defend them from foreign capital through the affectionate language of ‘Austrian family enterprises’. The discussion reveals the importance of understanding demarcation and categorisation to legitimise exclusions by rhetorics of sharing.
Music style transfer and creation method based on transfer learning algorithm
Authors: Chi Shuiyi , Chen Hao
Published: February 2025

With the growth of people’s demand for personalized music, how to use AI technology to achieve accurate understanding and creative transformation of music styles has become an important topic. In this study, a transfer learning algorithm based on a deep learning framework is designed to automatically identify and simulate different music style characteristics in order to break through the traditional music creation mode. By pre-training a large-scale multi-style music library and then fine-tuning it for a specific target style, the effective migration of music styles is achieved. The experimental data show that this method can significantly improve the accuracy of style conversion and make the similarity of the generated music works in timbre, melody, rhythm, and other dimensions reach more than 92% while maintaining good novelty and diversity. In order to verify the audience acceptance of the generated works, this study invited participants from different age groups and musical preferences to conduct a listening comparison experiment. The results show that compared with the direct use of non-transfer learning models or artificially created music, the works generated based on transfer learning algorithms have achieved higher praise rates, especially in the two key indicators of innovation and emotional resonance, which have improved, respectively. About 23% and 16%.
Counseling Andy
Authors: Pierce J Rush
Published: February 2025

In this first-person narrative, the Dean instructs a young supervising physician to counsel a medical student about why he should not talk to patients about his religion. The essay reflects some of the emotions, ethical considerations and ambiguities that caregivers face in these situations.
Participatory Member Checking: A Novel Approach for Engaging Participants in Co-Creating Qualitative Findings
Authors: Kullman Sasha M. , Chudyk Anna M.
Published: February 2025

Member checking is a technique which aims to increase the trustworthiness or rigour of qualitative research by asking participants to comment on study findings. However, traditional methods of member checking (e.g., transcript reviews) face scrutiny for being ineffective or tokenistic ways of eliciting participant feedback. Emerging member checking approaches seek to evoke feedback in more meaningful ways. While these alternatives have merit, persistent challenges include eliciting critical feedback, time constraints, supporting an ongoing dialogue with participants, and setting future research directions. To address these challenges, we introduce a novel alternative to member checking, “Participatory Member Checking” (PMC). PMC draws from the principles of Patient Engagement (a participatory approach) and promotes the co-creation of qualitative research findings between participants and researchers across five steps: (1) Elicit Feedback, (2) Summarize Feedback, (3) Check for Understanding, (4) Implement Feedback, and (5) Demonstrate Accountability. PMC encourages critical feedback, is practical and efficient, promotes ongoing dialogue through both written and verbal feedback, and involves participants in setting future research directions. The present article presents PMC in the context of a qualitative study exploring patient partners’ experiences of being engaged in research projects supported by the Canadian Institutes of Health Research. We describe PMC in sufficient detail to facilitate uptake by other researchers, show how PMC meaningfully impacted our research findings, and demonstrate the acceptability of PMC among a group of 11 participants (Median age = 62, range = 25–82, 81.8% women). Considerations for adopting PMC in future research are discussed.
Nursing Students’ Experiences of Medical Simulation: A Mixed-Method Study
Authors: Eide Camilla Ingrid , Magnusson Ann-Sofie , Jansson Inger
Published: February 2025

Introduction

Nursing students need to be prepared for the realities of acute situations or crises. Medical simulation training is a well-known pedagogical method for teaching acute care and teamwork. Despite that, there is a lack of knowledge about students’ experiences with the training. Such knowledge could contribute to the development of the training program.

Objective

To describe nursing students’ experiences of medical simulation.

Design

Mixed-method.

Method

A total of 175 nursing students in semesters three and five answered a questionnaire with quantitative questions and open-ended comments. The qualitative data from the open-ended questions were analyzed inductively using thematic analysis. Quantitative data from the closed-ended questions were analyzed using descriptive statistics. Finally, a mixed-method synthesis was conducted, in which the findings from the qualitative analysis guided the synthesis, while the quantitative data supported the themes and sub-themes that emerged from the qualitative analysis.

Result

An overall theme in the results emerged, which was: “Students need and want more simulation in their curriculum.” This theme was then divided into five sub-themes: “Well-structured model,” “Being prepared by practical training,” “Enhanced knowledge,” “Reflection gives self-awareness,” and “Feelings of fun and positive nervousness.”

Conclusions

The result highlights medical simulation as a reliable pedagogic method because it was a well-structured model which made them prepared, gave them enhanced knowledge, and helped their self-reflection. Students recognize the need for additional medical simulation training and express a desire for both longer sessions and more opportunities. They believe that simulation training is beneficial for their future roles as nurses because it enhances their competence in acute care and improves their teamwork skills. Bloom's taxonomy is a valuable framework for designing and developing curricula, particularly when medical simulation plays a key role in achieving all levels of high cognitive skills.
E-Cigarettes in the Young Generation and Future Health Risks in Indonesia
Authors: Tebay Vince , Ratang Westim , Ohoiwutun Yosephina , Muttaqin M Zaenul
Published: February 2025

The proliferation of e-cigarette use has emerged as a pressing global concern, as articulated in the research conducted by Toluwalashe et al. Their study elucidates the intricate relationship between e-cigarette use and the risk of seizures, a finding with profound ramifications for public health. In the context of developing countries, these findings assume particular significance in light of the rapid growth of the e-cigarette market and its increasing prevalence among the younger demographic.
Integrating advanced analytical methods to assess epigenetic marks affecting response to hypomethylating agents in higher risk myelodysplastic syndrome
Authors: Nikolopoulos Theodoros , Bochalis Eleftherios , Chatzilygeroudi Theodora , Chondrou Vasiliki , Dereki Irene , Athanasopoulou Katerina , Zafeiropoulos John , Bourikas Kyriakos , Patrinos George P. , Symeonidis Argiris , Sgourou Argyro
Published: February 2025

Background

Patients with higher-risk (HR) myelodysplastic syndrome (MDS), ineligible for allogeneic hematopoietic stem cell transplantation (alloHSCT), require prompt therapeutic interventions, such as treatment with hypomethylating agents (HMAs) to restore normal DNA methylation patterns, mainly of oncosuppressor genes, and consequently to delay disease progression and increase overall survival (OS). However, response assessment to HMA treatment relies on conventional methods with limited capacity to uncover a wide spectrum of underlying molecular events.

Methods

We implemented liquid chromatography-tandem mass spectrometry (LC-MS/MS) to assess 5’ methyl-2’ deoxycytidine (5mdC), 5’ hydroxy-methyl-2’-deoxycytidine (5hmdC) levels and global adenosine/thymidine ([dA]/[T]) ratio in bone marrow aspirates from twenty-one HR MDS patients, pre- and post-HMA treatment. Additionally, targeted methylation analysis was performed by interpretation of NGS-methylation (MeD-seq) data obtained from the same patient cohort.

Results

LC/MS-MS analysis revealed a significant hypomethylation status in responders (Rs), already established at baseline and a trend for further DNA methylation reduction post-HMA treatment. Non-responders (NRs) reached statistical significance for DNA hypomethylation only post-HMA treatment. The 5hmdC epigenetic mark was approximately detected at 37.5–40% among NRs and Rs, implying the impairment of the natural active demethylation pathway, mediated by the ten-eleven (TET) 5mdC dioxygenases. R and NR subgroups displayed a [dA]/[T] ratio < 1 (0.727 − 0.633), supporting high frequences of 5mdC transition to thymidine. Response to treatment, according to whole genome MeD-seq data analysis, was associated with specific, scattered hypomethylated DMRs, rather than presenting a global effect across genome. MeD-seq analysis identified divergent epigenetic effects along chromosomes 7, 9, 12, 16, 18, 21, 22, X and Y. Within statistically significant selected chromosomal bins, genes encoding for proteins and non-coding RNAs with reversed methylation profiles between Rs and NRs, were highlighted.

Conclusions

Implementation of powerful analytical tools to identify the dynamic DNA methylation changes in HR MDS patients undergoing HMA therapy demonstrated that LC-MS/MS exerts high efficiency as a broad-based but rapid and cost-effective methodology (compared to MeD-seq) to decode different perspectives of the epigenetic background of HR MDS patients and possess discriminative efficacy of the response phenotype to HMA treatment.
Influence of fiber dimensions on the mechanical properties of silica glass nanofibers
Authors: Barciela Raúl , Quintero Félix , Mahadevan Thiruvilla S. , Riveiro Antonio , Pou Juan , Du Jincheng
Published: February 2025

The understanding of the mechanical properties in glass nanofibers remains a challenge. As the fiber diameter decreases, surface-to-volume atom fraction increases, making the impact of surface defects more significant. To elucidate these effects, we employed classical molecular dynamics (MD) simulations to investigate how fiber dimensions and the surface layer influence the mechanical properties of silica glass nanofibers. Our simulation methodology included fibers of varying diameters, generated using two different production methods (i.e. “cutting” and “casting” methods) that produce different degrees of surface atomic defects, and compared with bulk samples without surface atoms. The defect-rich surface layer of these fibers was carefully analyzed. Then, MD tensile simulations were performed to analyze the effect of the fiber surface on the mechanical properties and to explain the onset of the brittle-to-ductile transition experimentally observed at a few tens of nanometers. The results revealed that the surface layer maintains a fixed thickness independent of the fiber diameter, resulting in a pronounced increase of the fiber defects in thin fibers. Also, the tensile test simulations show that surface defects significantly reduce tensile strength, without appreciably increasing ductility compared to bulk samples. In turn, we show that the brittle-to-ductile transition is not caused by the surface defects, but related to a balance between fracture energy and elastic energy, which varies with fiber length. Using experimental values of different glass properties, our theory predicted a threshold length of around 200 nm, below which ductile fracture dominates, in reasonable agreement with experimental results.

Graphic abstract
Regulation of antibiotic persistence and pathogenesis in Acinetobacter baumannii by glutamate and histidine metabolic pathways
Authors: Sim Ho Seok , Kwon Yong-Kook , Song Hokyung , Hwang Geum-Sook , Yeom Jinki
Published: February 2025

Background

Metabolite production is essential for the proliferation and environmental adaptation of all living organisms. In pathogenic bacteria, metabolite exchange during host infection can regulate their physiology and virulence. However, there is still much unknown about which specific metabolic pathways in pathogenic bacteria respond to changes in the environment during infections. This study examines how pathogenic bacterium Acinetobacter baumannii uses particular metabolic pathways to regulate its ability to antibiotic persistence and pathogenesis.

Results

To determine specific metabolic pathways in pathogenic antibiotic resistance bacteria, metabolite profiles of bacteria were constructed using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry and multivariate statistical analysis. A. baumannii generates amino acid derivative metabolites, which are precursors for fatty acid production. Comparative genomic analysis identified specific genes regulating the production of these metabolites and fatty acids in A. baumannii. Inactivation of genes involved in glutamate metabolism, gdhA, aspB, murI1, and racD, impairs antibiotic persistence, while inactivation of the hisC gene, encoding histidinol − phosphate aminotransferase enzyme in histidine metabolic pathway, increases bacterial survival inside macrophages during infections.

Conclusions

This study reports that A. baumannii regulates antibiotic persistence and pathogenesis through glutamate and histidine metabolic pathways, respectively. These findings suggest that specific metabolic pathways regulate bacterial pathogenesis and antibiotic persistence during infections, providing potential therapeutic targets for pathogenic bacteria.
A systematic review exploring the role of tuberculosis stigma on test and treatment uptake for tuberculosis infection
Authors: Kılıç Ayşenur , Zhou Xuanyu , Moon Zoe , Hamada Yohhei , Duong Trinh , Layton Charlotte , Jhuree Sobhash , Abubakar Ibrahim , Rangaka Molebogeng X. , Horne Robert
Published: February 2025

Background

Tuberculosis (TB) stigma may be a barrier to engagement in testing and treatment for TB infection (TBI). We systematically reviewed the available evidence on how TB stigma influences engagement with TBI testing and treatment.

Methods

Electronic databases (e.g., CINAHL, Central, OVID) were searched from 1963 to 1st August 2024. Quantitative, qualitative, and mixed-method studies reporting the effects of TB stigma on engagement with TBI testing and treatment were included in the review. Descriptive synthesis was applied to the quantitative studies, and thematic analysis was applied to qualitative studies. The risk of bias was assessed by using the mixed methods appraisal tool.

Results

Seventeen studies were included in the review (12 qualitative, four quantitative and one mixed methods). TB stigma was complex and multifactorial with six overlapping domains: public, anticipated, self, experienced, secondary, and structural. Perceptions or experiences of stigma were associated with lower rates of engagement in testing and adherence to treatment in TBI.

Conclusions

Perceptions of TB stigma among people with TBI were related to the common social representation of TB disease such as its being contagious or disease of the poor. Negative perceptions of active TB appear to carry over to its infection, despite people being informed about the nature of TBI. Our findings could inform more effective communication to support TBI testing and treatment engagement.
A mixed methods descriptive study of a diverse cohort of African American/Black and Latine young and emerging adults living with HIV: Sociodemographic, background, and contextual factors
Authors: Gwadz Marya , Wilton Leo , Cleland Charles M. , Serrano Samantha , Sherpa Dawa , Zaldivar Maria Fernanda , Freeman Robin , Campos Stephanie , Beharie Nisha , Rosmarin-DeStefano Corey , Filippone Prema , Munson Michelle R.
Published: February 2025

Background

American/Black and Latine (AABL) young/emerging adults living with HIV in the United States (US) have consistently failed to meet targets for HIV care/medication engagement. Among this population, those with non-suppressed HIV viral load are understudied, along with immigrants and those with serious socioeconomic deprivation. Guided by social action theory, we took a mixed methods approach (sequential explanatory design) to describe sociodemographic, background, and contextual factors, and their relationships to HIV management, among a diverse cohort.

Methods

Participants (N = 271) received structured baseline assessments and HIV viral load testing. Primary outcomes were being well-engaged in HIV care and HIV viral suppression. A subset (N = 41) was purposively sampled for maximum variability for in-depth interviews. Quantitative data were analyzed with descriptive statistics and logistic regression, and used to develop a research question about life contexts. Qualitative data were analyzed with directed content analysis, and the joint display method was used to integrate results.

Results

Participants were 25 years old, on average (SD = 2). The majority (59%) were Latine/Hispanic and the reminder African American/Black. Almost all were assigned male sex at birth (96%) and sexual minorities (93%). Half (49%) were born outside the US and 33% spoke primarily Spanish. They were diagnosed with HIV four years prior on average (SD = 3). Most were well-engaged in HIV care (72%) and evidenced viral suppression (81%). Speaking Spanish was associated with a higher odds of care engagement, and adverse childhood experiences and income from federal benefits were associated with a lower odds. None of the factors predicted viral suppression. Qualitative results highlighted both developmentally typical (insufficient financial resources, unstable housing) and atypical challenges (struggles with large bureaucracies, HIV disclosure, daily medication use). Federal benefits and the local HIV social services administration were critical to survival. Immigrant participants came to the US to escape persecution and receive HIV care, but HIV management was often disrupted. Overall qualitative results highlighted both risk and protective factors, and resilience. Qualitative results added detail, nuance, and richness to the quantitative findings.

Conclusions

The present study advances what is known about the backgrounds and contexts of diverse and understudied AABL young/emerging adults living with HIV.
Preclinical evaluation of a hydraulic actuation system with guide tube for robotic cochlear implant electrode insertion
Authors: Cramer Jakob , Salcher Rolf , Fröhlich Max , Böttcher-Rebmann Georg , Artukarslan Eralp , Lenarz Thomas , Rau Thomas S.
Published: February 2025

Background

Automated insertion of the cochlear implant electrode array can reduce the risk of intracochlear trauma. To address this, our group previously developed a hydraulic electrode insertion device, the Cochlea Hydrodrive (CHD), which automates the process using a syringe piston driven by an infusion pump. This study aims to characterize the hydraulic actuation process of the CHD and to preclinically evaluate its design.

Methods

A camera-based motion tracking test setup was developed to obtain hydraulic motion profiles. Various syringes were evaluated for their actuation properties and the optimal syringe was selected. The CHD design was adapted based on the selected syringe, incorporating a slotted stainless steel guide tube to surround the electrode during insertion. This enhanced design was tested in ex vivo insertion trials into human head specimens.

Results

The final design of the CHD demonstrated smooth and steady motion profiles at all tested velocities (0.4 mm/s, 0.1 mm/s, 0.03 mm/s). Ex vivo insertion trials confirmed these findings, with the guide tube facilitating easy alignment of the CHD in front of the round window and preventing electrode buckling.

Conclusion

Our study validates that the CHD provides reliably smooth actuation properties despite its low complexity. The use of a guide tube appears promising and could further enhance the standardization of automated electrode insertion.
Identifying traditional Chinese medicine combinations for breast cancer treatment based on transcriptional regulation and chemical structure
Authors: Li Shensuo , Zhang Lijun , Zhang Wen , Chen Hongyu , Hong Mei , Xia Jianhua , Zhang Weidong , Luan Xin , Zheng Guangyong , Lu Dong
Published: February 2025

Breast cancer (BC) is a prevalent form of cancer among women. Despite the emergence of numerous therapies over the past few decades, few have achieved the ideal therapeutic effect due to the heterogeneity of BC. Drug combination therapy is seen as a promising approach to cancer treatment. Traditional Chinese medicine (TCM), known for its multicomponent nature, has been validated for its anticancer properties, likely due to the synergy effect of the key components. However, identifying effective component combinations from TCM is challenging due to the vast combination possibilities and limited prior knowledge. This study aims to present a strategy for discovering synergistic compounds based on transcriptional regulation and chemical structure. First, BC-related gene sets were used to screen TCM-derived compound combinations guided by synergistic regulation. Then, machine learning models incorporating chemical structural features were established to identify potential compound combinations. Subsequently, the pair of honokiol and neochlorogenic acid was selected by integrating the results of compound combination screening. Finally, cell experiments were conducted to confirm the synergistic effect of the pair against BC. Overall, this study offers an integrated screening strategy to discover compound combinations of TCM against BC. The tumor cell suppression effect of the honokiol and neochlorogenic acid pair validated the effectiveness of the proposed strategy.
The healthcare burden of pulmonary alveolar proteinosis (PAP)
Authors: Lee Elinor , Ataya Ali , McCarthy Cormac , Godart Erica , Cosenza John , King Alysse , Robinson Brian , Wang Tisha
Published: February 2025

Introduction

Pulmonary alveolar proteinosis (PAP) is a rare lung syndrome characterized by the accumulation of surfactant in the alveoli. Using a longitudinal claims database, we compared measures of clinical and economic burden between a sample of diagnosed PAP patients and non-PAP matched controls.

Methods

PAP patients were identified leveraging IPM.ai’s longitudinal U.S. claims database spanning January 1, 2009, through May 1, 2022. PAP patients were selected based on the presence of ICD-10: J84.01 or ICD-9: 516.0 in their claims history and were indexed for observation. An age, gender, and geographically matched control cohort was created (ratio of 1:4) for comparison. A third cohort, consisting of likely undiagnosed PAP patients, was identified using a machine learning model. The PAP and control cohorts were tracked longitudinally, depending on individual index dates, from January 1, 2018, through May 1, 2023. Inclusion criteria required evidence of continual claims activity 12 months prior to and after the index date, which reduced the total number of diagnosed PAP and control patients in the analysis. Demographics, comorbidities, procedures, medication use, annual healthcare resource utilization (HCRU), and costs were calculated for eligible PAP and control patients and were compared 12 months prior to, and 12 months after each patient’s index date.

Results

After inclusion criteria were applied, 2312 confirmed PAP patients and 9247 matched controls were included in the analysis. Compared with matched controls, PAP patients had significantly higher rates of diagnosed conditions at baseline as defined by the Charlson Comorbidity Index (CCI). During the follow-up period, PAP patients had higher rates of diagnosed conditions, procedures, medication use, and cost-of-care compared with controls. PAP patients also had higher rates of emergency room visits (35% vs. 14%; P < 0.001), outpatient visits (87% vs. 56%; P < 0.001), inpatient visits (20% vs. 5%; P < 0.001) and had longer lengths of stay for inpatient hospitalizations (2.8 days vs. 0.56 days; P < 0.001), respectively.

Conclusion

This study represents the largest dataset of PAP patients and matched controls to be analyzed to date. Findings indicate that PAP patients have higher rates of diagnosed conditions, procedures, medication use, HCRU, and costs compared with non-PAP patients.
A novel KDM5C mutation associated with intellectual disability: molecular mechanisms and clinical implications
Authors: Meng Yunlong , Wang Xinyao , Liu Kangyu , Tang Xingkun , Li Haining , Chen Jianjun , Zhong Zilin
Published: February 2025

Background

Among the disease-causing genes associated with X-linked intellectual disability (XLID), KDM5C is one of the most frequently mutated ones. KDM5C is a widely expressed gene that is most highly expressed in the brain. KDM5C modulates the transcriptional activity of genes through demethylation of H3K4, thereby regulating neural development and normal function. We identified a gene from a Chinese family and found that a nonsense mutation of KDM5C was co-segregated with the intellectual disability (ID).

Methods

The candidate mutant genes of patients with ID phenotype were screened by Whole Exome Sequencing (WES), and DNA Sanger sequencing was performed for genetic analysis. Pathogenicity prediction tools were used to evaluate the pathogenicity of new mutations. The fusion plasmid was constructed and transfected into the cells, and the changes of mRNA and protein levels of the mutants were detected by semi-qRT-PCR and Western Blot, and the subcellular localization changes of mutant proteins were detected by Immunofluorescence technique.

Result

The nonsense mutation in KDM5C (c.2785 C > T, p. R929X) was identified by whole exome sequencing (WES) and confirmed by Sanger sequencing, resulting in a truncated protein. The mutation was determined by pathogenicity prediction tool able to find non-sense mediated mRNA decay (NMD). Semi-qRT-PCR and Western Blot showed that the mRNA levels of the mutant gene were down-regulated, while the protein level was up-regulated. Additionally, the subcellular localization of the mutant protein changed.

Conclusions

The KDM5C mutation found in our study leads to changes in protein levels through NMD and/or protein degradation, and produces residues lacking nuclear localization, thus altering the subcellular localization of the protein. These results may lead to changes in the expression of KDM5C target genes, ultimately contributing to the clinical phenotype observed in the patients.
Impact of the intensity of infection in birds on Plasmodium development within Culex pipiens mosquitoes
Authors: Isaïa Julie , Baur Molly , Wassef Jérôme , Monod Sarah , Glaizot Olivier , Christe Philippe , Pigeault Romain
Published: February 2025

Background

In vector-borne diseases, invertebrate hosts are exposed to highly variable quantities of parasites during their blood meal. This heterogeneity may partly explain the overdispersed distribution of parasites within the vector population and the variability in the extrinsic incubation period (EIP) of the parasite. Indeed, the quantity of parasites ingested is often considered as a good predictor of the quantity of parasites that will develop within the vectors, as well as the speed at which they will develop (i.e. EIP). However, density-dependent processes can influence the relationship between parasite burden in the vertebrate host and in vectors, making this relationship unclear at times.

Methods

Here, we used an avian malaria system to investigate whether the proportion of red blood cells infected by sexual and/or asexual stages of Plasmodium relictum influences the intensity of infection and the EIP within vectors. For this purpose, we experimentally infected 12 birds in order to generate a range of infection intensity. More than 1000 mosquitoes took a blood meal on these hosts, and the development of Plasmodium within the vectors was followed for more than 20 days.

Results

Our study reveals a negative relationship between the intensity of infection in birds and the time until 10% of mosquitoes become infectious (EIP10). A period of only 4 days was sufficient to detect sporozoites in at least 10% of mosquitoes fed on the most infected hosts. However, the number of sporozoites did not vary significantly according to the vertebrate host intensity of infection, but was positively correlated to the oocyst burden (parasitic stage preceding the sporozoite stage).

Conclusions

While the quantity of ingested parasites had no impact on oocyst and sporozoite burden in infectious mosquitoes, the EIP10 was affected. Studies have demonstrated that small changes in the EIP can have a significant effect on the number of mosquitoes living long enough to transmit parasites. Here, we observed a difference of 4–6 days in the detection of the first sporozoites, depending on the intensity of infection of the bitten vertebrate host. Considering that a gonotrophic cycle lasts 3–4 days, the shortened EIP may have significant effects on Plasmodium transmission.

Graphical Abstract
Translating and communicating evidence on allergy prevention in children to parents: implementation study protocol
Authors: Lander Jonas , Altawil Hala , Apfelbacher Christian , Bitzer Eva Maria , Brandstetter Susanne , Fillenberg Barbara , Hartmann Marius , Holmberg Christine , von Sommoggy Julia , Dierks Marie-Luise
Published: February 2025

Background

When seeking advice on allergy prevention in early childhood (Early Childhood Allergy Prevention, ECAP), parents often turn to health and social care providers, such as paediatricians, midwives, and family centres. However, these actors fulfil various, often care-related, roles, and cannot be considered ‘health information providers’ by default. In addition, although the scientific evidence for ECAP is often known by health professionals, it is not actively communicated. In this study protocol, we describe the planned procedure for the development and implementation of a process to communicate ECAP information to parents, with a focus on reaching out to those from migrant communities. Thereby, we also aim to contribute to the understanding of how to design more robust approaches to deliver health information.

Methods

We have chosen the Implementation Research Logic Model as our framework for a multi-stage process. Firstly, we will map regional and local health and social care providers to find potential providers of ECAP information. We will then approach actors from each mapping category for qualitative interviews to assess facilitators and barriers to implementation. Next, we will define actions to ease the implementation process, develop exemplary ECAP information materials for parents, and deliver these to pre-selected health and social care individuals and organizations. Each step will be adapted to meet the needs and preferences of culturally and linguistically diverse populations. Finally, the process will be evaluated for key implementation outcomes (e.g., acceptability, feasibility, effectiveness) by interviewing information providers and surveying information recipients.

Discussion

From a Public Health perspective, studies seem warranted that investigate how evidence from health research may be effectively communicated to the public, rather than merely focusing on, e.g., intervention development. Also, it has often been highlighted that the dissemination of health information needs to better target those who face the greatest difficulties when seeking advice, i.e. individuals/parents who recently migrated. ECAP is a good use case, as scientific evidence is constantly evolving, and the communication of information is hampered by low awareness of high quality sources.
A comparative study of using scorpion antivenom versus scorpion antivenom and prazosin drug for scorpion stings management in Sohag University Hospitals
Authors: Shokry Zaghary Meray Medhat , Abd ElKader Mai Mostafa
Published: February 2025

Background

Scorpion envenomation is a worldwide problem, especially in tropical and subtropical areas like Egypt. Scorpion envenomation is responsible for the high mortality rate all over the world, which makes much research carried out to see the efficacy of other drugs as supportive treatment in addition to antivenom.

Aim

To see the efficacy of prazosin drug with scorpion antivenom compared to antivenom alone.

Methods

It is a prospective randomized comparative study between two groups from February 2023 to July 2024. Each group is 50 cases to compare the efficacy of prazosin with antivenom (group 1) and the antivenom alone (group 2) in scorpion stings cases.

Results

The median age of the 100 cases was 7 years old. 54% of the study population were males. 46% of cases were females. Most of the cases were from rural areas. There was no significant difference in age, sex, and the patients’ residence between the two groups. There was no significant difference between the 2 groups regarding the duration of stay in the hospital till mortality or discharge, with a median of 3 days in each group. However, there was a significant difference in the antivenom received in each case between the 2 groups, with a median of 6 vials in group 1 and 9 vials in group 2. Mortality and complications were observed to occur more in group 2 than in group 1 despite the insignificant p values. The study’s mortality rate was 14%, 4/50 (8%) in group 1 and 10/50 (20%) in group 2. The number of antivenoms significantly increased with an increase in duration of stay, heart rate, respiratory rate, troponin level, and mortality outcome. While the number of antivenoms significantly decreased with the rise in systolic and diastolic blood pressure.

Conclusion and recommendations

: The study concluded that prazosin can be added to antivenom to increase its efficacy and decrease the number of needed antivenoms. Prazosin is a safe drug when used with precautions to avoid the first-dose phenomenon. Prazosin decreases complications and mortality when added to antivenom, but not significantly. The study recommends using prazosin with precautions for all manifested scorpion cases with antivenoms to increase the efficacy of the antivenom and treat the adrenergic manifestation.
Chromosome number variation and phylogenetic divergence of East Asian Cirsium sect. Onotrophe subsect. Nipponocirsium (Compositae), with a new species from Taiwan
Authors: Chang Chih-Yi , Liao Pei-Chung , Tzeng Hsy-Yu , Kusumi Junko , Su Zhi-Hui , Tseng Yen-Hsueh
Published: February 2025

Background

This study explored chromosome number variation, phylogenetic divergence, and mechanisms underlying speciation in East Asian thistle Cirsium Mill. sect. Onotrophe (Cass.) DC. subsect. Nipponocirsium Kitam. (Compositae). The study focused on the newly identified species from Taiwan: Cirsium pengii Y.H. Tseng, P.C. Liao & Chih Y. Chang. Utilizing phylotranscriptomic data to reconstruct evolutionary relationships between the Taiwanese and Japanese taxa of Cirsium subsect. Nipponocirsium as well as their divergence times and chromosomal characteristics. Additionally, the chromosome number, morphology, and pollen morphology of the unknown Cirsium taxon are compared with other known subsect. Nipponocirsium taxa from Taiwan.

Results

Phylotranscriptomic analysis reveals a division within subsect. Nipponocirsium into Japanese and Taiwanese clades. In the Taiwanese clade, C. pengii is basal, while C. tatakaense remains monophyletic with other Taiwanese species despite higher genetic diversity. The prevalent chromosome number in this subsection is tetraploid (2n = 4x = 68), common in Japanese taxa, while Taiwanese members have 2n = 4x = 64. Notably, C. pengii has a diploid number (2n = 32), indicating descending dysploidy followed by polyploidization in Taiwan. This polyploidization, driven by glaciations, likely shaped the evolution of Nipponocirsium. Divergence time estimates suggest the separation of Japanese and Taiwanese clades around 0.74 million years ago (Myr) during glacial periods. Cirsium pengii diverged around 0.47 Myr, while tetraploid species C. kawakamii and C. tatakaense diverged around 0.35 Myr. These species likely evolved in separate refugia, with distinct species boundaries confirmed through species delimitation analysis, karyotype, morphology, and pollen morphology comparisons.

Conclusions

These findings enhance our understanding of chromosomal evolution and speciation within subsect. Nipponocirsium and underscore the importance of integrating transcriptomic data in phylogenetic studies. This study provides a comprehensive framework for further investigations into the genetic diversity and adaptive mechanisms of this ecologically vital group.