bluuebunny/crossref_metadata_2025_split huggingface dataset:
Targeted long-read sequencing to quantify methylation of the C9orf72 repeat expansion
Authors: Udine Evan , Finch NiCole A. , DeJesus-Hernandez Mariely , Jackson Jazmyne L. , Baker Matthew C. , Saravanaperumal Siva Arumugam , Wieben Eric , Ebbert Mark T.W. , Shah Jaimin , Petrucelli Leonard , Rademakers Rosa , Oskarsson Björn , van Blitterswijk Marka 
Published: December 2024

Abstract
Background
The gene C9orf72 harbors a non-coding hexanucleotide repeat expansion known to cause amyotrophic lateral sclerosis and frontotemporal dementia. While previous studies have estimated the length of this repeat expansion in multiple tissues, technological limitations have impeded researchers from exploring additional features, such as methylation levels.

Methods
We aimed to characterize C9orf72 repeat expansions using a targeted, amplification-free long-read sequencing method. Our primary goal was to determine the presence and subsequent quantification of observed methylation in the C9orf72 repeat expansion. In addition, we measured the repeat length and purity of the expansion. To do this, we sequenced DNA extracted from blood for 27 individuals with an expanded C9orf72 repeat.

Results
For these individuals, we obtained a total of 7,765 on-target reads, including 1,612 fully covering the expanded allele. Our in-depth analysis revealed that the expansion itself is methylated, with great variability in total methylation levels observed, as represented by the proportion of methylated CpGs (13 to 66%). Interestingly, we demonstrated that the expanded allele is more highly methylated than the wild-type allele (P-Value = 2.76E-05) and that increased methylation levels are observed in longer repeat expansions (P-Value = 1.18E-04). Furthermore, methylation levels correlate with age at collection (P-Value = 3.25E-04) as well as age at disease onset (P-Value = 0.020). Additionally, we detected repeat lengths up to 4,088 repeats (~ 25 kb) and found that the expansion contains few interruptions in the blood.

Conclusions
Taken together, our study demonstrates robust ability to quantify methylation of the expanded C9orf72 repeat, capturing differences between individuals harboring this expansion and revealing clinical associations.
Accuracy of POC testing systems for HPV screening: the importance of disease prevalence and characteristics of the screened population
Authors: Giorgi Rossi Paolo , Ronco Guglielmo 
Published: December 2024

AbstractInfectious Agents and Cancer journal has recently launched a new collection of papers about “Point-of-Care (POC) for HPV-related genital cancers” putting together some interesting works on the accuracy of HPV tests for screening. This editorial initiative gave us the opportunity to reflect on the relations between accuracy measures, prevalence and characteristics of the tested population in the case of HPV-based screening. In screening test evaluation, we look at the clinical accuracy of the test as an intrinsic characteristic of the assay, which interacts with the characteristics of the population, the result being the screening performance. In the case of HPV testing, the clinical accuracy should be conceptualized in two steps, the analytical accuracy of the assay for HPV infection and the biological link between HPV infection and the target disease, i.e. the high-grade cervical intraepithelial neoplasia (hgCIN). This approach highlights that just a few false positive cases result from a lack of analytical specificity while most derive from women who have the infection but it did not progress to hgCIN. In addition, increasing prevalence of hgCIN results in relevant increases of PPV only if due or associated with exposures which increase the progression from infection to hgCIN or the duration of the latter; while an increase due to a higher prevalence of HPV infection would only marginally affect PPV. This approach may help in modelling the performance of HPV-based cervical screening.
Glutathione peroxidase 4 overexpression induces anomalous subdiffusion and impairs glioblastoma cell growth
Authors: Teferi Nahom , Ekanayake Akalanka , Owusu Stephenson B. , Moninger Thomas O. , Sarkaria Jann N. , Tivanski Alexei V. , Petronek Michael S. 
Published: December 2024

AbstractGlioblastoma tumors are the most common and aggressive adult central nervous system malignancy. Nearly all patients experience disease progression, which significantly contributes to disease mortality. Recently, it has been suggested that recurrent tumors may be characterized by a ferroptosis-prone phenotype with a significant decrease in glutathione peroxidase 4 (GPx4) expression. This led to the hypothesis that GPx4 expression negatively influences GBM cell growth. This study utilizes a doxycycline inducible GPx4 overexpression model to test this hypothesis. Consistently, the overexpression of GPx4 significantly impairs cell growth and colony formation while also causing an accumulation of cells in G1/G0 phase of the cell cycle. From a biophysical perspective, GPx4 overexpressing cells have significantly greater surface area, increased Young’s modulus, and experience anomalous sub-diffusion as opposed to normal diffusion associated with Brownian motion. Moreover, analysis of patient derived GBM cells reveal that cell growth rates, plating efficiency, and Young’s modulus are all inversely proportional to GPx4 expression. Therefore, GPx4 appears to be a biophysical regulator of GBM cell growth that warrants further mechanistic investigation in its role in GBM progression.
Ecteinascidin synthetic analogues: a new class of selective inhibitors of transcription, exerting immunogenic cell death in refractory malignant pleural mesothelioma
Authors: Salaroglio I. C. , Aviles P. , Kopecka J. , Merlini A. , Napoli F. , Righi L. , Novello S. , Sullivan H. , Cuevas C. , Scagliotti G. V. , Riganti C. 
Published: December 2024

Abstract
Background
Malignant pleural mesothelioma (MPM) is a highly chemo-refractory and immune-evasive tumor that presents a median overall survival of 12–14 months when treated with chemotherapy and immunotherapy. New anti-tumor therapies as well as the concomitant reactivation of immune destruction are urgently needed to treat patients with this tumor. The aim of this work is to investigate the potential effect of ecteinascidin derivatives as lurbinectedin as new first-line treatment option in MPM, alone and in combination with immunotherapy.

Methods
The antitumor activity of ecteinascidin synthetic analogues: lurbinectedin, ecubectedin and PM54 was evaluated in an array of patient-derived MPM cells in terms of cell proliferation, cell cycle, apoptosis, DNA damage and repair. Immunoblot was used to assess the cGAS/STING pathway. ELISA and flow cytometry-based assays were used to evaluate immunogenic cell death parameters and the effect on the immunophenotype in autologous peripheral blood monocyte-MPM cells co-cultures. Patient-derived xenografts (PDX) in humanized mice were used to evaluate the efficacy of ecteinascidins in vivo.

Results
Lurbinectedin, ecubectedin, and PM54 were effective in reducing cell proliferation and migration, as well as inducing S-phase cell cycle arrest and DNA damage in malignant pleural mesothelioma cells. These effects were more pronounced compared to the standard first-line treatment (platinum-based plus pemetrexed). Mechanistically, the drugs downregulated DNA repair genes, activated the cGAS/STING pathway, and promoted the release of pro-inflammatory cytokines. They also induced immunogenic cell death of mesothelioma cells, enhancing the activation of anti-tumor CD8+T-cells and natural killer cells while reducing tumor-tolerant T-regulatory cells and myeloid-derived suppressor cells in ex vivo co-cultures. These promising results were also observed in humanized patient-derived xenograft models, where the drugs were effective in reducing tumor growth and increasing the ratio anti-tumor/pro-tumor infiltrating immune populations, either alone or combined with the anti-PD-1L atezolizumab.

Conclusions
Collectively, these findings reveal a previously unknown mechanism of action of ecteinascidins that merits further investigation for potential clinical applications in the treatment of MPM, as new first line treatment in monotherapy or in association with immunotherapy.
Implementation of a parent training intervention (SPARCK) to prevent childhood mental health problems: study protocol for a pragmatic implementation trial in Norwegian municipalities
Authors: Grønlie Anette Arnesen , Backer-Grøndahl Agathe , Nes Ragnhild Bang , Gomez Maria Begoña , Tømmerås Truls 
Published: December 2024

Abstract
Background
Effective evidence-based interventions (EBI) are necessary to prevent and avoid negative life trajectories for children with mental health problems. Even though many EBIs prove effective when tested, few are successfully implemented and used in real-world clinical practice. As a result, many children and families do not receive the best care in due time or at all. To reduce this research-practice gap, a combined RCT and implementation study of Supportive Parents—Coping Kids (SPARCK), a parent training intervention to prevent childhood mental health problems, will be performed. This study protocol concerns the implementation part of the larger effectiveness-implementation project.

Methods
The study is a correlational multi-site implementation study of SPARCK performed alongside a two-armed RCT, in 24 Norwegian municipalities. A quantitative three-wave longitudinal web-based data collection will be conducted among SPARCK practitioners and leaders in relevant services. We will investigate the relations between theory-driven and empirical implementation determinants and implementation outcomes, measured by fidelity, acceptability, appropriateness, and feasibility. In addition, we will examine how these implementation determinants and outcomes are associated with the clinical outcomes of SPARCK.

Discussion
The current study will investigate implementation determinants and their relation to indicators of implementation success, while simultaneously investigating effectiveness of an intervention optimized to the needs of both the target group and relevant stakeholders. Together, this may improve clinical effect, contextual fit, implementation success, and reduce the time lag between research findings and application in real-world settings.

Trial registration
ClinicalTrials.gov NCT05800522. Registered on 2023.03.23.
Acoustic scene classification using inter- and intra-subarray spatial features in distributed microphone array
Authors: Kawamura Takao , Kinoshita Yuma , Ono Nobutaka , Scheibler Robin 
Published: December 2024

AbstractIn this study, we investigate the effectiveness of spatial features in acoustic scene classification using distributed microphone arrays. Under the assumption that multiple subarrays, each equipped with microphones, are synchronized, we investigate two types of spatial feature: intra- and inter-generalized cross-correlation phase transforms (GCC-PHATs). These are derived from channels within the same subarray and between different subarrays, respectively. Our approach treats the log-Mel spectrogram as a spectral feature and intra- and/or inter-GCC-PHAT as a spatial feature. We propose two integration methods for spectral and spatial features: (a) middle integration, which fuses embeddings obtained by spectral and spatial features, and (b) late integration, which fuses decisions estimated using spectral and spatial features. The evaluation experiments showed that, when using only spectral features, employing all channels did not markedly improve the F1-score compared with the single-channel case. In contrast, integrating both spectral and spatial features improved the F1-score compared with using only spectral features. Additionally, we confirmed that the F1-score for late integration was slightly higher than that for middle integration.
Multiband in-band full-duplexing using fractal concentric circular antenna arrays
Authors: Elsanousi Geili , Abbas Mohammed , Hirtenfelder Franz , AbdAlhameed Raed , Yang Xin-She , Le Tuan , Nguyen Huan X. 
Published: December 2024

AbstractIn this work, we present an innovative approach to enhance multiband communication systems by enabling the antenna subsystems to simultaneously transmit and receive across multiple independent in-band full-duplex (IBFD) channels, i.e. multiband-IBFD (MIBFD). This capability is powered by fractal antenna arrays, specifically using hexagonal star array (HSA) geometry. The approach provides a unique self-interference cancellation (SIC) capability across multiple bands (MB-SIC), achieved through translation or rotational transformations of self-similar or self-affine array structures. Simulation results demonstrate significantly enhanced SIC bandwidth for three signals at sub-frequencies near 5 GHz, with the integration of subbands’ SIC bandwidths achieving 1.4 GHz across these subbands. Further enhancements include combining this method with a technique involving the elevation of the central receiving element, significantly broadening the SIC bandwidth compared to traditional methods. Additionally, the multiband functionality is validated with pilot signals at 2.68 and 5.2 GHz, showing effective SIC in these narrow bands. This research presents a promising path for optimising radio resources in multiband communication systems.
Promoting hand hygiene in a chemotherapy day center: the role of a robot
Authors: Wong Shuk-Ching , Ip Stephen Chun-Yat , Kwok Monica Oi-Tung , Siu Crystal Yuen-Ki , Chen Jonathan Hon-Kwan , So Simon Yung-Chun , Chiu Kelvin Hei-Yeung , Yuen Kwok-Keung , Cheng Vincent Chi-Chung 
Published: December 2024

Abstract
Background
Hand hygiene is a critical component of infection prevention in healthcare settings. Innovative strategies are required to enhance hand hygiene practices among patients and healthcare workers (HCWs).

Methods
This study was conducted at the Chemotherapy Day Center of Queen Mary Hospital, Hong Kong. It comprised three phases: phase 1 involved observational audits of hand hygiene practices among patients and HCWs by infection control nurse (ICN); phase 2 included the installation of 53 pressure sensors on alcohol-based hand rub (AHR) bottles at designated sites to monitor usage; phase 3 introduced the robot named Temi Medic to promote hand hygiene through video broadcasts at strategic locations in the center. The mean counts of pressure sensor-equipped AHR per 100 attendances per day (hereafter referred to as the mean count) across phases 2 and 3 were analyzed.

Results
A total of 2580 patient attended the center from April to September 2023. The ICN observed a significant increase in hand hygiene practices among patients at the entrance and reception area, rising from phase 1 (0.2%, 1/583) and phase 2 (0.5%, 3/656) to phase 3 (5.0%, 33/654) (p < 0.001). Meanwhile, the overall hand hygiene compliance among HCWs was 74.1% (1341/1810) throughout the study period. From phase 2 to phase 3, the mean counts of 7 AHR bottles designated for patient use (P1–P7) significantly increased (35 ± 17 vs. 64 ± 24, p < 0.001), as did the 33 AHR bottles shared by both patients and HCWs (207 ± 104 vs. 267 ± 113, p = 0.027). In contrast, there was no significant change in the mean count among the 13 AHR bottles designated for HCWs (H1–H13). The mean count of H1–H13 was significantly higher than that of P1–P7 throughout phases 2 and 3 (214 ± 93 vs. 49 ± 25, p < 0.001), indicating a 4.4-fold difference.

Conclusions
While HCWs maintained stable hand hygiene compliance, the introduction of the robot significantly improved hand hygiene practices among patients in the chemotherapy day center. This underscores the importance of integrating technology into routine practices to promote infection prevention and control in healthcare settings.
Myocardial mRNA expression of interleukin-6 and hypoxia inducible factor-1α in neonates with congenital cardiac defects
Authors: Farhat Nesrine , Vazquez-Jimenez Jaime , Heying Ruth , Seghaye Marie-Christine 
Published: December 2024

Abstract
Background
In neonates with congenital heart disease (CHD), myocardial remodelling involves activation of inflammatory pathways. The role of hypoxemia related pathways is however unknown. This study was therefore designed to investigate myocardial mRNA expression of interleukin (IL)-6 and hypoxia-inducible factor (HIF)-1α in neonates with CHD and analyse its influence on post-operative outcome.

Results
14 neonates with CHD scheduled for open cardiac surgery were studied. In group 1 (n = 5), pre-operative transcutaneous arterial oxygen saturation (SaO2) was ≤ 85% and in group 2 (n = 9) > 85%. Expression of IL-6- and HIF-1α-mRNA was studied on right atrial biopsy by RT-PCR and corelated to post-operative (po) outcome. Group 1 patients showed higher mean arterial blood pressure (MAP) and lower glycaemia 4 h po (p = 0.047 and p = 0.021, respectively). In the whole cohort, SaO2 correlated negatively with MAP (Pearson R: -0.662, p = 0.010). mRNA coding for IL-6 and HIF-1α was detected in the myocardium of all neonates independently of age, gender, or type of CHD. IL6-mRNA expression was not influenced by pre-operative hypoxemia but was associated with higher lactate levels in early po period (Pearson R: 0,611, p = 0,020). HIF-1α-mRNA expression correlated negatively with pre-operative SaO2 (Pearson R: -0.551, p = 0.04) and with aspartate aminotransferase levels 4 h po (Pearson R: 0.625, p = 0.017).

Conclusion
Our study shows that besides inflammatory pathways, hypoxemia related pathways are activated in the myocardium of neonates with CHD. Myocardial expression of both IL-6-mRNA and HIF-1α-mRNA relates to biological markers of a worse po outcome.
CHMP2B promotes CHMP7 mediated nuclear pore complex injury in sporadic ALS
Authors: Keeley Olivia , Mendoza Emma , Menon Druv , Coyne Alyssa N. 
Published: December 2024

AbstractAlterations to the composition and function of neuronal nuclear pore complexes (NPCs) have been documented in multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis (ALS). Moreover, recent work has suggested that injury to the NPC can at least in part contribute to TDP-43 loss of function and mislocalization, a pathological hallmark of ALS and related neurodegenerative diseases. Collectively, these studies highlight a role for disruptions in NPC homeostasis and surveillance as a significant pathophysiologic event in neurodegeneration. The ESCRT-III nuclear surveillance pathway plays a critical role in the surveillance and maintenance of NPCs and the surrounding nuclear environment. Importantly, pathologic alterations to this pathway and its protein constituents have been implicated in neurodegenerative diseases such as ALS. However, the mechanism by which this pathway contributes to disease associated alterations in the NPC remains unknown. Here we use an induced pluripotent stem cell (iPSC) derived neuron (iPSN) model of sALS to demonstrate that CHMP7/ESCRT-III nuclear maintenance/surveillance is overactivated in sALS neurons. This overactivation is dependent upon the ESCRT-III protein CHMP2B and sustained CHMP2B dependent “activation” is sufficient to contribute to pathologic CHMP7 nuclear accumulation and POM121 reduction. Importantly, partial knockdown of CHMP2B was sufficient to alleviate NPC injury and downstream TDP-43 dysfunction in sALS neurons thereby highlighting CHMP2B as a potential therapeutic target in disease.
Prognostic value of metabolic tumor volume on [18F]FDG PET/CT in addition to the TNM classification system of locally advanced non-small cell lung cancer
Authors: Brose Alexander , Miederer Isabelle , König Jochem , Gkika Eleni , Sahlmann Jörg , Schimek-Jasch Tanja , Schreckenberger Mathias , Nestle Ursula , Kappes Jutta , Miederer Matthias 
Published: December 2024

Abstract
Purpose
Staging of non-small cell lung cancer (NSCLC) is commonly based on [18F]FDG PET/CT, in particular to exclude distant metastases and guide local therapy approaches like resection and radiotherapy. Although it is hoped that PET/CT will increase the value of primary staging compared to conventional imaging, it is generally limited to the characterization of TNM. The first aim of this study was to evaluate the PET parameter metabolic tumor volume (MTV) above liver background uptake as a prognostic marker in lung cancer. The second aim was to investigate the possibility of incorporating MTV into the TNM classification system for disease prognosis in locally advanced NSCLC treated with chemoradiotherapy.

Methods
Retrospective evaluation of 235 patients with histologically proven, locally advanced NSCLC from the multi-centre randomized clinical PETPLAN trial and a clinical cohort from a hospital registry. The PET parameters SUVmax, SULpeak, MTV and TLG above liver background uptake were determined. Kaplan-Meier curves and stratified Cox proportional hazard regression models were used to investigate the prognostic value of PET parameters and TNM along with clinical variables. Subgroup analyses were performed to compare hazard ratios according to TNM, MTV, and the two variables combined.

Results
In the multivariable Cox regression analysis, MTV was associated with significantly worse overall survival independent of stage and other prognostic variables. In locally advanced disease stages treated with chemoradiotherapy, higher MTV was significantly associated with worse survival (median 17 vs. 32 months). Using simple cut-off values (45 ml for stage IIIa, 48 ml for stage IIIb, and 105 ml for stage IIIc), MTV was able to further predict differences in survival for stages IIIa-c. The combination of TNM and MTV staging system showed better discrimination for overall survival in locally advanced disease stages, compared to TNM alone.

Conclusion
Higher metabolic tumor volume is significantly associated with worse overall survival and combined with TNM staging, it provides more precise information about the disease prognosis in locally advanced NSCLC treated with chemoradiotherapy compared to TNM alone. As a PET parameter with volumetric information, MTV represents a useful addition to TNM.