bluuebunny/crossref_metadata_2025_split huggingface dataset:
Local delivery of hrBMP4 as an anticancer therapy in patients with recurrent glioblastoma: a first-in-human phase 1 dose escalation trial
Authors: Bos Eelke M. , Binda Elena , Verploegh Iris S.C. , Wembacher Eva , Hoefnagel Daphna , Balvers Rutger K. , Korporaal Anne L. , Conidi Andrea , Warnert Esther A. H. , Trivieri Nadia , Visioli Alberto , Zaccarini Paola , Caiola Laura , van Wijck Rogier , van der Spek Peter , Huylebroeck Danny , Leenstra Sieger , Lamfers Martine L.M. , Ram Zvi , Westphal Manfred , Noske David , Legnani Federico , DiMeco Francesco , Vescovi Angelo Luigi , Dirven Clemens M.F. 
Published: August 2023

Abstract
Background
This Phase 1 study evaluates the intra- and peritumoral administration by convection enhanced delivery (CED) of human recombinant Bone Morphogenetic Protein 4 (hrBMP4) – an inhibitory regulator of cancer stem cells (CSCs) – in recurrent glioblastoma.

Methods
In a 3 + 3 dose escalation design, over four to six days, fifteen recurrent glioblastoma patients received, by CED, one of five doses of hrBMP4 ranging from 0·5 to 18 mg. Patients were followed by periodic physical, neurological, blood testing, magnetic resonance imaging (MRI) and quality of life evaluations. The primary objective of this first-in-human study was to determine the safety, dose-limiting toxicities (DLT) and maximum tolerated dose (MTD) of hrBMP4. Secondary objectives were to assess potential efficacy and systemic exposure to hrBMP4 upon intracerebral infusion.

Results
Intra- and peritumoral infusion of hrBMP4 was safe and well-tolerated. We observed no serious adverse events related to this drug. Neither MTD nor DLT were reached. Three patients had increased hrBMP4 serum levels at the end of infusion, which normalized within 4 weeks, without sign of toxicity. One patient showed partial response and two patients a complete (local) tumor response, which was maintained until the most recent follow-up, 57 and 30 months post-hrBMP4. Tumor growth was inhibited in areas permeated by hrBMP4.

Conclusion
Local delivery of hrBMP4 in and around recurring glioblastoma is safe and well-tolerated. Three patients responded to the treatment. A complete response and long-term survival occurred in two of them. This warrants further clinical studies on this novel treatment targeting glioblastoma CSCs.

Trial registration
: ClinicaTrials.gov identifier: NCT02869243.
Lung abscess as a complication of Lemierre Syndrome in adolescents: a single center case reports and review of the literature
Authors: Venditto Laura , Ferrante Giuliana , Caccin Anna , Franchini Giulia , Zaffanello Marco , Tenero Laura , Piazza Michele , Di Gioia Stefano , Piacentini Giorgio , Pietrobelli Angelo 
Published: August 2023

Abstract
Background
Fusobacterium necrophorum is an anaerobic, gram-negative, non-motile, filamentous, non-spore forming bacillus found in the oral cavity, gastrointestinal tract, and female genital tract, responsible of a rare disease named Lemierre Syndrome, characterized by septic thrombophlebitis of the internal jugular vein, which mainly affects previously healthy adolescents and young adults; some risk factors are reported, as smoking or primary viral or bacterial infection leading to the disruption of mucosa. The syndrome originates commonly from an upper respiratory infection such as pharyngotonsillitis, acute otitis media, cervical lymphadenitis, sinusitis, or odontogenic abscess, and may result in multiorgan metastasis, more frequently leading to pulmonary complications, especially lung abscesses.

Case presentation
We describe two cases of adolescents with atypical Lemierre Syndrome evaluated in a tertiary care center, one with a confirmed infection by Fusobacterium necrophorum and one with a presumptive diagnosis based on clinical features, who developed lung abscesses needing a prolonged antibiotic course and hospitalization. Of interest, both were user of electronic cigarette, configuring a possible new risk factor. The proper diagnosis of Lemierre Syndrome is often difficult to establish, so a high degree of suspicion is needed, especially in the case of lung abscesses in otherwise healthy adolescents.

Conclusion
The current study will contribute to providing insight into Lemierre Syndrome clinical presentation and management in adolescents, promoting awareness for a rare but potentially fatal disease. Moreover, it suggests a possible relationship between Lemierre syndrome and the use of electronic cigarette, that should be investigated by future studies.
Introduction of a multiplex amplicon sequencing assay to quantify DNA methylation in target cytosine markers underlying four selected epigenetic clocks
Authors: Pośpiech Ewelina , Pisarek Aleksandra , Rudnicka Joanna , Noroozi Rezvan , Boroń Michał , Masny Aleksander , Wysocka Bożena , Migacz-Gruszka Kamila , Lisman Dagmara , Pruszkowska-Przybylska Paulina , Kobus Magdalena , Szargut Maria , Dowejko Joanna , Stanisz Kamila , Zacharczuk Julia , Zieliński Piotr , Sitek Aneta , Ossowski Andrzej , Spólnicka Magdalena , Branicki Wojciech 
Published: August 2023

Abstract
Background
DNA methylation analysis has proven to be a powerful tool for age assessment. However, the implementation of epigenetic age prediction in diagnostics or routine forensic casework requires appropriate laboratory methods. In this study, we aimed to compare the performance of large-scale DNA methylation analysis protocols that show promise in terms of accuracy, throughput, multiplexing capacity, and high sensitivity.

Results
The protocols were designed to target a predefined panel of 161 genomic CG/CA sites from four known estimators of epigenetic age-related parameters, optimized and validated using artificially methylated controls or blood samples. We successfully targeted 96% of these loci using two enrichment protocols: Ion AmpliSeq™, an amplicon-based method integrated with Ion Torrent S5, and SureSelectXT Methyl-Seq, a hybridization-based method followed by MiSeq FGx sequencing. Both protocols demonstrated high accuracy and robustness. Although hybridization assays have greater multiplexing capabilities, the best overall performance was observed for the amplicon-based protocol with the lowest variability in DNA methylation at 25 ng of starting DNA, mean observed marker coverage of ~ 6.7 k reads, and accuracy of methylation quantification with a mean absolute difference between observed and expected methylation beta value of 0.054. The Ion AmpliSeq method correlated strongly with genome-scale EPIC microarray data (R = 0.91) and showed superiority in terms of methylation measurement accuracy. Method-to-method bias was accounted for by the use of linear transformation, which provided a highly accurate prediction of calendar age with a mean absolute error of less than 5 years for the VISAGE and Hannum age clocks used. The pace of aging (PoAm) and the mortality risk score (MRS) estimators included in our panel represent next-generation clocks, were found to have low to moderate correlations with the VISAGE and Hannum models (R < 0.75), and thus may capture different aspects of epigenetic aging.

Conclusions
We propose a laboratory tool that allows the quantification of DNA methylation in cytosines underlying four different clocks, thus providing broad information on epigenetic aging while maintaining a reasonable number of CpG markers, opening the way to a wide range of applications in forensics, medicine, and healthcare.
Willingness to use novel reversible methods of male birth control: a community-based survey of cisgender men in the United States
Authors: Martins Summer L. , Boraas Christy M. 
Published: August 2023

Abstract
Background
There is high global demand for new methods of male birth control (MBC). However, contemporary evidence regarding men’s method-specific attitudes and their determinants is sparse.

Methods
Non-sterilized cisgender men ages 18–45 with recent history of female sex partners were surveyed at a large community event in the Midwestern US. We examined variation in participants’ willingness to use MBC by method (gel, pill, injection, implant, and vas occlusion), potential side effects, and potential barriers. We estimated crude and adjusted prevalence ratios (aPRs) for associations between participant characteristics and willingness to use ≥ 1 MBC method.

Results
Overall, 72% of participants (n = 187; mean age, 29) were very willing to use ≥ 1 MBC method although support for individual methods ranged widely from 62% (pill) to 24% (vas occlusion). In bivariate analysis of sociodemographic and health characteristics, few demonstrated associations with MBC willingness. In a multivariable model, willingness was independently related to age (30–39 vs. 18–29 years old, aPR = 1.24, 95% CI 1.04–1.48) and having ever been tested for HIV (aPR = 1.27, 95% CI 1.07–1.51). Willingness to tolerate side effects was < 10% for most items. The most commonly endorsed barriers to MBC use were high cost (77%) and side effects (66%).

Conclusions
Enthusiasm for MBC was high but waned in the context of potential side effects and barriers. Additional research on MBC attitudes in socioeconomically and culturally diverse populations worldwide is sorely needed.
Pathogenicity and other characteristics of the endophytic Beauveria bassiana strain (Bals.) (Hypocreales: Cordycipitaceae)
Authors: El-Maraghy Saad S. Mohamed , Abdel-Rahman Mohamed A. A. , Hassan Shimaa Hassan Mohamed , Hussein Khalid A. 
Published: August 2023

Abstract
Background
Agriculture crops such as tomatoes and wheat are frequently targeted by insect pests which have a significant negative impact on the agricultural economies. The deployment of entomopathogenic fungi (EPF) for the control of the insect pests is an important alternative to synthetic insecticides. The EPF, Beauveria bassiana (Balsamo) Vuillemin, has been reported widely as a suitable biological control agent of many agricultural pests.

Results
In this study, B. bassiana SS-1 was isolated from local plant crops and its pathogenicity was assessed against the greater wax moth larvae Galleria mellonella (L.). The development of the pathogenic B. bassiana SS-1 on the insect was visualized using scanning electron microscopy (SEM). Results showed the ability of B. bassiana SS-1 to secrete extracellularly the important enzymes essential for insect cuticle penetration. B. bassiana SS1 recorded the maximum mean lipase (5.3 U/ml), protease (32.13 U/ml), and chitinase activities (2.95 U/ml). The endophytic pathogenic fungus B. bassiana SS-1 demonstrated pathogenicity against the fourth instar larvae of G. mellonella showing LC50 at 2.47 × 102 conidia/ml and LC95 at 3.98 × 105 conidia/ml. The SEM results showed physical contact with B. bassiana SS-1 hyphae on the surface of the G. mellonella larvae. Thus, the isolated EPF B. bassiana SS-1, even endophytic, could be a promising biocontrol agent to manage agricultural insect pests.

Conclusion
This study provided a comprehensive characterization of the pathogenicity of B. bassiana SS-1 with its microbiological characteristics. Future studies are needed to focus on the detection of highly virulent isolates against different insect pests and to assess their field contribution as a favorable biological control agent.
Anaplastic Lymphoma Kinase Inhibitors for Therapy of Neuroblastoma in Adults
Authors: Stiefel Jessica , Kushner Brian H. , Roberts Stephen S. , Iglesias-Cardenas Fiorella , Kramer Kim , Modak Shakeel 
Published: August 2023

PURPOSE Adult-onset neuroblastoma (AON) differs significantly in biology and clinical behavior from childhood-onset disease. AON poses therapeutic challenges since tolerance of intensive multimodality therapies that are standard of care for pediatric neuroblastoma (NB) is poor. AON is enriched for somatic mutations including anaplastic lymphoma kinase ( ALK), deemed to be an oncogenic driver in NB. ALK inhibitors (ALKis), therefore, have the potential to be of therapeutic benefit. The purpose of this study is to report on their use in AON. METHODS A single-center retrospective review of adults with NB receiving ALKi (2012-2022) was performed. Response was evaluated using International Neuroblastoma Response Criteria. RESULTS Fifteen patients with ALK-mutated AON were treated with US Food and Drug Administration–approved ALKi starting at a median age of 34 (16-71) years. Initial ALKi was lorlatinib, crizotinib, and alectinib in seven, five, and three patients respectively; seven received multiple ALKis due to progressive disease/intolerability of one agent. All patients experienced ≥grade 2 adverse events (AEs): crizotinib and alectinib were associated primarily with gastrointestinal AEs, lorlatinib with neurologic AEs, weight gain, and hyperlipidemia resulting in dose reduction or discontinuation of ALKi in several patients. No responses were observed with crizotinib (n = 5 patients), ceritinib, alectinib, or brigatinib (n = 1 each). Of the 13 patients receiving lorlatinib, four, five, and four patients had a complete or partial response (major response rate 69%), and stable disease, respectively. Responses were noted in all disease compartments; complete metabolic response was seen in two L2 patients. Ten of 13 patients remain progression-free at a median of 19 (6-50) months on lorlatinib. Three (two receiving dose-reduced therapy) had progressive disease. Median survival from start of first ALKi was 43 ± 26 months. CONCLUSION ALKis, particularly lorlatinib, are effective treatment options for AON. However, AEs necessitating dose reduction are common.
Effects of Single-Stranded DNA Base Number and Duplex DNA Formation on Intraparticle Diffusion Behavior
Authors: Miyagawa Akihisa , Fukushima Asahi , Nagatomo Shigenori , Nakatani Kiyoharu 
Published: August 2023

Abstract
We investigated the effects of the base number of single-stranded DNA and duplex DNA formation on the intraparticle diffusion behavior in amino-functionalized silica particles. The sigmoidal distribution behavior of 50 base single-stranded DNA was explained using the DNA aggregation model. Similar results to those previously reported using 20 base DNA were obtained. However, the DNA aggregate was less likely to form and the diffusion coefficient (D) decreased likely because of electrostatic repulsion and pore hindrance, respectively. The intraparticle diffusion of the duplex DNA participated in its dissociation. After duplex DNA distribution in the particle, the single-stranded DNA formed in solution inside the pores was released. The D values ((3.5–8.1) × 10−8 cm2 s−1) obtained from the initial rate were 10-fold those of single-stranded DNA ((0.69–5.0) × 10−9 cm2 s−1). Therefore, the distribution mechanisms of longer single-stranded and duplex DNA were revealed based on the kinetic analysis.
Validation of a modified Care and Comfort Score and responsiveness to hip surgery in children with cerebral palsy in Gross Motor Function Classification System levels IV and V
Authors: Makaram Navnit S. , Prescott Robin J. , Alexander Phyllida , Robb James E. , Gaston Mark S. 
Published: August 2023

AimsThe purpose of this study was to assess the reliability and responsiveness to hip surgery of a four-point modified Care and Comfort Hypertonicity Questionnaire (mCCHQ) scoring tool in children with cerebral palsy (CP) in Gross Motor Function Classification System (GMFCS) levels IV and V.MethodsThis was a population-based cohort study in children with CP from a national surveillance programme. Reliability was assessed from 20 caregivers who completed the mCCHQ questionnaire on two occasions three weeks apart. Test-retest reliability of the mCCHQ was calculated, and responsiveness before and after surgery for a displaced hip was evaluated in a cohort of children.ResultsTest-retest reliability for the overall mCCHQ score was good (intraclass correlation coefficient 0.78), and no dimension demonstrated poor reliability. The surgical intervention cohort comprised ten children who had preoperative and postoperative mCCHQ scores at a minimum of six months postoperatively. The mCCHQ tool demonstrated a significant improvement in overall score from preoperative assessment to six-month postoperative follow-up assessment (p < 0.001).ConclusionThe mCCHQ demonstrated responsiveness to intervention and good test-retest reliability. The mCCHQ is proposed as an outcome tool for use within a national surveillance programme for children with CP.Cite this article: Bone Jt Open 2023;4(8):580–583.
Mock trial as a simulation strategy allowing undergraduate nursing students to experience evidence-based practice: A scoping-review
Authors: Song Chieun , Jang Aeri 
Published: August 2023

Objective
The purpose of this scoping review was to determine the underlying design of simulations that help undergraduate nursing students acquire evidence-based practice (EBP) experiences.

Method
The JBI methodology was used for this review. The inclusion criteria were studies conducted in academic, clinical, or virtual settings that examined simulation programs designed to facilitate the acquisition of EBP by undergraduate nursing students. A comprehensive search was performed on Jan 3, 2022, using the Medical Literature Analysis and Retrieval System Online (MEDLINE; PubMed), the Cumulative Index to Nursing and Allied Health Literature (CINAHL), the Education Resources Information Center (ERIC), and the Excerpta Medica database (EMBASE). Grey literature was not included. Publication year was limited to 2020 and later. There was no language restriction. Data were extracted using a tool developed by the reviewers and based on the National League for Nursing Jeffries Simulation Theory.

Result
A total of 12,931 articles were found, and after duplicate articles and articles deemed ineligible based on the title and abstract (12,914 articles), 17 published papers were examined. The full texts of these studies were reviewed for eligibility, and one study was selected for the present scoping review. The selected study examined a mock trial designed to allow undergraduate nursing students to experience the ethical decision-making based on a diversity of evidence. The program reported in the study consisted of a prebriefing—simulation (mock)—debriefing structure with verified positive effects on EBP education.

Conclusion
A mock trial is a useful educational strategy for allowing undergraduate nursing students to experience EBP, but a creative method should be found that can modify the mock trial for practical operation as the designing the program demands high levels of human and material resources.

Registration
OSF Registries, https://osf.io/gdtyu, We updated OSF registry data for documenting important protocol amendments.
Perspectives of older people with uncontrolled type 2 diabetes mellitus towards medication adherence: A qualitative study
Authors: Upamali Sathma , Rathnayake Sarath 
Published: August 2023

Background
Better medication adherence among people with diabetes mellitus was found to be associated with improved glycaemic control. However, medication non-adherence is a significant concern in older people with uncontrolled type 2 diabetes mellitus.

Purpose
To explore the perspectives of older people with uncontrolled type 2 diabetes mellitus towards medication adherence.

Design
A qualitative descriptive exploratory study.

Methodology
A purposive sample of older people with uncontrolled type 2 diabetes mellitus living in the community was recruited. Snowball sampling was applied in community recruitment. In‐depth telephone interviews were conducted using a semi‐structured interview guide. Interviews were transcribed verbatim. Thematic analysis was used in data analysis. The consolidated criteria for reporting qualitative research (COREQ) guidelines were followed.

Results
The emerged six themes were: (a) impact of knowledge, attitudes and practices on medication adherence, (b) treatment-related barriers to medication adherence, (c) impact of age-related changes on medication adherence, (d) person-related barriers to medication adherence, (e) impact of COVID-19 on medication adherence and, (f) role of support systems in medication adherence. Knowledge of the disease process and medications, attitudes towards medication adherence, the practice of different treatment approaches, self-medication and dosing, negative experiences related to medications, polypharmacy, changes in lifestyle and roles, the influence of work-life, motivation, negligence, family support, support received from health workers, facilities available and financial capability are the main factors influence medication adherence. Age-related memory impairment, visual disturbances and physical weaknesses affect medication adherence in older people. Additionally, COVID-19-related guidelines imposed by the government and healthcare system-related issues during the COVID-19 pandemic also affected medication adherence.

Conclusion
Adherence to medications among older people is hampered by a variety of factors, including their knowledge, attitudes and practices, person and treatment-related factors and age-related changes. The COVID-19 pandemic has brought additional challenges. Individualised patient care for older people with uncontrolled type 2 diabetes mellitus to improve medication adherence is timely. Strengthening support mechanisms for the above population is essential.
Understanding and optimising support resources to facilitate CALD student and supervisor allied health fieldwork experiences
Authors: Newton Fiona J. , Lee Den-Ching A. , Brito Sara 
Published: August 2023

Background
Although fieldwork supervisors and culturally and linguistically diverse (CALD) students can experience challenges during allied health placements, there is little holistic understanding of how they view and use support resources to address these challenges. This study sought to identify, codify, and map the perceived value attached to support resources used or sought by CALD students and fieldwork supervisors and to ascertain areas where they could be optimised and better presented to users.

Methods
We conducted a thematic analysis to examine interview and open-ended survey responses from CALD students (n = 18) and fieldwork supervisors (n = 161) respectively.

Findings
The six generated themes depicted different patterns of perceived value in university and non-university support resources and spanned three levels of specificity: general, discipline-contextualised, and individualised. Fieldwork supervisors valued a staged approach to support resource design and use for CALD students commencing with general level resources to build foundational language skills and socio-cultural familiarisation and moving on to include disciple-contextualised supports, preplacement mechanisms to monitor student readiness, and formalised mechanisms to enable tailoring of placements. CALD students, however, often undervalued institutional general resources relative to discipline-contextualised resources. The commonality of support resources valued and sought by supervisors from different fields suggests they could be optimised for delivery via an inter-professional community of practice.

Conclusion
Identifying and mapping the perceived value attached to support resources provides actionable insights into how to enhance the ‘fit’ between resources and user needs. Drawing the often-fragmented support resources into a cohesive ecosystem focused around perceived value at different levels of specificity allows CALD students and educators to better conceptualise the types of benefits that can accrue from taking a broader and staged approach to fieldwork placement preparations. Knowing this ecosystem encapsulates what prior uses find of value may enhance perceptions of resource relevance in the minds of new users.