bluuebunny/crossref_metadata_2025_split huggingface dataset:
A preventive integrated eHealth approach for individuals with a low socioeconomic position: protocol for a realist evaluation
Authors: Israel Adriana M.C. , van Lenthe Frank J. , Beenackers Mariëlle A. 
Published: October 2024

Abstract
Background
Adoption of standalone eHealth tools is low among persons in lower socioeconomic groups. The preventive integrated eHealth approach combines blended care with an active and personal approach to facilitate access to local care, tailored to the needs of the participant. We describe the four step preventive integrated eHealth approach for individuals with a low socioeconomic position and the realist evaluation protocol of the intervention and implementation. The realist evaluation centers around the question, ‘what works for whom in what circumstances and why’.

Methods
The study population will consist of adult individuals with a low socioeconomic position, who participate in the preventive integrated eHealth approach in one of the participating locations in the Netherlands. The four-step intervention consists of: (1) a proactive invitation of participants by care professionals, (2) the use of an eHealth tool that produces a personalized health report, (3) a personal consultation with a care professional to discuss the personalized health report and set a goal to work on, and (4) active referral to local social and health care. An initial program theory theorized from literature and stakeholder involvement is presented. Qualitative and quantitative data collection and analysis with participants (survey at zero, three and twelve months and focus groups at six months) and professionals (interviews at three months) will inform the realist evaluation and serves to test and refine the initial program theory.

Discussion
Our mixed-methods realist evaluation on the effect and implementation of a personal and active blended care approach will elucidate what elements trigger the mechanisms and responses of how individuals with a low socioeconomic position experience the preventive integrated eHealth approach. This will inform the way a preventative health check incorporating eHealth can be used to its full potential for low socioeconomic positioned groups to help close the digital divide and contribute to reduce health disparities.
Impact of refrigeration of different Resin composite restorative materials on the marginal adaptation in class II restorations
Authors: El-Maksoud Omar Abd , Hamama Hamdi , Wafaie Ramy Ahmed , El-Wassefy Noha , Mahmoud Salah Hasab 
Published: October 2024

Abstract
Background
The pre-polymerization temperature of resin composite restorative materials could influence their adaptation to cavity details. As a current debate is existing about the refrigeration of resin composite restorative materials, this study was designed to assess the effect of refrigeration of 3 types of resin composite restorative materials with different matrix systems on their marginal adaptation in Class II restorations.

Methods
Forty-two sound maxillary molars, each with two separated Class II cavities, were used in this study. The teeth were assigned into 3 main groups (n = 14) according to the restorative /adhesive system used; an Ormocer-based composite (Admira Fusion/Futurabond M+, Voco GmbH, Cuxhaven, Germany), a methacrylate modified Ormocer-based (Ceram.X SphereTEC One/Prime&Bond Universal, Dentsply Sirona GmbH Konstanz, Germany), and a methacrylate-based (Tetric N-Ceram/Tetric N-Bond Universal, Ivoclar Vivadent AG, Schaan, Liechtenstein). Each group was then divided into 2 subgroups (n = 14) according to the gingival margin location; 1 mm above and 1 mm below the cemento-enamel junction (C.E.J). Each subgroup was further divided into 2 categories (n = 7) according to the storage temperature; stored at room temperature or stored in refrigerator at 4°- 5° C. Epoxy resin replicas were observed under scanning electron microscope (SEM) to examine the marginal gaps. A gab scoring system was used to assess the marginal adaptation of each restoration by giving scores on the basis of measurements of the maximum marginal gaps. The data obtained were statistically analyzed using the Chi-square test at a significance level of p < 0.05.

Results
None of the tested groups exhibited 100% gap-free margins irrespective of margin location or storage temperature. For both storage temperatures, no statistically significant difference was observed among all tested groups either with margins located above or below C.E.J (p > 0.05). As well, there was no statistically significant difference when comparing both marginal locations for each material (p > 0.05). Regarding the effect of storage temperature, statistically significant difference was only observed between the room-temperature stored groups with margins located above C.E.J and their corresponding groups stored in refrigerator (p < 0.05).

Conclusion
The refrigeration of resin composite restorative materials prior to the restorative procedures revealed a deleterious effect on marginal adaptation of the restorations with margins located in enamel regardless the type of material used.
Expiratory flow limitation development index (ELDI): a novel method of assessing respiratory mechanics in COPD
Authors: Dean James , Fowler Stephen J. , Singh Dave , Beech Augusta 
Published: October 2024

Abstract
Background
Expiratory flow limitation (EFL) can be detected using oscillometric reactance and is associated with a worse clinical presentation in chronic obstructive pulmonary disease (COPD). Reactance can show negative swings upon exhalation, which may develop at different rates between patients. We propose a new method to quantify the rate of EFL development; the EFL Development Index (ELDI).

Methods
A retrospective analysis of data from 124 COPD patients was performed. Data included lung function tests, Impulse Oscillometry (IOS), St Georges Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) scale and COPD Assessment Test (CAT) score. Fifty four patients had repeat data after 6 months. Twenty two patients had data recorded after 5 days of treatment with long acting bronchodilator therapy. EDLI was calculated as the mean expiratory reactance divided by the minimum expiratory reactance.

Results
The mean ELDI was used to categorise patients with rapid onset of EFL (> 0.63; n = 29) or gradual onset (≤ 0.63; n = 34). Those with rapid development had worse airflow obstruction, lower quality of life scores, and greater resting hyperinflation, compared to those with gradual development. In patients with EFL, ELDI correlated with symptoms scores, airflow obstruction, lung volumes and gas diffusion. Both EFL and ELDI were stable over 6 months. EFL and EDLI improved with bronchodilator treatment.

Conclusions
COPD patients with rapid EFL development (determined by ELDI) had worse clinical characteristics than those with gradual EFL development. The rate of EFL development appears to be associated with clinical and physiological characteristics.
Working in a relational way is everything: Perceptions of power and value in a drug policy-making network
Authors: Zakimi Naomi , Bouchard Martin , Ritter Alison , Greer Alissa 
Published: October 2024

Abstract
Background
The development of drug policies has been a major focus for policy-makers across North America in light of the ongoing public health emergency caused by the overdose crisis. In this context, the current study examined stakeholders’ experiences and perceptions of power and value in a drug policy-making process in a North American city using qualitative, questionnaire, and social network data.

Methods
We interviewed 18 people who participated in the development of a drug policy proposal between October 2021 and March 2022. They represented different groups and organizations, including government (n = 3), people who use drugs-led advocacy organizations (n = 5), other drug policy advocacy organizations (n = 5), research (n = 3) and police (n = 2). Most of them identified as men (n = 8) and white (n = 16), and their ages ranged between 30 and 80 years old (median = 50). Social network analysis questionnaires and semi-structured qualitative interviews were administered via Zoom. Social network data were analysed using igraph in R, and qualitative data were analysed using thematic analysis. The analyses explored perceptions of value and power within a drug policy-making network.

Results
The policy-making network showed that connections could be found across participants from different groups, with government officials being the most central. Qualitative data showed that inclusion in the network and centrality did not necessarily translate into feeling powerful or valued. Many participants were dissatisfied with the process despite having structurally advantageous positions or self-reporting moderately high quantitative value scores. Participants who viewed themselves as more valued acknowledged many process shortcomings, but they also saw it as more balanced or fair than those who felt undervalued.

Conclusions
While participation can make stakeholders and communities feel valued and empowered, our findings highlight that inclusion, position and diversity of connections in a drug policy-making network do not, in and of itself, guarantee these outcomes. Instead, policy-makers must provide transparent terms of reference guidelines and include highly skilled facilitators in policy discussions. This is particularly important in policy processes that involve historical power imbalances in the context of a pressing public health emergency.
Hyperspectral imaging for pest symptom detection in bell pepper
Authors: Krüger Marvin , Zemanek Thomas , Wuttke Dominik , Dinkel Maximilian , Serfling Albrecht , Böckmann Elias 
Published: October 2024

Abstract
Background
The automation of pest monitoring is highly important for enhancing integrated pest management in practice. In this context, advanced technologies are becoming increasingly explored. Hyperspectral imaging (HSI) is a technique that has been used frequently in recent years in the context of natural science, and the successful detection of several fungal diseases and some pests has been reported. Various automated measures and image analysis methods offer great potential for enhancing monitoring in practice.

Results
In this study, the use of hyperspectral imaging over a wide spectrum from 400 to 2500 nm is investigated for noninvasive identification and the distinction of healthy plants and plants infested with Myzus persicae (Sulzer) and Frankliniella occidentalis (Pergande) on bell peppers. Pest infestations were carried out in netted areas, and images of single plants and dissected leaves were used to train the decision algorithm. Additionally, a specially modified spraying robot was converted into an autonomous platform used to carry the hyperspectral imaging system to take images under greenhouse conditions. The algorithm was developed via the XGBoost framework with gradient-boosted trees. Signals from specific wavelengths were found to be associated with the damage patterns of different insects. Under confined conditions, M. persicae and F. occidentalis infestations were distinguished from each other and from the uninfested control for single leaves. Differentiation was still possible when small whole plants were used. However, application under greenhouse conditions did not result in a good fit compared to the results of manual monitoring.

Conclusion
Hyperspectral images can be used to distinguish sucking pests on bell peppers on the basis of single leaves and intact potted bell pepper plants under controlled conditions. Wavelength reduction methods offer options for multispectral camera usage in high-grown vegetable greenhouses. The application of automated platforms similar to the one tested in this study could be possible, but for successful pest detection under greenhouse conditions, algorithms should be further developed fully considering real-world conditions.
Long-term follow-up of givosiran treatment in patients with acute intermittent porphyria from a phase 1/2, 48-month open-label extension study
Authors: Sardh Eliane , Balwani Manisha , Rees David C. , Anderson Karl E. , Jia Gang , Sweetser Marianne T. , Wang Bruce 
Published: October 2024

Abstract
Background
Acute hepatic porphyria is a group of multisystem disorders of which acute intermittent porphyria is the most common subtype. Givosiran, a subcutaneously administered RNA interference therapeutic targeting liver ALAS mRNA, is approved for treating these disorders. This Phase 1/2 open-label extension study (NCT02949830) evaluated the long-term safety and efficacy of givosiran in adults with acute intermittent porphyria, with follow-up of up to 48 months, which is the longest follow-up of givosiran treatment to date. Participants were adults aged 18–65 years who completed part C of the Phase 1 givosiran study (NCT2452372).

Methods
Enrollees received givosiran for up to 48 months. Primary and secondary endpoints included the incidence of adverse events, changes in urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels, annualized rate of porphyria attacks, and annualized hemin use. Quality of life was assessed using the EQ-5D-5L instrument as an exploratory endpoint.

Results
Sixteen patients (median age: 39.5 years) participated. Common adverse events included abdominal pain, nasopharyngitis, and nausea (50% each), with injection-site erythema (38%) and injection-site pruritus (25%) noted as frequent treatment-related reactions. Givosiran therapy reduced annualized rates of porphyria attacks and hemin use by 97% and 96%, respectively. From months > 33 to 48, all patients were free from attacks requiring significant medical intervention and did not use hemin. There were substantial reductions in median urinary ALA and PBG of 95% and 98%, respectively. Additionally, a clinically meaningful improvement in quality of life was observed.

Conclusions
In the longest follow-up of givosiran-treated patients reported to date, the therapy maintained an acceptable safety profile and demonstrated sustained improvements in clinical outcomes over 4 years in patients with acute intermittent porphyria.
Different diseases, different needs: Patient preferences for gene therapy in lysosomal storage disorders, a probabilistic threshold technique survey
Authors: Corazolla Eleonore M. , Eskes Eline C. B. , Veldwijk Jorien , Brands Marion M. M. G. , Dekker Hanka , van de Mheen Erica , Langeveld Mirjam , Hollak Carla E. M. , Sjouke Barbara 
Published: October 2024

Abstract
Background
Gene therapy is currently in development for several monogenetic diseases including lysosomal storage disorders. Limited evidence is available on patient preferences for gene therapy in this population. In this study, we compare gene therapy-related risk tolerance between people affected by three lysosomal storage diseases currently faced with different therapeutic options and prognoses.

Methods
A survey including the probabilistic threshold technique was developed in which respondents were asked to choose between gene therapy and the current standard of care. The attributes included to establish participants’ risk tolerance were previously identified in focus groups of affected people or their representatives, namely: risk of mild side effects, severe side effects, the need for additional medication, and the likelihood of long-term effectiveness. The survey was distributed among people receiving outpatient care for type 1 Gaucher disease (good prognosis with current treatment options), Fabry disease (varying prognosis with current treatment options, XY-genotype on average more severely affected than XX), and parents representing people with severe forms of mucopolysaccharidosis type III A/B (poor prognosis, no disease-specific therapy available).

Results
A total of 85 surveys were completed (15 Gaucher disease respondents, 62 Fabry disease respondents (17 self-identifying male), eight parents of ten people with mucopolysaccharidosis type III). Disease groups with higher disease severity trended towards higher risk tolerance: Gaucher disease respondents were most cautious and predominantly preferred the current standard of care as opposed to MPS III representatives who were more risk tolerant. Respondents with Fabry disease were most heterogeneous in their risk tolerance, with male participants being more risk tolerant than female participants. Long-term effectiveness was the attribute in which respondents tolerated the least risk.

Conclusions
People affected by a lysosomal storage disease associated with a poorer prognosis and less effective current treatment options trended towards more risk tolerance when choosing between gene therapy and the current standard of care. This study shows the importance of involvement of patient preferences before and during the development process of new treatment modalities such as gene therapy for rare diseases, to ensure that innovative therapies align with the wishes and needs of people affected by these diseases.
Analysis of binary mixture of oxytetracycline and bromohexine in their combined veterinary formulation by four simple spectrophotometric methods with greenness assessment
Authors: Sharkawi Marco M.Z. , Safwat Mark T. , Abdelwahab Nada S. 
Published: October 2024

AbstractTetracyclines family is considered as the first-line antibiotic drugs for food animals. Formulating bromhexine (BR) with oxytetracycline (OTC) improved the antibacterial activity of OTC, besides it is considered as a mucolytic agent. Four precise, rapid, and simple spectrophotometric methods were successfully developed for resolution of the overlapped spectra of OTC and BR in their pure form and in their pharmaceutical formulation. The proposed methods are absorption correction (AC), dual wavelength (DW), induced dual wavelength (IDW), and spectrum subtraction (SS) spectrophotometric methods. The developed methods were used for the determination of OTC and BR in the ranges of 2–50 µg/mL and 1–30 µg/mL, respectively for all methods. For (AC) and (SS) methods, OTC and BR were determined at 380 nm and 245.6 nm, respectively after spectral resolution steps. While for (DW) method, the absorbance difference between λ (271.8 –287.6 nm) and λ (245.6 –283.2 nm) were used for the determination of OTC and BR, in order. For IDW, it depended on using the absorbance difference between 271.8 nm and 245.6 nm as well as the equality factor (F) calculated for each drug at the selected wavelengths. In all methods, HCl was used as a solvent and they are validated according to ICH guidelines. Several green metric tools have been developed to evaluate the greenness of the analytical methods like National Environmental Methods Index (NEMI), Modified NEMI, Analytical Eco-scale, Green Analytical Procedure Index (GAPI) and Analytical GREEnness calculator (AGREE), and all ensured the low impact of the suggested approaches on health and environment. The proposed methods are highly selective, robust and precise. Additionally they are time and money effective and can be used in any analytical laboratory.
Epigenomic biomarkers insights in PBMCs for prognostic assessment of ECMO-treated cardiogenic shock patients
Authors: Hsiao Yi-Jing , Chiang Su-Chien , Wang Chih-Hsien , Chi Nai-Hsin , Yu Hsi-Yu , Hong Tsai-Hsia , Chen Hsuan-Yu , Lin Chien-Yu , Kuo Shuenn-Wen , Su Kang-Yi , Ko Wen-Je , Hsu Li-Ming , Lin Chih-An , Cheng Chiou-Ling , Chen Yan-Ming , Chen Yih-Sharng , Yu Sung-Liang 
Published: October 2024

Abstract
Objective
As the global use of extracorporeal membrane oxygenation (ECMO) treatment increases, survival rates have not correspondingly improved, emphasizing the need for refined patient selection to optimize resource allocation. Currently, prognostic markers at the molecular level are limited.

Methods
Thirty-four cardiogenic shock (CS) patients were prospectively enrolled, and peripheral blood mononuclear cells (PBMCs) were collected at the initiation of ECMO (t0), two-hour post-installation (t2), and upon removal of ECMO (tr). The PBMCs were analyzed by comprehensive epigenomic assays. Using the Wilcoxon signed-rank test and least absolute shrinkage and selection operator (LASSO) regression, 485,577 DNA methylation features were analyzed and selected from the t0 and tr datasets. A random forest classifier was developed using the t0 dataset and evaluated on the t2 dataset. Two models based on DNA methylation features were constructed and assessed using receiver operating characteristic (ROC) curves and Kaplan–Meier survival analyses.

Results
The ten-feature and four-feature models for predicting in-hospital mortality attained area under the curve (AUC) values of 0.78 and 0.72, respectively, with LASSO alpha values of 0.2 and 0.25. In contrast, clinical evaluation systems, including ICU scoring systems and the survival after venoarterial ECMO (SAVE) score, did not achieve statistical significance. Moreover, our models showed significant associations with in-hospital survival (p < 0.05, log-rank test).

Conclusions
This study identifies DNA methylation features in PBMCs as potent prognostic markers for ECMO-treated CS patients. Demonstrating significant predictive accuracy for in-hospital mortality, these markers offer a substantial advancement in patient stratification and might improve treatment outcomes.
Biomarkers of bone metabolism in [223Ra] RaCl2 therapy - association with extent of disease and prediction of overall survival
Authors: Fosbøl Marie Øbro , Jørgensen Niklas Rye , Petersen Peter Meidahl , Kjaer Andreas , Mortensen Jann 
Published: October 2024

Abstract
Background
The alpha-emitting radionuclide therapy [223Ra]RaCl2 (Radium-223) improves overall survival (OS) and time to symptomatic skeletal event (SSE) in patients with metastatic castration-resistant prostate cancer (mCRPC). Evidence suggests that the effect of Radium-223 is partly exerted through an impact on the surrounding bone matrix. We hypothesized that bone metabolism markers (BMM) could provide predictive information regarding response to Radium-223. Accordingly, the aim of this study was to investigate changes in BMM during Radium-223 therapy and evaluate association with clinical outcome.

Methods
Prospective study of BMM in patients with mCRPC receiving Radium-223. Blood samples were collected before each administration of Radium-223 and the following BMM were quantified; bone-specific alkaline phosphatase (BALP), osteocalcin, procollagen type I N-propeptide (PINP), C-terminal telopeptide of type I collagen (CTX), C-terminal cross-linking telopeptide of type I collagen generated by matrix metalloproteinases (CTX-MMP), tartrate-resistant acid phosphatase isoform 5b (TRACP5b), receptor-activated nuclear factor κB ligand (RANKL), osteoprotegerin (OPG), and sclerostin. Clinical outcomes were scintigraphic progression during/after therapy, change in bone scan index (BSI), occurrence of SSE, and OS.

Results
A total of 55 mCRPC patients were included. There was a significant linear association between skeletal extent of disease and CTX-MMP, PINP, BALP, and osteocalcin. No significant association between dynamics in BSI and BMM were detected. Median OS for the cohort was 14 months (95% CI: 10.7–16.8). Baseline levels of Log2-CTX-MMP (HR = 2.15 (95%CI: 1.1–4.1)) and Log2-BALP (HR = 1.59 (95%CI: 1.1–2.1)) were associated with OS. Patients with increasing CTX-MMP during therapy had significantly shorter OS (Median OS = 4 mo. (95%CI: 2.3–5.7)) than patients with stable or decreasing CTX-MMP (Median OS = 12 mo. (95%CI: 10.1–13.9), P < 0.001).

Conclusion
BMM are significantly associated with scintigraphic extent of skeletal disease and OS in patients with mCRPC. Particularly, the bone resorption marker CTX-MMP is a promising surrogate marker for prediction of outcome in patients receiving Radium-223 therapy and could potentially improve selection of patients for therapy and assessment of response.

Trial registration
Clinicaltrials.gov, NCT03247010. Registered 10th of August 2017, https://clinicaltrials.gov/study/NCT03247010?term=NCT03247010&rank=1.