bluuebunny/crossref_metadata_2025_split huggingface dataset:
The SHOW RESPECT adaptable framework of considerations for planning how to share trial results with participants, based on qualitative findings from trial participants and site staff
Authors: South Annabelle , Snowdon Claire , Burnett Eva , Bierer Barbara E. , Gillies Katie , Isaacs Talia , Sydes Matthew R. 
Published: July 2024

Abstract
Background
Sharing trial results with participants is a moral imperative, but too often does not happen in appropriate ways.

Methods
We carried out semi-structured interviews with patients (n = 13) and site staff (n = 11), and surveyed 180 patients and 68 site staff who were part of the Show RESPECT study, which tested approaches to sharing results with participants in the context of the ICON8 ovarian cancer trial (ISRCTN10356387). Qualitative and free-text data were analysed thematically, and findings used to develop the SHOW RESPECT adaptable framework of considerations for planning how to share trial results with participants. This paper presents the framework, with illustrations drawn from the Show RESPECT study.

Results
Our adaptable ‘SHOW RESPECT’ framework covers (1) Supporting and preparing trial participants to receive results, (2) HOw will the results reach participants?, (3) Who are the trial participants?, (4) REsults—what do they show?, (5) Special considerations, (6) Provider—who will share results with participants?, (7) Expertise and resources, (8) Communication tools and (9) Timing of sharing results. While the data upon which the framework is based come from a single trial, many of our findings are corroborated by findings from other studies in this area, supporting the transferability of our framework to trials beyond the UK ovarian cancer setting in which our work took place.

Conclusions
This adaptable ‘SHOW RESPECT’ framework can guide researchers as they plan how to share aggregate trial results with participants. While our data are drawn from a single trial context, the findings from Show RESPECT illustrate how approaches to communication in a specific trial can influence patient and staff experiences of feedback of trial results. The framework generated from these findings can be adapted to fit different trial contexts and used by other researchers to plan the sharing of results with their own participants.

Trial registration
ISRCTN96189403. Registered on February 26, 2019. Show RESPECT was supported by the Medical Research Council (MC_UU_12023/24 and MC_UU_00004/08) and the NIHR CRN.
Propionate production by Bacteroidia gut bacteria and its dependence on substrate concentrations differs among species
Authors: Döring Carolin , Basen Mirko 
Published: July 2024

Abstract
Background
Propionate is a food preservative and platform chemical, but no biological process competes with current petrochemical production routes yet. Although propionate production has been described for gut bacteria of the class Bacteroidia, which also carry great capacity for the degradation of plant polymers, knowledge on propionate yields and productivities across species is scarce. This study aims to compare propionate production from glucose within Bacteroidia and characterize good propionate producers among this group.

Results
We collected published information on propionate producing Bacteroidia, and selected ten species to be further examined. These species were grown under defined conditions to compare their product formation. While propionate, acetate, succinate, lactate and formate were produced, the product ratios varied greatly among the species. The two species with highest propionate yield, B. propionicifaciens (0.39 gpro/ggluc) and B. graminisolvens (0.25 gpro/ggluc), were further examined. Product formation and growth behavior differed significantly during CO2-limited growth and in resting cells experiments, as only B. graminisolvens depended on external-added NaHCO3, while their genome sequences only revealed few differences in the major catabolic pathways. Carbon mass and electron balances in experiments with resting cells were closed under the assumption that the oxidative pentose pathway was utilized for glucose oxidation next to glycolysis in B. graminisolvens. Finally, during pH-controlled fed-batch cultivation B. propionicifaciens and B. graminisolvens grew up to cell densities (OD600) of 8.1 and 9.8, and produced 119 mM and 33 mM of propionate from 130 and 105 mM glucose, respectively. A significant production of other acids, particularly lactate (25 mM), was observed in B. graminisolvens only.

Conclusions
We obtained the first broad overview and comparison of propionate production in Bacteroidia strains. A closer look at two species with comparably high propionate yields, showed significant differences in their physiology. Further studies may reveal the molecular basis for high propionate yields in Bacteroidia, paving the road towards their biotechnological application for conversion of biomass-derived sugars to propionate.
Differentiating between benign and malignant breast lesions using dual-energy CT-based model: development and validation
Authors: Xia Han , Chen Yueyue , Cao Ayong , Wang Yu , Huang Xiaoyan , Zhang Shengjian , Gu Yajia 
Published: July 2024

Abstract
Objectives
To develop and validate a dual-energy CT (DECT)-based model for noninvasively differentiating between benign and malignant breast lesions detected on DECT.

Materials and methods
This study prospectively enrolled patients with suspected breast cancer who underwent dual-phase contrast-enhanced DECT from July 2022 to July 2023. Breast lesions were randomly divided into the training and test cohorts at a ratio of 7:3. Clinical characteristics, DECT-based morphological features, and DECT quantitative parameters were collected. Univariate analyses and multivariate logistic regression were performed to determine independent predictors of benign and malignant breast lesions. An individualized model was constructed. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic ability of the model, whose calibration and clinical usefulness were assessed by calibration curve and decision curve analysis.

Results
This study included 200 patients (mean age, 49.9 ± 11.9 years; age range, 22–83 years) with 222 breast lesions. Age, lesion shape, and the effective atomic number (Zeff) in the venous phase were significant independent predictors of breast lesions (all p < 0.05). The discriminative power of the model incorporating these three factors was high, with AUCs of 0.844 (95%CI 0.764–0.925) and 0.791 (95% CI 0.647–0.935) in the training and test cohorts, respectively. The constructed model showed a preferable fitting (all p > 0.05 by the Hosmer-Lemeshow test) and provided enhanced net benefits than simple default strategies within a wide range of threshold probabilities in both cohorts.

Conclusion
The DECT-based model showed a favorable diagnostic performance for noninvasive differentiation between benign and malignant breast lesions detected on DECT.

Critical relevance statement
The combination of clinical and morphological characteristics and DECT-derived parameter have the potential to identify benign and malignant breast lesions and it may be useful for incidental breast lesions on DECT to decide if further work-up is needed.

Key Points

It is important to characterize incidental breast lesions on DECT for patient management.

DECT-based model can differentiate benign and malignant breast lesions with good performance.

DECT-based model is a potential tool for distinguishing breast lesions detected on DECT.

Graphical Abstract
MicroRNA-21 modulates brown adipose tissue adipogenesis and thermogenesis in a mouse model of polycystic ovary syndrome
Authors: Rezq Samar , Huffman Alexandra M. , Basnet Jelina , Alsemeh Amira E. , do Carmo Jussara M. , Yanes Cardozo Licy L. , Romero Damian G. 
Published: July 2024

Abstract
Background
Polycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with increased obesity, hyperandrogenism, and altered brown adipose tissue (BAT) thermogenesis. MicroRNAs play critical functions in brown adipocyte differentiation and maintenance. We aim to study the role of microRNA-21 (miR-21) in altered energy homeostasis and BAT thermogenesis in a PCOS mouse model of peripubertal androgen exposure.

Methods
Three-week-old miR-21 knockout (miR21KO) or wild-type (WT) female mice were treated with dihydrotestosterone (DHT) or vehicle for 90 days. Body composition was determined by EchoMRI. Energy expenditure (EE), oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER) were measured by indirect calorimetry. Androgen receptor (AR), and markers of adipogenesis, de novo lipogenesis, angiogenesis, extracellular matrix remodeling, and thermogenesis were quantified by RT-qPCR and/or Western-blot.

Results
MiR-21 ablation attenuated DHT-mediated increase in body weight while having no effect on fat or BAT mass. MiR-21 ablation attenuated DHT-mediated BAT AR upregulation. MiR-21 ablation did not alter EE; however, miR21KO DHT-treated mice have reduced VO2, VCO2, and RER. MiR-21 ablation reversed DHT-mediated decrease in food intake and increase in sleep time. MiR-21 ablation decreased some adipogenesis (Adipoq, Pparγ, and Cebpβ) and extracellular matrix remodeling (Mmp-9 and Timp-1) markers expression in DHT-treated mice. MiR-21 ablation abolished DHT-mediated increases in thermogenesis markers Cpt1a and Cpt1b, while decreasing CIDE-A expression.

Conclusions
Our findings suggest that BAT miR-21 may play a role in regulating DHT-mediated thermogenic dysfunction in PCOS. Modulation of BAT miR-21 levels could be a novel therapeutic approach for the treatment of PCOS-associated metabolic derangements.
“It’s just politics”: an exploration of people’s frames of the politics of mobility in Germany and their consequences
Authors: Sonnberger Marco , Leger Matthias , Radtke Jörg 
Published: July 2024

Abstract
Background
The decarbonization of the mobility sector is one of the main challenges in the context of climate mitigation. In Germany, as in many other countries, policy measures aiming to make the mobility system greener frequently fail to produce substantial results, not least due to a lack of support by large sections of the general public. Policy measures directed at reducing car traffic in particular are often met with indifference and resistance. The question thus arises: what basis do citizens use to form their (often negative) opinions about sustainable mobility policies? As a conceptual starting point for our empirical analysis, we draw on the frame concept and focus on people’s frames of the politics of mobility. With “politics of mobility” we refer to everything people could consider as political with regard to mobility. We understand frames as culturally mediated patterns of interpretation that ultimately motivate and guide actions.

Results
Based on interviews and focus group data gathered in the region of the city of Stuttgart (Germany), we identify two dominant frames as well as combinations of these frames by which people make sense of the activities of political actors in the field of mobility. In one frame, which we labeled “politics-as-actor”, mobility politics are interpreted with reference to politics as some kind of monolithic abstract actor. In the other, which we labeled as “politics-as-staged-process”, mobility politics are portrayed as an interest-driven, opaque process that only purport to being democratic.

Conclusions
In terms of policy recommendations, we use our findings to derive suggestions for how to increase support for green mobility policies: transparent implementation of policy measures, pragmatic policy styles and the involvement of intermediaries.
Revised cardiac risk index in predicting cardiovascular complications in patients receiving chronic kidney replacement therapy undergoing elective general surgery
Authors: Palamuthusingam Dharmenaan , Pascoe Elaine M. , Hawley Carmel M. , Johnson David Wayne , Fahim Magid 
Published: July 2024

Abstract
Introduction
The Revised Cardiac Risk Index (RCRI) is a six-parameter model that is commonly used in assessing individual 30-day perioperative cardiovascular risk before general surgery, but its use in patients on chronic kidney replacement therapy (KRT) is unvalidated. This study aimed to externally validate RCRI in this patient group over a 15-year period.

Methods
Data linkage was used between the the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry and jurisdictional hospital admisisons data across Australia and New Zealand to identify all incident and prevalent patients on chronic KRT between 2000 and 2015 who underwent elective abdominal surgery. Chronic KRT was categorised as haemodialysis (HD), peritoneal dialysis (PD), home haemodialysis (HHD) and kidney transplant. The outcome of interest was major adverse cardiovascular event (MACE) which was defined as nonfatal myocardial infarction, nonfatal stroke, non-fatal cardiac arrest and cardiovascular mortality at 30 days. Logistic regression was used with the RCRI score included as a continuous variable to estimate discrimination by area under the receiver operating curve (AUROC). Calibration was evaluated using a calibration plot. Clinical utility was assessed using a decision curve analysis to determine the net benefit.

Results
A total of 5094 elective surgeries were undertaken, and MACE occurred in 153 individuals (3.0%). Overall, RCRI had poor discrimination in patients on chronic KRT undergoing elective surgery (AUROC 0.67), particularly in patients aged greater than 65 years (AUROC 0.591). A calibration plot showed that RCRI overestimated risk of MACE. The expected-to-observed outcome ratio was 6.0, 5.1 and 2.5 for those with RCRI scores of 1, 2 and ≥ 3, respectively. Discrimination was moderate in patients under 65 years and in kidney transplant recipients, with AUROC values of 0.740 and 0.718, respectively. Overestimation was common but less so for kidney transplant recipients. Decision curve analysis showed that there was no net benefit of using the tool in neither the overall cohort nor patients under 65 years, but a slight benefit associated with threshold probability > 5.5% in kidney transplant recipients.

Conclusions
The RCRI tool performed poorly and overestimated risk in patients on chronic dialysis, potentially misinforming patients and clinicians about the risk of elective surgery. Further research is needed to define a more comprehensive means of estimating risk in this unique population.
Mechanistic insights into the conversion of flavin adenine dinucleotide (FAD) to 8-formyl FAD in formate oxidase: a combined experimental and in-silico study
Authors: Wen Kai , Wang Sirui , Sun Yixin , Wang Mengsong , Zhang Yingjiu , Zhu Jingxuan , Li Quanshun 
Published: July 2024

AbstractFormate oxidase (FOx), which contains 8-formyl flavin adenine dinucleotide (FAD), exhibits a distinct advantage in utilizing ambient oxygen molecules for the oxidation of formic acid compared to other glucose-methanol-choline (GMC) oxidoreductase enzymes that contain only the standard FAD cofactor. The FOx-mediated conversion of FAD to 8-formyl FAD results in an approximate 10-fold increase in formate oxidase activity. However, the mechanistic details underlying the autocatalytic formation of 8-formyl FAD are still not well understood, which impedes further utilization of FOx. In this study, we employ molecular dynamics simulation, QM/MM umbrella sampling simulation, enzyme activity assay, site-directed mutagenesis, and spectroscopic analysis to elucidate the oxidation mechanism of FAD to 8-formyl FAD. Our results reveal that a catalytic water molecule, rather than any catalytic amino acids, serves as a general base to deprotonate the C8 methyl group on FAD, thus facilitating the formation of a quinone-methide tautomer intermediate. An oxygen molecule subsequently oxidizes this intermediate, resulting in a C8 methyl hydroperoxide anion that is protonated and dissociated to form OHC-RP and OH−. During the oxidation of FAD to 8-formyl FAD, the energy barrier for the rate-limiting step is calculated to be 22.8 kcal/mol, which corresponds to the required 14-hour transformation time observed experimentally. Further, the elucidated oxidation mechanism reveals that the autocatalytic formation of 8-formyl FAD depends on the proximal arginine and serine residues, R87 and S94, respectively. Enzymatic activity assay validates that the mutation of R87 to lysine reduces the kcat value to 75% of the wild-type, while the mutation to histidine results in a complete loss of activity. Similarly, the mutant S94I also leads to the deactivation of enzyme. This dependency arises because the nucleophilic OH− group and the quinone-methide tautomer intermediate are stabilized through the noncovalent interaction provided by R87 and S94. These findings not only explain the mechanistic details of each reaction step but also clarify the functional role of R87 and S94 during the oxidative maturation of 8-formyl FAD, thereby providing crucial theoretical support for the development of novel flavoenzymes with enhanced redox properties.
Improving Likert scale big data analysis in psychometric health economics: reliability of the new compositional data approach
Authors: Lehmann René , Vogt Bodo 
Published: July 2024

AbstractBipolar psychometric scales data are widely used in psychologic healthcare. Adequate psychological profiling benefits patients and saves time and costs. Grant funding depends on the quality of psychotherapeutic measures. Bipolar Likert scales yield compositional data because any order of magnitude of agreement towards an item assertion implies a complementary order of magnitude of disagreement. Using an isometric log-ratio (ilr) transformation the bivariate information can be transformed towards the real valued interval scale yielding unbiased statistical results increasing the statistical power of the Pearson correlation significance test if the Central Limit Theorem (CLT) of statistics is satisfied. In practice, however, the applicability of the CLT depends on the number of summands (i.e., the number of items) and the variance of the data generating process (DGP) of the ilr transformed data. Via simulation we provide evidence that the ilr approach also works satisfactory if the CLT is violated. That is, the ilr approach is robust towards extremely large or infinite variances of the underlying DGP increasing the statistical power of the correlation test. The study generalizes former results pointing out the universality and reliability of the ilr approach in psychometric big data analysis affecting psychometric health economics, patient welfare, grant funding, economic decision making and profits.
CONUT score as a predictor for anamorelin efficacy in patients with cancer cachexia receiving chemotherapy
Authors: Fujii Hironori , Makiyama Akitaka , Nishimura Kayoko , Iihara Hirotoshi , Hirose Chiemi , Ohata Koichi , Yamada Yunami , Watanabe Daichi , Yasufuku Itaru , Okumura Naoki , Tanaka Yoshihiro , Takahashi Takao , Kobayashi Ryo , Matsuhashi Nobuhisa , Suzuki Akio 
Published: July 2024

Abstract
Background
Anamorelin is expected to improve cancer cachexia by increasing lean body mass (LBM) due to increased appetite and protein synthesis. However, the effect of anamorelin on cancer cachexia in real-world practice is unclear. The purpose of this study was to evaluate the efficacy and safety of anamorelin and to identify predictors of efficacy on treatment with anamorelin.

Methods
We retrospectively analyzed data from patients with cancer cachexia treated with chemotherapy between May 2021 and August 2022. Efficacy of anamorelin was evaluated using LBM, with “12-week sustained effective response” to anamorelin treatment defined as maintenance or an increase in LBM for 12 weeks. We examined factors associated with “12-week sustained effective response” to anamorelin treatment using a multivariable logistic model that included controlling nutritional status (CONUT) score, an objective assessment of nutritional disorders, and the modified Glasgow prognostic score (mGPS), which scores the cachexia status of cancer patients. To assess patient subjective quality of life (QOL) changes related to eating after starting anamorelin treatment, we used a questionnaire (QOL-ACD appetite-related items: Q8, 9, 11). Adverse events were evaluated in accordance with the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0.

Results
On analysis of data from 40 patients, 23 patients showed a 12-week sustained effective response to anamorelin (57.5%). At 12 weeks, LBM significantly increased by 1.63 ± 3.73 kg (mean ± SD). Multivariable logistic analysis revealed that a low CONUT score was significantly associated with “12-week sustained effective response” to anamorelin treatment (adjusted odds ratio: 13.5, 95% confidence intervals: 2.2–84.2, P = 0.004). QOL assessment showed a trend toward increased appetite and enjoyment of meals after anamorelin initiation. Five patients (12.5%) had an increase in HbA1c of more than 1.0% during the 12 weeks after the start of anamorelin. No patient had QT interval prolongation or grade 3 or higher hepatic transaminase elevation.

Conclusion
Anamorelin may maintain or increase LBM with tolerable safety in patients with cancer cachexia undergoing chemotherapy. A low CONUT score, despite meeting criteria for cancer cachexia, is suggested as a predictor for the efficacy of anamorelin, indicating that patients with a low CONUT score may benefit from early introduction of anamorelin.
Demonstrating the benefit of a cellulitis-specific patient reported outcome measure (CELLUPROM©) as part of the National Cellulitis Improvement Programme in Wales
Authors: Gabe-Walters Marie , Thomas Melanie , Jenkins Linda 
Published: July 2024

Abstract
Purpose
Despite a known risk of cellulitis recurrence, the management of the wider impact and risk factors has been neglected. The innovative National Cellulitis Improvement Programme (NCIP) addresses this by providing evidence-based and individualised care to improve patient reported outcomes and reduce the risk of recurrence. The aim of this paper is to examine the longer-term impact of cellulitis and to identify a suitable and clinically relevant Patient Reported Outcome Measure (PROM).

Methods
A review of existing cellulitis-specific PROMs was undertaken, alongside literature detailing the patient-focused impact of cellulitis, to identify a suitable PROM for clinical use. A group of expert therapists and patient representatives (n = 14) shared their individual and collective experiences over a series of events to discuss and debate the impact of cellulitis and review available PROMs. CELLUPROM© is introduced with anonymised PROM data and case study information reported to establish the impact of CELLUPROM© within usual NCIP care.

Results
No cellulitis-specific PROMs were identified. Literature focused on the signs and symptoms of an acute episode of cellulitis, with outcome measures primarily used to evidence the impact of an intervention. An enduring physical, social and emotional impact of cellulitis was identified in this study, providing the basis for the new cellulitis-specific PROM (CELLUPROM©), which has been implemented with good effect in clinical care.

Conclusion
This study has highlighted the lasting impact of cellulitis. Using CELLUPROM© within the risk-reduction NCIP has helped develop Value-Based Healthcare and support programme evaluation.