bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reimbursement of care does not equal the distribution of hospital resources: an explorative case study on a missing link among Dutch hospitals
Authors: van Leeuwen L. V. L. , Mesman R. , Berden H. J. J. M. , Jeurissen P. P. T. 
Published: September 2023

Abstract
Background
Affordability and accessibility of hospital care are under pressure. Research on hospital care financing focuses primarily on incentives in the financial system outside the hospital. It is notable that little is known about (incentives in) internal funding in hospitals. Therefore, our study focuses on the budget allocation in hospitals: the distribution model. Based on our hypothesis that the reimbursement and distribution models in hospitals might interact, we gain knowledge about-, and insight into, the interaction of different reimbursement and distribution models used in Dutch hospitals, and how they affect the financial output of hospital care.

Methods
An online survey with 22 questions was conducted among financial senior management as an expert group in 49 Dutch hospitals.

Results
Ultimately, 38 of 49 approached experts fully completed the survey, which amounts to 78% of the hospitals we approached and 60% of all Dutch hospitals. The results on the reimbursement model indicate price * volume with adjusted prices above a maximum cap as the most common dominant contract type. On the internal distribution model, 75–80% of the experts reported incremental budgeting as the dominant budgeting method. Results on the interaction between the reimbursement and the distribution model show that both general and specific changes in contract agreements are only partially incorporated in hospital budgets. In 28 out of 31 hospitals with self-employed medical specialists, a relation is reported between the reimbursement model and the contracts with the Medical Consultant Group(s) in which the medical specialists are united.

Conclusions
Our results in Dutch setting indicate a limited interaction between the reimbursement model and the distribution model. This lack of congruence between both models might limit the desired effects of incentives in contractual agreements aimed at the financial output. This applies to different reimbursement and distribution models. Further research into the various interactions and incentives, as visualized in our conceptual framework, could result in evidence-based advice for achieving affordable and accessible hospital care.
Evidencing general acceptability of open-label placebo use for tackling overtreatment in primary care: a mixed methods study
Authors: Krockow E. M. , Emerson T. , Youssef E. , Scott S. , Tromans S. 
Published: September 2023

Abstract
Background
Overtreatment poses a challenge to healthcare systems due to harmful consequences of avoidable side-effects and costs. This study presents the first account for examining the feasibility of placebo use for reducing overtreatment in primary care, including whether public attitudes support the use of different placebo types in place of inappropriate prescriptions of antibiotics, antidepressants, or analgesics.

Methods
We used a multi-study, mixed-methods design, including patient and public (PPI) consultations, focus groups (Study 1) and two pre-registered online experiments (Studies 2 and 3).

Results
Study 1 (N = 16) explored everyday conceptions and practicalities of potential placebo use in the context of respiratory infections. Findings highlighted the importance of trusting doctor-patient relationships and safety-netting. Study 2 employed a randomised experiment with a representative UK sample (N = 980), investigating attitudes towards 5 different treatment options for respiratory infections: (1) blinded + pure placebo, (2) open-label + pure placebo, (3) open-label + impure placebo, (4) antibiotic treatment, and (5) no treatment. Study 2 also examined how attitudes varied based on wording and individual differences. Findings indicated general support (ηp2 = .149, large effect size) for replacing inappropriate antibiotics with open-label + impure placebos, although personal placebo acceptability was lower. Also, older people, individuals suffering from chronic illness or those showing higher levels of health anxiety appeared less amenable to placebo use. Study 3 (N = 1177) compared attitudes towards treatment options across three clinical scenarios: respiratory infection, depression and pain. Findings suggested significant differences in the acceptability of placebo options based on the clinical context. In the infection scenario, options for open-label + pure placebos, open-label + impure placebos and no treatment were rated significantly more acceptable (ηp2 = .116, medium effect size) compared to the depression and pain scenarios. Again, general support for placebos was higher than placebo acceptability for personal use.

Conclusions
Findings from PPI and three studies indicate general support for combatting overprescribing in primary care through clinical placebo use. This is an indicator for wider UK public support for a novel, behavioural strategy to target a long-standing healthcare challenge. General acceptability appears to be highest for the use of open-label + impure placebos in the context of antibiotic overprescribing.
A temperature dependent pilin promoter for production of thermostable enzymes in Thermus thermophilus
Authors: Kirchner Lennart , Müller Volker , Averhoff Beate 
Published: September 2023

Abstract
Background
Enzymes from thermophiles are of great interest for research and bioengineering due to their stability and efficiency. Thermophilic expression hosts such as Thermus thermophilus [T. thermophilus] can overcome specific challenges experienced with protein production in mesophilic expression hosts, such as leading to better folding, increased protein stability, solubility, and enzymatic activity. However, available inducible promoters for efficient protein production in T. thermophilus HB27 are limited.

Results
In this study, we characterized the pilA4 promoter region and evaluated its potential as a tool for production of thermostable enzymes in T. thermophilus HB27. Reporter gene analysis using a promoterless β-glucosidase gene revealed that the pilA4 promoter is highly active under optimal growth conditions at 68 °C and downregulated during growth at 80 °C. Furthermore, growth in minimal medium led to significantly increased promoter activity in comparison to growth in complex medium. Finally, we proved the suitability of the pilA4 promoter for heterologous production of thermostable enzymes in T. thermophilus by producing a fully active soluble mannitol-1-phosphate dehydrogenase from Thermoanaerobacter kivui [T. kivui], which is used in degradation of brown algae that are rich in mannitol.

Conclusions
Our results show that the pilA4 promoter is an efficient tool for gene expression in T. thermophilus with a high potential for use in biotechnology and synthetic biology applications.
Tuberculosis prevention, diagnosis, and treatment financial profile during 2006–2021: PART A
Authors: Meskini Maryam , Madadi Nahid , Ahmadi Kamal , Vaziri Farzam , Fateh Abolfazl , Siadat Seyed Davar 
Published: September 2023

Abstract
Background
Tuberculosis (TB) is a communicable disease that is a major cause of death and one of the leading causes of death worldwide. Currently, there is no analyzed data to examine the financial profile of TB by country, continent, and year; this article analyzed TB prevention, diagnosis, and treatment financial profile during the last two decades.

Methods
Original research, reviews, and governmental databases are analyzed to present the financial profile of TB.

Results
Analyzed data showed Europe (23137.133), Asia (20137.073), and Africa (15237.973) had the most allocated funds (US $ million), and Oceania (236.702), and America (4745.043) had the lowest allocated fund (US $ million) during 2006–2021. Additionally, the allocation of funds (domestic funds, global funds, and grants [excluding global funds]) in different countries and proper planning for TB eradication has caused that in the last two decades, the slope of the confirmed cases and deaths graph line is negative.

Conclusion
The number of confirmed cases and deaths reported globally is decreasing. The trend lines showed that the assigned funds are increasing, indicating that the TB eradication plan can be apprehended soon.
The impact of calorie labelling and proportional pricing on out of home food orders: a randomised controlled trial study using a virtual food and drink delivery app
Authors: Finlay Amy , Boyland Emma , Jones Andrew , Witkam Rozemarijn , Robinson Eric 
Published: September 2023

Abstract
Background
Mandatory calorie labelling in the out-of-home food sector was introduced in England in 2022, and menu pricing strategies that ensure cost is equivalent to portion size (proportional pricing) have been proposed as a policy to reduce obesity. Food delivery app-based platforms now contribute significantly to diet, and evidence suggests that those at a socioeconomic disadvantage may have greater exposure to unhealthy options on these platforms. However, public health policies to improve nutritional quality of food ordered from food delivery apps has received limited examination.

Objective
This experimental study assessed the impact of calorie labelling and proportional pricing on item and meal size selection, calories ordered, and money spent when selecting food and drinks from three outlet types on a virtual delivery app.

Methods
UK adult participants (N = 1126, 49% female), stratified by gender and education level completed an online study where they ordered items from three branded food and beverage outlets (coffee shop, sandwich outlet, fast food outlet) using a virtual delivery app. Participants were presented food and beverage options with vs. without calorie labels and with value (larger portions are proportionally cheaper) vs. proportional pricing.

Results
Calorie labelling did not influence portion size selection for any outlets, but significantly reduced calories ordered from the coffee shop (-18.95kcals, 95% CI -33.07 to -4.84) and fast food outlet (-54.19kcals, 95% CI -86.04 to -22.33). Proportional pricing reduced the likelihood of choosing a larger beverage from the coffee shop (OR = 0.58, 95% CI 0.45 to 0.75), but was associated with increased calories ordered from the fast food outlet (51.25kcals, 95% CI 19.59 to 82.90). No consistent interactions were observed with participant characteristics, suggesting that effects of calorie labelling and pricing on outcomes were similar across sociodemographic groups.

Conclusions
Calorie labelling on food delivery platforms may effectively reduce calories ordered. Proportional pricing may be useful in prompting consumers to select smaller portion sizes, although further research in real-world settings will now be valuable.
Understanding sexual behaviors of youth from the lens of caregivers, teachers, local leaders and youth in Homabay County, Kenya
Authors: Omanga Eunice , Inwani Irene , Agot Kawango , Buttolph Jasmine , Nduati Ruth , Macharia Paul , Onyango Jacob , Kurth Ann 
Published: September 2023

AbstractIn Kenya similar to other countries in Eastern and Southern Africa There is a disproportionately high burden of the global HIV incidence among youth ages 15–24 years, and where adolescent girls and young women account for up to a third of all incident HIV infections and more than double the burden of HIV compared to their male peers. Previous work has shown early sexual debut as entry point into risks to sexual and reproductive health among young people including STI/HIV acquisition. This was a formative assessment of the local context of three sexual risk behaviors among youth ages of 15–24 years: early sexual debut, multiple sexual partnerships, and age-mixing /intergenerational sex for purposes of informing comprehensive combination HIV intervention program design. We conducted a cross-sectional formative qualitative study in four sub-counties within Homabay county a high HIV prevalence region of Kenya. Participants were recruited through youth groups, schools, government offices and, community gatekeepers using approved fliers, referred to a designated venue for focus group discussion (FGD). After oral informed consent, twelve FGDs of 8–10 participants were carried out. Transcripts and field notes were uploaded to Atlas.ti qualitative data analysis and research software (version 8.0, 2017, ATLAS.ti GmbH). Open coding followed by grouping, categorization of code groups, and thematic abstraction was used to draw meaning for the data. A total of 111 youth participated in the FGD, 65 males and 46 females. The main findings were that youth engaged in early sex for fear of being labeled ‘odd’ by their peers, belief (among both male and female) that ‘practice makes perfect’, curiosity about sex, media influence, need to prove if one can father a child (among male), the notion that sex equals love with some of the youth using this excuse to coerce their partners into premature sex, and the belief that sex is a human right and parents/guardians should not intervene. Male youth experienced more peer-pressure to have sex earlier. Female youths cited many reasons to delay coitarche that included fear of pregnancy, burden of taking care of a baby, and religious doctrines. Having multiple sexual partners and intergenerational sexual relationships were common among the youth driven by perceived financial gain and increased sexual prowess. HIV prevention strategies need to address gender vulnerabilities, as well as promoting a protective environment, hence application of combination prevention methods is a viable solution to the HIV pandemic.Trial registration number: The study was approved by the KNH/UoN Ethics review committee (KNH/UoN ERC-P73/03/2011) and New York University (NYU Reg no.–00000310).
Regulation of the hippocampal translatome by Apoer2-ICD release
Authors: Wasser Catherine R. , Werthmann Gordon C. , Hall Eric M. , Kuhbandner Kristina , Wong Connie H. , Durakoglugil Murat S. , Herz Joachim 
Published: September 2023

Abstract
Background
ApoE4, the most significant genetic risk factor for late-onset Alzheimer’s disease (AD), sequesters a pro-synaptogenic Reelin receptor, Apoer2, in the endosomal compartment and prevents its normal recycling. In the adult brain, Reelin potentiates excitatory synapses and thereby protects against amyloid-β toxicity. Recently, a gain-of-function mutation in Reelin that is protective against early-onset AD has been described. Alternative splicing of the Apoer2 intracellular domain (Apoer2-ICD) regulates Apoer2 signaling. Splicing of juxtamembraneous exon 16 alters the γ-secretase mediated release of the Apoer2-ICD as well as synapse number and LTP, and inclusion of exon 19 ameliorates behavioral deficits in an AD mouse model. The Apoer2-ICD has also been shown to alter transcription of synaptic genes. However, the role of Apoer2-ICD release upon transcriptional regulation and its role in AD pathogenesis is unknown.

Methods
To assess in vivo mRNA-primed ribosomes specifically in hippocampi transduced with Apoer2-ICD splice variants, we crossed wild-type, cKO, and Apoer2 cleavage-resistant mice to a Cre-inducible translating ribosome affinity purification (TRAP) model. This allowed us to perform RNA-Seq on ribosome-loaded mRNA harvested specifically from hippocampal cells transduced with Apoer2-ICDs.

Results
Across all conditions, we observed ~4,700 altered translating transcripts, several of which comprise key synaptic components such as extracellular matrix and focal adhesions with concomitant perturbation of critical signaling cascades, energy metabolism, translation, and apoptosis. We further demonstrated the ability of the Apoer2-ICD to rescue many of these altered transcripts, underscoring the importance of Apoer2 splicing in synaptic homeostasis. A variety of these altered genes have been implicated in AD, demonstrating how dysregulated Apoer2 splicing may contribute to neurodegeneration.

Conclusions
Our findings demonstrate how alternative splicing of the APOE and Reelin receptor Apoer2 and release of the Apoer2-ICD regulates numerous translating transcripts in mouse hippocampi in vivo. These transcripts comprise a wide range of functions, and alterations in these transcripts suggest a mechanistic basis for the synaptic deficits seen in Apoer2 mutant mice and AD patients. Our findings, together with the recently reported AD-protective effects of a Reelin gain-of-function mutation in the presence of an early-onset AD mutation in Presenilin-1, implicate the Reelin/Apoer2 pathway as a target for AD therapeutics.

Graphical Abstract
Athletes’ experiences of using a self-directed psychological support, the BAck iN the Game (BANG) smartphone application, during rehabilitation for return to sports following anterior cruciate ligament reconstruction
Authors: Ringberg Magnus , Eldh Ann Catrine , Ardern Clare L , Kvist Joanna 
Published: September 2023

Abstract
Background
Following anterior cruciate ligament reconstruction (ACLR), many athletes do not return to their sport, often driven by concerns about re-injury. Psychological support strategies might help, but are not routinely included in rehabilitation after ACLR. The BAck iN the Game (BANG) intervention is a 24-week eHealth program delivered via smartphone application (app), beginning directly after ACLR, with a self-directed approach that aims to target the specific challenges athletes encounter in rehabilitation.

Aim
To describe athletes’ experiences of using the BANG app during rehabilitation, to support returning to sport following ACLR.

Method
Participants were athletes, in contact and/or non-contact pivoting sports, who had ACLR with the goal to return to sports. Semi-structured, individual interviews were conducted 6–10 months after their ACLR; all had access to the BANG intervention. Verbatim transcripts were analysed with a qualitative content analysis.

Results
The 19 participants were 17–30 years, mean 21.6 years (SD 3.5); 7 men and 12 women. The analysis generated three main categories. (A) Interacting with the app illustrated how, when, or why the participants engaged with the app. The app was helpful because of its varying content, the notifications served as reminders and participants stopped using the app when no longer needing it. (B) Challenging experiences with the app illustrated that the app itself came with some difficulties e.g., content not appearing with the right timing and material not tailored to their sport. (C) Supportive experiences with the app reflected how the app facilitated the participants’ rehabilitation progress; it included positive aspects of the app content and navigation, boosting their confidence to return to sport, and motivated them to continue with rehabilitation.

Conclusion
The analysis of the interviews illustrates athletes’ awareness in interacting with, and the challenging and supportive experiences of using the app. The BANG app might provide support for returning to sport, primarily psychological support, as an adjunct to regular physiotherapy-guided rehabilitation. Athletes’ experiences of the BANG app could be improved by healthcare professionals providing additional advice about when to use which content and why.

Trial registration
ClinicalTrials.gov, NCT03959215. Registered 22 May 2019.
Novel multi-objective affinity approach allows to identify pH-specific μ-opioid receptor agonists
Authors: Secker Christopher , Fackeldey Konstantin , Weber Marcus , Ray Sourav , Gorgulla Christoph , Schütte Christof 
Published: September 2023

AbstractOpioids are essential pharmaceuticals due to their analgesic properties, however, lethal side effects, addiction, and opioid tolerance are extremely challenging. The development of novel molecules targeting the $$\mu$$
μ
-opioid receptor (MOR) in inflamed, but not in healthy tissue, could significantly reduce these unwanted effects. Finding such novel molecules can be achieved by maximizing the binding affinity to the MOR at acidic pH while minimizing it at neutral pH, thus combining two conflicting objectives. Here, this multi-objective optimal affinity approach is presented, together with a virtual drug discovery pipeline for its practical implementation. When applied to finding pH-specific drug candidates, it combines protonation state-dependent structure and ligand preparation with high-throughput virtual screening. We employ this pipeline to characterize a set of MOR agonists identifying a morphine-like opioid derivative with higher predicted binding affinities to the MOR at low pH compared to neutral pH. Our results also confirm existing experimental evidence that NFEPP, a previously described fentanyl derivative with reduced side effects, and recently reported $$\beta$$
β
-fluorofentanyls and -morphines show an increased specificity for the MOR at acidic pH when compared to fentanyl and morphine. We further applied our approach to screen a >50K ligand library identifying novel molecules with pH-specific predicted binding affinities to the MOR. The presented differential docking pipeline can be applied to perform multi-objective affinity optimization to identify safer and more specific drug candidates at large scale.
Staphylococcus aureus surgical site infection rates in 5 European countries
Authors: Mellinghoff Sibylle C. , Bruns Caroline , Albertsmeier Markus , Ankert Juliane , Bernard Louis , Budin Sofia , Bataille Camille , Classen Annika Y. , Cornely Florian B. , Couvé-Deacon Elodie , Fernandez Ferrer Maria , Fortún Jesús , Galar Alicia , Grill Eva , Guimard Thomas , Hampl Jürgen A. , Wingen-Heimann Sebastian , Horcajada Juan P. , Köhler Felix , Koll Carolin , Mollar Joan , Muñoz Patricia , Pletz Mathias W. , Rutz Jule , Salmanton-García Jon , Seifert Harald , Serracino-Inglott Ferdinand , Soriano Alex , Stemler Jannik , Vehreschild Janne J. , Vilz Tim O. , Naendrup Jan-Hendrik , Cornely Oliver A. , Liss Blasius J. 
Published: September 2023

Abstract
Objective
To determine the overall and procedure-specific incidence of surgical site infections (SSI) caused by Staphylococcus aureus (S. aureus) as well as risk factors for such across all surgical disciplines in Europe.

Methods
This is a retrospective cohort of patients with surgical procedures performed at 14 European centres in 2016, with a nested case–control analysis. S. aureus SSI were identified by a semi-automated crossmatching bacteriological and electronic health record data. Within each surgical procedure, cases and controls were matched using optimal propensity score matching.

Results
A total of 764 of 178 902 patients had S. aureus SSI (0.4%), with 86.0% of these caused by methicillin susceptible and 14% by resistant pathogens. Mean S. aureus SSI incidence was similar for all surgical specialties, while varying by procedure.

Conclusions
This large procedure-independent study of S. aureus SSI proves a low overall infection rate of 0.4% in this cohort. It provides proof of principle for a semi-automated approach to utilize big data in epidemiological studies of healthcare-associated infections.
Trials registration The study was registered at clinicaltrials.gov under NCT03353532 (11/2017).