bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nature-based approaches: a mixed methods study of facilitators and barriers to implementation in CAMHS
Authors: Mitchell Siobhan B. , Chapman Beth , Hayes Rachel , Bonnici Hélène , Banks Hazel , Mareva Silvana , Hardwick Rebecca 
Published: November 2024

Abstract
Background
There is growing evidence that spending time with or in nature can be beneficial for health and wellbeing. Emerging evidence suggests potential benefits for staff and service users in healthcare settings, yet little is known about how to put Nature-based approaches (NBAs) into practice within the Child and Adolescent Mental Health Services (CAMHS) setting. The CAMHS Goes Wild project in Southwest England aimed to explore the implementation of NBAs within CAMHS, examining staff attitudes and understanding to identify potential benefits and challenges through a mixed methods study.

Methods
The study involved three phases of data collection: an online survey with two waves, the first wave prior to the training, and the second four months post-training, and semi-structured interviews. Data collection was designed to fit around NatureWell training, attended by sixty-four CAMHS staff, which took place alongside the study. All participants were sampled from one NHS Trust and the study was open to both those who had attended the NatureWell training and those who had not. Data were synthesised to produce an understanding of staff attitudes towards NBAs and perceived barriers and facilitators to the implementation of this approach.

Results
Ninety-seven staff responded to the wave 1 survey and 57 responded to the wave 2 survey. Fourteen staff members were interviewed. Data synthesis generated three themes: Tension between the culture of CAMHS and NBAs (Theme 1) and the need for buy-in and governance support (Theme 2). Theme three described the potential benefits of NBAs for staff and service users in CAMHS and is presented in a separate paper. The first two themes are presented in this paper.

Conclusions
The implementation of NBAs in mental health service settings for CYP presents both significant challenges and opportunities. Our findings suggest multiple barriers to implementation, often in the form of organisational or cultural factors, such as the risk averse nature of the service. Our work also elucidates several potential facilitators which may address or mitigate some of these barriers. These potential enablers, such as harnessing the role of firsthand experience, warrant further exploration in the implementation of NBAs in CAMHS.
Prognostic value of computed tomography-derived fractional flow reserve in patients with diabetes mellitus and unstable angina
Authors: Zhao Qi , Liu Li , Xian Huimin , Luo Xing , Zhang Donghui , Hou Shenglong , Qu Chao , Zhang Ruoxi , Qu Xiufen 
Published: November 2024

Abstract
Background
Coronary artery calcification is commonly found in patients with type 2 diabetes mellitus (T2DM), which may compromise the diagnostic accuracy of coronary computed tomography angiography (CTA). Computed tomography-derived fractional flow reserve (CT-FFR), which integrates coronary anatomy with functional assessment, holds the potential to become a powerful diagnostic tool for evaluating calcified lesions.

Objective
We aim to assess the prognostic value of CT-FFR for calcific lesions in patients with T2DM and unstable angina (UA).

Methods
We conducted a retrospective study involving 3,392 patients who were diagnosed with T2DM and UA who underwent coronary CTA, with at least one visible calcification site. Of those, 1,091 patients and 1,372 vessels were recommended by cardiovascular specialists and completed invasive coronary angiography (ICA) and invasive fractional flow reserve (FFR) measurements. Simultaneously, those patients also underwent CT-FFR measurements and were divided into two groups based on CT-FFR values: one group with CT-FFR > 0.80 and the other with CT-FFR ≤ 0.80. Demographics, clinical data, the diagnostic performance of CT-FFR, analysis of calcified lesions on CTA, and major adverse events during follow-up were recorded.

Results
The diagnostic accuracy, sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and the area under the curve (AUC) of CT-FFR were 84.8%, 84.6%, 85.1%, 84.7%, 85.0%, and 84.8%, respectively, per patient, and 82.2%, 80.3.2%, 81.8%, 79.7%, 81.1%, and 82.9% respectively, per vessel. For lesion and calcification characteristics, the degree of stenosis, lesion length, rate of bifurcation lesions, diffusive lesions, occlusion, calcium volume, and coronary artery calcification score (CACS) were significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. In contrast, the minimum cross-sectional area was smaller in the CT-FFR ≤ 0.8 group than in the CT-FFR > 0.8 group. Major adverse cardiovascular and cerebrovascular events (MACCE) at the 3-year follow-up was significantly higher in the CT-FFR ≤ 0.8 group compared to the CT-FFR > 0.8 group. The CT-FFR value is an independent predictor of MACCE at the 3-year follow-up.

Conclusion
CT-FFR demonstrated significant diagnostic performance using invasive FFR as the reference standard and proved to be an important predictive tool for assessing prognosis not only in calcified lesions but also in lesions with a CACS score of zero in patients with T2DM and UA. CT-FFR may serve as a valuable tool for guiding treatment decisions in these patients.

Graphical abstract
How to ensure an appropriate oral health workforce? Modelling future scenarios for the Netherlands
Authors: Janssen Jip , Pöld Ave , Islam Md Monirul , Németh Orsolya , Grytten Jostein , Woods Noel , Listl Stefan 
Published: November 2024

Abstract
Background
Current methods for oral health workforce planning lack responsiveness to dynamic needs, hampering efficiency, equity and sustainability. Effective workforce planning is vital for resilient health care systems and achieving universal health coverage. Given this context, we developed and operationalised a needs-adaptive oral health workforce planning model and explored the potential of various future scenarios.

Methods
Using publicly available data, including the Special Eurobarometer 330 Oral Health Survey, we applied the model in a hypothetical context focusing on the Dutch population’s dental needs from 2022 to 2050. We compared current and future provider supply and requirement and examined, in addition to a base case scenario, several alternative scenarios. These included epidemiological transition scenarios with different oral health morbidity trajectories, skill-mix scenarios with independent oral hygienists conducting check-ups and multiple dental student intake and training duration (5 instead of 6 years) scenarios.

Results
Based on the aforementioned historical data, our model projects that provider requirement will exceed supply for the planning period. If the percentage of people having all natural teeth increases by 10% or 20% in 2032, 34 or 68 additional full-time equivalent (FTE) dentists will be required, respectively, compared to the base case scenario. In the skill-mix scenario, the model indicates that prioritising oral hygienists for check-ups and shifting dentists’ focus to primarily complex care could address population needs more efficiently. Among the student intake and training duration scenarios, increasing intake to 375 and, to a lesser extent, reducing training to 5 years is projected to most effectively close the provider gap.

Conclusions
The study underscores the importance of understanding oral health morbidity trajectories for effective capacity planning. Due to limited dental epidemiological data, projections carry substantial uncertainty. Currently, demand for FTE dentists seems to exceed supply, though this may vary with epidemiological changes. Skill-mix strategies could offer efficiency gains by redistributing tasks, while adjustments in dental intake and training duration could also help address the requirement-supply gap. Resolving dentistry workforce challenges requires a multifaceted approach, including strengthening oral epidemiology projections, addressing the root causes of dental health issues and prioritising harmonious dental public health and general practice prevention measures.
Expediting treatments in the 21st century: orphan drugs and accelerated approvals
Authors: Domike Reuben , Raju G. K. , Sullivan Jamie , Kennedy Annie 
Published: November 2024

Abstract
Background
In response to activated patient communities’ catalyzation, two significant efforts by the FDA to expedite treatments have now been in place for multiple decades. In 1983, the United States Congress passed the Orphan Drug Act to provide financial incentives for development of drugs for rare diseases. In 1992, partly in response to the HIV epidemic, the FDA implemented Accelerated Approval (AA) to expedite access to promising new therapies to treat serious conditions with unmet medical need based on surrogate marker efficacy while additional clinical data is confirmed.
The uses of these regulatory approaches over time are assessed in this study.

Methods
The following U.S. FDA CDER published lists were used in this analysis: 1. all orphan designations and approvals; 2. all AA and their details updated through December 31, 2022; new molecular entities (NMEs).

Results
Orphan drug designations and approvals have increased several-fold over the past four decades. The largest increase recently has been in therapies targeting oncological diseases (comprised of both oncology and malignant hematology).
Although orphan drug approvals based on NMEs are the minority of orphan drug designations, the count of approved orphan drug NMEs has increased in recent years.
The characteristics of orphan drug approvals show notable differences by disease area with rare diseases and medical genetics (49%) having a relatively large fraction of orphan drug approvals with NMEs compared to the oncological diseases (32%).
Similar to the use of orphan drug designation, oncological disease therapies have been the largest utilizers of AA. Many therapies targeting these diseases address unmet medical need and can leverage surrogate markers that have previously been used in similar trials.
The timings of conversion of AA (confirmed or withdrawn) were assessed and found to be consistent across decades and to have some dependency upon the broad disease area (when assessed by three large groups: HIV conversions were fastest; followed by oncology; followed by all others). By the end of 2022, 98% of the first 105 (approved in 2010 or earlier) AA had been converted to confirmed or withdrawn.

Conclusions
Although the typical timings for AA to be confirmed or withdrawn has not changed significantly over the decades, the disease areas utilizing orphan drug designation and AA have changed significantly over time. Both programs have had increases in their use for therapies targeting oncological diseases.
The re-use of surrogate markers for oncological diseases has been an advantage in a way that may not be scientifically feasible in many other disease areas that have greater differentiation across disease etiology. For non-oncological diseases, applicability of AA is, in part, dependent upon greater focus on characterization and acceptance of novel surrogate markers.
Validation of a guidelines-based digital tool to assess the need for germline cancer genetic testing
Authors: Russell Callan D. , Daley Ashley V. , Van Arnem Durand R. , Hila Andi V. , Johnson Kiley J. , Davies Jill N. , Cytron Hanah S. , Ready Kaylene J. , Armstrong Cary M. , Sylvester Mark E. , Caleshu Colleen A. 
Published: November 2024

Abstract
Background
Efficient and scalable solutions are needed to identify patients who qualify for germline cancer genetic testing. We evaluated the clinical validity of a brief, patient-administered hereditary cancer risk assessment digital tool programmed to assess if patients meet criteria for germline genetic testing, based on personal and family history, and in line with national guidelines.

Methods
We applied the tool to cases seen in a nationwide telehealth genetic counseling practice. Validity of the tool was evaluated by comparing the tool’s assessment to that of the genetic counselor who saw the patient. Patients’ histories were extracted from genetic counselor-collected pedigrees and input into the tool by the research team to model how a patient would complete the tool. We also validated the tool’s assessment of which specific aspects of the personal and family history met criteria for genetic testing. Descriptive statistics were used.

Results
Of the 152 cases (80% female, mean age 52.3), 56% had a personal history of cancer and 66% met genetic testing criteria. The tool and genetic counselor agreed in 96% of cases. Most disagreements (4/6; 67%) occurred because the genetic counselor’s assessment relied on details the tool was not programmed to collect since patients typically don’t have access to the relevant information (pathology details, risk models). We also found complete agreement between the tool and research team on which specific aspects of the patient’s history met criteria for genetic testing.

Conclusion
We observed a high level of agreement with genetic counselor assessments, affirming the tool’s clinical validity in identifying individuals for hereditary cancer predisposition testing and its potential for increasing access to hereditary cancer risk assessment.
Proceedings from an international consensus meeting on ablation in urogenital diseases
Authors: Iezzi Roberto , Contegiacomo Andrea , De Filippis Alessandra , Gunn Andrew J. , Atwell Thomas , Mcclure Timothy , Jing Zhang , Posa Alessandro , Scrofani Anna Rita , Maresca Alessandro , Madoff David C. , Goldberg Shraga Nahum , Kelekis Alexis , Filippiadis Dimitri , Sala Evis , Ahmed Muneeb 
Published: November 2024

Abstract
Percutaneous image-guided ablation techniques are a consolidated therapeutic alternative for patients with high preoperative surgical risk for the management of oncological diseases in multiple body districts. Each technique has both pros and cons according to the type of energy delivered, mechanism of action, and site of application. The present article reviews the most recent literature results on ablation techniques applied in the field of genitourinary diseases (kidney, adrenal glands, prostate, and uterus), describing the advantages of the use of each technique and their technical limitations and summarizing the major recommendations from an international consensus meeting.

Critical relevant statement
The article critically evaluates the efficacy and safety of ablation therapies for various genitourinary tract diseases, demonstrating their potential to improve patient outcomes and advance clinical radiology by offering minimally invasive, effective alternatives to traditional surgical treatments.

Key Points

Ablation therapies are effective alternatives to surgery for renal cell carcinoma.

Ablation techniques offer effective treatment for intermediate-risk prostate cancer.

Ablation is a promising tool for adrenal tumor management.

Ablation reduces fibroid symptoms and volume, offering an alternative to surgery.

Graphical Abstract
Design of two-dimensional reflective imaging systems: an approach based on inverse methods
Authors: Verma Sanjana , Anthonissen Martijn J. H. , ten Thije Boonkkamp Jan H. M. , IJzerman Wilbert L. 
Published: November 2024

AbstractImaging systems are inherently prone to aberrations. We present an optimization method to design two-dimensional (2D) freeform reflectors that minimize aberrations for various parallel ray beams incident on the optical system. We iteratively design reflectors using inverse methods from non-imaging optics and optimize them to obtain a system that produces minimal aberrations. This is done by minimizing a merit function that quantifies aberrations and is dependent on the energy distributions at the source and target of an optical system, which are input parameters essential for inverse freeform design. The proposed method is tested for two configurations: a single-reflector system and a double-reflector system. Classical designs consisting of aspheric elements are well-known for their ability to minimize aberrations. We compare the performance of our freeform optical elements with classical designs. The optimized freeform designs outperform the classical designs in both configurations.
Metabolomic profiling and 16 S rRNA metabarcoding of endophytes of two Aloe species revealed diverse metabolites
Authors: Marokane-Radebe Cynthia , Raimi Adekunle , Amoo Stephen , Adeleke Rasheed 
Published: November 2024

AbstractAloe species are often used interchangeably for medicinal and cosmeceutical applications, presenting a challenge to the biological efficacy consistency of some herbal preparations. Sustainable production of high-quality commonly used medicinal plants remains a limitation for commercialisation. Thus, this study investigated the potential for plant substitution by examining bacterial endophytes capable of producing similar host plant secondary metabolites. The metabolite profiles and endophytic bacterial communities of endangered Aloe lettyae were compared with those of Aloe longibracteata using nuclear magnetic resonance spectroscopy and 16 S rRNA gene sequencing. Only 15 metabolites were significantly different between A. lettyae and A. longibracteata based on metabolite concentrations. However, both plants’ functionality and potential application remain comparable. Phytohormones, including indole-3-acetate and 5-hydroxyindole-3-acetate, were more concentrated in A. lettyae than A. longibracteata. Metabolites such as tyrosine, allantoin, and myo-inositol, with human health benefits, were annotated in both species. Aloe lettyae harboured a phylogenetically diverse bacteria community compared to A. longibracteata, with a higher richness of bacterial species, indicating a likelihood of diverse metabolic capabilities among the bacteria. Dominant endophytes, including Bacillus, Comamonas, and Pseudomonas, possess enzymes contributing to various metabolic pathways. The enzymes have the potential to impact the synthesis, or breakdown of plant metabolites, consequently influencing the overall metabolic composition of the host plant. Therefore, this study supports the interchangeability of A. lettyae and A. longibracteata due to their ability to produce similar metabolites, and although the Aloe species exhibit phylogenetically diverse endophytic communities, the feasibility of utilizing their endophytes as producers of secondary metabolites remains viable.
Graphical abstract
Environmental cleaning barriers and mitigation measures identified through two initiatives in four countries, 2018–2023: a commentary
Authors: Patrick Molly , Kilpatrick Claire , Storr Julie , Gon Giorgia , Huynh Tuan , Thang Phung Manh , Adeniyi Damilola , Ogunsola Folasade , Manzi Fatuma , Por Ir , Sarpong Bernice , Sedekia Yovitha , Sokvy Ma , Tang Vouchnea , Vong Sreytouch , Graham Wendy 
Published: November 2024

AbstractIn recent years, there has been increased attention on the importance of healthcare environmental cleaning, including the need to professionalize and support the workforce responsible for performing cleaning. Global agendas and strategies on infection prevention and control (IPC) and water, sanitation and hygiene highlight the need for improvements to this sector, particularly in resource-limited healthcare facilities in low- and middle-income countries. Correspondingly, several resources have been developed that aim to (1) improve professional training of cleaners and (2) improve implementation of best practices in resource-limited settings. This commentary seeks to provide insight into the barriers and facilitators to implementing these resources, drawing on the practical experience from two initiatives across four countries from 2018 through 2023. Several common barriers were identified across the diverse settings, including (1) low empowerment and status of the workforce, (2) low pay, inadequate staff time for the high workload needed to achieve best practices and high turnover of staff, and (3) a lack of connection and integration of environmental cleaning with IPC and patient safety efforts at the participating hospitals. Despite barriers, local teams identified effective mitigation measures. While considerable time and effort will be needed to truly overcome these barriers, there are opportunities to build upon attention and momentum on this topic and IPC initiatives in resource-limited settings in low- and middle-income countries. We propose several broader actions, all of which require local leadership and context-specific approaches.
The gut microbial metabolite indole-3-aldehyde alleviates impaired intestinal development by promoting intestinal stem cell expansion in weaned piglets
Authors: Zhang Jiaqi , Chen Yahui , Guo Xin , Li Xuan , Zhang Ruofan , Wang Mengting , Zhu Weiyun , Yu Kaifan 
Published: November 2024

Abstract
Background
Weaning stress-induced diarrhea is widely recognized as being associated with gut microbiota dysbiosis. However, it has been challenging to clarify which specific intestinal microbiota and their metabolites play a crucial role in the antidiarrhea process of weaned piglets.

Results
In this study, we first observed that piglets with diarrhea exhibited a lower average daily gain and higher diarrhea score, and elevated levels of lipopolysaccharide (LPS) and D-lactate (D-LA) compared to healthy piglets. Subsequently, we analyzed the differences in intestinal microbial composition and metabolite levels between healthy and diarrheal weaned piglets. Diarrheal piglets demonstrated intestinal microbiota dysbiosis, characterized primarily by a higher Firmicutes to Bacteroidota ratio, a deficiency of Lactobacillus amylovorus and Lactobacillus reuteri, and an increased abundance of Bacteroides sp.HF-5287 and Bacteroides thetaiotaomicron. Functional profiling of the gut microbiota based on Kyoto Encyclopedia of Genes and Genomes (KEGG) data was performed, and the results showed that tryptophan metabolism was the most significantly inhibited pathway in piglets with diarrhea. Most tryptophan metabolites were detected at lower concentrations in diarrheal piglets than in healthy piglets. Furthermore, we explored the effects of dietary indole-3-aldehyde (IAld), a key tryptophan metabolite, on intestinal development and gut barrier function in weaned piglets. Supplementation with 100 mg/kg IAld in the diet increased the small intestine index and improved intestinal barrier function by promoting intestinal stem cell (ISC) expansion in piglets. The promotion of ISC expansion by IAld was also confirmed in porcine intestinal organoids.

Conclusions
These findings revealed that intestinal microbial tryptophan metabolite IAld alleviates impaired intestinal development by promoting ISC expansion in weaned piglets.