bluuebunny/crossref_metadata_2025_split huggingface dataset:
Design of a dual randomized trial in a type 2 hybrid effectiveness—implementation study
Authors: Stevens June , Mills Sarah Denton , Millett Mary-Louise , Lin Feng-Chang , Leeman Jennifer 
Published: November 2023

Abstract

Background
Dual randomized controlled trials (DRCT) are type 2 hybrid studies that include two randomized trials: one testing implementation strategies and one testing an intervention. We argue that this study design offers efficiency by providing rigorous investigation of both implementation and intervention in one study and has potential to accelerate generation of the evidence needed to translate interventions that work into real-world practice. Nevertheless, studies using this design are rare in the literature.

Main text
We construct a paradigm that breaks down the components of the DRCT and provide a step-by-step explanation of features of the design and recommendations for use. A clear distinction is made between the dual strands that test the implementation versus the intervention, and a minimum of three randomized arms is advocated. We suggest an active treatment arm that includes both the implementation strategy and intervention that are hypothesized to be superior. We suggest two comparison/control arms: one to test the implementation strategy and the second to test the intervention. Further, we recommend selection criteria for the two control arms that place emphasis on maximizing the utility of the study design to advance public health practice.

Conclusions
On the surface, the design of a DRCT can appear simple, but actual application is complex. We believe it is that complexity that has limited its use in the literature. We hope that this paper will give both implementation scientists and trialists who are not familiar with implementation science a better understanding of the DRCT design and encouragement to use it.
Prospective evaluation of clinical and radiographic 10-year results of Fitmore short-stem total hip arthroplasty
Authors: Schader Jana F. , Thalmann Caroline , Maier Katharina S. , Schiener Tom , Stoffel Karl , Frigg Arno 
Published: November 2023

Abstract
Background
Short stems were introduced into total hip arthroplasty (THA) to preserve bone stock, to transmit more load to the proximal femur, and to enable minimal invasive approaches. This study is the first long-term study (with a follow-up of 10 years) of the survival as well as the clinical and radiographic outcomes of the Fitmore hip stem, a short curved uncemented stem.

Methods
In total, 123 Fitmore hip stems were prospectively evaluated. At the final 10-year follow-up, 80 Fitmore stems (78 patients: 30 female, 48 male) were eligible for evaluation. Clinical parameters were thigh pain, EQ-5D, Harris Hip Score (HHS) and Oxford Hip Score. Radiographic parameters were cortical hypertrophy (CH), bone condensation, cortical thinning, radiolucency, reactive lines, calcar rounding, calcar resorption, subsidence and varus/valgus position.

Results
After 10 years, there was a survival rate of 99% (1 revision because of aseptic stem loosening). HHS had improved from 59 to 94 and Oxford Hip Score from 22 to 43. CH rate after 1 year was 69% and after 10 years 74%. In the first year, radiolucency was found in 58% and in 17.5% after 10 years. Subsidence after 1 year was 1.6 ± 1.6 mm and 5.0 ± 3.1 mm after 10 years.

Conclusions
The Fitmore hip stem showed a survival rate of 99% as well as good clinical and radiographic outcomes in the long-term follow-up of 10 years.
Prioritization of research engaged with rare disease stakeholders: a systematic review and thematic analysis
Authors: Yoon Soho , Lee Minjee , Jung Hoi-In , Khan M. Mahmud , Kim So-Yoon , Kim Hannah , Wasti Sophia 
Published: November 2023

Abstract
Background
Although rare diseases (RD) are increasingly becoming a priority for healthcare activities and services around the world, developing research policy for investigating RD in public settings proves challenging due to the limited nature of existing evidence. Rare conditions require the involvement of a wide range of stakeholders in order to promote general awareness and garner political support. Consequently, it is critically important to identify trends in the various types of research focusing on rare disease stakeholders, including the specific topics or issues to be included in surveys and studies focused on RD stakeholders. This systematic review and thematic analysis analyses the existing literature based on RD surveys, including the stakeholders involved, and proposes potential research priorities and initiatives for policy-making related to RD.

Methods
Articles were downloaded and analyzed from across five electronic databases (PubMed, EMBASE, Cochrane Central, Web of Science, and CINHAL) and 115 studies were included.

Results
Across 115 studies, the main research participants were patients and/or caregivers (n = 77, 67.0%), health professionals (n = 18, 15.7%), and the public (n = 7, 6.1%). The studies discussed RDs in general (n = 46, 40.0%), endocrine, nutritional, and metabolic diseases (n = 20, 17.4%) and other RDs. Experiences with RD were examined by more than half of the selected studies (n = 74, 64.3%), followed by the opinions of stakeholders (n = 24, 20.9%). Most of the studies used surveys in order to collect relevant data (n = 114, 99.1%). Additionally, the majority of the studies were conducted in high-income countries (n = 92, 80.0%) and rarely in middle and low-income countries (n = 12, 13.8%).

Conclusion
Stakeholder research on RD reveals that there are significant instances of unmet needs and various challenges faced by the medical system in dealing with RDs.
Furthermore, public awareness and support is critical to ensuring political feasibility of increasing national-level investments for RDs and development of medical products and treatment.
Multi-omics analysis reveals the molecular response to heat stress in a “red tide” dinoflagellate
Authors: Dougan Katherine E. , Deng Zhi-Luo , Wöhlbrand Lars , Reuse Carsten , Bunk Boyke , Chen Yibi , Hartlich Juliane , Hiller Karsten , John Uwe , Kalvelage Jana , Mansky Johannes , Neumann-Schaal Meina , Overmann Jörg , Petersen Jörn , Sanchez-Garcia Selene , Schmidt-Hohagen Kerstin , Shah Sarah , Spröer Cathrin , Sztajer Helena , Wang Hui , Bhattacharya Debashish , Rabus Ralf , Jahn Dieter , Chan Cheong Xin , Wagner-Döbler Irene 
Published: November 2023

Abstract
Background
“Red tides” are harmful algal blooms caused by dinoflagellate microalgae that accumulate toxins lethal to other organisms, including humans via consumption of contaminated seafood. These algal blooms are driven by a combination of environmental factors including nutrient enrichment, particularly in warm waters, and are increasingly frequent. The molecular, regulatory, and evolutionary mechanisms that underlie the heat stress response in these harmful bloom-forming algal species remain little understood, due in part to the limited genomic resources from dinoflagellates, complicated by the large sizes of genomes, exhibiting features atypical of eukaryotes.

Results
We present the de novo assembled genome (~ 4.75 Gbp with 85,849 protein-coding genes), transcriptome, proteome, and metabolome from Prorocentrum cordatum, a globally abundant, bloom-forming dinoflagellate. Using axenic algal cultures, we study the molecular mechanisms that underpin the algal response to heat stress, which is relevant to current ocean warming trends. We present the first evidence of a complementary interplay between RNA editing and exon usage that regulates the expression and functional diversity of biomolecules, reflected by reduction in photosynthesis, central metabolism, and protein synthesis. These results reveal genomic signatures and post-transcriptional regulation for the first time in a pelagic dinoflagellate.

Conclusions
Our multi-omics analyses uncover the molecular response to heat stress in an important bloom-forming algal species, which is driven by complex gene structures in a large, high-G+C genome, combined with multi-level transcriptional regulation. The dynamics and interplay of molecular regulatory mechanisms may explain in part how dinoflagellates diversified to become some of the most ecologically successful organisms on Earth.
Use of continuous glucose monitoring in insulin-treated older adults with type 2 diabetes
Authors: Leite Silmara A O , Silva Michael P , Lavalle Ana C R , Bertogy Maria C V , Bastos Murilo , Kuklik Suelen C Vieira , Umpierrez Guillermo 
Published: November 2023

Abstract
Background
Few studies have reported the adherence to and efficacy of continuous glucose monitoring (CGM) for improving diabetes management in insulin-treated older adults with type 2 diabetes mellitus (T2DM).

Methods
Prospective observational cohort study using FreeStyle Libre Flash CGM in insulin-treated adults > 65 years with T2DM and HbA1c between 7% and 9%. The participants wore the CGM during the 6-weeks study period. The primary outcome was time in range (TIR) between 70 and 180 mg/dL. Secondary outcomes included time below range (TBR), glycemic variability (GV), adherence, and use of glucose data for self-insulin adjustment. Linear regressions with random effects verified the changes in TBR, TIR, time above range (TAR), GV, and GMI across the three visits using CGM (baseline, 4 weeks and 6 weeks), controlled for sex, age, educational level, and health system (private or public).

Results
A total of 66 participants completed the six weeks of CGM (age 72·8 ± 5·3 years; BMI 27·8 ± 3·6 kg/m2), HbA1c: 8·0 ± 0·6%, with an overall sensor utilization of 93·1 ± 6·0%. We observed a stability in TIR (baseline: 63.5 ± 18.9% vs. endpoint: 65.5 ± 18.8%; β = 1,0, p = 0.190). Despite the low TBR at the baseline, we observed statistically significant reduction over the study period (baseline: 5.8 ± 7.0% vs. endpoint: 3.8 ± 4.7%; (β=-1.00, p = 0.008). Glucose variability also reduced from the baseline (34.9 ± 7.2%) to the endpoint (33.0 ± 6.8%) (β=-0.99, p = < 0.001).

Conclusion
FreeStyle Libre Flash CGM is well accepted by older adults with T2DM and allows participants to make therapeutic decisions to reduce TBR and glycemic variability.
Reversible acute blindness in suspected metformin-associated lactic acidosis: a case report
Authors: Huang Rui , Sun Wentao 
Published: November 2023

Abstract
Background
Metformin is commonly used for the treatment of type 2 diabetes mellitus. Its multiple advantages include low risk of hypoglycemia, weight neutrality, low cost, and cardioprotective and anti-inflammatory effects. Renal insufficiency is one of the contraindications for its use. Inadvertent prescription in patients with renal insufficiency may lead to metformin-associated lactic acidosis, which brings a high risk of mortality. The early recognition and management of metformin-associated lactic acidosis are essential.

Case report
We present the case of a 58-year-old Hui woman with a history of type 2 diabetes mellitus with nephropathy and heart disease for which she was treated with metformin, insulin, and heart medications. She developed nausea, vomiting, anion gap metabolic acidosis due to hyperlactatemia, and acute kidney injury. She was hospitalized to receive intravenous hydration and correction of metabolic acidosis after she suddenly developed blindness. The diagnostic workup ruled out central causes and her symptoms resolved briefly after continuous venovenous hemodialysis was initiated, confirming the diagnosis of metformin-associated lactic acidosis.

Conclusions
Metabolic disruption can cause acute blindness. Metabolic acidosis in a patient with a history of metformin intake should suggest the possibility of metformin-associated lactic acidosis, which must be treated immediately, without waiting for the results of other examinations, especially in patients with sudden blindness. Further study of reversible blindness-associated severe metabolic acidosis is needed.
An explainability framework for deep learning on chemical reactions exemplified by enzyme-catalysed reaction classification
Authors: Probst Daniel 
Published: November 2023

AbstractAssigning or proposing a catalysing enzyme given a chemical or biochemical reaction is of great interest to life sciences and chemistry alike. The exploration and design of metabolic pathways and the challenge of finding more sustainable enzyme-catalysed alternatives to traditional organic reactions are just two examples of tasks that require an association between reaction and enzyme. However, given the lack of large and balanced annotated data sets of enzyme-catalysed reactions, assigning an enzyme to a reaction still relies on expert-curated rules and databases. Here, we present a data-driven explainable human-in-the-loop machine learning approach to support and ultimately automate the association of a catalysing enzyme with a given biochemical reaction. In addition, the proposed method is capable of predicting enzymes as candidate catalysts for organic reactions amendable to biocatalysis. Finally, the introduced explainability and visualisation methods can easily be generalised to support other machine-learning approaches involving chemical and biochemical reactions.
High-flow nasal cannula oxygen versus conventional oxygen therapy for acute respiratory failure due to COVID-19: a systematic review and meta-analysis
Authors: Le Pape Sylvain , Savart Sigourney , Arrivé François , Frat Jean-Pierre , Ragot Stéphanie , Coudroy Rémi , Thille Arnaud W. 
Published: November 2023

Abstract
Background
The effectiveness of high-flow nasal cannula oxygen therapy (HFNC) in patients with acute respiratory failure due to COVID-19 remains uncertain. We aimed at assessing whether HFNC is associated with reduced risk of intubation or mortality in patients with acute respiratory failure due to COVID-19 compared with conventional oxygen therapy (COT).

Methods
In this systematic review and meta-analysis, we searched MEDLINE, Embase, Web of Science, and CENTRAL databases for randomized controlled trials (RCTs) and observational studies comparing HFNC vs. COT in patients with acute respiratory failure due to COVID-19, published in English from inception to December 2022. Pediatric studies, studies that compared HFNC with a noninvasive respiratory support other than COT and those in which intubation or mortality were not reported were excluded. Two authors independently screened and selected articles for inclusion, extracted data, and assessed the risk of bias. Fixed-effects or random-effects meta-analysis were performed according to statistical heterogeneity. Primary outcomes were risk of intubation and mortality across RCTs. Effect estimates were calculated as risk ratios and 95% confidence interval (RR; 95% CI). Observational studies were used for sensitivity analyses.

Results
Twenty studies were analyzed, accounting for 8383 patients, including 6 RCTs (2509 patients) and 14 observational studies (5874 patients). By pooling the 6 RCTs, HFNC compared with COT significantly reduced the risk of intubation (RR 0.89, 95% CI 0.80 to 0.98; p = 0.02) and reduced length of stay in hospital. HFNC did not significantly reduce the risk of mortality (RR 0.93, 95% CI 0.77 to 1.11; p = 0.40).

Conclusions
In patients with acute respiratory failure due to COVID-19, HFNC reduced the need for intubation and shortened length of stay in hospital without significant decreased risk of mortality.
Trial registration The study was registered on the International prospective register of systematic reviews (PROSPERO) at https://www.crd.york.ac.uk/prospero/ with the trial registration number CRD42022340035 (06/20/2022).
Identification of physiological and metabolic networks involved in postharvest browning of cigar tobacco leaves
Authors: Zhao Gaokun , Zhang Qing , Kong Guanghui , Yao Heng , Wu Yuping , Cai Bo , Liu Tao , Zhang Guanghai 
Published: November 2023

AbstractThe surface color of cigar tobacco leaves (CTLs) is largely determined by the browning response and is one of the most important quality traits affecting consumer preferences. The physiological changes and metabolic network of browning in CTLs after harvest have not been reported. We investigated the molecular mechanism of browning in CTLs by comparing the physiological characteristics and metabolites of CTLs browning at five postharvest periods. Phenotypic traits and browning-related enzyme activity data indicated that the browning reaction was most intense at approximately 12 d when polyphenol oxidase and peroxidase activities reached their maximum. Postharvest CTLs polyphenols, polyacids, and carbon and nitrogen compounds were rapidly degraded during the yellowing phase, and the biosynthesis rate of polyphenols and carotenoids was greater than the degradation rate during the browning phase. Metabolomic analysis discovered 2027 metabolites that were annotated mainly to lipids and lipid-like molecules, organic acids and their derivatives, and organic heterocyclic components. Hierarchical cluster analysis discovered glutamate, serine, threonine, ornithine, and arginine as the major amino acids involved in the browning reaction. KEGG pathway enrichment analysis indicated that the metabolic pathways with important effects on enzymatic browning were phenylpropanoid biosynthesis, flavonoid biosynthesis, isoquinoline alkaloid biosynthesis, phenylalanine metabolism, and linoleic acid metabolism. The metabolic pathway network was mined, and the main polyphenols involved in the browning reaction of CTLs were found to be cyanidin, rutin, caffeoylquinic acid, kaempferol, naringin, and neohesperidin. This study provides a reference for the browning physiology and metabolism network of postharvest CTLs.
Graphical Abstract
On the use of solid 133Ba sources as surrogate for liquid 131I in SPECT/CT calibration: a European multi-centre evaluation
Authors: Tran-Gia Johannes , Denis-Bacelar Ana M. , Ferreira Kelley M. , Robinson Andrew P. , Bobin Christophe , Bonney Lara M. , Calvert Nicholas , Collins Sean M. , Fenwick Andrew J. , Finocchiaro Domenico , Fioroni Federica , Giannopoulou Katerina , Grassi Elisa , Heetun Warda , Jewitt Stephanie J. , Kotzasarlidou Maria , Ljungberg Michael , Lourenço Valérie , McGowan Daniel R. , Mewburn-Crook Jamie , Sabot Benoit , Scuffham James , Sjögreen Gleisner Katarina , Solc Jaroslav , Thiam Cheick , Tipping Jill , Wevrett Jill ,   The MRT Dosimetry Collaboration, Lassmann Michael 
Published: November 2023

Abstract
Introduction
Commissioning, calibration, and quality control procedures for nuclear medicine imaging systems are typically performed using hollow containers filled with radionuclide solutions. This leads to multiple sources of uncertainty, many of which can be overcome by using traceable, sealed, long-lived surrogate sources containing a radionuclide of comparable energies and emission probabilities. This study presents the results of a quantitative SPECT/CT imaging comparison exercise performed within the MRTDosimetry consortium to assess the feasibility of using 133Ba as a surrogate for 131I imaging.

Materials and methods
Two sets of four traceable 133Ba sources were produced at two National Metrology Institutes and encapsulated in 3D-printed cylinders (volume range 1.68–107.4 mL). Corresponding hollow cylinders to be filled with liquid 131I and a mounting baseplate for repeatable positioning within a Jaszczak phantom were also produced. A quantitative SPECT/CT imaging comparison exercise was conducted between seven members of the consortium (eight SPECT/CT systems from two major vendors) based on a standardised protocol. Each site had to perform three measurements with the two sets of 133Ba sources and liquid 131I.

Results
As anticipated, the 131I pseudo-image calibration factors (cps/MBq) were higher than those for 133Ba for all reconstructions and systems. A site-specific cross-calibration reduced the performance differences between both radionuclides with respect to a cross-calibration based on the ratio of emission probabilities from a median of 12–1.5%. The site-specific cross-calibration method also showed agreement between 133Ba and 131I for all cylinder volumes, which highlights the potential use of 133Ba sources to calculate recovery coefficients for partial volume correction.

Conclusion
This comparison exercise demonstrated that traceable solid 133Ba sources can be used as surrogate for liquid 131I imaging. The use of solid surrogate sources could solve the radiation protection problem inherent in the preparation of phantoms with 131I liquid activity solutions as well as reduce the measurement uncertainties in the activity. This is particularly relevant for stability measurements, which have to be carried out at regular intervals.
A community-based approach to identifying and prioritising young people’s mental health needs in their local communities
Authors: Santana de Lima Ediane , Preece Cristina , Potter Katie , Goddard Ellen , Edbrooke-Childs Julian , Hobbs Tim , Fonagy Peter 
Published: November 2023

Abstract
Background
Identifying locally relevant and agreed-upon priorities for improving young people’s mental health, aligned with social and environmental factors, is essential for benefiting target communities. This paper describes a participatory approach to engage young people and professionals in identifying such priorities, whilst considering the social determinants related to them.

Methods
We utilised a community-based participatory approach to support young people and professionals in identifying, reviewing, refining, and prioritising, locally relevant opportunity areas that are crucial for understanding and addressing social determinants of young people’s mental health. We adopted a flexible five-stage process, which enabled greater reflection and adaptation in response to young people’s and professionals’ feedback and reflections.

Results
Over seven months, we engaged with young people and professionals in Northern Devon, (a rural area in southwest England), involving over 290 individuals to identify locally relevant priorities for supporting young people’s mental health. Three priorities were identified for subsequent exploration using co-design approaches: (1) identity and belonging; (2) mental health awareness and literacy; and (3) diverse opportunities (for education, employment and leisure). The engagements suggested that designing initiatives and strategies in these areas could contribute to improvements in young people’s mental health.

Conclusion
Young people in Northern Devon prioritised three themes for the next phase of the Kailo Programme—mental health literacy, access to diverse careers and employment opportunities, and identity and belonging within their communities. Rural communities face unique barriers associated with these issues, related to less diverse populations, lack of access to reliable and affordable transport and local industries, and seasonal working. The perceived neglect by authorities towards rural young people has resulted in a lack of activities and opportunities catering to their specific needs, compared to urban areas. Although the government has recognised the need to address these disparities, community members suggest that there is still more work to be done.