bluuebunny/crossref_metadata_2025 huggingface dataset:
Sex differences in myocardial infarction care and outcomes: a longitudinal Scottish National Data-Linkage Study
Authors: Pana Tiberiu A , Mamas Mamas A , Myint Phyo K , Dawson Dana K
Published: November 2024

Aims

We investigate sex disparities in management and outcomes of myocardial infarction (MI) in contemporary practice in Scotland.

Methods and results

This was a longitudinal cohort study including all MI admissions aged 45-80 years across Scotland between 2010–2016 and 2:1 age, sex, and general practice-matched general population controls. Participants were followed up until the end of 2021. We analysed in-hospital outcomes (percutaneous coronary intervention, secondary prevention and mortality) using Poisson regressions, adjusting for age, comorbidities, and ST-elevation. We used Royston–Parmar models for long-term outcomes (all-cause and cardiovascular mortality, incident cardiovascular events), adjusting for age, comorbidities, and secondary prevention. Of a total 47 063 MI patients, 15 776 (33.5%) were women. Median (inter-quartile range) age was 66 (57, 73) years. Compared to men, women were older and more comorbid, but were less likely to undergo percutaneous coronary intervention [risk ratio (95% confidence interval) − 0.87 (0.86 – 0.89)] or receive secondary prevention at discharge [0.94 (0.93–0.95)]. No in-hospital mortality difference was observed between sexes [1.06 (0.99–1.13) after adjustment]. Over a median follow-up of 8.2 (6.7, 10.1) years, women had higher crude rates of adverse outcomes. After full adjustment, this translated into a lower risk for women compared to men of all-cause mortality [hazard ratio, 0.92 (0.89–0.95)], cardiovascular mortality [0.82 (0.78–0.87)], and cardiovascular events [0.92 (0.88–0.95)]. The female survival advantage seen in general population controls was attenuated in MI patients.

Conclusion

Women were undertreated compared to men after MI. Their survival and outcome benefits may be improved further. Poor outcomes in men despite better receipt of secondary prevention require further attention.
Could digital twins be the next revolution in healthcare?
Authors: de Oliveira El-Warrak Leonardo , Miceli de Farias Claudio
Published: November 2024

A Digital Twin (DT) can be understood as a representation of a real asset, a virtual replica of a physical object, process, or even a system. They have been used in managing healthcare facilities, streamlining care processes, personalizing treatments, and enhancing patient recovery. The potential impact of this tool on our society and its well-being is quite significant. A quick review of the literature was carried out using the terms (‘Digital Twins’) and (‘Digital Health’), and (Health Care) with a time interval of up to 5 years (2018–23). Using the PRISMA Method, the search was conducted in six academic databases: IEEE Xplore, Dimensions, Scopus, Web of Science, PubMed, and ACM. After applying the search strings and the exclusion criteria, a total of 13 publications were identified and listed to constitute and support the discussion of this article. The selected studies were categorized into 2 groups according to their application in healthcare: A group of clinical applications, subdivided into topics on personalized care and reproduction of biological structures and another group of operational applications, subdivided into topics such as optimization of operational processes, reproduction of physical structures, and development of devices and drugs. The use of DT in healthcare presents important challenges related to data integration, privacy, and interoperability. However, trends indicate exciting potential in personalizing treatment, prevention, remote monitoring, informed decision-making, and process management, which can result in significant improvements in quality and efficiency in healthcare.
Older adults in social housing: A systemically vulnerable population that needs to be prioritized
Authors: Dzerounian Jasmine , Mahal Guneet , AlShenaiber Leena , Angeles Ricardo , Marzanek Francine , Pirrie Melissa , Agarwal Gina
Published: November 2024

Older adults living in social housing are a vulnerable population with unique health challenges that often lead to poor health outcomes and high emergency service utilization. However, the needs of this population are frequently overlooked. This policy note describes the characteristics of older adults living in social housing in Canada and discusses why they are a vulnerable, underserved population in need of immediate attention and priority. Older adults in social housing have higher rates of chronic disease, lower quality of life, and lower health literacy and face challenges caused by various compounding social determinants of health. There is a large gap in research and tailored interventions focusing on this population. Based on these findings, the authors highlight the need for the allocation of resources to support this growing population, including dedicated funding, research, and programming. Proactively addressing the issues that exist in the health and social care of this high-needs population will also have larger implications for reducing healthcare system burden.
The ‘golden fleece of embryology’ eludes us once again: a recent RCT using artificial intelligence reveals again that blastocyst morphology remains the standard to beat
Authors: Sakkas Denny
Published: November 2024

Grading of blastocyst morphology is used routinely for embryo selection with good outcomes. A lot of effort has been placed in IVF to search for the prize of selecting the most viable embryo to transfer (‘the golden fleece of embryology’). To improve on morphology alone, artificial intelligence (AI) has also become a tool of interest, with many retrospective studies being published with impressive prediction capabilities. Subsequently, AI has again raised expectations that this ‘golden fleece of embryology’ was once again within reach. A recent RCT however was not able to demonstrate non-inferiority using a deep learning algorithm ‘iDAScore version 1’ for clinical pregnancy rate when compared to standard morphology. Good blastocyst morphology has again proven itself as a high bar in predicting live birth. We should however not give up on the development of further approaches which may allow us to identify extra features of viable embryos that are not captured by morphology.
A Phase 1b/2a Trial of a Half-life Extended Respiratory Syncytial Virus Neutralizing Antibody, Clesrovimab, in Healthy Preterm and Full-term Infants
Authors: Madhi Shabir A , Simões Eric A F , Acevedo Armando , Novoa Pizarro Jose M , Shepard Julie S , Railkar Radha A , Cao Xin , Maas Brian M , Zang Xiaowei , Krick Andrea , Roadcap Brad , Vora Kalpit A , Aliprantis Antonios O , Lee Andrew W , Sinha Anushua
Published: November 2024

Background

Clesrovimab is an investigational monoclonal antibody with an extended half-life targeting site IV of the respiratory syncytial virus (RSV) fusion protein for the prevention of RSV disease in infants.

Methods

In this phase 1b/2a, double-blind study, 183 healthy preterm and full-term infants 2 weeks to 8 months of age were randomized 4:1 within 5 panels (preterm 20, 50, 75, or 100 mg; full-term 100 mg) to receive 1 dose of clesrovimab or placebo. The objectives were to evaluate safety, pharmacokinetics, serum neutralizing antibodies (SNA), and antidrug antibodies (ADA). The incidence of RSV-associated end points (medically attended lower respiratory tract infection, hospitalization, and acute respiratory infection) were also evaluated through 150 days postdose.

Results

The most common adverse event through day 14 was irritability; no treatment-related serious AEs were reported. Clesrovimab serum concentrations displayed a geometric mean apparent half-life of 44.9 days. Of participants receiving clesrovimab, 51 (36.7%) developed ADA with no apparent impact in pharmacokinetics. SNA titers increased in a dose-dependent manner at day 150. The incidences of RSV-associated end points were lower in infants treated with clesrovimab compared with placebo.

Conclusions

Clesrovimab was generally well tolerated and exhibited an extended half-life compared to typical IgG1 antibodies, supporting its ongoing development in late-stage trials.

Clinical Trial Registration. NCT03524118.
LCD benchmark: long clinical document benchmark on mortality prediction for language models
Authors: Yoon WonJin , Chen Shan , Gao Yanjun , Zhao Zhanzhan , Dligach Dmitriy , Bitterman Danielle S , Afshar Majid , Miller Timothy
Published: November 2024

Objectives

The application of natural language processing (NLP) in the clinical domain is important due to the rich unstructured information in clinical documents, which often remains inaccessible in structured data. When applying NLP methods to a certain domain, the role of benchmark datasets is crucial as benchmark datasets not only guide the selection of best-performing models but also enable the assessment of the reliability of the generated outputs. Despite the recent availability of language models capable of longer context, benchmark datasets targeting long clinical document classification tasks are absent.

Materials and Methods

To address this issue, we propose Long Clinical Document (LCD) benchmark, a benchmark for the task of predicting 30-day out-of-hospital mortality using discharge notes of Medical Information Mart for Intensive Care IV and statewide death data. We evaluated this benchmark dataset using baseline models, from bag-of-words and convolutional neural network to instruction-tuned large language models. Additionally, we provide a comprehensive analysis of the model outputs, including manual review and visualization of model weights, to offer insights into their predictive capabilities and limitations.

Results

Baseline models showed 28.9% for best-performing supervised models and 32.2% for GPT-4 in F1 metrics. Notes in our dataset have a median word count of 1687.

Discussion

Our analysis of the model outputs showed that our dataset is challenging for both models and human experts, but the models can find meaningful signals from the text.

Conclusion

We expect our LCD benchmark to be a resource for the development of advanced supervised models, or prompting methods, tailored for clinical text.
Mating behaviour influences the direction and geographic extent of introgression in New Zealand fishing spiders (Dolomedes)
Authors: Connolly Simon J , Curtis Kate M , Vink Cor J , Painting Christina J
Published: November 2024

Introgression is a highly influential process in evolution, where genes flow between species that are not fully reproductively isolated. Studies on introgression often focus on describing gene transfer and environmental changes that facilitate the meeting of species. However, the impact of mating systems and behaviour that facilitate gene transfer is less well-known. Dolomedes aquaticus and D. minor are sister species of fishing spiders undergoing one-way, geographically limited mitochondrial introgression, making them an excellent case study for the factors that promote and limit introgression. We used a combination of field observations and crossing experiments to systematically investigate potential prefertilization barriers that could limit introgression and explain the one-way and geographic barriers to introgression in these species. We found that habitat overlap and timing of reproductive maturity were not likely to be important limiting factors to introgression. However, behaviour was an important factor, with male mate choice being implicated in the geographic limitation, and female mate choice being implicated in the one-way limitation. Our results show the importance of using behavioural approaches in the investigation of introgression.
Invasive Species, Health, and Global History Afterword: The Disavowal of Human Agency
Authors: Clarke Sabine
Published: November 2024

The papers in this special issue explore the metaphorical realms that inform discourses on disruptive plants and animals. They explore how species movements in the twentieth century were framed and interpreted, and the medical, scientific, legal, and bureaucratic processes that turned a non-native or mobile species into a formally designated “invasive” one. In doing so, they allow insight into the mechanisms of disavowal, how some species were constructed as the cause of disease and ecological change, while others escaped censure.
Acute mesenteric ischemia secondary to metastatic neuroendocrine tumor: a case analysis and review of the literature
Authors: Swafford Emily P , Magge Deepa R
Published: November 2024

Neuroendocrine tumors (NETs) are notably rare and frequently arise from the gastrointestinal tract. Generally asymptomatic, NETs uncommonly result in acute abdominal pain. We present a case of known metastatic NET manifesting as acute-on-chronic mesenteric ischemia due to the involvement of the superior mesenteric artery (SMA) and vein (SMV). A 63-year-old female with metastatic NET presented with acute-onset abdominal pain. The patient was hemodynamically stable but uncomfortable appearing with significant pain. Imaging demonstrated decreased enhancement of several small bowel loops within the right lower quadrant concerning for bowel ischemia with a mesenteric mass encasing the SMA and SMV. Surgical intervention revealed a nonviable loop of small bowel. Second-look laparotomy was performed with viable remaining bowel, and an ileocolic anastomosis was successfully created. Acute-onset abdominal pain in a patient with NET warrants urgent. Mesenteric ischemia, while rare, should not be overlooked, as timely diagnosis and intervention are imperative.
Black hole spin evolution across cosmic time from the NewHorizon simulation
Authors: Beckmann R S , Dubois Y , Volonteri M , Dong-Paez C A , Peirani S , Piotrowska J M , Martin G , Kraljic K , Devriendt J , Pichon C , Yi S K
Published: November 2024

Astrophysical black holes (BHs) have two fundamental properties: mass and spin. While the mass-evolution of BHs has been extensively studied, much less work has been done on predicting the distribution of BH spins. In this paper, we present the spin evolution for a sample of intermediate-mass and massive BHs from the NewHorizon simulation, which evolved BH spin across cosmic time in a full cosmological context through gas accretion, BH–BH mergers and BH feedback including jet spindown. As BHs grow, their spin evolution alternates between being dominated by gas accretion and BH mergers. Massive BHs are generally highly spinning. Accounting for the spin energy extracted through the Blandford–Znajek mechanism increases the scatter in BH spins, especially in the mass range $10^{5}{-}10^{7}\,\rm M_\odot$, where BHs had previously been predicted to be almost universally maximally spinning. We find no evidence for spin-down through efficient chaotic accretion. As a result of their high spin values, massive BHs have an average radiative efficiency of $\lt \varepsilon _{\rm r}^{\rm thin}\gt \approx 0.19$. As BHs spend much of their time at low redshift with a radiatively inefficient thick disc, BHs in our sample remain hard to observe. Different observational methods probe different sub-populations of BHs, significantly influencing the observed distribution of spins. Generally, X-ray-based methods and higher luminosity cuts increase the average observed BH spin. When taking BH spin evolution into account, BHs inject, on average, between three times (in quasar mode) and eight times (in radio mode) as much feedback energy into their host galaxy as previously assumed.
Update of the FANTOM web resource: enhancement for studying noncoding genomes
Authors: Nobusada Tomoe , Yip Chi Wai , Agrawal Saumya , Severin Jessica , Abugessaisa Imad , Hasegawa Akira , Hon Chung Chau , Ide Satoru , Koido Masaru , Kondo Atsushi , Masuya Hiroshi , Oki Shinya , Tagami Michihira , Takada Toyoyuki , Terao Chikashi , Thalhath Nishad , Walker Scott , Yasuzawa Kayoko , Shin Jay W , de Hoon Michiel J L , Carninci Piero , Kawaji Hideya , Kasukawa Takeya
Published: November 2024

The FANTOM web resource (https://fantom.gsc.riken.jp/) has been a unique resource for studying mammalian genomes, which is built on the research activities conducted in the international collaborative project FANTOM (Functional ANnoTation Of the Mammalian genome). In recent updates, we expanded annotations for long non-coding RNAs (lncRNAs) and transcribed cis-regulatory elements (CREs). The former was derived from the large-scale lncRNA perturbations in induced pluripotent stem cells (iPSCs) and integrative analysis of Hi-C data conducted in the sixth iteration of the project (FANTOM6). The resulting annotations of lncRNAs, according to the impact on cellular and molecular phenotypes and the potential RNA-chromatin interactions, are accessible via the interactive ZENBU-Reports framework. The latter involves a new platform, fanta.bio (https://fanta.bio/), which collects transcribed CREs identified via use of an extended dataset of CAGE profiles. The CREs, with their annotations including genetic and epigenetic information, are accessible via a dedicated interface as well as the UCSC Genome Browser Database. These updates offer enhanced opportunities to investigate the functions of non-coding regions within mammalian genomes.
Acute Effects of Nicotine on Non-Drug-Related Reward in Smokers and Non-Smokers
Authors: Rycroft Nicola , Kimber Catherine , Brazier Emke S E , Dawkins Lynne
Published: November 2024

Introduction

Nicotine increases the reward value of non-drug-related stimuli in animals and dependent smokers; however, research on people who are not dependent on nicotine is limited. This study aimed to explore whether nicotine delivered by oral spray can enhance responding to self-selected sensory rewards in both smokers and non-smokers.

Aims and Methods

Minimally abstinent smokers (n = 30) and non-smokers (n = 31) completed subjective ratings of nicotine withdrawal, and received either 2 mg nicotine or placebo oral spray and visual analogue scales to measure the perceived effects of the spray. An operant conditioning task (Applepicker) that required button clicks to find apples was completed twice, with and without a reward of 30 seconds of pre-prepared music for each reinforcer earned. Measures taken were the number of apples found (reinforcers), number of clicks (responses), and time spent on the task (in seconds).

Results

There were no differences between smokers and non-smokers on ratings of nicotine withdrawal or effects of the spray. All participants spent longer searching for apples, earned more reinforcers, and produced more responses when listening to music. Nicotine administration led to a higher number of reinforcers earned and, when music was playing, an increase in a number of responses. A three-way interaction revealed that non-smokers who had received nicotine spent the longest searching for apples.

Conclusions

Nicotinic enhancement of sensory rewards was seen in non-smokers only which cannot be accounted for by learned associations with nicotine or reversal of withdrawal effects. Smokers, however, may require higher doses of nicotine to achieve the same effect.

Implications

Nicotinic enhancement of sensory rewards was demonstrated in non-smokers, but not in everyday smokers, suggesting it is unlikely to be related to nicotine dependence or learned associations between nicotine and pleasure. The absence of this effect in smokers suggests that higher levels of nicotine than those obtained from 2 mg oral sprays may be required to achieve enhancement of reward in people who regularly consume nicotine. For nicotine replacement (including e-cigarettes) to become more effective at reducing anhedonia during quit attempts, smokers may require nicotine doses that more closely replicate levels achieved through smoking.
Magmatic Activity in Incipient Continental Break-Up as Revealed by Coupling Melt and Fluid Inclusions
Authors: Boudoire G , Bobrowski N , Burgi P-Y , Calabrese S , France L , Giuffrida G , Grassa F , Karume K , Kazadi Mwepu J-C , Kuhn J , Moritz R , Munguiko Munyamahoro O , Rizzo A L , Tedesco D
Published: November 2024

Deciphering deep magmatic processes driving the onset of continental break-up is fundamental to constrain our understanding of plate tectonics. The East African Rift System (EARS) represents the only opportunity to study a currently active system on Earth undergoing distinct stages of rift evolution. We present a coupled analysis of melt and fluid inclusions in the Virunga Volcanic Province (VVP) offering unprecedented insight into the dynamics of incipient rifting and its evolution. Our study highlights that melting of distinct metasomes in the deep lithosphere is a common feature of immature rifts. In the VVP, it leads to the emission of nephelinitic and basanitic melts at Nyiragongo and Nyamulagira volcanoes, respectively. Additionally, the chemical composition of melt and fluid inclusions supports the identification of another magmatic series in the area. We suggest that the related alkali basaltic melts were produced by contemporary melting of a less enriched domain in the upper lithosphere, a process that is more commonly documented in mature rifts. Various extents of mixing and crystallization of these three distinct magmatic series occur in the lower crust beneath the VVP where the barometric estimates are consistent with the presence of a thick seismic low velocity zone (LVZ). The involvement of alkali basaltic melts in the regional magma production would be also detected in the spread of gas emissions in the rift valley and in the fumaroles of the main active volcanoes. Melting of the corresponding mantle domain is an added source of gas release that may largely contribute to CO2 emissions along the EARS.
In silico screening of protein-binding peptides with an application to developing peptide inhibitors against antibiotic resistance
Authors: Xu Xianjin , Kao Wei-Ling , Wang Allison , Lee Hsin-Jou , Duan Rui , Holmes Hannah , Gallazzi Fabio , Ji Juan , Sun Hongmin , Heng Xiao , Zou Xiaoqin
Published: November 2024

The field of therapeutic peptides is experiencing a surge, fueled by their advantageous features. These include predictable metabolism, enhanced safety profile, high selectivity, and reduced off-target effects compared with small-molecule drugs. Despite progress in addressing limitations associated with peptide drugs, a significant bottleneck remains: the absence of a large-scale in silico screening method for a given protein target structure. Such methods have proven invaluable in accelerating small-molecule drug discovery. The high flexibility of peptide structures and the large diversity of peptide sequences greatly hinder the development of urgently needed computational methods. Here, we report a method called MDockPeP2_VS to address these challenges. It integrates molecular docking with structural conservation between protein folding and protein–peptide binding. Briefly, we discovered that when the interfacial residues are conserved, a sequence fragment derived from a monomeric protein exhibits a high propensity to bind a target protein with a similar conformation. This valuable insight significantly reduces the search space for peptide conformations, resulting in a substantial reduction in computational time and making in silico peptide screening practical. We applied MDockPeP2_VS to develop peptide inhibitors targeting the TEM-1 β-lactamase of Escherichia coli, a key mechanism behind antibiotic resistance in gram-negative bacteria. Among the top 10 peptides selected from in silico screening, TF7 (KTYLAQAAATG) showed significant inhibition of β-lactamase activity with a Ki value of 1.37 ± 0.37 µM. This fully automated, large-scale structure-based in silico peptide screening software is available for free download at https://zougrouptoolkit.missouri.edu/mdockpep2_vs/download.html.
Automated identification and segmentation of H i sources in CRAFTS using deep learning method
Authors: Song Zihao , Chen Huaxi , Quan Donghui , Li Di , Zheng Yinghui , Ni Shulei , Chen Yunchuan , Zheng Yun
Published: November 2024

Identifying neutral hydrogen (${\rm H}\, {\small I}$) galaxies from observational data is a significant challenge in ${\rm H}\, {\small I}$ galaxy surveys. With the advancement of observational technology, especially with the advent of large-scale telescope projects such as FAST and SKA, the significant increase in data volume presents new challenges for the efficiency and accuracy of data processing. To address this challenge, in this study, we present a machine learning-based method for extracting ${\rm H}\, {\small I}$ sources from the 3D spectral data obtained from the Commensal Radio Astronomy FAST Survey (CRAFTS). We have carefully assembled a specialized data set, HISF, rich in ${\rm H}\, {\small I}$ sources, specifically designed to enhance the detection process. Our model, Unet-LK, utilizes the advanced 3D-Unet segmentation architecture and employs an elongated convolution kernel to effectively capture the intricate structures of ${\rm H}\, {\small I}$ sources. This strategy ensures a reliable identification and segmentation of ${\rm H}\, {\small I}$ sources, achieving notable performance metrics with a recall rate of 91.6 per cent and an accuracy of 95.7 per cent. These results substantiate the robustness of our data set and the effectiveness of our proposed network architecture in the precise identification of ${\rm H}\, {\small I}$ sources.
Lack of WDFY4 leads to impaired immune response and poor cancer prognosis
Authors: Bao Hanxuan , Zhang Chen , Peng Xue , Jia Jingnan , Yang Yi
Published: November 2024

WDFY4 plays an essential role in the immune system by regulating B‐cell growth and development and participating in antigen processing during cross‐presentation. WDFY4 is closely related to asthma and systemic lupus erythematosus; however, its role in cancer remains unclear. The purpose of this study is to use bioinformatics to determine whether abnormal expression of WDFY4 is a risk factor for cancer and to preliminarily analyze the ways in which WDFY4 affects cancer through experiments. R language packages and bioinformatic database were used to mine the potential carcinogenic effect of WDFY4 and analyze the differential WDFY4 expression in cancer, gene mutations, different tumor prognoses, immune cell infiltration, tumor microenvironment, and DNA methylation correlation. H1975 and A549 cell lines were infected with lentiviruses to overexpress WDFY4, and the effect of WDFY4 on the activity, proliferation, apoptosis, and cell cycle of lung cancer cells was analyzed. WDFY4 was differentially expressed in human tumors in unpaired and paired samples. The differential expression of WDFY4 in unpaired and paired or protein samples from the Clinical Proteome Tumor Analysis Consortium of eight cancers was consistent. WDFY4 methylation was downregulated in 17 cancer types and caused prognostic differences in different directions in some cancers. WDFY4 overexpression significantly inhibited the activity and proliferation of lung cancer cell lines, promoted apoptosis, and caused cell cycle arrest. Differential WDFY4 expression in cancers leads to differences in the prognosis of various cancers. WDFY4 can be an independent prognostic factor for glioma, KIRC, and LUSC.
Dodecanedioic acid prevents and reverses metabolic‐associated liver disease and obesity and ameliorates liver fibrosis in a rodent model of diet‐induced obesity
Authors: Angelini Giulia , Russo Sara , Carli Fabrizia , Infelise Patrizia , Panunzi Simona , Bertuzzi Alessandro , Caristo Maria Emiliana , Lembo Erminia , Calce Roberta , Bornstein Stefan R. , Gastaldelli Amalia , Mingrone Geltrude
Published: November 2024

Dodecanedioic acid (DC12) is a dicarboxylic acid present in protective polymers of fruit and leaves. We explored the effects of DC12 on metabolic dysfunction‐associated steatohepatitis (MASH) and obesity. DC12 supplementation (100 mg/kg/day) was added to a high‐fat diet (HFD) for 8 weeks in rodents to assess its impact on obesity and MASH prevention. Rats given DC12 experienced significant reductions of weight gain, liver and visceral fat weight, and improved glucose tolerance and insulin sensitivity. Liver histology showed protection against diet‐induced MASH, with reduced steatosis, hepatocyte ballooning, and fibrosis. For weight‐loss and MASH reversion, rats were fed HFD for 14 weeks, followed by 6 weeks with or without DC12. DC12 supplementation (100 mg/kg/day) led to a significant reduction of weight gain and liver weight. DC12 induced white adipose tissue beiging and reduced adiposity with a decrease of visceral fat. It also improved glucose tolerance, insulin sensitivity, and reduced hepatic gluconeogenic gene expression. Liver histology revealed a significant reduction in steatosis, hepatocyte ballooning, and inflammation as well as fibrosis, indicating MASH reversal. DC12 reduced hepatic lipogenesis enzymes as well as de novo lipogenesis measured by deuterated water and increased fatty acid β‐oxidation. Plasma lipid profile showed lower triglycerides and phosphatidylcholines in the DC12 group. Notably, DC12 decreased mINDY expression, the cell membrane Na+‐coupled citrate transporter, reducing citrate uptake and de‐novo lipogenesis, linking its effects to improved lipid metabolism and reduced steatosis. We found that during the hepatic first pass, half of the DC12 ingested with water was taken up by the liver. The concentration of DC12 in the portal vein falls within the range identified in vitro as sufficient to inhibit citrate transport in hepatocytes.
Is excessive body weight related to energy level of injury in tibial tubercle fractures in adolescents?
Authors: Kralj Rok , Gržan Ivan Silvije , Vuković Ante , Pešorda Domagoj , Ivelj Renato , Jurić Filip , Višnjić Stjepan , Žic Rado
Published: November 2024

To assess whether excessive body weight or obesity predisposes adolescents to tibial tubercle fractures from less energetic traumas, prolongs the period of rehabilitation from these injuries or leads to worse outcomes. A retrospective study of patients who underwent surgical treatment for fracture of the tibial tubercle in the period from March 2013 to March 2022. Patients were classified according to age, gender, fracture type, BMI, mechanism and energy levels of injury, time to complete painless range of motion was achieved and rate of complications. We have surgically treated 33 patients who have sustained 34 tibial tubercle fractures. Twenty of our patients had a BMI in the ‘healthy weight’ range while 13 were either overweight or obese. A significant difference in the distribution of injury types between the two groups has been statistically confirmed, whereby more severe injuries were recorded in the ‘healthy weight’ group of patients. A statistically significant higher proportion of patients who sustained a fracture after a blow to the knee or during light activity could have been confirmed in the ‘overweight/obese’ group while patients in the ‘healthy weight’ group more often sustained fractures after a powerful concentric or eccentric contraction of the quadriceps muscle. All of the patients achieved full painless range of motion and a radiologically confirmed osseous union. The healthy weight group had a significantly shorter period of rehabilitation. Two minor complications have been recorded. A higher BMI may lead to tibial tubercle fractures caused by less energetic injuries in adolescent patients. We may also conclude that blows to the knee or injuries sustained while running most often do not cause the most severe type of fractures. However, operative treatment provides a good outcome regardless of the type of injury or BMI.
Managing Dyslipidemia in Children: Current Approaches and the Potential of Artificial Intelligence
Authors: Abdullah  , Zaheer Amna , Saeed Humza , Arshad Muhammad Khubaib , Zabeehullah  , Iftikhar Uswa , Abid Areesha , Khan Muhammad Hamza , Khan Alina Sami , Akbar Anum
Published: November 2024

Dyslipidemia is abnormal lipid and lipoprotein levels in the blood, influenced mainly by genetics, lifestyle, and environmental factors. The management of lipid levels in children involves early screening, nonpharmacological interventions such as lifestyle modifications and dietary changes, nutraceuticals, and pharmacological treatments, including drug therapy. However, the prevalence of dyslipidemia in the pediatric population is increasing, particularly among obese children, which is a significant risk factor for cardiovascular complications. This narrative review analyzes current literature on the management of dyslipidemia in children and explores the potential of artificial intelligence (AI) to improve screening, diagnosis, and treatment outcomes. A comprehensive literature search was conducted using Google Scholar and PubMed databases, focusing primarily on the application of AI in managing dyslipidemia. AI has been beneficial in managing lipid disorders, including lipid profile analysis, obesity assessments, and familial hypercholesterolemia screening. Deep learning models, machine learning algorithms, and artificial neural networks have improved diagnostic accuracy and treatment efficacy. While most studies are done in the adult population, the promising results suggest further exploring AI management of dyslipidemia in children.
Alternate Sampling Matrices for Therapeutic Drug Monitoring of Immunosuppressants
Authors: Sallustio Benedetta C.
Published: November 2024

Background:

Immunosuppressant (IS) therapeutic drug monitoring (TDM) relies on measuring mostly pharmacologically inactive erythrocyte-bound and/or plasma protein–bound drug levels. Variations in hematocrit and plasma protein levels complicate interpretation of blood calcineurin inhibitor (CNI) and inhibitors of the molecular target of rapamycin (mTORi) concentrations. Variable binding of mycophenolic acid (MPA) to albumin similarly complicates its TDM in plasma. A different matrix may improve IS concentration–response relationships and better reflect exposures at sites of action.

Methods:

This review explores the evidence for IS TDM using peripheral blood mononuclear cell (PBMC), graft tissue, and total or unbound plasma concentrations.

Results:

Tandem mass spectrometry provides the sensitivity for assessing these matrices. But several challenges must be addressed, including minimizing hemolysis during blood collection, preventing IS efflux during PBMC preparation, and determining the need for further purification of the PBMC fraction. Assessing and reducing nonspecific binding during separation of unbound IS are also necessary, especially for lipophilic CNIs/mTORi. Although TDM using PBMC or unbound plasma concentrations may not be feasible due to increased costs, plasma CNI/mTORi levels may be more easily integrated into routine TDM. However, no validated TDM targets currently exist, and published models to adjust blood CNI/mTORi concentrations for hematocrit or to predict PBMC, and total and unbound plasma IS concentrations have yet to be validated in terms of measured concentrations or prediction of clinical outcomes.

Conclusions:

Even if CNI/mTORi measurements in novel matrices do not become routine, they may help refine pharmacokinetic–pharmacodynamic relationships and improve mathematical models for TDM using whole blood. Notably, there is evidence to support measuring unbound MPA in patients with severe renal dysfunction, hypoalbuminemia, and hyperbilirubinemia, with some proposed TDM targets.
Progress to Life Transformation
Authors: Lashley Mary
Published: November 2024

Persons experiencing homelessness have higher rates of substance abuse, poorer overall health, and higher mortality from opioid overdose than the general population. Measuring progress throughout the addictions recovery process in these populations is challenging, given the multitude of factors that impact the recovery journey among persons experiencing homelessness. Despite these challenges, outcome assessment is essential for informing the continued improvement of recovery programs and validating effectiveness of evidence-based interventions. To better track and monitor progress throughout a 1-year residential faith-based addictions recovery program, the leadership of a large homeless service and residential recovery organization adapted the Progress to Life Transformation Model, a model based upon self-sufficiency, to measure improvements in self-sufficiency and stability across a diverse range of life domains. The purpose of this paper was to describe the experience of a homeless provider organization as it attempted to measure the impact of its programs on the self-sufficiency of persons experiencing homelessness as they work through the addiction recovery process. This case study of an evidence-based best practice may be used to inform public health nursing practice when working with organizations seeking to measure progress in serving persons experiencing homelessness who are in recovery from chemical addictions.
Scenario Validation for Opioid Use Disorder Stigma-Related Nursing Simulations
Authors: Tyo Mirinda , Viveiros Jennifer , McCurry Mary , Avery-Desmarais Shannon , Schuler Monika , Kauranen Brianna
Published: November 2024

Background

Six high-fidelity simulations were developed to promote empathetic, evidence-based care devoid of stigma for individuals with opioid use disorder (OUD). Study aim was to validate simulation scenario and content for accuracy and clinical relevance.

Method

Simulations were video recorded in August 2022 for content validation. Expert assessment was conducted in September 2022 via focus groups using videoconferencing.

Results

A panel of OUD experts that included healthcare providers (n = 10), who were also nurse educators (n = 5) or family members affected by OUD (n = 1), validated simulation content. Thematic analysis identified themes: (a) strategies for enhancing realism, (b) recognition for diverse patients, (c) additional cueing to generate empathetic responses, (d) refining cueing to focus on stigma, (e) recognizing OUD as a chronic illness, (f) novel approach to standardized patients, and (g) limitations of mannequins.

Conclusion

Evaluation of simulations provided content validation increasing the potential effectiveness of the simulations to achieve desired learning outcomes.
Utilizing Academic Detailing Intervention to Increase Screening, Referral, and Treatment for Opioid Use Disorder Among Primary Care Providers in Randolph County
Authors: Foreman Jennifer Key , Knisely Mitchell , Layton Jennifer , Lord Jamison
Published: November 2024

Background

Opioid use disorder is a national epidemic that has killed over one million United States residents since 1999. Randolph County, North Carolina (NC) has a significantly higher rate of drug overdose and emergency-department-related visits than the NC state average. Primary care providers are well positioned to intervene and offer screening, referral, and treatment of opioid use disorder, yet this does not often occur.

Objective

This quality improvement project serves as a pilot to evaluate the effectiveness of academic detailing (AD) to increase screening, referral, and treatment of opioid use disorder as well as to increase knowledge of community resources available.

Methods

Face-to-face one-to-one AD was provided to primary care providers. Content included an overview of the diagnosis, standardized screening tools, management, and community resources available for referral. Assessments pre and post were conducted to evaluate screening, referral and treatment practices, knowledge of available community resources, barriers to providing services, and satisfaction with the AD event.

Results

AD did not result in change in frequency of screening or referral for treatment for OUD. None of the providers who participated in the intervention were prescribing buprenorphine prior to the event, nor were they after the event. Results indicated that there was an increase in the knowledge level of providers after AD with a change in median knowledge level from “I know about some resources in the area” to “I am very knowledgeable about area resources.” Barriers to screening, referral, and treatment were identified, with lack of time being the most frequently cited.

Conclusions

AD did not increase screening, referral, or treatment of OUD in this pilot project. However, there was an increase in knowledge of community resources related to OUD. AD is labor and time intensive and may be difficult to scale.

Implications for Nursing

Providers are well positioned to impact patient lives and increase screening, referral, and treatment for OUD in primary care settings. Continued work is needed to overcome barriers for getting patients adequate OUD treatment. Additional research is needed to ascertain if varied forms of AD would be more time and cost effective.
Nurse-Led Evidence-Based Diabetes Prevention Study
Authors: Adejumo Oluremi A. , Ogunbiyi Elizabeth O. , Chen Ling-Yin
Published: November 2024

Background

Clients with substance use disorders (SUDs) have a substantial risk of developing Type 2 diabetes mellitus (T2DM). The connection between SUD and DM stems from rapid cell damage, pancreatic beta-cell dysfunction, and glucose dysregulation due to increased oxidative stress and decreased antioxidant activity. This study aims to reduce the risk of T2DM among individuals undergoing SUD recovery treatments.

Methods

This nurse-led diabetes prevention program, a 1-year-long, peer-based intervention, was implemented among clients at a federally funded, stand-alone drug addictions treatment center based on evidence that lifestyle modifications in dietary control, physical activity, and health behaviors can halt or delay the progression of Type 2 diabetes. Four trained peer educators delivered diabetes prevention interventions to a sample of individuals in drug addiction treatment in Nigeria. The nurse program leader provided weekly mentoring and guidance to the peer educators and collected, reviewed, and analyzed study participants' logs of weights and self-reported lifestyle modifications.

Results

There were significant differences in participants' behaviors pre- and post-lifestyle interventions, except in dairy product intakes as well as cigarette and cannabis use.

Conclusion

This diabetes prevention program is innovative and effective with this at-risk population. Interventions were delivered with minor financial resources.

Implications for Nursing and Patient Care

SUD treatment must address physical and psychological health and consider the heightened risks of chronic illness in this population. Preventing somatic diseases, such as T2DM, is vital to long-term health and well-being.
A Qualitative Study of Physician Assistant Student Reflections in a Service-Learning Community Clinic and the Influence on Professional Identity Formation
Authors: Giannelli Frank R. , Cogan-Drew Thea , Aceti Angelica , Di Prospero Elizabeth , Joseph Jennifer , Carbajal Alyssa M. , Gomes Jessica , O'Connell Claire , Rothpletz-Puglia Pamela
Published: November 2024

Introduction

Service learning is a commonly used teaching modality in physician assistant (PA) programs; however, the literature analyzing the written reflections of PA students who participate in these experiences is limited. The purpose of this study was to describe the experiences of PA students who participated in a service-learning clinic through analysis of their written reflections.

Methods

An exploratory qualitative research design, using conventional content analysis, was used to examine the reflections of both didactic and clinical-phase PA students who participated in a service-learning clinic between 2016 and 2020.

Results

The results demonstrate that these experiences contribute to the professional identity formation (PIF) of PA students, with faculty role modeling being an important facilitator in the process. Our analysis shows that students, regardless of their role in the clinic, reported a positive experience, and the reflections showed elements of PIF.

Discussion

Service-learning clinics play an important role in the PIF for PA students, with role modeling by faculty clinicians being an important facilitator in this process.
Basic Bronchoscopy Competence Achieved by a Nationwide One-day Simulation-based Training
Authors: Gerretsen Eveline C. F. , Groenier Marleen , Annema Jouke T. , van der Heijden Erik H. F. M. , van Mook Walther N. K. A. , Aldenkamp Arnoud F. , Citgez Emanuel , Crombag Laurence M. M. J. , Hagmolen of ten Have Wanda , Hiddinga Birgitta I. , Hoppe Bart P. C. , Ninaber Maarten K. , van de Pol Marianne A. , Robberts Bas , Rutten Marijke , Sprooten Roy , Wagenaar Michiel , Smeenk Frank W. J. M.
Published: November 2024

Background:

In 2020, a mandatory, nationwide 1-day bronchoscopy simulation-based training (SBT) course was implemented for novice pulmonology residents in the Netherlands. This pretest–posttest study was the first to evaluate the effectiveness of such a nationwide course in improving residents’ simulated basic bronchoscopy skills.

Methods:

After passing a theoretical test, residents followed a 1-day SBT course, available in 7 centers, where they practiced their bronchoscopy skills step-by-step on a virtual reality simulator under pulmonologist supervision. Residents practiced scope handling efficiency (task 1) and navigational skills combined with lung anatomy knowledge (task 2). Task 1 outcome measures were navigational skill simulator metrics: percentage of time at mid-lumen, percentage of time with scope-wall contact, procedure time (PT), number of wall contacts and number of wall contacts per minute of PT. Task 2 outcome measures were PT, observational assessment scores of a validated tool with a 5-point scale (1 representing the worst and 5 the best competence) and blinded dexterity assessments.

Results:

The study included 100 residents. All outcome measures of task 1 improved significantly (P<0.001), except for the number of wall contacts per minute of PT (4.3 [IQR 3.0 to 6.2] pre vs. 3.5 [IQR 2.6 to 5.3] post, P=0.07). For task 2, PT was reduced by 54% (10.3±2.7 minutes pre vs. 4.7±0.9 minutes post, P<0.001) with an improvement in overall-competence scores (2.0 [IQR 1.0 to 2.0] pre vs. 4.0 [IQR 4.0 to 5.0] post, P<0.001) and all dexterity parameters (P<0.001).

Conclusion:

Nationwide implementation of a SBT course led to rapid improvement of residents’ basic bronchoscopy skills while halving PT.
First-in-man study of a novel everolimus-coated balloon for the treatment of coronary in-stent restenosis
Authors: Alfonso Fernando , Shaburishvili Tamaz , Farah Bruno , Gogorishvili Ikrali , Monsegu Jacques , Baranauskas Arvydas , Bressollette Erwan , Shaburishvili George , Cuesta Javier , Rivero Fernando , Moreno Raul , Sabate Manel
Published: November 2024

Background

Treatment of patients with in-stent restenosis (ISR) remains challenging. In this setting the use of drug-coated balloons (DCB) represents an attractive approach to avoid adding another metal layer to the coronary wall.

Aims

The Chansu Vascular Technologies (CVT)-ISR trial aimed to evaluate the safety and efficacy of a novel everolimus-DCB (CVT-DCB) using a new coating formulation and crystalline everolimus.

Methods

The CVT-ISR trial was a prospective, multicenter, open, single-arm, first-in-man (FIM) study. A total of 51 patients (mean age 69.2 years, 74.5% male) with single ISR coronary lesions (≤24 mm in length) were enrolled at nine sites in Europe.

Results

The primary safety endpoint, freedom from target lesion failure (TLF) at 180 days, was 92.2%, with the lower bound of the 95% confidence interval (81.1%), above the protocol-defined objective performance criterion (OPC) (65% for conventional balloon angioplasty, P < 0.05). At 1 year freedom from TLF was 90.2%. The primary efficacy endpoint, in-stent late lumen loss at 180 days (evaluated in a predefined subgroup of 25 patients scheduled for late angiography), was 0.40 mm (median 0.30 mm), lower than the protocol-defined OPC of the plain balloon angioplasty historical control (0.80 mm, P < 0.001).

Conclusion

This FIM study demonstrated the superior efficacy of the new everolimus CVT-DCB compared with conventional balloon angioplasty in the treatment of patients with ISR.

Clinical trials registration

NCT05731700.