bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exploring the burden of paediatric acute otitis media with discharge in the UK: a qualitative study
Authors: Heward Elliot , Lunn Judith , Birkenshaw-Dempsey James , Molloy John , Isba Rachel , Ashcroft Darren M , Hay Alastair D , Nichani Jaya R , Bruce Iain A 
Published: October 2024

BackgroundAcute otitis media with discharge (AOMd) results from a tympanic membrane perforation secondary to a middle ear infection. Currently, the impact of AOMd on children and young people (CYP) and their families is not well understood. There is also a need to explore the experience of healthcare professionals in treating AOMd. Interviews with CYP and their parents, and focus groups with medical professionals, were conducted to explore these objectives.MethodsA total of 26 parents of CYP (age range: 7 months to 15 years) with a history of AOMd (within the last year) and 28 medical professionals were recruited across the UK between August 2023 and March 2024. Healthcare professionals were from primary care (n=17), ear, nose and throat (ENT) (n=7) and emergency medicine (n=4) backgrounds. Thematic analysis was performed independently by three reviewers.ResultsThe majority of CYP (n=25/26) (96.2%) had suffered from multiple episodes of AOMd. AOMd has a physical, psychological, educational, financial and social impact on CYP and their parents. Parents found accessing healthcare services and information difficult, which increased parental anxiety. Antibiotic overuse was also a concern among parents. The majority of general practitioners and emergency care staff described using oral amoxicillin, compared with ENT doctors who predominantly prescribed topical antibiotics.ConclusionsAOMd has a significant impact on CYP and their parent’s daily lives. Need for clear, easily accessible patient information was identified as a priority by the parents of CYP with AOMd. Evidence-based management guidelines should be developed once high-quality evidence is available.Trial registration numberISCTRN43760.
Public health unit funding per capita and seasonal influenza vaccination among youth and adults in Ontario, Canada in 2013/2014 and 2018/2019
Authors: Chew Jo Lin , Smith Brendan T , Buchan Sarah A , Senthilselvan Ambikaipakan , Pabayo Roman 
Published: October 2024

BackgroundInfluenza vaccines are crucial in reducing the risk of influenza symptoms. We aimed to: (1) estimate the association between public health unit (PHU) funding per capita and influenza vaccination among individuals aged 12 and older in Ontario in 2013/2014 and 2018/2019 and (2) determine whether any observed associations were heterogeneous across household income groups, gender and age categories.MethodsCross-sectional studies were conducted using the Canadian Community Health Survey, a population-representative survey that collects annual health data. PHU funding per capita was measured using the approved provincial funding for mandatory programmes and the Canadian Census Population Estimates. Self-reported influenza vaccination status in the past year was used. Multilevel logistic regression was used to estimate the association.ResultsA case-complete weighted dataset revealed that 33.2% in 2013/2014 and 35.1% in 2018/2019 of respondents were vaccinated. In 2013/2014, every standard deviation (SD) increase in PHU funding per capita was associated with vaccination (OR: 1.08; 95% CI: 1.01, 1.15; SD: 14.1). Furthermore, for every SD increase in PHU funding per capita in 2013/2014, individuals from the lowest household income and between the ages of 50 and 64 years were 29% (95% CI: 1.10, 1.50) and 13% (95% CI: 1.03, 1.23) more likely to be vaccinated, respectively, while adjusting for confounders. No heterogeneous associations were observed in 2018/2019.ConclusionFunding may have the potential to support PHU’s role in preventing diseases, promoting health and reducing health inequities among the population.
Mental health and support for rigorous tobacco control strategies in South Australia
Authors: Trigg Joshua , Bowden Jacqueline , Morris Julia , Daly Tony , Miller Caroline , Bonevski Billie 
Published: October 2024

IntroductionTobacco endgame strategy includes policies to end the tobacco epidemic. As tobacco smoking prevalence is higher among people with mental health conditions (MHC), understanding the impact of rigorous tobacco control strategies for this group is critical. This study examined support for five tobacco control strategies among people with MHCs: increasing tobacco product tax, reducing tobacco retail locations, ending tobacco sales in alcohol-licensed venues, limiting retailers to one tobacco point of sale and reduced nicotine in smoked tobacco.MethodsCross-sectional surveying of a representative sample of 3006 South Australians in 2021 aged ≥15 years included demographic, tobacco control strategy, smoking status and mental health indicators. Multivariable logistic regression was used to examine the influence of mental health on strategy support.ResultsSupport was high for all tobacco control strategies, highest for reducing nicotine content (80.4%) and lowest for increasing tobacco tax (67.2%). Support for increased tobacco tax was lower among people with MHCs than for those without by 7.8% (aged 18+ years) to 9.5% (aged 15+ years). People who smoked had significantly lower support for all strategies, and smoking status and MHC did not interact in influencing support.ConclusionsSupport for tax-focused strategies was lower among people with MHCs. Retail and product-focused strategies may support equity in public acceptability of tobacco control action. Policy-makers must aim to maximise tobacco endgame support from populations most impacted by tobacco harms when implementing tobacco control strategies. Tax-focused approaches might be enhanced with consultation and advocacy for people with MHCs.
Cardiovascular adverse events associated with norepinephrine–dopamine reuptake inhibitors: a pharmacovigilance study of the FDA Adverse Event Reporting System
Authors: Kandukuru Abhishek , Sharma Priyanka , Verghese Gupta Sheeba , Nkembo Augustine , Sutariya Vijaykumar 
Published: October 2024

Norepinephrine–dopamine reputake inhibitors (NDRIs), including bupropion, methylphenidate, atomoxetine, and reboxetine, are commonly prescribed for psychiatric disorders such as narcolepsy, attention-deficit/hyperactivity disorder, and depression. Cardiovascular adverse events have been reported to the FDA despite their effectiveness. This pharmacovigilance study analyzed cardiovascular adverse events associated with NDRIs using the FDA Adverse Event Reporting System data from January 2004 to December 2021. A retrospective analysis of adverse event reports was conducted, employing time-trend analysis and disproportionality evaluation to assess cardiovascular risks. Bupropion had the greatest reported odds ratios (RORs) for tachycardia (ROR = 4.2, 95% CI: 4.0–4.4) and hypertension (ROR = 3.5, 95% CI: 3.3–3.7), while methylphenidate showed greater ROR for arrhythmias (ROR = 2.8, 95% CI: 2.6–3.0) and palpitations (ROR = 3.1, 95% CI: 2.9–3.3). Reboxetine had signals for palpitations (ROR = 3.0, 95% CI: 2.8–3.2) and myocardial infarction (ROR = 2.7, 95% CI: 2.5–2.9), whereas atomoxetine revealed signals for hypertension (ROR = 2.9, 95% CI: 2.7–3.1) and syncope (ROR = 2.5, 95% CI: 2.3–2.7). Time-trend analysis revealed temporal variability in the cardiovascular risks connected with NDRIs. Our research elucidates cardiovascular safety profiles for NDRIs, highlighting the necessity for continuous pharmacovigilance. The observed variations in adverse events emphasize the need for ongoing surveillance to mitigate potential cardiovascular risks and enhance patient safety and treatment outcomes.
Impact of correlations on nuclear binding energies
Authors: Scalesi A. , Duguet T. , Demol P. , Frosini M. , Somà V. , Tichai A. 
Published: October 2024

AbstractA strong effort will be dedicated in the coming years to extend the reach of ab initio nuclear-structure calculations to heavy doubly open-shell nuclei. In order to do so, the most efficient strategies to incorporate dominant many-body correlations at play in such nuclei must be identified. With this motivation in mind, the present work analyses the step-by-step inclusion of many-body correlations and their impact on binding energies of Calcium and Chromium isotopes. Employing an empirically-optimal Hamiltonian built from chiral effective field theory, binding energies along both isotopic chains are studied via a hierarchy of approximations based on polynomially-scaling expansion many-body methods. More specifically, calculations are performed based on (i) the spherical Hartree–Fock–Bogoliubov mean-field approximation plus correlations from second-order Bogoliubov many-body perturbation theory or Bogoliubov coupled cluster with singles and doubles on top of it, along with (ii) the axially-deformed Hartree–Fock–Bogoliubov mean-field approximation plus correlations from second-order Bogoliubov many-body perturbation theory built on it. The corresponding results are compared to experimental data and to those obtained via valence-space in-medium similarity renormalization group calculations at the normal-ordered two-body level that act as a reference in the present study. The spherical mean-field approximation is shown to display specific shortcomings in Ca isotopes that can be understood analytically and that are efficiently corrected via the consistent addition of low-order dynamical correlations on top of it. While the same setting cannot appropriately reproduce binding energies in doubly open-shell Cr isotopes, allowing the unperturbed mean-field state to break rotational symmetry permits to efficiently capture the static correlations responsible for the phenomenological differences observed between the two isotopic chains. Eventually, the present work demonstrates that polynomially-scaling expansion methods based on unperturbed states that possibly break (and restore) symmetries constitute an optimal route to extend ab initio calculations to heavy closed- and open-shell nuclei.
Ulam’s Method for Computing Stationary Densities of Invariant Measures for Piecewise Convex Maps with Countably Infinite Number of Branches
Authors: Islam Md. Shafiqul , Góra Paweł , Mahbubur Rahman A. H. M. 
Published: October 2024

Let [Formula: see text] be a piecewise convex map with countably infinite number of branches. In [ Góra et al. , 2022 ], the existence of Absolutely Continuous Invariant Measure (ACIM) [Formula: see text] for [Formula: see text] and the exactness of the system [Formula: see text] have been proven. In this paper, we develop an Ulam method for approximation of [Formula: see text], the density of ACIM [Formula: see text]. We construct a sequence [Formula: see text] of maps [Formula: see text] s.t. [Formula: see text] has a finite number of branches and the sequence [Formula: see text] converges to [Formula: see text] almost uniformly. Using supremum norms and Lasota–Yorke-type inequalities, we prove the existence of ACIMs [Formula: see text] for [Formula: see text] with the densities [Formula: see text]. For a fixed n, we apply Ulam’s method with k subintervals to [Formula: see text] and compute approximations [Formula: see text] of [Formula: see text]. We prove that [Formula: see text] as [Formula: see text] both a.e. and in [Formula: see text]. We provide examples of piecewise convex maps [Formula: see text] with countably infinite number of branches and their approximations by [Formula: see text]’s with finite number of branches. For the increasing values of parameter [Formula: see text] we calculate the errors [Formula: see text].
Impact of Vitamin E Supplementation on High‐Density Lipoprotein in Patients With Haptoglobin Genotype–Stratified Diabetes: A Systematic Review of Randomized Controlled Trials
Authors: Zheng Pan-pan , Zhang Li-wen , Sheng Dan , Wang Min-zhen , Li Rong , Zhao Wei-li , Liu Rongmei , Xiu Xian , Zhao Yu-sha , Min Xi , Wang Zhi-kai , Liu Zan-chao 
Published: October 2024

Background: Vitamin E, an essential micronutrient with antioxidant potential, can dramatically reduce the cardiovascular risk in individuals with haptoglobin (Hp) 2‐2 genotype diabetes; however, the underlying mechanism remains unclear.Objective: The objective of this study is to evaluate the effect of vitamin E supplementation on high‐density lipoprotein (HDL) levels and function in individuals with diabetes stratified by Hp genotype.Methods: All relevant studies published up to May 2023 were systematically reviewed using PubMed, Cochrane Library, Web of Science, Chinese Wanfang, China Science and Technology Journal, and Chinese National Knowledge Infrastructure databases. Randomized controlled trials that evaluated the effects of vitamin E supplementation on HDL levels were included. The outcomes assessed were changes in HDL concentrations, cholesterol efflux, and HDL‐associated lipid peroxides.Results: In total, 163 publications were selected. Based on inclusion and exclusion selection and quality assessment, five studies with 463 participants were included. Vitamin E supplementation did not exert any effect on HDL levels in individuals with diabetes with any Hp genotype. Three of the five studies revealed that vitamin E improved cholesterol efflux and HDL lipid peroxides in individuals with Hp2‐2 diabetes but did not positively impact HDL function in Hp1 carriers.Conclusions: Although vitamin E supplementation did not significantly impact HDL levels in individuals with diabetes of any Hp genotype, it may improve HDL function in individuals with Hp2‐2 diabetes. These findings indicate a pharmacogenetic interaction between vitamin E and the Hp genotype on HDL function. Moreover, vitamin E supplementation may be an effective strategy for specific individuals with diabetes.
CD27-Armored BCMA CAR T-cell Therapy (CBG-002) for Relapsed and Refractory Multiple Myeloma: A Phase I Clinical Trial
Authors: Xu Yang , Zhang Xuzhao , Xin Dijia , Zhang Jiawei , Wang Luyao , Fan Yili , Chen Boxiao , Lei Wen , Qiu Xi , Jiang Huawei , Xiao Xibin , Huang Liansheng , Yu Jiandong , Yang Xin , Yang Wenjun , Zhu Jiangao , Qian Wenbin 
Published: October 2024

Abstract
B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR) T-cell therapy has been approved for the treatment of relapsed and refractory multiple myeloma (RRMM); however, whether patients have long-term responses has yet to be established. We investigated the feasibility of CBG-002, a CD27-armored BCMA CAR T-cell therapy, to improve clinical efficacy in patients with RRMM. We present preclinical data showing the activity of CBG-002 against myeloma and results from a phase I clinical trial (NCT04706936) evaluating its safety and efficacy in patients with RRMM. The primary endpoint was safety, as assessed by grade 3 or 4 adverse events (AE). Key secondary endpoints were overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS). A total of 11 patients were enrolled and received CBG-002 therapy. Nine patients developed grade 1 or 2 cytokine release syndrome (CRS), whereas no patients experienced grade 3 or higher CRS or immune effector cell–associated neurotoxicity syndrome. Other grade 3 or higher AEs included neutropenia (72.7%), thrombocytopenia (45.5%), and anemia (36.4%). At a median follow-up of 16.7 months, the ORR was 81.8%, including a stringent complete response/complete response rate of 45.5%, very good partial response rate of 18.2%, and partial response rate of 18.2%, with a median DOR of 8.9 (range 1.8–21.9) months. The median OS was not reached, and the median PFS was 8.5 (2.7–22.9) months. In this phase I study, CBG-002, a CD27-armored BCMA CAR T-cell therapy, demonstrated safety and clinical efficacy in patients with RRMM.
Arterial-Lymphatic-Like Endothelial Cells Appear in Hereditary Hemorrhagic Telangiectasia 2 and Contribute to Vascular Leakage and Arteriovenous Malformations
Authors: Yang Yang , Wu Xiuju , Zhao Yan , Zhang Daoqin , Zhang Li , Cai Xinjiang , Ji Jaden , Jing Zheng , Boström Kristina I. , Yao Yucheng 
Published: October 2024

BACKGROUND:

Arteriovenous malformations (AVMs) are characteristic of hereditary hemorrhagic telangiectasia. Loss-of-function mutations in the activin receptor‐like kinase 1 (
Alk1
) are linked to hemorrhagic telangiectasia type 2.

METHODS:

Endothelial-specific deletion of
Alk1,
endothelial lineage tracing, transcriptomics of single-cell analysis, and electron microscopy were performed to examine the vascular phenotype and characteristics of ALK1-deficient endothelial cells (ECs) after EC-specific
Alk1
deletion. Ischemia assays were used to examine the cell capacity for vascular malformation. Connectivity Map with transcriptomic analysis was applied to identify chemical compounds. Specific methods for arteriovenous malformations, such as micro–computed tomography, with other molecular and cell biological tools were also performed.

RESULTS:

We performed endothelial-specific deletion of
Alk1
in mice and found severe arteriovenous malformations and vascular leakage. The transcriptomics of single-cell analysis revealed a new distinctive cell cluster formed after
Alk1
deletion where the cells coexpressed arterial and lymphatic endothelial markers. The analysis projected that these cells potentially originated from arterial ECs after
Alk1
deletion. This new population was referred to as arterial-lymphatic-like ECs according to its cellular markers, and its appearance was validated in the pulmonary small arteries after
Alk1
deletion. Transplantation of these cells caused vascular malformations. Endothelial lineage tracing confirmed that these new arterial-lymphatic-like ECs were derived from ALK1 depleted ECs, potentially arterial ECs. We discovered that SOX17 (SRY-box transcription factor 17) induction was responsible for the derivation of these arterial-lymphatic-like ECs. We showed that direct binding of MDM2 (mouse double minute 2) was required for Sox17 to execute this activity. Inhibition of MDM2 reduced the arteriovenous malformations in the mouse model.

CONCLUSIONS:
Together, our studies revealed the mechanistic underpinnings of ALK1 signaling in regulating the endothelial phenotype and provided possibilities for new therapeutic strategies in hemorrhagic telangiectasia type 2.
Diffusion MRI with machine learning
Authors: Karimi Davood , Warfield Simon K. 
Published: October 2024

Abstract
Diffusion-weighted magnetic resonance imaging (dMRI) of the brain offers unique capabilities including noninvasive probing of tissue microstructure and structural connectivity. It is widely used for clinical assessment of disease and injury, and for neuroscience research. Analyzing the dMRI data to extract useful information for medical and scientific purposes can be challenging. The dMRI measurements may suffer from strong noise and artifacts, and may exhibit high intersession and interscanner variability in the data, as well as intersubject heterogeneity in brain structure. Moreover, the relationship between measurements and the phenomena of interest can be highly complex. Recent years have witnessed increasing use of machine learning methods for dMRI analysis. This manuscript aims to assess these efforts, with a focus on methods that have addressed data preprocessing and harmonization, microstructure mapping, tractography, and white matter tract analysis. We study the main findings, strengths, and weaknesses of the existing methods and suggest topics for future research. We find that machine learning may be exceptionally suited to tackle some of the difficult tasks in dMRI analysis. However, for this to happen, several shortcomings of existing methods and critical unresolved issues need to be addressed. There is a pressing need to improve evaluation practices, to increase the availability of rich training datasets and validation benchmarks, as well as model generalizability, reliability, and explainability concerns.
Inter–Intraseasonality of Meteorological Drivers of Chorabari Glacier, Central Himalaya: Implications for Mass Fluctuations and Associated Hazards
Authors: Yadav Jairam Singh , Tiwari Sameer K. , Bhambri Rakesh , Sain Kalachand , Patidar Pawan , Baiswar Ayushi 
Published: October 2024

Abstract
High-altitude meteorological data are scarce in the Himalayan region, particularly for glacierized catchments. In-depth knowledge of meteorological variables is crucial to describe numerous cryospheric processes and associated hazards. The present study comprehensively assesses time series data (2013–16) of meteorological parameters in the Chorabari Glacier catchment (CGC) using an automatic weather station (∼4270 m MSL). Results revealed that average near-surface air temperature varied seasonally, ranging from 6.4°C in the summer monsoon (June–September) to −6.3°C in the winter season (December–February). The minimum temperature (Tmin) remained positive throughout the monsoon seasons in the higher elevations (∼5050 m MSL), indicating the melting of glaciers and their reduced mass. The daily relative humidity in different seasons fluctuated from 39% to 90%, whereas the highest seasonal average (∼63%) was observed in the monsoon season. The average wind speed was high (∼1.7 m s−1) during winter and dropped to 1.1 m s−1 in the monsoon season. The average daily influx of solar radiation ranged from 19 to 374 W m−2, with the highest value recorded during the premonsoon (March–May ∼ 212 W m−2) and the lowest during the winter (∼149 W m−2) season. The daily outflux solar radiation varied from 18 to 186 W m−2, with the maximum value in premonsoon (∼145 W m−2) and the minimum value in the monsoon season (∼30 W m−2). The mean zero-degree isotherm was found above the equilibrium line altitude (ELA ∼ 5120 m MSL) during the monsoon season, indicating a considerable mass depletion of the Chorabari Glacier. The abnormal variations in climatic variables on 16–17 June 2013 were signs of the Kedarnath disaster.

Significance Statement
The main objective of this study is to understand the variability of meteorological drivers at daily, monthly, and seasonal scales and how these changes may impact glacier mass and downstream hydrology. Our research revealed considerable variations in maximum temperature throughout the year and positive minimum temperature at higher elevations during monsoon months, which significantly control the glacier mass changes. Meteorological variables showing cyclic behavior and indicators of the “monsoon lowering phenomenon” are important in determining the timing and intensity of the seasonal shift. Investigation of abnormal changes in the climatic drivers in the 2013 Kedarnath disaster provides valuable insight into the glacier-related hazards and draws attention to decision-makers to create robust strategies to monitor the dynamic response of Himalayan glaciers.