bluuebunny/crossref_metadata_2025 huggingface dataset:
Therapeutic outcomes with surgical and medical management for primary aldosteronism: protocol for a systematic review and meta-analysis
Authors: Rocca Aldo , Gkaniatsa Eleftheria , Brunese Maria Chiara , Hessman Eva , Muth Andreas , Nwaru Bright I , Ragnarsson Oskar , Bobbio Emanuele , Esposito Daniela
Published: July 2023

Introduction

Treatment strategies for primary aldosteronism (PA) include unilateral adrenalectomy and medical treatment with mineralocorticoid receptor (MR) antagonists. Whether these two different treatment strategies are comparable in mitigating the detrimental effect of PA on outcomes is still debated.

Objectives

The primary aim of this systematic review is to identify, appraise and synthesise existing literature comparing clinical outcomes after treatment in patients with PA.

Methods and analysis

A systematic and comprehensive search will be performed using PubMed, Web of Science and EMBASE, for studies published until December 2022. Observational and interventional studies will be eligible for inclusion. The quality of observational studies will be assessed using the Newcastle–Ottawa Scale, while interventional studies will be assessed using the Cochrane Effective Practice Organization of Care tool. The collected evidence will be narratively synthesised. We will perform meta-analysis to pool estimates from studies considered to be homogeneous. Reporting of the systematic review and meta-analysis will be in accordance with the Meta-analysis of Observational Studies in Epidemiology Preferred Reporting Items for Systematic reviews and Meta-Analysis guidelines.

Ethics and dissemination

As this study is based solely on the published literature, no ethics approval is required. This review will aim to provide some estimates on outcomes, including survival, rates of clinical and biochemical control, cardiovascular and cerebrovascular events, as well as data on quality of life and renal function, in patients with PA treated surgically or with MR antagonists. The study findings will be presented at scientific meetings and will be published in an international peer-reviewed scientific journal.

PROSPERO registration number

CRD42022362506.
Long-term neurological complications in COVID-19 survivors: study protocol of a prospective cohort study (NeurodegCoV-19)
Authors: Araújo Natália , Silva Isa , Campos Patrícia , Correia Rita , Calejo Margarida , Freitas Pedro , Seco Mariana , Ribeiro Luís , Costa Ana Rute , Morais Samantha , Pereira Susana , Firmino-Machado João , Rodrigues Rita , Pais Joana , Ruano Luís , Lunet Nuno , Tedim-Cruz Vítor
Published: July 2023

Background

Evidence suggests an association between SARS-CoV-2 infection and worse performance on cognitive tests, and a higher risk of Parkinson’s disease (PD) and dementia up to 6 and 12 months after infection, respectively. Longer follow-ups with comparison groups are needed to clarify the potentially increased risk of neurodegenerative diseases in COVID-19 survivors, namely those infected before mass vaccination.

Methods

A prospective study started in July 2022 with four cohorts of 150 individuals each, defined according to SARS-CoV-2 infection and hospitalisation status between March 2020 and February 2021: cohort 1—hospitalised due to SARS-CoV-2 infection; cohort 2—hospitalised, COVID-19-free; cohort 3—infected, not hospitalised; cohort 4—not infected, not hospitalised. Cohort 2 will be matched to cohort 1 according to age, sex, level of hospitalisation care and length of stay; cohort 4 will be age-matched and sex-matched to cohort 3. Baseline, 1-year and 2-year follow-up evaluations will include: cognitive performance assessed with the Montreal Cognitive Assessment (MoCA) and neuropsychological tests; the assessment of prodromal markers of PD with Rapid Eye Movement Sleep Behaviour Disorder single-question Screen and self-reported olfactory and gustative alterations; screening of PD with the 9-item PD screening questionnaire; gait evaluation with Timed Up&Go test. Suspected cases of cognitive impairment and PD will undergo a clinical evaluation by a neurologist. Frequency measures of neurological complications, prodromal markers and diagnoses of dementia and PD, will be presented. The occurrence of cognitive decline—the difference between baseline and 1-year MoCA scores 1.5 SD below the mean of the distribution of the variation—will be compared between cohorts 1 and 2, and cohorts 3 and 4 with OR estimated using multivariate logistic regression.

Ethics and dissemination

This study received ethics approval from the Ethics Committees of the health units Unidade Local de Saúde de Matosinhos and Centro Hospitalar de Entre Douro e Vouga, and informed consent is signed for participating. Results will be disseminated among the scientific community and the public.
Dietary metabolome profiles of a Healthy Australian Diet and a Typical Australian Diet: protocol for a randomised cross-over feeding study in Australian adults
Authors: Ferguson Jessica Jayne Anne , Clarke Erin , Stanford Jordan , Burrows Tracy , Wood Lisa , Collins Clare
Published: July 2023

Introduction

Traditional dietary assessment methods such as 24-hour recalls and food frequency questionnaires rely on self-reported data and are prone to error, bias and inaccuracy. Identification of dietary metabolites associated with different dietary patterns can provide objective markers of whole diet patterns that account for metabolism and individual responses to dietary interventions. Additionally, few studies have investigated country-specific healthy and unhealthy dietary patterns using metabolomics. Therefore, the current study aims to identify urinary and plasma metabolites that characterise a ‘healthy’ (aligned with current national dietary guidelines) and an ‘unhealthy’ dietary pattern (Typical Australian Diet) in Australian adults.

Methods and analysis

The Diet Quality Feeding Study (DQFS) is an 8-week cross-over feeding study that will recruit 40 healthy adults from the Hunter region (NSW, Australia). Data collected includes biospecimens (whole blood, urine, stool) for quantification of dietary metabolite biomarkers; questionnaires (medical history/demographic, physical activity, quality of life); physical measures (anthropometry, body composition, waist circumference, blood pressure, arterial pressure); skin carotenoids and dietary intake (24-hour recalls, food frequency questionnaire). Participants will attend the research facility every 2 weeks (end of the run-in, each diet intervention and washout period) for collection of physical measures. All food will be provided to participants for each dietary intervention period, and participants will return to their usual diet during the run-in and washout periods. Targeted and untargeted metabolomics using liquid chromatography-mass spectrometry and/or proton nuclear magnetic resonance (1H-NMR) spectroscopy will be used to identify metabolites in biospecimens associated with dietary intake.

Ethics and dissemination

This study is approved by the Hunter New England Human Research Ethics Committee (HNEHREC; 2022/ETH01649) and the University of Newcastle’s Human Research Ethics Committee (HREC; H-2022-0330). Findings will be disseminated to study participants, funding bodies supporting the DQFS, peer-review publications and presented at scientific conferences within the field of research.

Trial registration number

Australian New Zealand Clinical Trials Registry (ACTRN12622001321730).
RECREATE: a study protocol for a multicentre pilot cluster randomised controlled trial (cRCT) in UK stroke services evaluating an intervention to reduce sedentary behaviour in stroke survivors (Get Set Go) with embedded process and economic evaluations
Authors: Airlie Jennifer , Burton Louisa-Jane , Copsey Bethan , English Coralie , Farrin Amanda , Fitzsimons Claire F , Holloway Ivana , Horrocks Judith , Johansson Jessica Faye , Mead Gillian , Moreau Lauren A , Ozer Seline , Patel Anita , Yaziji Nahel , Forster Anne
Published: July 2023

Introduction

Sedentary behaviour (sitting or lying during waking hours without being otherwise active) is strongly associated with adverse health outcomes, including all-cause, cancer and cardiovascular mortality in adults. Stroke survivors are consistently reported as being more sedentary than healthy age-matched controls, spending more hours sedentary daily and sustaining longer unbroken bouts of sedentary time. An evidence-based and clinically feasible intervention (‘Get Set Go’) was developed. A pragmatic definitive trial to evaluate Get Set Go was planned; however, due to the unprecedented effects of the COVID-19 pandemic on National Health Service (NHS) services this study was reduced in size and scope to become an external pilot trial. We report the protocol for this external pilot trial, which aims to undertake a preliminary exploration of whether Get Set Go is likely to improve ability to complete extended activities of daily living in the first year post-stroke and inform future trial designs in stroke rehabilitation.

Methods and analysis

This study is a pragmatic, multicentre, two-arm, external pilot cluster randomised controlled trial with embedded process and economic evaluations. UK-based stroke services will be randomised 1:1 to the intervention (usual care plus Get Set Go) or control (usual care) arm. Fifteen stroke services will recruit 300–400 stroke inpatient and carer participants, with follow-up at 6, 12 and 24 months. The proposed primary endpoint is stroke survivor self-reported Nottingham Extended Activities of Daily Living scale at 12 months. Endpoint analyses will be exploratory and provide preliminary estimates of intervention effect. The process evaluation will provide valuable information on intervention fidelity, acceptability and how it can be optimised.

Ethics and dissemination

The study has been approved by Yorkshire and The Humber – Bradford-Leeds Research Ethics Committee (Ref: 19/YH/0403). Results will be disseminated through journal publications and conference presentations.

Trial registration number

This trial was registered prospectively on 01 April 2020 (ISRCTN ref:ISRCTN82280581).
Use of a targeted, computer/web-based guided self-help psychoeducation toolkit for distressing hallucinations (MUSE) in people with an at-risk mental state for psychosis: protocol for a randomised controlled feasibility trial
Authors: Hamilton Jahnese , Arnott Bronia , Aynsworth Charlotte , Barclay Nicola A , Birkett Lauren , Brandon Toby , Dixon Lyndsey , Dudley Robert , Einbeck J , Gibbs Christopher , Kharatikoopaei Ehsan , Simpson Jennifer , Dodgson Guy , Fernyhough Charles
Published: July 2023

Introduction

Individuals who access at-risk mental state (ARMS) services often have unusual sensory experiences and levels of distress that lead them to seek help. The Managing Unusual Sensory Experiences (MUSE) treatment is a brief symptom targeted intervention that draws on psychological explanations to help account for unusual experiences. Practitioners use formulation and behavioural experiments to support individuals to make sense of their experiences and enhance coping strategies. The primary objective of this feasibility trial is to resolve key uncertainties before a definitive trial and inform parameters of a future fully powered trial.

Methods and analysis

88 participants aged 14–35 accepted into ARMS services, experiencing hallucinations/unusual sensory experiences which are considered by the patient to be a key target problem will be recruited from UK National Health Service (NHS) sites and randomised using 1:1 allocation (stratified by site, gender, and age) to either 6–8 sessions of MUSE or time-matched treatment as usual. Participants and therapists will be unblinded, research assessors are blinded. Blinded assessment will occur at baseline, 12 weeks and 20 weeks postrandomisation. Data will be reported in line with Consolidated Standards of Reporting Trials. Primary trial outcomes are feasibility outcomes, primary participant outcomes are functioning and hallucinations. Additional analysis will investigate potential psychological mechanisms and secondary mental well-being outcomes. Trial progression criteria follows signal of efficacy and uses an analytical framework with a traffic-light system to determine viability of a future trial. Subsequent analysis of the NHS England Mental Health Services Data Set 3 years postrandomisation will assess long-term transition to psychosis.

Ethics and dissemination

This trial has received Research Ethics Committee approval (Newcastle North Tyneside 1 REC; 23/NE/0032). Participants provide written informed consent; young people provide assent with parental consent. Dissemination will be to ARMS Services, participants, public and patient forums, peer-reviewed publications and conferences.

Trial registration number

ISRCTN58558617.
Exercise intensity domains determined by heart rate at the ventilatory thresholds in patients with cardiovascular disease: new insights and comparisons to cardiovascular rehabilitation prescription recommendations
Authors: Milani Juliana Goulart Prata Oliveira , Milani Mauricio , Cipriano Graziella França Bernardelli , Hansen Dominique , Cipriano Junior Gerson
Published: July 2023

Objectives

To compare the elicited exercise responses at ventilatory thresholds (VTs: VT1 and VT2) identified by cardiopulmonary exercise testing (CPET) in patients with cardiovascular disease (CVD) with the guideline-directed exercise intensity domains; to propose equations to predict heart rate (HR) at VTs; and to compare the accuracy of prescription methods.

Methods

A cross-sectional study was performed with 972 maximal treadmill CPET on patients with CVD. First, VTs were identified and compared with guideline-directed exercise intensity domains. Second, multivariate linear regression analyses were performed to generate prediction equations for HR at VTs. Finally, the accuracy of prescription methods was assessed by the mean absolute percentage error (MAPE).

Results

Significant dispersions of individual responses were found for VTs, with the same relative intensity of exercise corresponding to different guideline-directed exercise intensity domains. A mathematical error inherent to methods based on percentages of peak effort was identified, which may help to explain the dispersions. Tailored multivariable equations yielded r2of 0.726 for VT1 and 0.901 for VT2. MAPE for the novel VT1 equation was 6.0%, lower than that for guideline-based prescription methods (9.5 to 23.8%). MAPE for the novel VT2 equation was 4.3%, lower than guideline-based methods (5.8%–19.3%).

Conclusion

The guideline-based exercise intensity domains for cardiovascular rehabilitation revealed inconsistencies and heterogeneity, which limits the currently used methods. New multivariable equations for patients with CVD were developed and demonstrated better accuracy, indicating that this methodology may be a valid alternative when CPET is unavailable.
Comparison of associations of household-level and neighbourhood-level poverty markers with paediatric asthma care utilisation by race/ethnicity in an open cohort of community health centre patients
Authors: Lucas Jennifer A , Marino Miguel , Bailey Steffani R , Hsu Audree , Datta Roopradha , Cottrell Erika , Kim Ye Ji , Suglia Shakira F , Bazemore Andrew , Heintzman John
Published: July 2023

Objective

The objective of this research was to examine how different measurements of poverty (household-level and neighborhood-level) were associated with asthma care utilisation outcomes in a community health centre setting among Latino, non-Latino black and non-Latino white children.

Design, setting and participants

We used 2012–2017 electronic health record data of an open cohort of children aged <18 years with asthma from the OCHIN, Inc. network. Independent variables included household-level and neighborhood-level poverty using income as a percent of federal poverty level (FPL). Covariate-adjusted generalised estimating equations logistic and negative binomial regression were used to model three outcomes: (1) ≥2 asthma visits/year, (2) albuterol prescription orders and (3) prescription of inhaled corticosteroids over the total study period.

Results

The full sample (n=30 196) was 46% Latino, 26% non-Latino black, 31% aged 6–10 years at first clinic visit. Most patients had household FPL <100% (78%), yet more than half lived in a neighbourhood with >200% FPL (55%). Overall, neighbourhood poverty (<100% FPL) was associated with more asthma visits (covariate-adjusted OR 1.26, 95% CI 1.12 to 1.41), and living in a low-income neighbourhood (≥100% to <200% FPL) was associated with more albuterol prescriptions (covariate-adjusted rate ratio 1.07, 95% CI 1.02 to 1.13). When stratified by race/ethnicity, we saw differences in both directions in associations of household/neighbourhood income and care outcomes between groups.

Conclusions

This study enhances understanding of measurements of race/ethnicity differences in asthma care utilisation by income, revealing different associations of living in low-income neighbourhoods and households for Latino, non-Latino white and non-Latino black children with asthma. This implies that markers of family and community poverty may both need to be considered when evaluating the association between economic status and healthcare utilisation. Tools to measure both kinds of poverty (family and community) may already exist within clinics, and can both be used to better tailor asthma care and reduce disparities in primary care safety net settings.
Frailty and emergency department utilisation in adults with systemic lupus erythematosus ≤65 years of age: an administrative claims data analysis of Medicaid beneficiaries
Authors: Lieber Sarah B , Nahid Musarrat , Navarro-Millán Iris , Rajan Mangala , Sattui Sebastian E , Mandl Lisa A
Published: July 2023

Objective

Frailty is a risk factor for adverse health in adults with SLE, including those <65 years. Emergency department (ED) utilisation is high in adults with SLE, but to our knowledge, whether frailty is associated with ED use is unknown. In a large administrative claims dataset, we assessed risk of ED utilisation among frail adults with SLE ≤65 years of age relative to non-frail adults ≤65 years of age with SLE.

Methods

Using the MarketScan Medicaid subset from 2011 to 2015, we identified beneficiaries 18–65 years with SLE (≥3 SLE International Classification of Diseases, Ninth Revision codes ≥30 days apart). Comparators without a systemic rheumatic disease (SRD) were matched 4:1 on age and gender. Frailty status in 2011 was determined using two claims-based frailty indices (CFIs). We compared risk of recurrent ED utilisation among frail and non-frail beneficiaries with SLE using an extension of the Cox proportional hazard model for recurrent events data.

Results

Of 2262 beneficiaries with SLE and 9048 non-SRD comparators, 28.8% and 11.6% were frail, respectively, according to both CFIs. Compared with non-frail beneficiaries with SLE, frail beneficiaries with SLE had significantly higher hazard of recurrent ED use (HR 1.75, 95% CI 1.48 to 2.08).

Conclusion

Frailty increased hazard of recurrent ED visits in frail adults ≤65 years of age with SLE relative to comparable non-frail adults with SLE. Frailty is a potential target for efforts to improve quality of care in SLE.
Antibiotics online: digital pharmacy marketplaces and pastiche medicine
Authors: Lyall Ben , Smith Anthony K J , Attwell Katie , Davis Mark D M David McGregor
Published: July 2023

The internet enables access to information and the purchasing of medical products of various quality and legality. Research and regulatory attention have focused on the trafficking of illicit substances, potential physical harms of pharmaceuticals, and possibilities like financial fraud. However, there is far less attention paid to antibiotics and other antimicrobials used to treat infections. With online pharmacies affording greater access, caution around antibiotic use is needed due to the increasing health risks of antimicrobial resistance (AMR). The COVID-19 pandemic has helped to normalise digital healthcare and contactless prescribing, amplifying the need for caution. Little is known of how antibiotics are consumed via digital pharmacy and implications for AMR prevention. To expand insight for AMR prevention policy in Australia and internationally, we use digital ethnographic methods to explore how digital pharmacies function in the context of health advice and policy related to AMR, commonly described as antimicrobial stewardship. We find that digital pharmacy marketplaces constitute ‘pastiche medicine’. They curate access to pharmaceutical and information products that emulate biomedical authority combined with emphasis on the ‘self-assembly’ of healthcare. Pastiche medicine empowers the consumer but borrows biomedical expertise about antibiotics, untethering these goods from critical medicine information, and from AMR prevention strategies. We reflect on the implications of pastiche medicine for AMR policy, what the antibiotics case contributes to wider critical scholarship on digital pharmacy, and how medical humanities research might consider researching online consumption in future.
Changing awareness and sources of tobacco and e-cigarettes among children and adolescents in Great Britain
Authors: Parnham Jennie C , Vrinten Charlotte , Cheeseman Hazel , Bunce Laura , Hopkinson Nicholas S , Filippidis Filippos T , Laverty Anthony A
Published: July 2023

Introduction

It is illegal in the UK to sell tobacco or nicotine e-cigarettes to people under the age of 18 years, as is displaying tobacco cigarettes at the point of sale. This paper examined changes in exposure to display of these products in shops and sources of these products among children and adolescent users over time

Methods

Data from representative repeated online cross-sectional surveys of youth in Great Britain (11–18 years) were used (2018–2022; n=12 445). Outcome measures included noticing product displays and sources of e-cigarettes and tobacco cigarettes. Logistic regressions examined the associations of these outcome variables over time and with sociodemographic variables.

Results

Of 12 040 participants with complete data, 10.1% used some form of nicotine product (4.2% cigarettes, 2.9% e-cigarettes, 3.0% both) at least occasionally. The likelihood of noticing tobacco cigarettes on display fell over time for both supermarkets (2018: 67.1% to 2022: 58.5%) and small shops (2018: 81.3% to 2022: 66.3%), but the likelihood of noticing e-cigarettes in supermarkets rose (2018: 57.4% to 2022: 66.5%). Sources of tobacco cigarettes did not differ over time, but e-cigarette users were more likely to get their e-cigarettes from small shops in 2022 (51.2%) vs 2019 (34.2%) (OR 2.02, 95% CI 1.24, 3.29).

Conclusion

This study provides evidence that current policies to limit awareness of and access to both tobacco and e-cigarettes among adolescents in the UK may not be effective. UK policies on the advertising, promotion and sale of both tobacco and e-cigarettes need to be reinforced to deter use among children and adolescents.
Is scientific inquiry still incompatible with government information control? A quarter-century later
Authors: Godwin Sean C. , Bateman Andrew W. , Mordecai Gideon , Jones Sean , Hutchings Jeffrey A.
Published: July 2023

Twenty-six years ago, in response to regionally devastating fisheries collapses in Canada, Hutchings et al. asked “Is scientific inquiry incompatible with government information control?” Now, a quarter-century later, we review how government science advice continues to be influenced by non-science interests, particularly those with a financial stake in the outcome of the advice. We use the example of salmon aquaculture in British Columbia, Canada, to demonstrate how science advice from Fisheries and Oceans Canada (DFO) can fail to be impartial, evidence-based, transparent, and independently reviewed—four widely implemented standards of robust science advice. Consequently, DFO's policies are not always supported by the best available science. These observations are particularly important in the context of DFO having struggled to sustainably manage Canada's marine resources, creating socio-economic uncertainty and putting the country's international reputation at risk as it lags behind its peers. We conclude by reiterating Hutchings et al.’s unheeded recommendation for a truly independent fisheries-science advisory body in Canada to be enshrined in the decision-making process.
Environmental drivers of juvenile dispersal and adult non-breeding movements in Ambystoma salamanders
Authors: Van Drunen S.G. , Linton J.E. , Bogart J.P. , Norris D.R.
Published: July 2023

Understanding the environmental drivers of species’ dispersal and migration patterns is needed to accurately predict climate change impacts on populations. For pond-breeding amphibians, adult movements associated with the breeding period are well studied but major gaps exist in our knowledge of the drivers of adult and juvenile non-breeding movements. Here, we assess environmental drivers of adult and juvenile Ambystoma maculatum (Shaw, 1802), Ambystoma jeffersonianum (Green, 1827), and their unisexual dependants’ ( Ambystoma laterale–jeffersonianum (Uzzell, 1964)) summer and fall non-breeding movements using data from pitfall trapping and radio telemetry tracking. We used generalized linear models to assess the influence of precipitation, minimum temperature, day of year, and days since last precipitation on salamander movements. Juvenile summer dispersal movements were related to days since last precipitation in Jefferson Salamander complex individuals and 24 h precipitation in Spotted Salamanders. Adult and juvenile fall movements were driven by minimum temperature, 24 h precipitation, and days since last precipitation, and the effect of these environmental factors varied slightly between species and between Jefferson bisexuals and unisexuals. Our work indicates that changes in both temperature and precipitation will likely impact non-breeding dispersal and migration in these species and, overall, improves our understanding of ecological patterns throughout their entire life cycle.
Theoretical concepts and measurement prospects for BSM trilinear couplings: a case study for scalar top quarks
Authors: Bahl Henning , Braathen Johannes , Weiglein Georg
Published: July 2023

After the possible discovery of new heavy particles at the LHC, it will be crucial to determine the properties and the underlying physics of the new states. In this work, we focus on scalar trilinear couplings, employing as an example the case of the trilinear coupling of scalar partners of the top quark to the Higgs boson. We discuss possible strategies for experimentally determining the scalar top (stop) trilinear coupling parameter, which controls the stop–stop–Higgs interaction, and we demonstrate the impact of different renormalisation prescriptions for this parameter. We find that the best prospects for determining the stop trilinear coupling arise from its quantum effects entering the model prediction for the mass of the SM-like Higgs boson in comparison to the measured value. We point out that the prediction for the Higgs-boson mass has a high sensitivity to the stop trilinear coupling even for heavy masses of the non-standard particles. Regarding the renormalisation of the stop trilinear coupling we identify a renormalisation scheme that is preferred in view of the present level of accuracy and we clarify the source of potentially large logarithms that cannot be resummed with standard renormalisation group methods.
Quantum semantic coding for structure extraction and matching applications
Authors: Han Yin-Xiao , Pan Yun , Wang Jing-Tao
Published: July 2023

Quantum Natural Language Processing (QNLP) is coded in the semantic space using a combined semantic distribution classification model with tensor operations. Its theoretical results on quantum circuit mapping and quantum semantic coding of text have been tested in practice with the recent development of quantum back-end equipment. In view of the small scale of quantum natural language processing tasks, single sentence structure of quantum semantic coding, low text coverage and lack of application, this paper proposes a combination of syntactic structure to extract text and extend the sentence components of quantum semantic coding, which improves the utilization of text processing task of quantum computing resources. In view of the fact that quantum natural language processing has few cases in specific applications, this paper studies the application expansion possibility of quantum text matching and question answering applications. The development path of classical natural language processing is referred to enhance the usefulness and explore the practical ability of QNLP in the current resource-constrained conditions.
FRACTAL DIMENSIONS OF SETS DEFINED BY DIGIT RESTRICTIONS IN ℝ2
Authors: WANG LIPENG , LI WENXIA
Published: July 2023

We introduce a class of sets defined by digit restrictions in [Formula: see text] and study its fractal dimensions. Let [Formula: see text] be a set defined by digit restrictions in [Formula: see text]. We obtain the Hausdorff and lower box dimensions of [Formula: see text]. Under some condition, we gain the packing and upper box dimensions of [Formula: see text]. We get the Assouad dimension of [Formula: see text] and show that it is 2 if and only if [Formula: see text] contains arbitrarily large arithmetic patches. Under some conditions, we study the upper spectrum, quasi-Assouad dimension and Assouad spectrum of [Formula: see text]. Finally, we give an intermediate value property of fractal dimensions of the class of sets.
Support of MISRA C++ Analyzer for Reliability of Embedded Systems
Authors: Lin Che-Chia , Chu Wei-Hsu , Chang Chia-Hsuan , Liao Hui-Hsin , Yang Chun-Chieh , Lee Jenq-Kuen , You Yi-Ping , Hsieh Tien-Yuan
Published: July 2023

Cyber-Physical Systems (CPS) are increasingly used in many complex applications, such as autonomous delivery drones, the automotive CPS design, power grid control systems, and medical robotics. However, existing programming languages lack certain design patterns for CPS designs, including temporal semantics and concurrency models. Future research directions may involve programming language extensions to support CPS designs. However, JSF++, MISRA, and MISRA C++ are providing specifications intended to increase the reliability of safety-critical systems. This article also describes the development of rule checkers based on the MISRA C++ specification using the Clang open-source tool, which allows for the annotation of code and the easy extension of the MISRA C++ specification to other programming languages and systems. This is potentially useful for future CPS language research extensions to work with reliability software specifications using the Clang tool. Experiments were performed using key C++ benchmarks to validate our method in comparison with the well-known Coverity commercial tool. We illustrate key rules related to class, inheritance, template, overloading, and exception handling. Open-source benchmarks that violate the rules detected by our checkers are also illustrated. A random graph generator is further used to generate diamond case with multiple inheritance test data for our software validations. The experimental results demonstrate that our method can provide information that is more detailed than that obtained using Coverity for nine open-source C++ benchmarks. Since the Clang tool is widely used, it will further allow developers to annotate their own extensions.
Swarm Robotics: A Survey from a Multi-Tasking Perspective
Authors: Debie Essam , Kasmarik Kathryn , Garratt Matt
Published: July 2023

The behaviour of social insects such as bees and ants has influenced the development of swarm robots. To enable robots to cooperate together, swarm robotics employs principles such as communication, coordination, and collaboration. Collaboration among multiple robots can lead to a faster task completion time compared to the utilisation of a single, complex robot. One of the key aspects of swarm robotics is that control is distributed uniformly across the robots in the swarm, which boosts the system’s resilience and fault tolerance. Through the use of the robots’ embodied sensors and actuators, this distributed control often facilitates the emergence of collective behaviours through the interaction of the robots with one another and with the environment. The purpose of this survey is to examine the reasons behind the lack of utilisation of swarm robots in multi-tasking applications, which will be accomplished by studying previous research works in the field. We examine the literature from the perspective of multi-tasking: we pay particular attention to concepts that contribute to the progress of swarm robotics for multi-tasking applications. To do this, we first examine the different studies in multi-tasking swarm robotics, covering platforms, multi-tasking scenarios, sub-task allocation methodologies, and performance metrics. We then highlight several swarm robotics related disciplines that have significant effect on the development of swarm robotics for multi-tasking problems. We propose two taxonomies: the first categorises works based on the characteristics of the scenarios being handled, whereas the second taxonomy categorises works based on the swarming strategies utilised to achieve multi-tasking capabilities. We finish with a discussion of swarm robots’ existing limitations for real-world multi-tasking applications, as well as recommendations for future research directions.
Array-Aware Matching: Taming the Complexity of Large-Scale Simulation Models
Authors: Fioravanti Massimo , Cattaneo Daniele , Terraneo Federico , Seva Silvano , Cherubin Stefano , Agosta Giovanni , Casella Francesco , Leva Alberto
Published: July 2023

Equation-based modelling is a powerful approach to tame the complexity of large-scale simulation problems. Equation-based tools automatically translate models into imperative languages. When confronted with nowadays’ problems, however, well assessed model translation techniques exhibit scalability issues that are particularly severe when models contain very large arrays. In fact, such models can be made very compact by enclosing equations into looping constructs, but reflecting the same compactness into the translated imperative code is nontrivial. In this paper, we face this issue by concentrating on a key step of equations-to-code translation, the equation/variable matching. We first show that an efficient translation of models with (large) arrays needs awareness of their presence, by defining a figure of merit to measure how much the looping constructs are preserved along the translation. We then show that the said figure of merit allows to define an optimal array-aware matching, and as our main result, that the so stated optimal array-aware matching problem is NP-complete. As an additional result, we propose a heuristic algorithm capable of performing array-aware matching in polynomial time. The proposed algorithm can be proficiently used by model translator developers in the implementation of efficient tools for large-scale system simulation.
Snippet Comment Generation Based on Code Context Expansion
Authors: Guo Hanyang , Chen Xiangping , Huang Yuan , Wang Yanlin , Ding Xi , Zheng Zibin , Zhou Xiaocong , Dai Hong-Ning
Published: July 2023

Code commenting plays an important role in program comprehension. Automatic comment generation helps improve software maintenance efficiency. The code comments to annotate a method mainly include header comments and snippet comments. The header comment aims to describe the functionality of the entire method, thereby providing a general comment at the beginning of the method. The snippet comment appears at multiple code segments in the body of a method, where a code segment is called a code snippet. Both of them help developers quickly understand code semantics, thereby improving code readability and code maintainability. However, existing automatic comment generation models mainly focus more on header comments, because there are public datasets to validate the performance. By contrast, it is challenging to collect datasets for snippet comments, because it is difficult to determine their scope. Even worse, code snippets are often too short to capture complete syntax and semantic information. To address this challenge, we propose a novel
S
nippet
C
omment
Gen
eration approach called
SCGen
. First, we utilize the context of the code snippet to expand the syntax and semantic information. Specifically, 600,243 snippet code-comment pairs are collected from 959 Java projects. Then, we capture variables from code snippets and extract variable-related statements from the context. After that, we devise an algorithm to parse and traverse abstract syntax tree (AST) information of code snippets and corresponding context. Finally,
SCGen
generates snippet comments after inputting the source code snippet and corresponding AST information into a sequence-to-sequence-based model. We conducted extensive experiments on the dataset we collected to evaluate our
SCGen
. Our approach obtains 18.23 in BLEU-4 metrics, 18.83 in METEOR, and 23.65 in ROUGE-L, which outperforms state-of-the-art comment generation models.
Role of glucose in daily torpor of Djungarian hamsters (Phodopus sungorus): challenge of continuous in vivo blood glucose measurements
Authors: Diedrich Victoria , Haugg Elena , Van Hee Justin , Herwig Annika
Published: July 2023

Djungarian hamsters use daily torpor to save energy during winter. This metabolic downstate is part of their acclimatization strategy in response to short photoperiod and expressed spontaneously without energy challenges. During acute energy shortage, torpor incidence, depth, and duration can be modulated. Torpor induction might rely on glucose availability as acute metabolic energy source. To investigate this, the present study provides the first continuous in vivo blood glucose measurements of spontaneous daily torpor in short photoperiod-acclimated and fasting-induced torpor in long photoperiod-acclimated Djungarian hamsters. Glucose levels were almost identical in both photoperiods and showed a decrease during resting phase. Further decreases appeared during spontaneous daily torpor entrance, parallel with metabolic rate but before body temperature, while respiratory exchange rates were rising. During arousal, blood glucose tended to increase, and pretorpor values were reached at torpor termination. Although food-restricted hamsters underwent a considerable energetic challenge, blood glucose levels remained stable during the resting phase regardless of torpor expression. The activity phase preceding a torpor bout did not reveal changes in blood glucose that might be used as torpor predictor. Djungarian hamsters show a robust, circadian rhythm in blood glucose irrespective of season and maintain appropriate levels throughout complex acclimation processes including metabolic downstates. Although these measurements could not reveal blood glucose as proximate torpor induction factor, they provide new information about glucose availability during torpor. Technical innovations like in vivo microdialysis and in vitro transcriptome or proteome analyses may help to uncover the connection between torpor expression and glucose metabolism.
The Effect of Changes in the Angular Position of Implants on Metal Artifact Reduction in Cone-Beam Computed Tomography Images: A Scoping Review
Authors: Asnaashari Maedeh , Sadeghipour Maryam , Bahrani Zeinab , Valizadeh Solmaz , Moshfeghi Mahkameh
Published: July 2023

Objective. Dental implant artifacts can compromise the quality of cone-beam computed tomography (CBCT) scans and challenge radiographic detection in surrounding regions. This literature review was conducted to examine the impact of implant angle modification on reducing metal artifacts in CBCT scans. Materials and Methods. A scoping review of literature was carried out in PubMed, Embase, Scopus, and Cochrane databases. Results. Different spatial planes, including alpha, beta, gamma, and phi, along with 0°, 5.2°, 9.8°, 14.5°, 15°, 30°, 45°, 60°, 75°, and 90° angles were studied. Changes in the angular position of implants may reduce metal artifacts and improve the quality of CBCT scans. Conclusions. Rotating implants within the alpha plane and angling them at 90° in the alpha plane enables reducing dental implant artifacts.
High-Throughput Drug Screening of Primary Tumor Cells Identifies Therapeutic Strategies for Treating Children with High-Risk Cancer
Authors: Mayoh Chelsea , Mao Jie , Xie Jinhan , Tax Gabor , Chow Shu-Oi , Cadiz Roxanne , Pazaky Karina , Barahona Paulette , Ajuyah Pamela , Trebilcock Peter , Malquori Angela , Gunther Kate , Avila Anica , Yun Doo Young , Alfred Stephanie , Gopalakrishnan Anjana , Kamili Alvin , Wong Marie , Cowley Mark J. , Jessop Sophie , Lau Loretta M.S. , Trahair Toby N. , Ziegler David S. , Fletcher Jamie I. , Gifford Andrew J. , Tsoli Maria , Marshall Glenn M. , Haber Michelle , Tyrrell Vanessa , Failes Timothy W. , Arndt Greg M. , Lock Richard B. , Ekert Paul G. , Dolman M. Emmy M.
Published: July 2023

For one-third of patients with pediatric cancer enrolled in precision medicine programs, molecular profiling does not result in a therapeutic recommendation. To identify potential strategies for treating these high-risk pediatric patients, we performed in vitro screening of 125 patient-derived samples against a library of 126 anticancer drugs. Tumor cell expansion did not influence drug responses, and 82% of the screens on expanded tumor cells were completed while the patients were still under clinical care. High-throughput drug screening (HTS) confirmed known associations between activating genomic alterations in NTRK, BRAF, and ALK and responses to matching targeted drugs. The in vitro results were further validated in patient-derived xenograft models in vivo and were consistent with clinical responses in treated patients. In addition, effective combinations could be predicted by correlating sensitivity profiles between drugs. Furthermore, molecular integration with HTS identified biomarkers of sensitivity to WEE1 and MEK inhibition. Incorporating HTS into precision medicine programs is a powerful tool to accelerate the improved identification of effective biomarker-driven therapeutic strategies for treating high-risk pediatric cancers.

Significance:

Integrating HTS with molecular profiling is a powerful tool for expanding precision medicine to support drug treatment recommendations and broaden the therapeutic options available to high-risk pediatric cancers.
Phase I Trial of the Multi-kinase Inhibitor Cabozantinib, a CYP3A4 Substrate, plus CYP3A4-Interacting Antiretroviral Therapy in People Living with HIV and Cancer (AMC-087)
Authors: Haigentz Missak , Lee Jeannette Y. , Chiao Elizabeth Y. , Aboulafia David M. , Ratner Lee , Ambinder Richard F. , Baiocchi Robert A. , Mitsuyasu Ronald T. , Wachsman William , Sparano Joseph A. , Rudek Michelle A.
Published: July 2023

Purpose:

To evaluate the safety, pharmacokinetics, and pharmacodynamic effects of cabozantinib, a CYP3A4 substrate, in people living with human immunodeficiency virus and cancer receiving antiretrovirals (ARV).

Patients and Methods:

Patients received a reduced dose of cabozantinib (20 mg orally daily) with strong CYP3A4 inhibitors (ARV ritonavir or non-ARV cobicistat, stratum A), or a standard 60 mg dose with ARVs that are CYP3A4 inducers (efavirenz or etravirine, stratum B) or noninteracting ARVs (stratum C). Initial dose escalation in stratum A and stratum B was performed on the basis of tolerability.

Results:

36 patients received cabozantinib plus ARVs, including 20 in stratum A, 9 in B, and 7 in C. The recommended initial cabozantinib doses for stratum A, B, and C were 20, 60, and 60 mg, respectively. Doses of 40 or 60 mg plus CYP3A4 inhibitors in stratum A and 100 mg plus CYP3A4 inducers in stratum B were associated with excessive toxicity, whereas 60 mg with noninteracting ARVs was not. The steady state minimal concentrations were lower at 20 mg in stratum A or 60 mg in stratum B compared with 60 mg in stratum C, while total exposure was only lower in 60 mg in stratum B compared with 60 mg in stratum C. Activity was observed in Kaposi sarcoma and an AXL-amplified sarcoma.

Conclusions:

Cabozantinib as a single agent should be initiated at 20 mg daily and 60 mg daily when taken concurrently with ARVs that are strong CYP3A4 inhibitors and inducers, respectively, with consideration for subsequent escalation per current cabozantinib guidelines.

See related commentary by Eisenmann and Sparreboom, p. 4999
Supplementary Data Tables from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Authors: Dickinson Michael J. , Barba Pere , Jäger Ulrich , Shah Nirav N. , Blaise Didier , Briones Javier , Shune Leyla , Boissel Nicolas , Bondanza Attilio , Mariconti Luisa , Marchal Anne-Laure , Quinn David S. , Yang Jennifer , Price Andrew , Sohoni Akash , Treanor Louise M. , Orlando Elena J. , Mataraza Jennifer , Davis Jaclyn , Lu Darlene , Zhu Xu , Engels Boris , Moutouh-de Parseval Laure , Brogdon Jennifer L. , Moschetta Michele , Flinn Ian W.
Published: July 2023

Supplementary Table S1. Bridging chemotherapies by ATC class and preferred term (safety set); Supplementary Table S2. Lymphodepleting chemotherapies (safety set); Supplementary Table S3. Cytokine release syndrome following YTB323 infusion; Supplementary Table S4. Neurological adverse reactions following YTB323 infusion; Supplementary Table S5. Summary of cellular kinetic parameters in peripheral blood by flow cytometry for YTB323 at DL1 and DL2; Supplementary Table S6. Summary of cellular kinetic parameters in peripheral blood by flow cytometry and qPCR for YTB323 at DL1 and DL2.
Supplementary Data Figures from A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-cell Stemness Shows Enhanced CAR T-cell Efficacy in Preclinical and Early Clinical Development
Authors: Dickinson Michael J. , Barba Pere , Jäger Ulrich , Shah Nirav N. , Blaise Didier , Briones Javier , Shune Leyla , Boissel Nicolas , Bondanza Attilio , Mariconti Luisa , Marchal Anne-Laure , Quinn David S. , Yang Jennifer , Price Andrew , Sohoni Akash , Treanor Louise M. , Orlando Elena J. , Mataraza Jennifer , Davis Jaclyn , Lu Darlene , Zhu Xu , Engels Boris , Moutouh-de Parseval Laure , Brogdon Jennifer L. , Moschetta Michele , Flinn Ian W.
Published: July 2023

Supplementary Fig. S1. Preclinical evaluation and characterization of YTB323 and CTL*019 for Donor 2 and 3; Supplementary Fig. S2. Differential gene expression of CTL*019 cells versus YTB323 cells (preclinical); Supplementary Fig. S3. Preclinical validation of YTB323; Supplementary Fig. S4. Dose-dependent expansion (Cmax and AUC0-21d) of YTB323 and CTL*019 in NSG mice with NALM6; Supplementary Fig. S5. CD4:CD8 ratio comparison of leukapheresis and cell products of YTB323 and tisagenlecleucel; Supplementary Fig. S6. Stemness and memory differentiation gene signatures are retained or enriched for in YTB323 final product; Supplementary Fig. S7. Differential gene expression of tisagenlecleucel versus YTB323 final product; Supplementary Fig. S8. Naive/TSCM cells and a naive stem-like gene signature correlate with higher expansion and a better response; Supplementary Fig. S9. T-cell subset and checkpoint inhibitor analysis by flow cytometry on PBMCs collected post-YTB323 infusion; Supplementary Fig. S10. Pre-clinical T-cell gating strategies.
Supplementary Table 2 from Multicellular complex tumor spheroid response to DNA repair inhibitors in combination with DNA-damaging drugs
Authors: Dexheimer Thomas S , Coussens Nathan P , Silvers Thomas , Wright John , Morris Joel , Doroshow James H. , Teicher Beverly A.
Published: July 2023

Table S2. Links to the PubChem assays.