bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

IntroductionIndividuals 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 analysis88 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 disseminationThis 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 numberISRCTN58558617.
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

ObjectivesTo 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.MethodsA 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).ResultsSignificant 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%).ConclusionThe 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

ObjectiveThe 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 participantsWe 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.ResultsThe 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.ConclusionsThis 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

ObjectiveFrailty 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.MethodsUsing 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.ResultsOf 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).ConclusionFrailty 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.
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

IntroductionIt 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 timeMethodsData 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.ResultsOf 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).ConclusionThis 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.
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

AbstractAfter 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.
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

Abstract

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

Abstract

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
A First-in-human, Dose-escalation Study of the Methionine Aminopeptidase 2 Inhibitor M8891 in Patients with Advanced Solid Tumors
Authors: Carducci Michael A. , Wang Ding , Habermehl Christina , Bödding Matthias , Rohdich Felix , Lignet Floriane , Duecker Klaus , Karpenko Oleksandr , Pudelko Linda , Gimmi Claude , LoRusso Patricia 
Published: July 2023

Methionine aminopeptidase 2 (MetAP2) is essential to endothelial cell growth and proliferation during tumor angiogenesis. M8891 is a novel orally bioavailable, potent, selective, reversible MetAP2 inhibitor with antiangiogenic and antitumor activity in preclinical studies. The safety, tolerability, pharmacokinetics, and pharmacodynamics of M8891 monotherapy were assessed in a phase I, first-in-human, multicenter, open-label, single-arm, dose-escalation study (NCT03138538). Patients with advanced solid tumors received 7–80 mg M8891 once daily in 21-day cycles. The primary endpoint was dose-limiting toxicity (DLT) during cycle 1, with the aim to determine the maximum tolerated dose (MTD). Twenty-seven patients were enrolled across six dose levels. Two DLTs (platelet count decrease) were reported, one each at 60 and 80 mg/once daily M8891, resolving after treatment discontinuation. MTD was not determined. The most common treatment-emergent adverse event was platelet count decrease. M8891 plasma concentration showed dose-linear increase up to 35 mg and low-to-moderate variability; dose-dependent tumor accumulation of methionylated elongation factor 1α, a MetAP2 substrate, was observed, demonstrating MetAP2 inhibition. Pharmacokinetic/pharmacodynamic response data showed that preclinically defined target levels required for in vivo efficacy were achieved at safe, tolerated doses. Seven patients (25.9%) had stable disease for 42–123 days. We conclude that M8891 demonstrates a manageable safety profile, with dose-proportional exposure and low-to-moderate interpatient variability at target pharmacokinetic/pharmacodynamic levels at ≤35 mg M8891 once daily. On the basis of the data, 35 mg M8891 once daily is the recommended phase II dose for M8891 monotherapy. This study forms the basis for future development of M8891 in monotherapy and combination studies.

Significance:
M8891 represents a novel class of reversible MetAP2 inhibitors and has demonstrated preclinical antitumor activity. This dose-escalation study assessed M8891 treatment for patients with advanced solid tumors. M8891 demonstrated favorable pharmacokinetics, tumoral target engagement, and a manageable safety profile, and thus represents a novel antitumor strategy warranting further clinical studies.
Inference in High-Dimensional Regression Models without the Exact or Lp Sparsity
Authors: Cha Jooyoung , Chiang Harold D. , Sasaki Yuya 
Published: July 2023

Abstract
We propose a new inference method in high-dimensional regression models and high-dimensional IV regression models. The method is shown to be valid without requiring the exact sparsity or Lp sparsity conditions. Simulation studies demonstrate superior performance of this proposed method over those based on the LASSO or the random forest, especially under less sparse models. We illustrate an application to production analysis with a panel of Chilean firms.