bluuebunny/crossref_metadata_2025_split huggingface dataset:
Shaping the Future: Proposed Bills to Regulate New and Emerging Tobacco and Nicotine Products in Latin America and the Caribbean Amidst Public Health Concerns and Industry Interests
Authors: Severini Luciana , de Figueiredo Beatriz Albuquerque , Severini Gianella , Tran Brian , Sebrié Ernesto M , Crosbie Eric 
Published: July 2024

Abstract

Introduction
To examine legislative efforts to regulate new and emerging tobacco and nicotine products (NETNPs) in Latin America and the Caribbean (LAC) between 2017 and 2022.

Aims and Methods
Analysis of online national legislation databases to track NETNP bills using standard snowball search methods.

Results
Bills were identified in 15 out of the 33 LAC countries, accounting for a total of 91 bills targeting NETNPs. Mexico had the highest number (n = 38) of bills, followed by Brazil (n = 16), Argentina (n = 10), Colombia (n = 8), and Chile (n = 5). The remaining countries introduced two or fewer NETNP bills. Among the identified 91 bills, the majority (n = 60) addressed both electronic cigarettes and heated tobacco products (HTPs), almost one-third of bills (n = 29) applied only to electronic cigarettes, and only two focused solely on HTPs. Six of the fifteen countries with identified bills, enacted one NETNP law including Barbados, Bolivia, Costa Rica, Guyana, Mexico, and Panama. Since 2019, there has been a steady increase in the amount of NETNP bills introduced in LAC. In 2017 and 2018, 10 NETNP bills were introduced each year followed by 23 NETNP bills introduced in each 2019 and 2020, 19 in 2021, and 16 by August 2022.

Conclusions
The substantial increase in the number of NETNP bills introduced since 2019 indicates the growing importance of regulating NETNPs in LAC. As NETNPs continue to evolve and grow it is important to continue monitoring and evaluating tobacco and nicotine regulatory initiatives while also staying ahead of the evolving market of NETNPs.

Implications
Previous studies have analyzed the regulatory environment of NETNPs but it is less known about legislative and regulatory efforts and attempts. This is the first known study to analyze legislative bills to regulate NETNPs in Latin America and the Caribbean (LAC). The substantial increase in the number of NETNP bills introduced in LAC since 2019 indicates the growing importance of regulating NETNPs in LAC. As NETNPs continue to evolve and grow it is important to continue monitoring and evaluating tobacco and nicotine regulatory initiatives while also staying ahead of the evolving market of NETNPs.
FDA approval summary: fam-trastuzumab deruxtecan-nxki for unresectable or metastatic non-small cell lung cancer with activating HER2 mutations
Authors: Mehta Gautam U , Vellanki Paz J , Ren Yi , Amatya Anup K , Mishra-Kalyani Pallavi S , Pan Lili , Zirkelbach Jeanne F , Pan Yuzhuo , Liu Jiang , Aungst Stephanie L , Miller Claudia P , Shah Mirat , Rahman Nam Atiqur , Theoret Marc , Kluetz Paul , Pazdur Richard , Beaver Julia A , Singh Harpreet 
Published: July 2024

Abstract
On August 11, 2022, FDA granted accelerated approval to fam-trastuzumab deruxtecan-nxki (DS-8201a, T-DXd, ENHERTU, Daiichi Sankyo) for adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumors have activating human epidermal growth factor receptor 2 (HER2) mutations, as detected by an FDA-approved test, and who have received a prior systemic therapy. The approval was based on a prespecified interim analysis of DESTINY-Lung02 (Study U206), a multi-center, randomized, dose-optimization trial in patients with NSCLC harboring activating HER2-mutations. At the approved dose of 5.4 mg/kg given intravenously every 3 weeks, the overall response rate (ORR) was 58% (95% confidence interval [CI]: 43, 71). The median duration of response was 8.7 months (95% CI: 7.1, not estimable). These results were consistent with response rates observed at the 6.4 mg/kg dose level. The most common (≥ 20%) adverse reactions were nausea, constipation, decreased appetite, vomiting, fatigue, and alopecia. The rate of interstitial lung disease (ILD) or pneumonitis was 6% at the 5.4 mg/kg dose level and 14% at the 6.4 mg/kg dose level. In the setting of similar efficacy and reduced toxicity, approval was granted for the 5.4 mg/kg dose level. The applicant conducted a randomized, dose-optimization study with guidance from the FDA Oncology Center of Excellence’s Project Optimus. This is the first approval of a targeted therapy for HER2-mutated NSCLC.
Prediction of moderate and severe toxicities of chemotherapy in older patients with cancer: a propensity weighted analysis of ELCAPA cohort
Authors: Benderra Marc-Antoine , Paillaud Elena , Broussier Amaury , Layese Richard , Tapia Claudia M , Mebarki Soraya , Boudou-Rouquette Pascale , Laurent Marie , Piero Monica , Rollot-Trad Florence , Gligorov Joseph , Caillet Philippe , Canoui-Poitrïne Florence 
Published: July 2024

Abstract

Background
Currently available predictive models for chemotherapy-related toxicity are not sufficiently discriminative in older patients with cancer and do not consider moderate toxicities. The purpose of this study was to identify factors associated with moderate and severe chemotherapy toxicities in older patients with cancer.

Materials and methods
Patients aged 70+ recruited in the prospective ELCAPA cohort were analyzed. A total of 837 patients with data on toxicities had received chemotherapy without other systemic treatment and were included between 2015 and 2022. To adjust for any imbalances in the distribution of covariates between patients receiving single-agent chemotherapy vs combination chemotherapy, we applied overlap weighting (a propensity-score-based technique). We used multinomial logistic regression.

Results
Median (interquartile range) age was 81 (77-84). Forty-one percent experienced moderate toxicity, and 33% experienced severe toxicity. Hematologic toxicities accounted for 53% of severe toxicities and 66% of moderate toxicities. Age &lt;80 years, cancer type, metastatic status, Eastern Cooperative Oncology Group performance status (ECOG-PS) &gt;1, no cognitive impairment were associated with combination chemotherapy decision. In a univariate analysis with overlap weighting, no factors were associated with moderate toxicity. Hemoglobin &lt; 10 g/dL and a CIRS-G score &gt;12 were associated with severe toxicity. In a multivariate analysis, only hemoglobin &lt; 10 g/dL was independently associated with severe toxicity, adjusted OR 2.96 (95% CI, 1.20-7.29).

Conclusion
By addressing indication bias for combination chemotherapy decision, only anemia and not cancer type, combination chemotherapy was predicting for severe chemotherapy-related toxicity in older patients with cancer. We did not find any predictors of moderate chemotherapy-related toxicity.
Improving the care of children with autism and related neurodevelopmental disorders in emergency department settings: Understanding the knowledge-to-practice continuum of emergency department providers
Authors: Niro Julia , Zubairi Mohammad S , Leung James S 
Published: July 2024

Abstract

Objectives
Emergency department (ED) healthcare providers (HCPs) frequently describe a lack of knowledge in caring for children with autism spectrum disorder (ASD) and related neurodevelopmental disorders (NDD). Our primary objective is to explore gaps in training and clinical exposure reported by ED HCPs caring for children with ASD/NDD.

Methods
A two-phase, mixed-methods cross-sectional study was conducted. In phase 1, an interprofessional sample of tertiary care paediatric ED HCPs (physicians, nurses, social workers, and child life specialists) were surveyed about their experiences and perceived gaps in managing children with ASD/NDD. These responses informed phase 2, where six semi-structured interviews were conducted. Interview transcripts were analyzed to determine themes around the discomfort of ED HCPs caring for children with ASD/NDD.

Results
The majority, 54/78 (69%) of eligible staff completed the survey. A minority (42.5%) of HCPs had mandatory training on ASD/NDD, and 80% would value continuing education. Some ED HCPs (41.2%) had previous personal or professional experiences with children with ASD/NDD that facilitated deeper empathy and awareness of system challenges. Interviews revealed four themes of ED HCP discomfort with this population: 1) added considerations of interacting with children and families with ASD/NDD; 2) the ED as a single touch point in complex and limited healthcare systems; 3) recognizing comfort in discomfort; and 4) the need to implement practical interventions to improve care.

Conclusions
ED HCPs are motivated to improve care for children with ASD/NDD. Alongside broader systems interventions, future educational interventions can narrow ED HCP gaps identified through this work.
How bodily perception parallels distal perception
Authors: Gray Richard 
Published: July 2024

Abstract
Bodily perception is standardly contrasted with distal perception. In this paper, I argue that the standard view overlooks a significant respect in which bodily perception parallels distal perception. The parallel is motivated by a comparison between two cross-modal illusions. The ventriloquism effect manifests cross-modal relations between the distal senses of vision and audition and multi-sensory experiences jointly constituted by vision and audition. Thermal referral is a laboratory induced illusion that involves the bodily sensory systems underlying the perception of pressure and heat. I argue that thermal referral indicates the presence of cross-modal relations and multi-sensory experiences of a type sufficiently similar to those manifested by the ventriloquism effect to suggest that pressure and thermal perception parallel vision and audition at the level of bodily perception.
A contribution to the mathematical theory of diffraction. Part II: Recovering the far-field asymptotics of the quarter-plane problem
Authors: Assier R C , Shanin A V , Korolkov A I 
Published: July 2024

Summary
We apply the stationary phase method developed in Assier, Shanin and Korolkov, QJMAM, 76 (2022) to the problem of wave diffraction by a quarter-plane subjected to Dirichlet boundary conditions. The wave field is written as a double Fourier transform of an unknown spectral function. We make use of the analytical continuation results of Assier and Shanin, QJMAM, 72 (2018) to uncover the singularity structure of this spectral function. This allows us to provide a closed-form far-field asymptotic expansion of the field by estimating the double Fourier integral near some special points of the spectral function. All the known results on the far-field asymptotics of the quarter-plane problem are recovered, and new mathematical expressions are derived for the secondary diffracted waves in the plane of the scatterer.
The forearm elevation–compression test: a novel test for carpal tunnel syndrome
Authors: Hawkes C H , Cutter G 
Published: July 2024

Abstract

Background
As the time available to spend with patients decreases, a rapid test for bedside diagnosis of carpal tunnel syndrome (CTS) could be useful.

Design and Methods
We describe the forearm elevation–compression test (FECT) in this context. The FECT was assessed in 40 patients with clinically suspected CTS and compared to Tinel’s and Phalen’s signs. Routine electromyography and nerve conduction tests (EMG/NCT) were performed in all cases. In addition, 85 healthy controls were examined by FECT and compared to the patient group.

Results
All three provocative tests, particularly FECT, were frequently positive in suspected CTS. Neurophysiological tests were normal in 5 of 40 cases of clinically suspected CTS, and the FECT was positive in all of these suggesting a positive predictive value of 87.5% if one accepts EMG/NCT as the reference. Amongst the healthy controls, 18 of 85 (21.2%) were positive on the FECT suggestive of a high false-positive rate or subclinical disease.

Conclusion
It is proposed that the FECT is a useful addition to the clinical examination of suspected CTS. Although the positive rate may be falsely elevated, this is offset by restricting the latency for tingling onset to 10 s or less (FECT2).
Are lessons being learnt from the replication crisis or will the revolution devour its children? Open Q science from the editor's perspective
Authors: Hüttel Silke , Hess Sebastian 
Published: July 2024

Abstract
The scientific production system is crucial in how global challenges are addressed. However, scholars have recently begun to voice concerns about structural inefficiencies within the system, as highlighted, for example, by the replication crisis, the p-value debate and various forms of publication bias. Most suggested remedies tend to address only partial aspects of the system's inefficiencies, but there is currently no unifying agenda in favour of an overall transformation of the system. Based on a critical review of the current scientific system and an exploratory pilot study about the state of student training, we argue that a unifying agenda is urgently needed, particularly given the emergence of artificial intelligence (AI) as a tool in scientific writing and the research discovery process. Without appropriate responses from academia, this trend may even compound current issues around credibility due to limited replicability and ritual-based statistical practice while amplifying all forms of existing biases. Naïve openness in the science system alone is unlikely to lead to major improvements. We contribute to the debate and call for a system reform by identifying key elements in the definition of transformation pathways towards open, democratic and conscious learning, teaching, reviewing and publishing supported by openly maintained AI tools. Roles and incentives within the review process will have to adapt and be strengthened in relation to those that apply to authors. Scientists will have to write less, learn differently and review more in the future, but need to be trained better in and for AI even today.
The relationship between obesity and patient-reported outcome measures in people with polymyalgia rheumatica
Authors: Scott Ian C , Bajpai Ram , Hider Samantha L , Helliwell Toby , Mallen Christian D , Muller Sara 
Published: July 2024

Abstract

Objective
To examine the association between obesity and patient-reported outcome measures (PROMs) in a primary care-based cohort of people with PMR.

Methods
The PMR Cohort Study recruited people with incident PMR from 382 general practices. Self-completed questionnaires (0, 12, 24 months) captured a range of PROMs for pain, stiffness, anxiety, depression, fatigue, function and quality of life, alongside data on BMI. People were categorized as underweight/normal weight (BMI &lt; 25kg/m2), overweight (25–29.99 kg/m2) or obese (≥30 kg/m2). Piecewise, multilevel, linear mixed-effects regression models examined relationships between BMI categories and PROMs over time, adjusting for confounding variables. Chi-squared tests examined the relationship between obesity and glucocorticoid persistence.

Results
644 people with PMR were included. At baseline, 33.9% were normal/underweight, 40.6% overweight and 25.5% obese. Compared with normal/underweight people, those with obesity had significantly worse scores for the following: pain and stiffness at 12 months; fatigue at 12 and 24 months; depression at baseline; physical function at all time points; and quality of life at baseline and 12 months. They also had significantly smaller improvements in stiffness (1.13 units on an 11-point numeric rating scale; P = 0.001) and physical function (0.14 units measured using the modified Health Assessment Questionnaire; P = 0.025) between 0 and 12 months. BMI categories did not relate to persistent glucocorticoid use at 12 months (P = 0.110) or 24 months (P = 0.166).

Conclusion
Obesity associates with poorer outcomes for a range of PROMs in people with PMR. Consideration should be given to providing weight management support to people with PMR and obesity.
Enhanced Bayesian RFI mitigation and transient flagging using likelihood reweighting
Authors: Anstey Dominic , Leeney Samuel A K 
Published: July 2024

Abstract
Contamination by radio frequency interference (RFI) is a ubiquitous challenge for radio astronomy. In particular, transient RFI is difficult to detect and avoid, especially in large data sets with many time bins. In this work, we present a Bayesian methodology for time-dependent, transient anomaly mitigation performed jointly with model fitting. The computation time for correcting transient anomalies in this manner in time-separated data sets grows proportionally with the number of time bins. We demonstrate that utilizing likelihood reweighting can allow our Bayesian anomaly mitigation method to be performed with a computation time close to independent of the number of time bins. In particular, we identify a factor of 44 improvement in computation time for a test case with 2000 time bins. We also demonstrate how this method enables the flagging threshold to be fit as a free parameter, fully automating the mitigation process. We find that this threshold fitting also prevents overcorrecting of the data in the case of wide priors. Finally, we investigate the potential of the methodology as a transient detector. We demonstrate that the method is able to reliably flag an individual anomalous data point out of 302 000 provided the Signal to Noise Ratio is $\ge\!{10}$.
Impact of conventional and biological disease-modifying anti-rheumatic drugs on arterial lesions in Takayasu arteritis
Authors: Bletry Diego , Meyblum Louis , Desseaux Kristell , Vautier Mathieu , Chiche Laurent , Le Joncour Alexandre , Redheuil Alban , Roux Charles , Cacoub Patrice , Gaudric Julien , Biard Lucie , Saadoun David 
Published: July 2024

Abstract

Background
The definition of Takayasu arteritis (TAK) remission and disease activity is still unclear. Vascular imaging is an essential tool for following-up patients. Herein, we aimed to compare the evolution of vascular lesions (i.e. vessel wall thickening and stenosis) under conventional cDMARDs relatively to biological DMARDs (bDMARDs) in TAK patients followed with the same CT angiography modalities.

Method
We compared 75 lines of therapy in TAK patients who received cDMARDs (n = 40 lines) and bDMARDs (n = 35 lines) using CT angiography. We established 1–3 main target vessels with vessel wall thickening and/or stenosis. Every targeted vessel had its thickness and its lumen diameter measured at the initiation of immunosuppressive treatment and at 12 months.

Results
We observed an overall reduction in arterial wall thickness in 73% of cases and 31% had &gt;25% relative decrease in the wall thickness. Using a linear mixed effects model, first-line immunosuppressive therapy (P = 0.012) and bDMARDs relatively to cDMARDs (P = 0.026) were independently associated with vessel wall thickness reduction in TAK. Thirty-eight percent of the stenotic vessels had a &gt; 25% relative increase in lumen diameter under immunosuppressive therapy. The relative increase &gt;25% in lumen diameter was noted in 56% vs 17% with bDMARDs compared with cDMARDs.

Conclusion
Immunosuppressive treatments can reduce arterial wall thickness and widen lumen diameter in TAK. bDMARDs seem to be more effective than cDMARDs to improve arterial lesions in TAK.
Refining treat-to-target strategies in cryopyrin-associated periodic syndromes: the role of inflammatory markers
Authors: Satirer Özlem , Welzel Tatjana , Zapf Beate , Benseler Susanne M , Kuemmerle-Deschner Jasmin B 
Published: July 2024

Abstract

Objectives
Cryopyrin-associated periodic syndromes (CAPS) encompasses a spectrum of IL-1 driven systemic diseases with dramatic individual and societal burden. The study aimed to identify parameters and instruments to refine real-life treat-to-target (T2T) strategies and control CAPS disease activity.

Methods
A single-centre, longitudinal study of consecutive children and adults diagnosed with CAPS and treated with anti-IL-1 therapy was performed. Demographics, clinical phenotype and NLRP3 gene variants in addition to serial inflammatory markers and physician and patient/parent global assessments (PGA/PPGA) were captured. Effectiveness of anti-IL-1 T2T strategies and factors associated with therapy escalation were determined.

Results
A total of 54 CAPS patients with 759 follow-up visits were included; 31/54 (57%) were children; the median follow-up was 108 months (12–620). The moderate CAPS phenotype was present in 89%; overall 59% had pathogenic/likely pathogenic NLRP3 variants. Therapy adjustments were documented in 50/759 visits including 35 therapy escalations and 15 reductions; 74% of the therapy escalation visits were for children. At time of visit, 63% showed moderate, 37% severe clinical disease activity. Inflammatory markers remained largely normal. Significant improvement was observed in both PGA/PPGA throughout the study (P &lt; 0.01). At the last follow-up, 96% of patients achieved remission.

Conclusion
Guidance for refining real-life T2T strategies in CAPS cohorts can be drawn from serial assessments of PGA and PPGA, reliably reflecting changes in disease activity. Individual parameters including age and NLRP3 gene variants are important predictors, while the sensitivity of inflammatory markers is limited due to the confounding anti-IL-1 therapy.
A systematic review of aspects of NUDT15 pharmacogenomic variants and thiopurine-induced myelosuppression
Authors: Palmer Rachel , Peters Jaime 
Published: July 2024

Abstract

Objectives
Evidence for NUDT15 pharmacogenomic variants and thiopurine-induced myelosuppression (TIM), consists predominantly of association data in Asian, mixed variant homozygote/heterozygote populations. We therefore sought evidence on; (i) NUDT15 genotype-guided thiopurine dosing. (ii) Association data for TIM in NUDT15 variant heterozygotes with inflammatory bowel disease. (iii) Association data for NUDT15 variants with TIM in Europeans. (iv) Health economic data for NUDT15 genotyping in inflammatory bowel disease.

Methods
A systematic review was conducted, consisting of database searches, screening against pre-defined inclusion/exclusion criteria, and assessment of risk of bias using study-specific appraisal tools.

Key findings
Titles/abstracts of 493 articles were screened, with 29 studies included. (i) Significant reductions in TIM with genotype-guided thiopurine dosing were reported by both trials and a cohort study. (ii) TIM rates were significantly higher in NUDT15*3 heterozygotes vs. wild type. Data were conflicting for rarer variants. (iii) Four of five studies reported an association with TIM for at least one or a combination of NUDT15 variants in Europeans (OR 9.5–38.2), but data were conflicting. (iv) Both health economic analyses found TPMT/NUDT15 genotyping cost-effective in Asian populations, but not when a European population was considered.

Conclusion
Limited data showed an association with TIM in NUDT15 variant heterozygotes and Europeans and the potential for genotype-guided dosing to reduce TIM. Studies were generally small, heterogenous, and of variable quality. The low prevalence of rarer NUDT15 variants/variants in Europeans likely contributed to contradictory findings. Further research on the clinical utility of genotyping in diverse populations will help inform future economic analyses.