bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long-term impact of ivacaftor on mortality rate and health outcomes in people with cystic fibrosis
Authors: Merlo Christian A , Thorat Teja , DerSarkissian Maral , McGarry Lisa J , Nguyen Catherine , Gu Yuqian M , Healy Joe , Rubin Jaime L , Brookhart M Alan 
Published: June 2024

BackgroundIvacaftor (IVA) has been shown to improve lung function and other clinical outcomes in people with cystic fibrosis (CF). A decade of real-world IVA availability has enabled the examination of long-term outcomes with this treatment. This retrospective, longitudinal cohort study investigated the impact of IVA on mortality rate and health outcomes among people with CF in the US.MethodsData from the US CF Foundation Patient Registry from January 2010 to December 2019 were analysed. The IVA-treated cohort included people with a CF transmembrane conductance regulator (CFTR) gating mutation (excludingR117H); age-matched comparator cohort included people with aF508deland a minimal functionCFTRmutation who had no prior CFTR modulator treatment. Baseline characteristics were balanced between cohorts using standardised mortality ratio weighting generated from propensity scores. Outcomes of interest were overall survival, lung transplant, percent predicted forced expiratory volume in 1 s (ppFEV1), body mass index (BMI), pulmonary exacerbations (PEx), outpatient visits and hospitalisations.FindingsOver a maximum follow-up of 7.9 years, the IVA-treated cohort (N=736) had lower rates of mortality (hazard ratio [HR] (95% CI): 0.22 (0.09 to 0.45)), lung transplant (HR: 0.11 (95% CI 0.02 to 0.28)), PEx (rate ratio: 0.49 (95% CI 0.42 to 0.55)) and all-cause hospitalisations (rate ratio: 0.50 (95% CI 0.43 to 0.56)) as well as better lung function (mean difference in ppFEV1: 8.46 (95% CI 7.34 to 9.75)) and higher BMI/BMIz-scores (mean difference 1.20 (95% CI 0.92 to 1.71) kg/m2and 0.27 (95% CI 0.25 to 0.40), respectively) than the comparator cohort (N=733).InterpretationOur analysis suggests that IVA provides sustained clinical benefits in people with CF over a follow-up period of approximately 8 years. These findings reinforce the existing real-world evidence that IVA can slow disease progression and decrease the healthcare burden of CF over the long term.
Paleoenvironmental and chemostratigraphic implications of variations in geochemical proxies across the Upper Jurassic–Lower cretaceous boundary: a case study from the Flemish Pass Basin
Authors: Bingham-Koslowski N. , Azmy K. , Layton-Matthews D. 
Published: June 2024

The Jurassic–Cretaceous boundary is the only Phanerozoic period-level boundary that lacks a golden spike on the geological timescale despite significant global geological and environmental change during this time related to the opening of the Atlantic Ocean. Paleoenvironmental proxy profiles (total organic carbon, δ34S, δ15N, Fe, Mn, Ce/Ce*, Th/U, δ13Corg, P, Ni, Zn, Cu, and B/Ga) for core 3 of the Baccalieu I-78 well in the Flemish Pass Basin, offshore eastern Canada, exhibit a geochemical anomaly between 3288.5 and 3289 m, overlapping with the biostratigraphic placement of the Jurassic–Cretaceous boundary. Collectively the geochemical analyses are interpreted to indicate that the anomaly is associated with a fall in relative sea level, followed by a rise, which led to restricted circulation, stratification, and widespread anoxia. This anoxia, coupled with an arid climate, further resulted in reduced weathering, limited nutrient supply, and an overall reduction in primary productivity. The results of this study, in conjunction with previous biostratigraphic studies on core 3, suggest that the Jurassic–Cretaceous boundary in Baccalieu I-78 likely falls within the geochemical anomaly, specifically between 3228.5 and 3288.85 m. Furthermore, the paleoenvironmental interpretations derived in this study agree with published reports on global sea level and climate trends around the Jurassic–Cretaceous boundary, implying the influence of global, rather than regional, factors on deposition. This suggests that geochemical proxies may be useful in providing additional paleoenvironmental insights and helping to constrain stratigraphic boundaries, particularly in intervals that lack significant lithological or biological change.
Hamiltonian, geometric momentum and force operators for a spin zero particle on a curve: physical approach
Authors: Shikakhwa M. S. , Chair N. 
Published: June 2024

AbstractThe Hamiltonian for a spin zero particle that is confined to a 1D curve embedded in the 3D space is constructed. Confinement is achieved by starting with the particle living in a small tube surrounding the curve, and assuming an infinitely strong normal force that squeezes the thickness of the tube to zero, eventually pinning the particle to the curve. We follow the new approach that we applied to confine a particle to a surface, in that we start with an expression for the 3D momentum operators whose components along and normal to the curve directions are separately Hermitian. The kinetic energy operator expressed in terms of the momentum operator in the normal direction is then a Hermitian operator in this case. When this operator is dropped and the thickness of the tube surrounding the curve is set to zero, one automatically gets the Hermitian curve Hamiltonian that contains the geometric potential term as expected. It is demonstrated that the origin of this potential lies in the ordering or symmetrization of the original 3D momentum operators in order to render them Hermitian. The Hermitian momentum operator for the particle as it is confined to the curve is also constructed and is seen to be similar to what is known as the geometric momentum of a particle confined to a surface in that it has a term proportional to the curvature that is along the normal to the curve. The force operator of the particle on the curve is also derived, and is shown to reduce, for a curve with a constant curvature and torsion, to a -apparently- single component normal to the curve that is a symmetrization of the classical expression plus a quantum term. All the above quantities are then derived for the specific case of a particle confined to a cylindrical helix embedded in 3D space.
RGB LED for Communication, Harvesting and Sensing in IoT Applications
Authors: Mir Muhammad Sarmad Shahab 
Published: June 2024

RGB LED bulbs have entered the market as a promising alternative to traditional phosphor-coating LEDs to meet illumination standards. In this article, we introduce and propose solutions to address the challenges of RGB LED lighting for the Internet of Things applications, performing communication, harvesting energy, and sensing tasks. Through experiments, we demonstrate that we can use RGB LEDs for multiple tasks. We can achieve a bandwidth in the order of 50 kHz and distances of around 3.5 m using commercial RGB LED bulbs as transceivers, without using any dedicated photodetector. RGB LED links are composed of three main colors, and we show that red is the best color both for communicating to another receiving RGB LED bulb, as well as for harvesting with a solar cell; green and blue can instead be exploited for standard-compliant lighting and/or sensing purposes. We evaluate the system in two proofs of concept and provide insights for operating RGB LEDs for multiple tasks including vertical farming.
Facts and Hopes in the Systemic Therapy of Biliary Tract Carcinomas
Authors: Lamarca Angela , Macarulla Teresa 
Published: June 2024

Abstract
Biliary tract cancers (BTC) are a heterogeneous group of cancers that continue to present a particularly poor prognosis. BTC treatment is rapidly evolving yet facing many challenges to improve patient outcomes and maximize benefit from treatment. Only a minority of patients are diagnosed with early-stage disease and are suitable for curative resection. Current surgical strategies are limited by a high relapse rate, and despite extensive efforts focused on adjuvant strategies, the development of more effective adjuvant strategies remains a challenge. In addition, the role of locoregional strategies, liver transplant, and neoadjuvant treatment remains unclear. Systemic treatment in the advanced setting is based on three main pillars: first, cytotoxic chemotherapy options; second, the addition of immunotherapy to chemotherapy; and third, targeted therapies. The role of targeted therapies is oriented by many promising targets, including IDH1 mutations, FGFR2 fusions, BRAF-V600E mutations, and HER2 amplifications. The aim of this review is to provide an overview of current facts and future hopes in the management of BTC, including an overview of the unmet need, and particularly focus on systemic therapies.
Maximizing Treatment Opportunities: Assessing Protocol Waivers’ Impact on Safety and Outcome in the Drug Rediscovery Protocol
Authors: van Berge Henegouwen Jade M. , Zeverijn Laurien J. , Geurts Birgit S. , Hoes Louisa R. , van der Wijngaart Hanneke , van der Noort Vincent , Huitema Alwin D.R. , de Vos Filip Y.F. , Grünberg Katrien , Bloemendal Haiko J. , Verheul Henk M.W. , Voest Emile E. , Gelderblom Hans 
Published: June 2024

Abstract

Purpose:
Although eligibility criteria are essential in trial design, overly restrictive criteria contribute to low accrual and limited generalizability. To enhance trial inclusivity, there has been growing interest in broadening eligibility criteria, especially for patients with advanced or treatment-refractory disease. Yet, the impact on patient safety remains uncertain. In the Drug Rediscovery Protocol (DRUP), protocol exceptions are frequently requested and occasionally granted. Here we describe the impact of these waivers on treatment safety and efficacy.

Experimental Design:
DRUP is a multicenter, nonrandomized clinical basket trial treating patients with therapy-refractory cancer with molecularly targeted and immunotherapies outside their registered indications (NCT02925234). Here, all granted waivers were revised, analyzed in terms of safety and efficacy outcome, and comparedwithoutcomes of includedpatientswho didnot receive awaiver.

Results:
Between September 1, 2016, and September 1, 2021, protocol waivers were granted for 82 patients (8%) of 1,019 included patients in DRUP. Most waivers (45%) were granted for general- or drug-related eligibility criteria; other categories were out-of-window testing, treatment, and testing exceptions. Serious adverse event rate was similar between patients who received a waiver (pW) and patients who did not (pNW): 39% vs. 41%, respectively (P = 0.81). The clinical benefit (either objective response or stable disease ≥ 16 weeks) rate of pW was 40% versus 33% in pNW (P = 0.43).

Conclusions:
Safety and clinical benefit were preserved in patients for whom a waiver was granted. These data support a more personalized approach in assessing eligibility criteria, especially in trials with widely used and approved drugs accruing patients without other treatment options.
See related commentary by Waqar and Govindan, p. 3655
A Dual-Armed Oncolytic Virus Shows Clinical Efficacy in Advanced Solid Cancers
Authors: Silva-Pilipich Noelia , Smerdou Cristian 
Published: June 2024

Summary
An oncolytic adenovirus armed with tumor necrosis factor-α and interleukin-2 was tested in patients with advanced solid tumors. Antitumor effects were observed in both treated and non-treated lesions, leading to long-term survival in some patients. This clinical trial shows the potential of oncolytic virotherapy for patients refractory to standard therapies.
See related article by Pakola et al., p. 3715
Effects of an Intervention to Improve Evidence-Based Care for People With Diabetes and Cardiovascular Disease Across Sex, Race, and Ethnicity Subgroups: Insights From the COORDINATE-Diabetes Trial
Authors: Tannu Manasi , Kaltenbach Lisa , Pagidipati Neha J. , McGuire Darren K. , Aroda Vanita R. , Pop-Busui Rodica , Kondamudi Nitin , Al-Khalidi Hussein R. , Lopes Renato D. , Cavender Matthew A. , Nelson Adam J. , Kirk Julienne , Lingvay Ildiko , Magwire Melissa , Richardson Caroline Regina , Webb Laura , Leyva Monica , Pandey Ambarish , Washington Alana , Pak Jonathan , Gaynor Tanya , Khan Waqar , Weston Patrick , Granger Christopher B. , Green Jennifer 
Published: June 2024

BACKGROUND:
Results from the COORDINATE-Diabetes trial (Coordinating Cardiology Clinics Randomized Trial of Interventions to Improve Outcomes - Diabetes) demonstrated that a multifaceted, clinic-based intervention increased prescription of evidence-based medical therapies to participants with type 2 diabetes and atherosclerotic cardiovascular disease. This secondary analysis assessed whether intervention success was consistent across sex, race, and ethnicity.

METHODS:
COORDINATE-Diabetes, a cluster randomized trial, recruited participants from 43 US cardiology clinics (20 randomized to intervention and 23 randomized to usual care). The primary outcome was the proportion of participants prescribed all 3 groups of evidence-based therapy (high-intensity statin, angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, and sodium-glucose cotransporter-2 inhibitor or glucagon-like peptide 1 receptor agonist) at last trial assessment (6 to 12 months). In this prespecified analysis, mixed-effects logistic regression models were used to assess the outcome by self-reported sex, race, and ethnicity in the intervention and usual care groups, with adjustment for baseline characteristics, medications, comorbidities, and site location.

RESULTS:

Among 1045 participants with type 2 diabetes and atherosclerotic cardiovascular disease, the median age was 70 years, 32% were female, 16% were Black, and 9% were Hispanic. At the last trial assessment, there was an absolute increase in the proportion of participants prescribed all 3 groups of evidence-based therapy in women (36% versus 15%), Black participants (41% versus 18%), and Hispanic participants (46% versus 18%) with the intervention compared with usual care, with consistent benefit across sex (male versus female;
P
interaction
=0.44), race (Black versus White;
P
interaction
=0.59), and ethnicity (Hispanic versus Non-Hispanic;
P
interaction
= 0.78).

CONCLUSIONS:
The COORDINATE-Diabetes intervention successfully improved delivery of evidence-based care, regardless of sex, race, or ethnicity. Widespread dissemination of this intervention could improve equitable health care quality, particularly among women and minority communities who are frequently underrepresented in clinical trials.

REGISTRATION:

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT03936660.
Achieving adherence to positive airway pressure in commercial drivers using an employer-mandated remote management programme
Authors: Kneeland Elizabeth , Ali Nadia , Maislin David G. , Chang Yoon Hee , Epelboim Joyce , Keenan Brendan T. , Pack Allan I. 
Published: June 2024

BackgroundObstructive sleep apnoea (OSA) is common in commercial drivers, and associated with increased risk of crashes if untreated, making diagnosis and effective treatment crucial in this population.Study design and methodsThis is a retrospective summary of a clinical programme based on telemedicine and remote treatment monitoring developed with a national trucking company to screen new hires in the USA for OSA and implement positive airway pressure (PAP) management. New hires were informed of the programme and consented as part of their employment. Drivers who did not comply with the evaluation or with PAP after diagnosis were removed from driving commercial vehicles by the company or did not pursue further employment.ResultsA total of 975 drivers were enrolled. Among screened drivers, 35.5% were cleared without a sleep study, 15.0% were cleared following a sleep study (apnoea–hypopnoea index (AHI) <5 events·h−1), 22.1% had mild OSA (AHI 5–15) and 27.4% had moderate–severe OSA (AHI ≥15). Those with moderate–severe OSA were more obese (body mass index 36.2±6.3 kg·m−2) and had more comorbidities. Of 269 drivers starting PAP, 160 (59.5%) maintained participation in a care management programme, 80 (29.7%) resigned or were terminated, 23 (8.6%) were cleared to discontinue PAP and six (2.2%) were complex cases requiring transfer of care. Illustrating effectiveness, those that maintained participation had excellent PAP adherence (5.27±1.61 h·night−1; 88.5±12.9% days used; 79.7±17.7% days used ≥4 h).InterpretationRemote assessment of OSA and PAP management in commercial drivers is feasible and effective. This approach has wide-ranging applications, particularly in populations and areas with a lack of sleep medicine providers.
Assessing post-COVID-19 respiratory dynamics: a comprehensive analysis of pulmonary function, bronchial hyperresponsiveness and bronchodilator response
Authors: Huang Chun-Yao , Wu Yao-Kuang , Yang Mei-Chen , Huang Kuo-Liang , Su Wen-Lin , Huang Yi-Chih , Chih-Wei Wu , Tzeng I-Shiang , Lan Chou-Chin 
Published: June 2024

BackgroundCoronavirus disease 2019 (COVID-19) has a considerable impact on the global healthcare system. Individuals who have recovered from COVID often experience chronic respiratory symptoms that affect their daily lives. This study aimed to assess respiratory dynamics such as airway hyperresponsiveness (AHR) and bronchodilator response in post-COVID patients.MethodsThis study included 282 adults with respiratory symptoms who underwent provocation tests. The demographic details, clinical symptoms and medical histories were recorded. Baseline spirometry, methacholine challenge tests (MCT) and post-bronchodilator spirometry were performed. Patients were divided into the following four groups: Group 1: non-COVID-19 and negative MCT; Group 2: post-COVID-19 and negative MCT; Group 3: non-COVID-19 and positive MCT; and Group 4: post-COVID-19 and positive MCT.ResultsMost post-COVID-19 patients (43.7%) experienced AHR, and wheezing was more common. Patients in Group 4 exhibited increased intensities of dyspnoea, cough and wheezing with the lowest pulmonary function test (PFT) parameters at baseline. Moreover, significant decreases in PFT parameters after the MCT were observed in these patients. Although the prevalence of a low forced expiratory volume in 1 s to forced vital capacity ratio (<70%) was initially 2% in Group 4, it increased to 29% after MCT. No significant differences in allergic history or underlying diseases were observed between the groups.ConclusionsThese findings provide comprehensive insights into the AHR and respiratory symptoms of post-COVID-19 individuals, highlighting the characteristics and potential exacerbations in patients with positive MCT results. This emphasises the need of MCT to address respiratory dynamics in post-COVID-19 individuals.
The noninvasive ventilation outcomes score in patients requiring NIV for COPD exacerbation without prior evidence of airflow obstruction
Authors: Lane Nicholas D. , Hartley Tom M. , Steer John , Bourke Stephen C. 
Published: June 2024

IntroductionExacerbation of COPD complicated by respiratory acidaemia is the commonest indication for noninvasive ventilation (NIV). The NIV outcomes (NIVO) score offers the best estimate of survival for those ventilated. Unfortunately, two-thirds of cases of COPD are unrecognised, and patients may present without COPD having been confirmed by spirometry.MethodsIn the 10-centre NIVO validation study there was no pre-admission spirometry in 111 of 844 consecutive patients (termed “clinical diagnosis” patients). We compared the performance of the NIVO, DECAF and CURB-65 scores for in-hospital mortality in the clinical diagnosis cohort. Usual clinical practice was not influenced, but confirmation of COPD in the year following discharge was captured.ResultsIn the clinical diagnosis cohort, in-hospital mortality was 19.8% and rose incrementally across the NIVO risk categories, consistent with the NIVO validation cohort. NIVO showed good discrimination in the clinical diagnosis cohort: area under the receiver operating curve 0.724,versus0.79 in the NIVO validation cohort. At 1 year after discharge, 41 of 89 clinical diagnosis patients had undertaken diagnostic spirometry; 33 of 41 had confirmation of airflow obstruction (forced expiratory volume in 1 s/(forced) vital capacity <0.7), meaning the diagnosis of COPD was incorrect in 19.5% of cases.DiscussionThese data support the use of the NIVO score in patients with a “clinical diagnosis” of COPD. NIVO can help guide shared decision-making, assess risk-adjusted outcomes by centre and challenge prognostic pessimism. Accurate diagnosis is critical to ensure that acute and long-term treatment is optimised; this study highlights failings in the follow-up of such patients.
Lipomatous hypertrophy of the interatrial septum: a distinct adipose tissue type in COPD?
Authors: Lacaita Pietro G. , Kindl Benedikt , Plank Fabian , Beyer Christoph , Bilgeri Valentin , Barbieri Fabian , Senoner Thomas , Dichtl Wolfgang , Tancevski Ivan , Swoboda Michael , Luger Anna , Deeg Johannes , Widmann Gerlig , Feuchtner Gudrun M. 
Published: June 2024

ObjectiveLipomatous hypertrophy of the interatrial septum (LHIS) is a distinct section of epicardial adipose tissue. However, its association with COPD is poorly documented.MethodsPatients undergoing coronary computed tomography angiography (CTA) for clinical indications were recruited retrospectively and screened for LHIS and COPD. LHIS density and the coronary artery disease profile were quantified by CTA: stenosis severity (coronary artery disease radiological reporting system (CADRADS)), coronary artery calcium (CAC) and high-risk plaque (HRP). COPD patients with LHIS were matched for age and sex, the major cardiovascular risk factors (CVRFs), and compared to controls.ResultsThe prevalence of LHIS in all 5466 patients was 5.9%. 151 (72.6%) of 208 patients with COPD had LHIS. LHIS density in COPD patients was higher (−10.93 HUversus−21.1 HU; p<0.001), despite body mass index (BMI) (28.8versus27.01 kg·m−2; p=0.002) being lower. LHIS density was lower in obese (BMI >30 kg·m−2) patients (20.4versus13.6 HU; p=0.02). BMI was inversely correlated with LHIS density (BetaR −0.031; 95% CI: −0.054– −0.008; p=0.007). LHIS density was associated with COPD, but not with BMI on multivariate models. CAC and coronary stenosis severity (CADRADS and >50% stenosis) were not different (p=0.106, p=0.156 and p=0.350, respectively). HRPs were observed more frequently in COPD patients with severe Global Initiative for Chronic Obstructive Lung Disease (GOLD) stages ≥2 (32.3%versus20.1%; p=0.044), but not when adding mild GOLD stages.ConclusionsThe prevalence of LHIS in COPD patients is high (72.6%), and the adipose tissue density is higher, indicating a higher brown fat component. In obese, patients LHIS density is lower and declines along with BMI. Coronary stenosis severity and calcium were not different; however HRPs were more frequent in severe COPD.