bluuebunny/crossref_metadata_2025_split huggingface dataset:
Innovators’ views on involving users and patients in surgical device development: a qualitative interview study
Authors: Woudstra Kas , Tummers Marcia , Rovers Maroeska M , Reuzel Rob 
Published: August 2021

ObjectivesInvolving end-users and patients in the development of surgical devices, even when patients are not end-users, is deemed important in policy and in academia since it could improve strategic choices in research and development (R&D). Nonetheless, research into innovators’ views on end-user and patient involvement is rare. This study explores what end-users and patients are being involved by innovators during development, what methods for involvement are being used and what topics are being discussed with these end-users and patients.DesignA qualitative study featuring semi-structured interviews with innovators of surgical devices. Interviews were recorded and a thematic analysis was performed on verbatim transcripts.Participants15 interviews were conducted with 19 innovators of 14 surgical devices.SettingInnovation practices of surgical devices in the Netherlands and Belgium.ResultsEnd-users were engaged in R&D with formal methods and in unsystematic ways. These users all work in the clinical domain, for example, as surgeons or nurses. The innovators engaged users to analyse problems for which a device could be a solution, define functionalities, make design choices, analyse usability, ensure safety and improve aesthetics. Patients were rarely involved. Innovators stated that patients are not considered to be end-users, that physicians can represent patient interests and that involving patients is unethical as false expectations could be raised.ConclusionInnovators involve end-users with methods and unsystematic ways in the development of surgical devices. Despite governmental calls for patient involvement in the development of medical devices and surgical devices, innovators do not generally involve patients.
Remote ischaemic conditioning in ST elevation myocardial infarction: a registry-based randomised trial
Authors: Bainey Kevin R , Zheng Yinggan , Coulden Richard , Sonnex Emer , Thompson Richard , Mei Junyi , Bastiany Alexandra , Welsh Robert 
Published: August 2021

ObjectivesRemote ischaemic conditioning (RIC) has been tested as a possible strategy for mitigating reperfusion injury in ST elevation myocardial infarction (STEMI) with primary percutaneous coronary intervention (PPCI). However, surrogate outcomes have shown inconsistent effects with lack of clinical correlation.MethodsWe performed a registry-based randomised study of patients with STEMI allocated to RIC (4 cycles of blood pressure cuff inflation to 200 mm Hg for 5 min of ischaemia followed by 5 min of reperfusion) or standard of care (SOC) during PPCI. We examined the associations of RIC on core laboratory measurements of myocardial perfusion, infarct size (IS), left ventricular (LV) performance and clinical outcomes.ResultsA total of 252 patients were enrolled. The median age was 61 (IQR: 55–70) years and 72.8% were male. Sum ST segment deviation resolution ≥50% was similar between RIC and SOC (65.2% vs 55.7%, p=0.269). In those with 3-day cardiovascular MRI (n=88), no difference in median (25th, 75th percentiles) IS (14.9% (4.5%, 23.1%) vs 16.1% (3.3%, 22.0%), p=0.980), LV dimensions (LV end-diastolic volume index: 78.7 (71.1, 91.2) mL/m2 vs 79.9 (71.2, 88.8) mL/m2, p=0.630; LV end-systolic volume index: 48.8 (35.7, 51.4) mL/m2 vs 37.9 (31.8, 47.5) mL/m2, p=0.551) or ejection fraction (50.0% (41.0%–55.0%) vs 50.0% (43.0%–56.0%), p=0.554) was demonstrated. Similar results were observed with 90-day cardiovascular MRI. At 1 year, the clinical composite of death, congestive heart failure, cardiogenic shock and recurrent myocardial infarction was similar in RIC and SOC (21.7% vs 13.3%, p=0.110).ConclusionsIn a contemporary registry-based randomised study of patients with STEMI undergoing PPCI, adjunctive therapy with RIC did not improve myocardial perfusion, reduce IS or alter LV performance. Consequently, there was no difference in clinical outcomes within 1 year.Trial registration numberNCT03930589.
Lung and extrathoracic cancer incidence among underground uranium miners exposed to radon progeny in the Příbram region of the Czech Republic: a case–cohort study
Authors: Kelly-Reif Kaitlin , Sandler Dale P , Shore David , Schubauer-Berigan Mary , Troester Melissa , Nylander-French Leena , Richardson David B 
Published: August 2021

ObjectivesRadon is carcinogenic, but more studies are needed to understand relationships with lung cancer and extrathoracic cancers at low exposures. There are few studies evaluating associations with cancer incidence or assessing the modifying effects of smoking.MethodsWe conducted a case–cohort study with 16 434 underground uranium miners in the Czech Republic with cancer incidence follow-up 1977–1996. Associations between radon exposure and lung cancer, and extrathoracic cancer, were estimated with linear excess relative rate (ERR) models. We examined potential modifying effects of smoking, time since exposure and exposure rate.ResultsUnder a simple ERR model, assuming a 5-year exposure lag, the estimated ERR of lung cancer per 100 working level months (WLM) was 0.54 (95% CI 0.33 to 0.83) and the estimated ERR of extrathoracic cancer per 100 WLM was 0.07 (95% CI −0.17 to 0.72). Most lung cancer cases were observed among smokers (82%), and the estimated ERR of lung cancer per 100 WLM was larger among smokers (ERR/100 WLM=1.35; 95% CI 0.84 to 2.15) than among never smokers (ERR/100 WLM=0.12; 95% CI −0.05 to 0.49). Among smokers, the estimated ERR of lung cancer per 100 WLM decreased with time since exposure from 3.07 (95% CI −0.04 to 10.32) in the period 5–14 years after exposure to 1.05 (95% CI 0.49 to 1.87) in the period 25+ years after exposure.ConclusionsWe observed positive associations between cumulative radon exposure and lung cancer, consistent with prior studies. We observed a positive association between cumulative radon exposure and extrathoracic cancers, although the estimates were small. There was evidence that the association between radon and lung cancer was modified by smoking in a multiplicative or super-multiplicative fashion.
Airflow obstruction, impaired lung function and risk of sudden cardiac death: a prospective cohort study
Authors: Cheng Yun-Jiu , Chen Zhen-Guang , Yao Feng-Juan , Liu Li-Juan , Zhang Ming , Wu Su-Hua 
Published: August 2021

BackgroundGrowing evidence suggests that compromised lung health may be linked to cardiovascular disease. However, little is known about its association with sudden cardiac death (SCD).ObjectivesWe aimed to assess the link between impaired lung function, airflow obstruction and risk of SCD by race and gender in four US communities.MethodsA total of 14 708 Atherosclerosis Risk in Communities (ARIC) study participants who underwent spirometry and were asked about lung health (1987–1989) were followed. The main outcome was physician-adjudicated SCD. Fine-Gray proportional subdistribution hazard models with Firth’s penalised partial likelihood correction were used to estimate the HRs.ResultsOver a median follow-up of 25.4 years, 706 (4.8%) subjects experienced SCD. The incidence of SCD was inversely associated with FEV1in each of the four race and gender groups and across all smoking status categories. After adjusting for multiple measured confounders, HRs of SCD comparing the lowest with the highest quintile of FEV1were 2.62 (95% CI 1.62 to 4.26) for white males, 1.80 (95% CI 1.03 to 3.15) for white females, 2.07 (95% CI 1.05 to 4.11) for black males and 2.62 (95% CI 1.21 to 5.65) for black females. The above associations were consistently observed among the never smokers. Moderate to very severe airflow obstruction was associated with increased risk of SCD. Addition of FEV1significantly improved the predictive power for SCD.ConclusionsImpaired lung function and airflow obstruction were associated with increased risk of SCD in general population. Additional research to elucidate the underlying mechanisms is warranted.
Strategic and contested use of food laws to ban smokeless tobacco products in India: a qualitative analysis of litigation
Authors: Dsouza Riddhi , Bhojani Upendra 
Published: August 2021

ObjectiveTo understand how food laws are used, contested and interpreted to ban certain forms of chewing tobacco in India.MethodsA qualitative study analysing all the tobacco-related litigation under the food laws in India. We used an inductive thematic analysis of the litigation contents.ResultsThe tobacco industry systematically deployed litigation to (1) challenge the categorisation of smokeless tobacco products as food, and hence, questioned the use of food laws for regulating these products; (2) challenge the regulatory power of the state government in banning tobacco products via the food laws; and (3) challenge the applicability of the general food laws that enabled stricter regulations beyond what is prescribed under the tobacco-specific law.ConclusionDespite facing several legal challenges from the tobacco industry, Indian states optimised food laws to enable stricter regulations on smokeless tobacco products than were feasible through use of a tobacco-specific law.
Growth and morphological responses of gerbera seedlings to narrow-band lights with different light spectral combinations as sole-source lighting in a controlled environment
Authors: Kamath Devdutt , Kong Yun , Dayboll Chevonne , Blom Theo , Zheng Youbin 
Published: August 2021

To optimize light-emitting diode (LED) spectral recipes for gerbera (Gerbera jamesonii) seedling propagation, seed germination and seedling morphology, biomass, flowering, and storage quality were observed in four cultivars, ‘Midi Dark Purple’, ‘Majorette Red Dark Eye’, ‘Maxi Pink’, and ‘Maxi White’, under six spectrum treatments: (1) FL, cool white fluorescent light; (2) RB, a photon flux ratio of 85% red and 15% blue (RB-LED); (3) RB + UVB, RB-LED combined with 0.5 μmol·m−2·s−1 of ultraviolet-B; (4) RB + UVA, RB-LED combined with 9.6 μmol·m−2·s−1 of ultraviolet-A; (5) RB + G, a photon flux ratio of 60% red, 15% blue, and 25% green; (6) RB + FR, RB-LED combined with 17.3 μmol·m−2·s−1 of far-red. For all treatments, the photosynthetic photon flux density was 165 μmol·m−2·s−1 under a 16-h photoperiod. Seedling growth and morphology were similar under FL and RB for all cultivars, except for a wider canopy of ‘Majorette Red Dark Eye’ under RB. Each of the tri-chromatic light treatments (i.e., RB + UVB, RB + UVA, RB + G or RB + FR) showed similar effects as RB, except for thicker ‘Maxi Pink’ stems under RB + FR. Furthermore, the quality index, an integrated evaluation of seedling quality, was similar under all the treatments for each cultivar. Given the similar seedling quality and the advantages of LEDs, RB-LED can potentially replace FL for controlled-environment gerbera seedling production, but the tri-chromatic lights tested in this study appear to be unnecessary.
The peculiar Jeans length
Authors: Tsagas Christos G. 
Published: August 2021

AbstractTypical observers in the universe do not follow the smooth Hubble expansion, but move relative to it. Such bulk peculiar motions introduce a characteristic scale that is closely analogous to the familiar Jeans length. This “peculiar Jeans length” marks the threshold below which relative-motion effects dominate the linear kinematics. There, cosmological measurements can vary considerably between the bulk-flow frame and that of the Hubble expansion, entirely due to the observers’ relative motion. When dealing with the deceleration parameter, we find that the peculiar Jeans length varies between few and several hundred Mpc. On these scales, the deceleration parameter measured by the bulk-flow observers can be considerably larger (or smaller) than its Hubble-frame counterpart. This depends on whether the peculiar motion is locally expanding (or contracting), relative to the background expansion. Then, provided expanding and contracting bulk flows are randomly distributed, nearly half of the observers in the universe could be misled to think that their cosmos is over-decelerated. The rest of them, on the other hand, may come to believe that their universe is under-decelerated, or even accelerated in some cases. We make two phenomenological predictions that could in principle support this scenario.
Two-sided constraints on Lorentz invariance violation from Tibet-AS$$\gamma $$ and LHAASO very-high-energy photon observations
Authors: Satunin Petr 
Published: August 2021

AbstractWe present new two-sided constraints on the Lorentz Invariance violation energy scale for photons with quartic dispersion relation from recent gamma ray observations by the Tibet-AS$$\gamma $$
γ
and LHAASO experiments. The constraints are based on the consideration of the processes of photon triple splitting (superluminal scenario) and the suppression of shower formation (subluminal). The constraints in the subluminal scenario are better than the pair production constraints and are the strongest in the literature.
Well-posedness in weighted spaces for the generalized Hartree equation with p < 2
Authors: Arora Anudeep K. , Riaño Oscar , Roudenko Svetlana 
Published: August 2021

We investigate the well-posedness in the generalized Hartree equation [Formula: see text], [Formula: see text], [Formula: see text], for low powers of nonlinearity, [Formula: see text]. We establish the local well-posedness for a class of data in weighted Sobolev spaces, following ideas of Cazenave and Naumkin, Local existence, global existence, and scattering for the nonlinear Schrödinger equation, Comm. Contemp. Math. 19(2) (2017) 1650038. This crucially relies on the boundedness of the Riesz transform in weighted Lebesgue spaces. As a consequence, we obtain a class of data that exists globally, moreover, scatters in positive time. Furthermore, in the focusing case in the [Formula: see text]-supercritical setting we obtain a subset of locally well-posed data with positive energy, which blows up in finite time.
Cheap IR evaluation
Authors: Roitero Kevin 
Published: August 2021

To evaluate Information Retrieval (IR) effectiveness, a possible approach is to use test collections, which are composed of a collection of documents, a set of description of information needs (called topics), and a set of relevant documents to each topic. Test collections are modelled in a competition scenario: for example, in the well known TREC initiative, participants run their own retrieval systems over a set of topics and they provide a ranked list of retrieved documents; some of the retrieved documents (usually the first ranked) constitute the so called pool, and their relevance is evaluated by human assessors; the document list is then used to compute effectiveness metrics and rank the participant systems. Private Web Search companies also run their in-house evaluation exercises; although the details are mostly unknown, and the aims are somehow different, the overall approach shares several issues with the test collection approach.
The aim of this work is to: (i) develop and improve some state-of-the-art work on the evaluation of IR effectiveness while saving resources, and (ii) propose a novel, more principled and engineered, overall approach to test collection based effectiveness evaluation.
In this thesis we focus on three main directions: the first part details the usage of few topics (i.e., information needs) in retrieval evaluation and shows an extensive study detailing the effect of using fewer topics for retrieval evaluation in terms of number of topics, topics subsets, and statistical power. The second part of this thesis discusses the evaluation without relevance judgements, reproducing, extending, and generalizing state-of-the-art methods and investigating their combinations by means of data fusion techniques and machine learning. Finally, the third part uses crowdsourcing to gather relevance labels, and in particular shows the effect of using fine grained judgement scales; furthermore, explores methods to transform judgements between different relevance scales.

Awarded by:
University of Udine, Udine, Italy on 19 March 2020.

Supervised by:
Professor Stefano Mizzaro.

Available at:
https://kevinroitero.com/resources/kr-phd-thesis.pdf.
Datopotamab Deruxtecan, a Novel TROP2-directed Antibody–drug Conjugate, Demonstrates Potent Antitumor Activity by Efficient Drug Delivery to Tumor Cells
Authors: Okajima Daisuke , Yasuda Satoru , Maejima Takanori , Karibe Tsuyoshi , Sakurai Ken , Aida Tetsuo , Toki Tadashi , Yamaguchi Junko , Kitamura Michiko , Kamei Reiko , Fujitani Tomomichi , Honda Tomoyo , Shibutani Tomoko , Muramatsu Sumie , Nakada Takashi , Goto Riki , Takahashi Shu , Yamaguchi Miki , Hamada Hirofumi , Noguchi Yutaka , Murakami Masato , Abe Yuki , Agatsuma Toshinori 
Published: August 2021

AbstractTrophoblast cell surface antigen 2 (TROP2) is highly expressed on various epithelial tumors and correlates with poor prognosis. We developed the novel TROP2-directed antibody–drug conjugate (ADC), datopotamab deruxtecan (Dato-DXd, DS-1062a), with a potent DNA topoisomerase I inhibitor (DXd), and evaluated its antitumor activity and safety profiles in preclinical models.The pharmacologic activity and mechanism of action of Dato-DXd were investigated in several human cancer cell lines and xenograft mouse models including patient-derived xenograft (PDX) models. Safety profiles were also assessed in rats and cynomolgus monkeys.Dato-DXd bound specifically to TROP2 and was internalized into tumor cells followed by intracellular trafficking to lysosome and DXd release, which induced DNA damage and apoptosis in TROP2-expressing tumor cells in vitro. Dato-DXd exhibited in vivo antitumor activity with DNA damage induced by the accumulated DXd in TROP2-expressing xenograft tumors, but neither isotype control IgG-ADC nor anti-TROP2 antibody had this effect. Dato-DXd also showed potent antitumor activity with tumor regression in several TROP2-expressing xenograft tumors including NSCLC PDX models. Safety profiles of Dato-DXd in rats and cynomolgus monkeys were acceptable.Dato-DXd demonstrated potent antitumor activity against TROP2-expressing tumors by efficient payload delivery into tumors and acceptable safety profiles in preclinical models. These results suggest Dato-DXd could be a valuable treatment option for patients with TROP2-expressing tumors in the clinical setting.
Spatiotemporal Immune Landscape of Colorectal Cancer Liver Metastasis at Single-Cell Level
Authors: Wu Yingcheng , Yang Shuaixi , Ma Jiaqiang , Chen Zechuan , Song Guohe , Rao Dongning , Cheng Yifei , Huang Siyuan , Liu Yifei , Jiang Shan , Liu Jinxia , Huang Xiaowu , Wang Xiaoying , Qiu Shuangjian , Xu Jianmin , Xi Ruibin , Bai Fan , Zhou Jian , Fan Jia , Zhang Xiaoming , Gao Qiang 
Published: August 2021

Abstract

Liver metastasis, the leading cause of colorectal cancer mortality, exhibits a highly heterogeneous and suppressive immune microenvironment. Here, we sequenced 97 matched samples by using single-cell RNA sequencing and spatial transcriptomics. Strikingly, the metastatic microenvironment underwent remarkable spatial reprogramming of immunosuppressive cells such as MRC1+ CCL18+ M2-like macrophages. We further developed scMetabolism, a computational pipeline for quantifying single-cell metabolism, and observed that those macrophages harbored enhanced metabolic activity. Interestingly, neoadjuvant chemotherapy could block this status and restore the antitumor immune balance in responsive patients, whereas the nonresponsive patients deteriorated into a more suppressive one. Our work described the immune evolution of metastasis and uncovered the black box of how tumors respond to neoadjuvant chemotherapy.

Significance:
We present a single-cell and spatial atlas of colorectal liver metastasis and found the highly metabolically activated MRC1+ CCL18+ M2-like macrophages in metastatic sites. Efficient neoadjuvant chemotherapy can slow down such metabolic activation, raising the possibility to target metabolism pathways in metastasis.
This article is highlighted in the In This Issue feature, p. 1
Early Preventive Treatment With Enalapril Improves Cardiac Function and Delays Mortality in Mice With Arrhythmogenic Right Ventricular Cardiomyopathy Type 5
Authors: Domínguez Fernando , Lalaguna Laura , López-Olañeta Marina , Villalba-Orero María , Padrón-Barthe Laura , Román Marta , Bello-Arroyo Elísabet , Briceño Ana , Gonzalez-Lopez Esther , Segovia-Cubero Javier , García-Pavía Pablo , Lara-Pezzi Enrique 
Published: August 2021

Background:

Arrhythmogenic right ventricular cardiomyopathy type 5 (ARVC5) is an inherited cardiac disease with complete penetrance and an aggressive clinical course caused by mutations in
TMEM43
(transmembrane protein 43). There is no cure for ARVC5 and palliative treatment is started once the phenotype is present. A transgenic mouse model of ARVC5 expressing human TMEM43-S358L (TMEM43mut) recapitulates the human disease, enabling the exploration of preventive treatments. The aim of this study is to determine whether preventive treatment with heart failure drugs (β-blockers, ACE [angiotensin-converting enzyme] inhibitors, mineralocorticoid-receptor antagonists) improves the disease course of ARVC5 in TMEM43mut mice.

Methods:
TMEM43mut male/female mice were treated with metoprolol (β-blockers), enalapril (ACE inhibitor), spironolactone (mineralocorticoid-receptor antagonist), ACE inhibitor + mineralocorticoid-receptor antagonist, ACE inhibitor + mineralocorticoid-receptor antagonist + β-blockers or left untreated. Drugs were initiated at 3 weeks of age, before ARVC5 phenotype, and serial ECG and echocardiograms were performed.

Results:

TMEM43mut mice treated with enalapril showed a significantly increased median survival compared with untreated mice (26 versus 21 weeks;
P
=0.003). Enalapril-treated mice also exhibited increased left ventricular ejection fraction at 4 months compared with controls (37.0% versus 24.9%;
P
=0.004), shorter QRS duration and reduced left ventricle fibrosis. Combined regimens including enalapril also showed positive effects. Metoprolol decreased QRS voltage prematurely and resulted in a nonsignificant decrease in left ventricular ejection fraction compared with untreated TMEM43mut mice.

Conclusions:
Preventive enalapril-based regimens reduced fibrosis, improved ECG, echocardiographic parameters and survival of ARVC5 mice. Early metoprolol did not show positive effects and caused premature ECG abnormalities. Our findings pave the way to consider prophylactic enalapril in asymptomatic ARVC5 genetic carriers.