bluuebunny/crossref_metadata_2025_split huggingface dataset:
Does real-time artificial intelligence-based visual pathology enhancement of three-dimensional optical coherence tomography scans optimise treatment decision in patients with nAMD? Rationale and design of the RAZORBILL study
Authors: Holz Frank G , Abreu-Gonzalez Rodrigo , Bandello Francesco , Duval Renaud , O'Toole Louise , Pauleikhoff Daniel , Staurenghi Giovanni , Wolf Armin , Lorand Daniel , Clemens Andreas , Gmeiner Benjamin 
Published: August 2021

Background/rationaleArtificial intelligence (AI)-based clinical decision support tools, being developed across multiple fields in medicine, need to be evaluated for their impact on the treatment and outcomes of patients as well as optimisation of the clinical workflow. TheRAZORBILLstudy will investigate the impact of advanced AI segmentation algorithms on the disease activity assessment in patients with neovascular age-related macular degeneration (nAMD) by enriching three-dimensional (3D) retinal optical coherence tomography (OCT) scans with automated fluid and layer quantification measurements.MethodsRAZORBILLis an observational, multicentre, multinational, open-label study, comprising two phases: (a) clinical data collection (phase I): an observational study design, which enforces neither strict visit schedule nor mandated treatment regimen was chosen as an appropriate design to collect data in a real-world clinical setting to enable evaluation inphase IIand (b) OCT enrichment analysis (phase II): de-identified 3D OCT scans will be evaluated for disease activity. Within this evaluation, investigators will review the scans once enriched with segmentation results (i.e., highlighted and quantified pathological fluid volumes) and once in its original (i.e., non-enriched) state. This review will be performed using an integrated crossover design, where investigators are used as their own controls allowing the analysis to account for differences in expertise and individual disease activity definitions.ConclusionsIn order to apply novel AI tools to routine clinical care, their benefit as well as operational feasibility need to be carefully investigated.RAZORBILLwill inform on the value of AI-based clinical decision support tools. It will clarify if these can be implemented in clinical treatment of patients with nAMD and whether it allows for optimisation of individualised treatment in routine clinical care.
Determinants of poor inhaler technique and poor therapy adherence in obstructive lung diseases: a cross-sectional study in community pharmacies
Authors: Vanoverschelde Anna , van der Wel Paulien , Putman Barbara , Lahousse Lies 
Published: August 2021

BackgroundCorrect inhaler use can be challenging in real life, with incorrect use resulting in poor symptom control. The aim of this study was to examine factors associated with poor inhaler technique and poor therapy adherence among patients with obstructive lung disease in community pharmacies.MethodsA cross-sectional study was conducted in patients with obstructive lung diseases in nine Belgian community pharmacies. Logistic regression analyses identified factors associated with poor inhaler technique and poor therapy adherence (assessed by the Test of Adherence to Inhalers and the modified Medication Possession Ratio).ResultsSeventy obstructively impaired community patients (median age 64 y, 56% females) were included and the technique of 122 inhalers was assessed. Inhaler technique scored generally poor, with half of patients making critical errors in using at least one of their inhalers. In multivariable analysis, the use of multiple devices (adjusted OR, aOR 11.68; 95% CI 3.29 to 41.51) and a diagnosis of asthma-Chronic Obstructive Pulmonary Disease overlap (ACO; aOR 7.06; 95% CI 1.15 to 43.35), were associated with making critical errors in inhaler technique independent of quality of life. Non-adherence occurred in more than one-third of patients, and occurred in up to one half of the patients when also taking overuse into account. In multivariable analysis for therapy adherence, current smoking was associated with poor therapy adherence (aOR 0.15; 95% CI 0.02 to 0.96) independently of age and poor treatment knowledge. Therapy adherence was poor in patients with asthma compared with those with ACO. Current smokers and highly educated patients seemed to be at increased risk for inhaler overuse.ConclusionsGiven the important role of a correct inhaler technique and therapy adherence in disease control, these findings emphasise the need for patient education and aiming uniformity in the inhaler device.Trial registration numberB670201835229.
Can categorised values of maximal oxygen uptake discriminate patterns of exercise dysfunction in pectus excavatum: a prospective cohort study?
Authors: Satur Christopher M R , Cliff Ian , Watson Nicholas 
Published: August 2021

Cohort studies of patients with pectus excavatum have inadequately characterised exercise dysfunction experienced. Cardiopulmonary exercise test data were delineated by maximal oxygen uptake values >80%, which was tested to examine whether patterns of exercise physiology were distinguished.MethodsSeventy-two patients considered for surgical treatment underwent assessment of pulmonary function and exercise physiology with pulmonary function tests and cardiopulmonary exercise test between 2006 and 2019. Seventy who achieved a threshold respiratory gas exchange ratio of >1.1 were delineated by maximal oxygen uptake>80%, (group A, n=33) and <80% (group B, n=37) and comparison of constituent physiological parameters performed.ResultsThe cohort was 20.8 (±SD 6.6) years of age, 60 men, with a Haller’s Index of 4.1 (±SD 1.4). Groups A and B exhibited similar demography, pulmonary function test results and Haller’s index values. Exercise test parameters of group B were lower than group A; work 79.2% (±SD 11.3) versus 97.7 (±SD 10.1), anaerobic threshold 38.1% (±SD 7.8) versus 49.7% (±SD 9.1) and O2pulse 77.4% (±SD 9.8) versus 101.8% (±SD 11.7), but breathing reserve was higher, 54.9% (±SD 13.1) versus 44.2% (±SD 10.8), p<0.001 for each. Both groups exhibited similar incidences of carbon dioxide retention at peak exercise. A total of 65 (93%) exhibited abnormal values of at least one of four exercise test measures.ConclusionThis study showed that patients with pectus excavatum exhibited multiple physiological characteristics of compromised exercise function. It is the first study that defines differing patterns of exercise dysfunction and provides evidence that patients with symptomatic pectus excavatum should be considered for surgical treatment.
Novel oncolytic adenovirus expressing enhanced cross-hybrid IgGA Fc PD-L1 inhibitor activates multiple immune effector populations leading to enhanced tumor killing in vitro, in vivo and with patient-derived tumor organoids
Authors: Hamdan Firas , Ylösmäki Erkko , Chiaro Jacopo , Giannoula Yvonne , Long Maeve , Fusciello Manlio , Feola Sara , Martins Beatriz , Feodoroff Michaela , Antignani Gabriella , Russo Salvatore , Kari Otto , Lee Moon Hee , Järvinen Petrus , Nisen Harry , Kreutzman Anna , Leusen Jeanette , Mustjoki Satu , McWilliams Thomas G , Grönholm Mikaela , Cerullo Vincenzo 
Published: August 2021

BackgroundDespite the success of immune checkpoint inhibitors against PD-L1 in the clinic, only a fraction of patients benefit from such therapy. A theoretical strategy to increase efficacy would be to arm such antibodies with Fc-mediated effector mechanisms. However, these effector mechanisms are inhibited or reduced due to toxicity issues since PD-L1 is not confined to the tumor and also expressed on healthy cells. To increase efficacy while minimizing toxicity, we designed an oncolytic adenovirus that secretes a cross-hybrid Fc-fusion peptide against PD-L1 able to elicit effector mechanisms of an IgG1 and also IgA1 consequently activating neutrophils, a population neglected by IgG1, in order to combine multiple effector mechanisms.MethodsThe cross-hybrid Fc-fusion peptide comprises of an Fc with the constant domains of an IgA1 and IgG1 which is connected to a PD-1 ectodomain via a GGGS linker and was cloned into an oncolytic adenovirus. We demonstrated that the oncolytic adenovirus was able to secrete the cross-hybrid Fc-fusion peptide able to bind to PD-L1 and activate multiple immune components enhancing tumor cytotoxicity in various cancer cell lines, in vivo and ex vivo renal-cell carcinoma patient-derived organoids.ResultsUsing various techniques to measure cytotoxicity, the cross-hybrid Fc-fusion peptide expressed by the oncolytic adenovirus was shown to activate Fc-effector mechanisms of an IgA1 (neutrophil activation) as well as of an IgG1 (natural killer and complement activation). The activation of multiple effector mechanism simultaneously led to significantly increased tumor killing compared with FDA-approved PD-L1 checkpoint inhibitor (Atezolizumab), IgG1-PDL1 and IgA-PDL1 in various in vitro cell lines, in vivo models and ex vivo renal cell carcinoma organoids. Moreover, in vivo data demonstrated that Ad-Cab did not require CD8+ T cells, unlike conventional checkpoint inhibitors, since it was able to activate other effector populations.ConclusionArming PD-L1 checkpoint inhibitors with Fc-effector mechanisms of both an IgA1 and an IgG1 can increase efficacy while maintaining safety by limiting expression to the tumor using oncolytic adenovirus. The increase in tumor killing is mostly attributed to the activation of multiple effector populations rather than activating a single effector population leading to significantly higher tumor killing.
Short-distance constraints for the longitudinal component of the hadronic light-by-light amplitude: an update
Authors: Colangelo G. , Hagelstein F. , Hoferichter M. , Laub L. , Stoffer P. 
Published: August 2021

AbstractWe reassess the impact of short-distance constraints for the longitudinal component of the hadronic light-by-light amplitude on the anomalous magnetic moment of the muon, $$a_\mu =(g-2)_\mu /2$$

a
μ

=

(
g
-
2
)

μ

/
2

, by comparing different solutions that have recently appeared in the literature. In particular, we analyze the relevance of the exact axial anomaly and its impact on $$a_\mu $$

a
μ

and conclude that it remains rather limited. We show that all recently proposed solutions agree well within uncertainties on the numerical estimate of the impact of short-distance constraints on $$a_\mu $$

a
μ

, despite differences in the concrete implementation. We also take into account the recently calculated perturbative corrections to the massless quark loop to update our estimate and outline the path towards future improvements.
N6-methyladenosine–Mediated Upregulation of WTAPP1 Promotes WTAP Translation and Wnt Signaling to Facilitate Pancreatic Cancer Progression
Authors: Deng Junge , Zhang Jialiang , Ye Ying , Liu Kaijing , Zeng Lingxing , Huang Jingyi , Pan Ling , Li Mei , Bai Ruihong , Zhuang Lisha , Huang Xudong , Wu Guandi , Wei Lusheng , Zheng Yanfen , Su Jiachun , Zhang Shaoping , Chen Rufu , Lin Dongxin , Zheng Jian 
Published: August 2021

AbstractPseudogenes may play important roles in cancer. Here, we explore the mechanism and function of a pseudogene WTAPP1 in the progress of pancreatic ductal adenocarcinoma (PDAC). WTAPP1 RNA was significantly elevated in PDAC and was associated with poor prognosis in patients. Overexpression of WTAPP1 RNA promoted PDAC proliferation and invasiveness in vitro and in vivo. Mechanistically, N6-methyladenosine (m6A) modification stabilized WTAPP1 RNA via CCHC-type zinc finger nucleic-acid binding protein (CNBP), resulting in increased levels of WTAPP1 RNA in PDAC cells. Excessive WTAPP1 RNA bound its protein-coding counterpart WT1-associated protein (WTAP) mRNA and recruited more EIF3 translation initiation complex to promote WTAP translation. Increased WTAP protein enhanced the activation of Wnt signaling and provoked the malignant phenotypes of PDAC. Decreasing WTAPP1 RNA significantly suppressed the in vivo growth and metastasis of PDAC cell lines and patient-derived xenografts. These results indicate that m6A-mediated increases in WTAPP1 expression promote PDAC progression and thus may serve as a therapeutic target.Significance:This study reveals how aberrant m6A modification of the WTAPP1 pseudogene results in increased translation of its protein-coding counterpart to promote Wnt signaling, which contributes to pancreatic cancer progression.
A Comprehensive Circulating Tumor DNA Assay for Detection of Translocation and Copy-Number Changes in Pediatric Sarcomas
Authors: Shah Avanthi Tayi , Azad Tej D. , Breese Marcus R. , Chabon Jacob J. , Hamilton Emily G. , Straessler Krystal , Kurtz David M. , Leung Stanley G. , Spillinger Aviv , Liu Heng-Yi , Behroozfard Inge H. , Wittber Frederick M. , Hazard Florette K. , Cho Soo-Jin , Daldrup-Link Heike E. , Vo Kieuhoa T. , Rangaswami Arun , Pribnow Allison , Spunt Sheri L. , Lacayo Norman J. , Diehn Maximilian , Alizadeh Ash A. , Sweet-Cordero E. Alejandro 
Published: August 2021

AbstractMost circulating tumor DNA (ctDNA) assays are designed to detect recurrent mutations. Pediatric sarcomas share few recurrent mutations but rather are characterized by translocations and copy-number changes. We applied Cancer Personalized Profiling by deep Sequencing (CAPP-Seq) for detection of translocations found in the most common pediatric sarcomas. We also applied ichorCNA to the combined off-target reads from our hybrid capture to simultaneously detect copy-number alterations (CNA). We analyzed 64 prospectively collected plasma samples from 17 patients with pediatric sarcoma. Translocations were detected in the pretreatment plasma of 13 patients and were confirmed by tumor sequencing in 12 patients. Two of these patients had evidence of complex chromosomal rearrangements in their ctDNA. We also detected copy-number changes in the pretreatment plasma of 7 patients. We found that ctDNA levels correlated with metastatic status and clinical response. Furthermore, we detected rising ctDNA levels before relapse was clinically apparent, demonstrating the high sensitivity of our assay. This assay can be utilized for simultaneous detection of translocations and CNAs in the plasma of patients with pediatric sarcoma. While we describe our experience in pediatric sarcomas, this approach can be applied to other tumors that are driven by structural variants.
Una lectura de la doctrina kantiana del genio
Authors: Martínez Luciana 
Published: August 2021

En este artículo se examina la doctrina kantiana del genio. En primer lugar, se estudia el desarrollo de esa doctrina en el período precrítico. Se muestra que durante ese período Kant restringe el ámbito de injerencia del genio. Hacia comienzos de los ‘80, el genio es el productor de bellas artes. En segundo lugar, se estudia la argumentación crítica. Se detalla la naturaleza del genio y se explica su función sistemática para la Crítica del Juicio.
Safety and Effectiveness of the SVELTE Fixed-Wire and Rapid Exchange Bioresorbable-Polymer Sirolimus-Eluting Coronary Stent Systems for the Treatment of Atherosclerotic Lesions: Results of the OPTIMIZE Randomized Study
Authors: Kereiakes Dean J. , Feldman Robert L. , Ijsselmuiden A.J.J. , Saito Shigeru , Amoroso Giovanni , Zidar James P. , Wong S. Chiu , Stella Pieter , Yakubov Steven , Lasala John , Cohen David J. , Doros Gheorghe , Cutlip Donald E. , Rao Sunil V. 
Published: August 2021

Background:
The SVELTE fixed-wire and rapid exchange bioresorbable-polymer sirolimus-eluting coronary stent systems (SVELTE sirolimus-eluting stent [SES]) are novel, low-profile devices designed to facilitate direct stenting, transradial access, and enhance procedural efficiencies.

Methods:
Eligible subjects (N=1639) scheduled to undergo percutaneous coronary intervention for non–ST-segment–elevation myocardial infarction or stable coronary artery disease were randomly assigned (1:1) to treatment with either SVELTE SES or a control durable polymer everolimus-eluting coronary stent. The primary end point was 12-month target lesion failure and a noninferiority margin was specified as 3.58% with an expected event rate of 6.5%.

Results:

Target lesion failure was observed in 10.3% of SVELTE SES and 9.5% of control everolimus-eluting stent subjects under intention to treat analysis (difference=0.8%;
P
NI
=0.034). Clinically indicated target lesion revascularization and stent thrombosis were observed in 1.5% versus 1.9% (
P
=0.57) and 0.38% versus 0.51% (
P
=0.72) of SVELTE SES versus control everolimus-eluting stent–treated subjects, respectively. Protocol-defined target vessel myocardial infarction (9.4% versus 8.2%) was higher than anticipated and more frequent at sites that utilized troponin versus creatine kinase myocardial band assays.

Conclusions:
The SVELTE SES did not meet the prespecified threshold for noninferiority. Unexpectedly, high rates of target vessel myocardial infarction in both treatment groups contributed to higher than expected rates of target lesion failure, effectively underpowering the study. No differences between the SVELTE SES and control everolimus-eluting stent were observed for primary clinical or angiographic end point events.

Registration:

URL:
https://www.clinicaltrials.gov
; Unique identifier: NCT03190473.
The Excellence of Yamazakura: Mountain Cherries and the Disappearing Tradition of Ukiyo-e Craft
Authors: Moilanen Tuula 
Published: August 2021

Abstract
Cherry blossom, sakura, is one of the visual symbols of Japan. For Japanese people it represents the beauty and fragility of life. Cherry tree belongs to the Rose family, which includes nearly 3000 different sub-species of flowering plants. Prunus serrulata, sometimes called as Oriental Cherry, is a species native to Japan, Korea and China. In Japan, cherry trees are roughly divided in yamazakura, wild mountain cherries and satozakura, cultivated cherry trees growing in residential areas. Moilanen’s research concentrates on the special properties of yamazakura, and its use in manufacturing printing blocks for traditional ukiyo-e woodblock prints. The unique craft of ukiyo-e is gradually fading into history due to lack of successors. Difficulties in finding proper yamazakura wood material for making the printing blocks add to the problem. Moilanen gives an overview to the art of ukiyo-e and the present day situation in printing block manufacturing. Her article also includes an introduction of other wood qualities used in Japan for printmaking and a short report about a Finnish attempt for finding an alternative wood material to yamazakura. Research on heat-treated alder and birch was conducted in Aalto University in Helsinki 2008–2012. Finally, the current state of yamazakura in Japan is estimated, and the future prospects of ukiyo-e printmaking.
Systematic Review and Meta-Analysis of Post-Treatment PET/CT in HPV-Associated Oropharyngeal Cancer
Authors: Mathews Fasil , Irizarry Rachel , Rosenfeld Richard , Sundaram Krishnamurthi 
Published: August 2021

Objective: To perform a systematic review with meta-analysis to investigate the utility of post-treatment PET/CT specifically in HPV-associated oropharyngeal squamous cell carcinoma following curative intent treatment. Methods: Random-effects meta-analysis was used to pool data from 7 observational studies (2013-2019) obtained from a database search of PubMed, Web of Science, and EMBASE using an a priori protocol with dual independent evaluation for inclusion, risk of bias assessment for acceptable methodology, and extraction of data for analysis. PET/CT results, treatment failure, imaging and interventions subsequent to PET/CT findings, and efficacy of salvage therapy were extracted. Results: Of the 907 post-treatment scans, PET/CT results were largely negative (76.2%; 95% CI, 63.4-85.6) and least often positive (11.3%; 95% CI, 8.8-14.4). PET/CT results were equivocal for 22.5% (95% CI, 12.5-36.9) and equivocal/positive for 34.2% of patients (95% CI, 25.1-44.5). Patients with an initial positive scan had the highest treatment failure rates (43.1%; 95% CI, 21.4-67.7) and those with an initial negative scan had the lowest rates (7.4%; 95% CI, 5.7-9.7). The equivocal and equivocal/positive scans had intermediate prevalence of 16.5% (95% CI, 9.4-27.6) and 16.7% (95% CI, 9.1-28.7), respectively. Conclusion: The low treatment failure rate following a negative PET/CT scan is reassuring, but the data are consistent with treatment failure rates up to 9.7% suggesting follow-up of these patients is prudent. Additionally, the low positive predictive value for treatment failure observed alludes to use of post-treatment PET/CT in HPV-associated disease frequently leading to unnecessary subsequent imaging and intervention.
Structures and functions of complex evaluation systems: comparison of six Central and Eastern European countries
Authors: Kupiec Tomasz , Wojtowicz Dominika , Olejniczak Karol 
Published: August 2021

Evaluation practice is vital for the accountability and learning of administrations implementing complex policies. This article explores the relationships between the structures of the evaluation systems and their functions. The findings are based on a comparative analysis of six national systems executing evaluation of the European Union Cohesion Policy. The study identifies three types of evaluation system structure: centralized with a single evaluation unit, decentralized with a coordinating body and decentralized without a coordinating body. These systems differ in terms of the thematic focus of evaluations and the targeted users. Decentralized systems focus on internal users of knowledge and produce mostly operational studies; their primary function is inward-oriented learning about smooth programme implementation. Centralized systems fulfil a more strategic function, recognizing the external audience and external accountability for effects. Points for practitioners Practitioners who design multi-organizational evaluation systems should bear in mind that their structure and functions are interrelated. If both accountability and learning are desired, the evaluation system needs at least a minimum degree of decentralization on the one hand and the presence of an active and independent coordination body on the other.
Association between religious beliefs and discussions regarding advance care planning: A nationwide survey
Authors: Miyashita Jun , Shimizu Sayaka , Fukuhara Shunichi , Yamamoto Yosuke 
Published: August 2021

Background: The relationship between advance care planning and religious beliefs, which are important for palliative care, is controversial in Western countries and has not been verified in Asian countries. Aim: To investigate the association between advance care planning discussions and religious beliefs in Japan. Design: A nationwide survey conducted in 2016 using a quota sampling method to obtain a representative sample of Japan’s general population. Setting/participants: We analyzed responses from 3167 adults aged 20–84 years (mean age ± standard deviation, 50.9 ± 16.8 years). The outcome was measured by asking whether the respondents had ever discussed advance care planning, and the main exposure by whether they had any religious beliefs or affiliations, and if so, their degree of devoutness. We analyzed religious beliefs, affiliations, and devoutness in relation to the occurrence of discussions using multivariable logistic regression models adjusted for possible sociodemographic covariates. Results: Compared with respondents without, those with religious beliefs had significantly higher odds of having had discussions (adjusted odds ratio: 1.45, 95% confidence interval: 1.22–1.73). The devoutness of religious belief was proportional to the propensity of the occurrence of discussions ( p for trend < 0.001). In addition, Buddhists and Christians had higher odds of having had discussions than did nonbelievers. Conclusion: The results suggest that holding religious beliefs, especially in Japanese Buddhism and Christianity, facilitates advance care planning discussions among Japanese adults, and thus, may help health-care providers identify those prioritized for facilitating engagement in advance care planning, especially in palliative and spiritual care settings.