bluuebunny/crossref_metadata_2025_split huggingface dataset:
Study protocol of a randomised, double-blind, placebo-controlled, two-arm parallel-group, multi-centre phase 3 pivotal trial to investigate the efficacy and safety of recombinant human alkaline phosphatase for treatment of patients with sepsis-associated acute kidney injury
Authors: Pickkers Peter , Angus Derek C , Arend Jacques , Bellomo Rinaldo , van den Berg Erik , Bernholz Juliane , Bestle Morten , Broglio Kristine , Carlsen Jan , Doig Christopher J , Ferrer Ricard , Joannidis Michael , Francois Bruno , Doi Kent , Kellum John A , Laterre Pierre-François , Liu Kathleen , Mehta Ravindra L , Murray Patrick T , Ostermann Marlies , Pettilä Ville , Richards Sharon , Young Paul , Zarbock Alexander , Kjølbye Anne Louise 
Published: April 2023

IntroductionSepsis, the leading cause of acute kidney injury (AKI), is associated with a high morbidity and mortality. Alkaline phosphatase (ALP) is an endogenous detoxifying enzyme. A recombinant human ALP compound, ilofotase alfa, showed no safety or tolerability concerns in a phase 2 trial. Renal function improvement over 28 days was significantly greater in the ilofotase alfa group. Moreover, a significant relative reduction in 28-day all-cause mortality of >40% was observed. A follow-up trial has been designed to confirm these findings.Methods and analysisThis is a phase 3, global, multi-centre, randomised, double-blind, placebo-controlled, sequential design trial in which patients are randomly assigned to either placebo or 1.6 mg/kg ilofotase alfa. Randomisation is stratified by baseline modified Sequential Organ Failure Assessment (mSOFA) score and trial site. The primary objective is to confirm the survival benefit with ilofotase alfa by demonstrating a reduction in 28-day all-cause mortality in patients with sepsis-associated AKI requiring vasopressors. A maximum of 1400 patients will be enrolled at ∼120 sites in Europe, North America, Japan, Australia and New Zealand. Up to four interim analyses will take place. Based on predefined decision rules, the trial may be stopped early for futility or for effectiveness. In addition, patients with COVID-19 disease and patients with ‘moderate to severe’ chronic kidney disease are analysed as 2 separate cohorts of 100 patients each. An independent Data Monitoring Committee evaluates safety data at prespecified intervals throughout the trial.Ethics and disseminationThe trial is approved by relevant institutional review boards/independent ethics committees and is conducted in accordance with the ethical principles of the Declaration of Helsinki, guidelines of Good Clinical Practice, Code of Federal Regulations and all other applicable regulations. Results of this study will determine the potential of ilofotase alfa to reduce mortality in critically ill patients with sepsis-associated AKI and will be published in a peer-reviewed scientific journal.Trial registration numberEudraCT CT Number 2019-0046265-24. US IND Number 117 605 Pre-results. ClinicalTrials.gov number:NCT04411472.
Pneumoconiosis combined with connective tissue disease in China: a cross-sectional study
Authors: Xu Wenjing , Ma Ruimin , Wang Jingwei , Sun Di , Yu Shiwen , Ye Qiao 
Published: April 2023

ObjectiveTo describe the prevalence, clinical features and potential risk factors of pneumoconiosis in combination with connective tissue disease (CTD) or positive autoantibodies.DesignCross-sectional study.SettingA retrospective study of adults recruited in China between December 2016 and November 2021.ParticipantsA total of 931 patients with pneumoconiosis at Beijing Chao-Yang Hospital were enrolled in this study; of these, 580 patients were included in the final analysis.Main outcome measuresPneumoconiosis combined with CTD or positive autoantibodies was a major adverse outcome.ResultsIn total, 13.8% (80/580) of the patients had combined pneumoconiosis with CTD, among whom the prevalence of CTD was 18.3% (46/251) in asbestosis and 11.4% (34/298) in silicosis/coal mine workers’ pneumoconiosis. In comparison to the general Chinese adult population, the relative risk of various CTD in pneumoconiosis, including rheumatoid arthritis, systemic lupus erythematosus, systemic sclerosis, primary Sjögren’s syndrome, idiopathic inflammatory myopathy and antineutrophil cytoplasmic antibodies-associated vasculitis, were 11.85, 12.12, 127.40, 4.23, 9.94 and 644.66, respectively. Multivariate analysis revealed that female sex (OR 2.55, 95% CI 1.56 to 4.17) and a later stage of pneumoconiosis (OR 2.04, 95% CI 1.24 to 3.34) were the independent risk factors for CTD in patients with pneumoconiosis (all p<0.050).ConclusionCTD is highly prevalent in patients with pneumoconiosis, especially in patients of asbestosis, and silicosis/coal mine workers’ pneumoconiosis. Female sex and later stages of pneumoconiosis are associated with an increased risk of combined with CTD.
Barriers and facilitators to improving patient safety learning systems: a systematic review of qualitative studies and meta-synthesis
Authors: Mahmoud Hassan Assem , Thavorn Kednapa , Mulpuru Sunita , McIsaac Daniel , Abdelrazek Mohamed A , Mahmoud Amr Assem , Forster Alan J 
Published: April 2023

BackgroundThe implementation and continuous improvement of patient safety learning systems (PSLS) is a principal strategy for mitigating preventable harm to patients. Although substantial efforts have sought to improve these systems, there is a need to more comprehensively understand critical success factors. This study aims to summarise the barriers and facilitators perceived by hospital staff and physicians to influence the reporting, analysis, learning and feedback within PSLS in hospitals.MethodsWe performed a systematic review and meta-synthesis by searching MEDLINE (Ovid), EMBASE (Ovid), CINAHL, Scopus and Web of Science. We included English-language manuscripts of qualitative studies evaluating effectiveness of the PSLS and excluded studies evaluating specific individual adverse events, such as systems for tracking only medication side effects, for example. We followed the Joanna Briggs Institute methodology for qualitative systematic reviews.ResultsWe extracted data from 22 studies, after screening 2475 for inclusion/exclusion criteria. The included studies focused on reporting aspects of the PSLS, however, there were important barriers and facilitators across the analysis, learning and feedback phases. We identified the following barriers for effective use of PSLS: inadequate organisational support with shortage of resources, lack of training, weak safety culture, lack of accountability, defective policies, blame and a punitive environment, complex system, lack of experience and lack of feedback. We identified the following enabling factors: continuous training, a balance between accountability and responsibility, leaders as role models, anonymous reporting, user-friendly systems, well-structured analysis teams, tangible improvement.ConclusionMultiple barriers and facilitators to uptake of PSLS exist. These factors should be considered by decision makers seeking to enhance the impact of PSLS.Ethics and disseminationNo formal ethical approval or consent were required as no primary data were collected.
Prevalence of pulmonary hypertension in aortic stenosis and its influence on outcomes
Authors: Ratwatte Seshika , Stewart Simon , Strange Geoff , Playford David , Celermajer David S 
Published: April 2023

ObjectiveThe significance of pulmonary hypertension (PHT) complicating aortic stenosis (AS) is poorly characterised. In a large cohort of adults with at least moderate AS, we aimed to describe the prevalence and prognostic importance of PHT in such patients.MethodsIn this retrospective study, we analysed the National Echocardiography Database of Australia (data from 2000 to 2019). Adults with an estimated right ventricular systolic pressure (eRVSP), left ventricular ejection fraction (LVEF) >50% and with moderate or greater AS were included (n=14 980). These subjects were then categorised according to their eRVSP. The relationship between PHT severity and mortality outcomes were evaluated (median follow-up of 2.6 years, IQR 1.0–4.6 years).ResultsSubjects were aged 77±13 years and 57.4% were female. Overall, 2049 (13.7%), 5085 (33.9%), 4380 (29.3%), 1956 (13.1%) and 1510 (10.1%) patients had no (eRVSP<30.00 mm Hg), borderline (30.00–39.99 mm Hg), mild (40.00–49.99 mm Hg), moderate (50.00–59.99 mm Hg) and severe PHT (>60.00 mm Hg), respectively. An echocardiographic phenotype was evident with worsening PHT, showing rising E:e’ ratio and right and left atrial sizes(p<0.0001, for all). Adjusted analyses showed that the risk of long-term mortality progressively rose as eRVSP level increased (HR 1.14–2.94, borderline to severe PHT, p<0.0001 for all). A mortality threshold was identified in the 4th decile of eRVSP categories (35.01–38.00 mm Hg; HR 1.19, 95% CI 1.04 to 1.35), with risk progressively increasing through to the 10th decile (HR 2.86, 95% CI 2.54 to 3.21).ConclusionsIn this large cohort study, we find that PHT is common in ≥moderate AS and mortality increases as PHT becomes more severe. A threshold for higher mortality lies within the range of ‘borderline-mild’ PHT.Trial registration numberACTRN12617001387314.
Axions, WIMPs, proton decay and observable r in SO(10)
Authors: Okada Nobuchika , Raut Digesh , Shafi Qaisar 
Published: April 2023

AbstractWe explore some experimentally testable predictions of an SO(10) axion model which includes two 10-plets of fermions in order to resolve the axion domain wall problem. The axion symmetry can be safely broken after inflation, so that the isocurvature perturbations associated with the axion field are negligibly small. An unbroken gauge $$Z_2$$

Z
2

symmetry in SO(10) ensures the presence of a stable WIMP-like dark matter, a linear combination of the electroweak doublets in the fermion 10-plets and an SO(10) singlet fermion with mass $$\sim 62.5 \; \textrm{GeV}\; (1 \; \textrm{TeV}) $$

∼
62.5

GeV

(
1

TeV
)

when it is mostly the singlet (doublet) fermion, that co-exists with axion dark matter. We also discuss gauge coupling unification, proton decay, inflation with non-minimal coupling to gravity and leptogenesis. With the identification of the SM singlet Higgs field in the 126 representation of SO(10) as inflaton, the magnetic monopoles are inflated away, and we find $$0.963 \lesssim n_s \lesssim 0.965$$

0.963
≲

n
s

≲
0.965

and $$0.003 \lesssim r \lesssim 0.036$$

0.003
≲
r
≲
0.036

, where $$n_s$$

n
s

and r denote the scalar spectral index and tensor-to-scalar ratio, respectively. These predictions can be tested in future experiments such as CMB-S4.
Supplemental Methods; Supplemental Tables S1-S7; and Supplemental Figures S1-S6 from Synthetic Lethal Strategy Identifies a Potent and Selective TTK and CLK1/2 Inhibitor for Treatment of Triple-Negative Breast Cancer with a Compromised G<sub>1</sub>–S Checkpoint
Authors: Zhu Dan , Xu Shuichan , Deyanat-Yazdi Gordafaried , Peng Sophie X. , Barnes Leo A. , Narla Rama Krishna , Tran Tam , Mikolon David , Ning Yuhong , Shi Tao , Jiang Ning , Raymon Heather K. , Riggs Jennifer R. , Boylan John F. 
Published: April 2023

<p>SUPPLEMENTAL METHODS â€¢	Correlative analysis of CC-671 sensitivity data with genomic features in the 240 Oncopanel â€¢	Correlative analysis of CC-671 sensitivity data with genomic features or tumor subtypes in 49 breast cancer cell lines â€¢	Molecular of action studies â€¢	Xenograft efficacy studies SUPPLEMENTAL DATA â€¢	Table S1. Primer sequences for PCR â€¢	Table S2. Invitrogen kinase panel data â€¢	Table S3. Growth inhibition (IC50 and AUCR Values) of CC-671 in breast cancer panel â€¢	Table S4. CC-671 effects on cancer cell proliferation, apoptosis, and cell cycle â€¢	Table S5. Cell lines in Oncopanel with mutations in CTNNB1 exon 3 â€¢	Table S6. Correlation between CC-671 IC50 values and mutations in CTNNB1 exon 3 in cancer cell lines â€¢	Table S7. Correlation of CDKN2A and TP53 mutations with sensitivity or resistance to CC-671 in lung and melanoma cell lines from the Oncopanel â€¢	Figure S1. CLK2 knockdown by siRNA reduced phosphorylation of SRp75 in CAL51 cells â€¢	Figure S2. Induction of apoptosis in vivo with a single dose of CC-671 in MDA-MB-231 tumors â€¢	Figure S3. Antitumor activity of CC-671 in CAL51 and MDA-MB-231 TNBC xenograft models â€¢	Figure S4. CC-671 potently and selectively inhibits proliferation and induces apoptosis in cancer cell lines from different anatomic origins â€¢	Figure S5. Cancer cell lines with CTNNB1 exon 3 mutations tend to be more sensitive to CC-671 in Oncopanel, but the correlation does not reach statistical significance â€¢	Figure S6. TTK expression and CC-671 potency correlate with the growth rates (t0) of cell lines in both breast cancer panel and Oncopanel</p>
Supplementary Table 3 from Comparative Study on the Efficacy and Exposure of Molecular Target Agents in Non–small Cell Lung Cancer PDX Models with Driver Genetic Alterations
Authors: Jo Hitomi , Yagishita Shigehiro , Hayashi Yoshiharu , Ryu Shoraku , Suzuki Mikiko , Kohsaka Shinji , Ueno Toshihide , Matsumoto Yuji , Horinouchi Hidehito , Ohe Yuichiro , Watanabe Shun-ichi , Motoi Noriko , Yatabe Yasushi , Mano Hiroyuki , Takahashi Kazuhisa , Hamada Akinobu 
Published: April 2023

Supplementary Table 3<p>(A)	Establishment status by histological subtype(B)	Establishment status by gene aberration.</p>
Supplementary Data from Expanding the Repertoire for “Large Small Molecules”: Prodrug ABBV-167 Efficiently Converts to Venetoclax with Reduced Food Effect in Healthy Volunteers
Authors: Salem Ahmed Hamed , Tao Zhi-Fu , Bueno Orlando F. , Chen Jie , Chen Shuang , Edalji Rohinton , Elmore Steven W. , Fournier Keith M. , Harper Kaid C. , Hong Richard , Jenkins Gary J. , Ji Jianguo , Judge Russell A. , Kalvass John C. , Klix Russell C. , Ku Yi-Yin , Leverson Joel D. , Marks Richard A. , Marsh Kennan C. , Menon Rajeev M. , Park Chang H. , Phillips Darren C. , Pu Yu-Ming , Rosenberg Saul H. , Sanzgiri Yeshwant D. , Sheikh Ahmad Y. , Shi Yi , Stolarik Deanne , Suleiman Ahmed A. , Wang Xilu , Zhang Geoff G.Z. , Catron Nathaniel D. , Souers Andrew J. 
Published: April 2023

<p>1.	Measured pKa values of ABBV-167 (Table S1. Ionization constants of ABBV-167) 2.	Preparation of ABBV-167 on large scale (Scheme S1: Synopsis of GMP synthesis of ABBV-167) 3.	Preparation of clinical ABBV-167 drug supply 4.	Animal pharmacokinetics (Table S2. Single dose pharmacokinetics of prodrug 3 and parent venetoclax in mouse and dog after IV dosing of prodrug 3. Table S3. Single dose pharmacokinetics of 3 after oral dosing in mouse and dog. Table S4. Single dose pharmacokinetics of parent venetoclax in mouse and dog after oral dosing of 3.) 5.	Clinical study (Study design, Pharmacokinetic and statistical analysis, Safety and tolerability assessments, Clinical pharmacokinetic results, Table S5. Effect of prodrug and food on venetoclax bioavailability, Safety results) 6.	Crystallography methods (Protein preparation. BCL-2 ABBV-167 complex crystallization. X-ray structure determination. Table S6. Diffraction data collection and refinement statistics for BCL-2 in complex with ABBV-167 (PDB code 7LHB))</p>
Common Usage vs Codified Standard: Problems with the Codification of Anglicisms in the Contemporary Russian Language
Authors: Romanik Anna 
Published: April 2023

Common Usage vs Codified Standard: Problems with the Codification of Anglicisms in the Contemporary Russian Language
This article focuses on the important problem of codification of the most recent borrowings of British and American English origins in the contemporary Russian language. Standardization of loanwords is a current issue of vital importance, as it has a global reach, which means that it affects not only the Russian language but many other national languages that are under the influence of the English language – the contemporary lingua franca. The codification of the lexis of foreign origin is examined based on material obtained from contemporary lifestyle maga­zines published in Russian. This type of press disseminates borrowed neologisms particularly intensively and, at the same time, creates the language use of the given discourse. The excerpted vocabulary items have been confronted with the lexis of the most recent Russian spelling dictionaries. The deliberations contained in this paper show a fragment of linguistic reality changing under the influence of ubiq­uitous English language, where common usage competes with the linguistic norm. The article shows the difficulties caused by lexical transfer of loanwords faced by specialists in prescriptive linguistics (e.g. a common problem of orthographic variation).

Norma uzualna vs norma skodyfikowana. O problemach kodyfikacji anglicyzmów we współczesnym języku rosyjskim
Niniejszy artykuł zwraca uwagę na istotny problem kodyfikacji najnowszych zapożyczeń anglo-amerykańskiej proweniencji we współczesnej ruszczyźnie. Temat standaryzacji zapożyczeń jest aktualny i niezwykle ważny, bowiem ma on zasięg globalny, zatem dotyczy nie tylko języka rosyjskiego, lecz wielu innych języków narodowych, które znajdują się pod wpływem angielszczyzny – współ­czesnej lingua franca. Badanie kodyfikacji leksyki obcego pochodzenia oparto na materiale zaczerpniętym z najnowszych rosyjskojęzycznych czasopism kolorowych typu life style. Ten rodzaj prasy szczególnie ochoczo rozpowszechnia zapoży­czone neologizmy, jednocześnie kreuje uzus danego dyskursu. Wyekscerpowany materiał porównano z leksyką zawartą w najnowszych słownikach ortograficznych języka rosyjskiego. Niniejsze rozważania dają obraz fragmentu rzeczywistości językowej zmieniającej się pod wpływem wszechobecnej angielszczyzny, w której uzus konkuruje z normą językową. Ponadto wskazano tu szereg problemów wywoływanych zapożyczeniami leksykalnymi, z którymi zmagają się specjaliści z obszaru językoznawstwa normatywnego (np. powszechny problem wariantywności ortograficznej zapożyczeń).
Multispectral Satellite Imagery Products for Fire Weather Applications
Authors: Seaman Curtis J. , Line William , Ziel Robert , Jenkins Jennifer , Dierking Carl , Hanson Greg 
Published: April 2023

Abstract
Two multispectral satellite imagery products are presented that were developed for use within the fire management community. These products, which take the form of false color red–green–blue composites, were designed to aid fire detection and characterization, and for assessment of the environment surrounding a fire. The first, named the Fire Temperature RGB, uses spectral channels near 1.6, 2.2, and 3.9 μm for fire detection and rapid assessment of the range of fire intensity through intuitive coloration. The second, named the Day Fire RGB, uses spectral channels near 0.64, 0.86, and 3.9 μm for rapid scene assessment. The 0.64 μm channel provides information on smoke, the 0.86 μm channel provides information on vegetation health and burn scars, and the 3.9 μm channel provides active fire detections. Examples of these red–green–blue composite images developed from observations collected by three operational satellite imagers (VIIRS on the polar-orbiting platform and the Advanced Baseline Imager and Advanced Himawari Imager on the geostationary platform) demonstrate that both red–green–blue composites are useful for fire detection and contain valuable information that is not present within operational fire detection algorithms. In particular, it is shown that Fire Temperature RGB and Day Fire RGB images from VIIRS have similar utility for fire detection as the operational VIIRS Active Fire products, with the added benefit that the imagery provides context for more than just the fires themselves.

Significance Statement
The current generation of operational polar-orbiting weather satellites that began with the launch of Suomi NPP offers new capabilities with regard to fire detection and monitoring. In particular, false color red–green–blue composite imagery is now being used by fire managers, incident meteorologists, and others in the fire management community to visualize a fire’s behavior and the context in which it occurs. This paper outlines two of these red–green–blue composites that have gained widespread use throughout the U.S. National Weather Service and the Alaska Fire Service. These red–green–blue composites have been applied to the current generation of geostationary and polar-orbiting satellites to great effect and have changed how incident management teams respond to wildland fires.
Correlative Factors for Types of Tracheobronchial Foreign Bodies Encountered in Children
Authors: Su Shuping , Zhang Hengci , Xiao Ling , Yao Hongbing , Ding Ling 
Published: April 2023

Objective To characterize the correlative factors for types of tracheobronchial foreign bodies (TFBs) encountered in children. Methods All included patients diagnosed with TFB underwent rigid bronchoscopy as the first surgery in the Children’s Hospital of Chongqing Medical University. The data of 1026 patients aged 0–18 years were retrospectively collected between February 2019 and January 2022. Results About 94.44% of the children with TFB had organic FBs, among which, peanuts were the most common FBs, followed by melon seeds and walnuts. The most common inorganic FBs included pen points or caps, plastic toys, and plastic papers. As compared to the children with organic FBs, those with inorganic FBs consisted of a higher proportion of children aged ≥3 years old, a time before surgery of >7 days, dyspnea, FBs size of >10 mm, longer operation time, more than two operation procedures, and atelectasis. On the other hand, the proportion of children with aspiration history, cough, and obstructive emphysema in the inorganic FB group was lower as compared to the organic FBs ( P< .05). Conclusions The related factors related to the patient’s characteristics, symptoms, operation situations, and preoperative complications can be predicted based on the identification of FB type.
Optimizing Outpatient Oral Contrast Use in Abdominal CT–A Radiology Pandemic Response Initiative to Reduce Patient Time in the Waiting Room and Reduce Costs, While Improving Patient Experience
Authors: Renton Mary , Kielar Ania Z. , Toubassy Daniel , May Mary , Maganti Manjula , Burton Corwin , Krishna Satheesh 
Published: April 2023

Purpose: The aim was to reduce outpatient wait time and improve patient experience by optimising oral contrast use . Methods: Our multidisciplinary stakeholder collaboration implemented two simultaneous interventions: (1) Creation of ‘oral contrast policy’, limiting recommended indications. (2) Creation of a new shorter oral contrast regime (30 vs 60 min). We conducted a retrospective service evaluation of oral contrast use in outpatient (OP) abdominal CT at baseline and post-intervention. Patient wait times were measured and per-patient cost-savings were reported. An image quality review was performed by 2 blinded abdominal radiologists. Patient experience was evaluated with a standard voluntary survey. Statistical analysis was performed comparing baseline and evaluation outcomes using Chi-square or Fisher Exact test for categorical variables and Student’s t-test or ANOVA for continuous data. Results: Over 1-month periods, OP CT scans were assessed in baseline (pre-pandemic) n = 575, baseline (pandemic) n = 495 and post-intervention n = 545 groups. Oral contrast use reduced from 420/575, 73.0% at baseline to 178/545, 32.7% post intervention. The turn-around time reduced by 15.8 minutes per patient from 70.3 to 54.5 minutes, P < .001 (Interventions 1 and 2). The diagnostic quality did not differ between the oral contrast regimes (Intervention 2, P = 1.0, P = .08). No repeat CTs were needed due to lack of oral contrast (Intervention 1) or poor opacification (Intervention 2). There was oral contrast cost reductions of 69.1–78.4% ( P < .001). Patients reported their overall experience was improved post-intervention (Interventions 1 and 2). Conclusions: Optimising the CT oral contrast service through judicious use and a shorter regime, reduced patient wait times, improved patient experience and preserved diagnostic quality.