bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of temporary deferrals on future blood donation behavior across the donor life cycle
Authors: Clement Michel , Shehu Edlira , Chandler Torsten 
Published: March 2021

AbstractBackgroundDonor retention is essential for blood banks because acquiring new donors is more expensive than retaining existing ones. Previous studies show that the temporary deferral of donors negatively impacts future donation likelihood. In this study, we analyze the impact of temporary deferrals on future donation behavior while correcting for potential endogeneity, depending on the level of donor experience and number of previous deferrals.Study Design and MethodWe use data from more than 123,000 whole blood donors of the Austrian Red Cross over a period of 5.5 years. We estimate logit models to analyze how a deferral affects future donation behavior while controlling for potential selection biases because donors are not deferred randomly. We control for gender, blood type, years since first donation, and number of previous donations and deferrals. We analyze the direct deferral effect, its interaction with donor experience, and the number of previous deferrals.ResultsOur results confirm that temporary deferrals hurt future donation behavior. This effect varies with donor experience and the number of previous deferrals. The effect is weaker with a higher number of previous donations and is stronger with a higher number of previous deferrals. The results suggest that donors learn to cope with deferrals the more they donate. However, the negative effect of deferrals amplifies over time, and each additional deferral decreases donation likelihood.ConclusionBlood banks that seek to overcome the negative effect of deferrals should be aware that this effect varies with donor experience and with the number of previous deferrals. Our results suggest that blood banks should focus on early‐stage donors who are deferred because the negative deferral effect is stronger for more experienced donors. At the same time, blood banks should be careful with donor groups who have experienced deferrals in the past because every additional deferral demotivates future donation behavior. Overall, researchers should be careful to correct for endogeneity because our results suggest that ignoring these effects could lead to substantial underestimation of the negative deferral effect.
Evaluation and classification of water quality of glacier‐fed channels using supervised learning and water quality index
Authors: Ahmed Muhammad Farooq , Waqas Umer , Khan Muhammad Saleem , Rashid Hafiz Muhammad Awais , Saqib Shahab 
Published: March 2021

AbstractIn this study, a series of laboratory tests were performed on 25 water samples obtained from the high‐altitude glacier‐fed water resources of Gilgit‐Baltistan Pakistan. The variations in the measured physico‐chemical parameters were found as follows: conductivity 62–989 (µS/cm), turbidity 0.94–10.86 (NTU), pH 6–8.4, TDS 40–830 (mg/L), hardness 30–305 (mg/L), Ca2+ 35–135 (mg/L), K+ 2–12.2 (mg/L), Mg2+ 0–17.9 (mg/L), Na+ 2–27.6 (mg/L), Zn2+ 0–3.5 (mg/L), Cu2+ 0.27–3.51 (mg/L), Cl− 25–162 (mg/L), SO42− 0–83 (mg/L), NO3− 0–0.94 (mg/L), and HCO3− 15–327 (mg/L). The ion charge balance error was found within the range of ±10% with a mean value of 5.36%. The Gibbs plot and ionic ratios showed that the rock‐weathering, especially carbonate dissolution, was the major hydrogeochemical process that influenced water chemistry. The water samples were classified as excellent (56%), good (40%), and medium (4%) quality based on the entropy water quality index (EWQI). The specificity and sensitivity of the discriminant model were found 100% and 90% respectively with a model‐hit‐ratio of 95.8% which satisfied this analysis.
Salmonella spp. prevalence and antimicrobial resistance in broiler chicken and turkey flocks in Canada from 2013 to 2018
Authors: Caffrey Niamh , Agunos Agnes , Gow Sheryl , Liljebjelke Karen , Mainali Chunu , Checkley Sylvia L. 
Published: March 2021

AbstractSalmonella infections are a major human health concern. In the elderly and immunocompromised, infections can be life‐threatening and may require antibiotic therapy. Where antibiotic therapy is required, antimicrobials of choice include fluoroquinolones and extended‐spectrum cephalosporins (ESC). The aim of this study is to utilize data from the Canadian Integrated Program for Antimicrobial Resistance Surveillance (CIPARS) to compare the prevalence of Salmonella serovars between broiler chicken and turkey flocks across Canada, and to gain an understanding of the prevalence of resistance to antimicrobials categorized as important to human health. There were 1,596 Salmonella isolates obtained from 514 broiler chicken flocks, and 659 Salmonella isolates obtained from 217 turkey flocks (2013–2018). All isolates were obtained from pooled faecal samples. Among broiler chicken flocks, the top three serovars were Kentucky (n = 573, 36%), Enteritidis (n = 314, 20%) and Heidelberg (n = 127, 8%). Resistance to ceftriaxone among Salmonella ser. Kentucky decreased from 27% in 2013 to 22% in 2018. There was no resistance among Salmonella ser. Enteritidis reported until 2018 when one isolate from British Columbia was resistant to ampicillin, streptomycin, sulphisoxazole and tetracycline. Salmonella ser. Heidelberg resistance to ceftriaxone decreased from 19% in 2013 to 14% in 2018. Among turkey flocks the top three serovars were Uganda (n = 109, 16.5%), Hadar (n = 85, 12%) and Muenchen (n = 66, 10%). No isolates of Salmonella ser. Uganda or Salmonella ser. Muenchen were resistant to any β‐lactams. Salmonella ser. Hadar (34/81, 42%) exhibited resistance to ampicillin. There was no resistance to quinolones among turkey isolates. Emerging resistance among Salmonella ser. Enteritidis, and resistance to β‐lactams and fluoroquinolones among Salmonella ser. Kentucky from broilers are cause for concern as these classes of antimicrobials are important for treatment of salmonellosis.
AF-React study: atrial fibrillation management strategies in clinical practice—retrospective longitudinal study from real-world data in Northern Portugal
Authors: Silva Pinto Susana , Teixeira Andreia , Henriques Teresa S , Monteiro Hugo , Martins Carlos 
Published: March 2021

ObjectivesTo determine the prevalence of atrial fibrillation (AF) and to assess how these patients are being cared for: what anticoagulants are being prescribed and are they being prescribed as recommended?DesignRetrospective longitudinal study.SettingThis study was conducted in the Regional Health Administration of Northern Portugal.ParticipantsThis study used a database that included 63526 patients with code K78 of the International Classification of Primary Care between January 2016 and December 2018.ResultsThe prevalence of AF among adults over 40 years in the northern region of Portugal was 2.3% in 2016, 2.8% in 2017 and 3% in 2018. From a total of 63 526 patients, 95.8% had an indication to receive anticoagulation therapy. Of these, 44 326 (72.9%) are being treated with anticoagulants: 17 936 (40.5%) were prescribed vitamin K antagonists (VKAs) and 26 390 (59.5%) were prescribed non-VKA anticoagulants. On the other hand, 2688 patients of the total (4.2%) had no indication to receive anticoagulation therapy. Of these 2688 patients, 1100 (40.9%) were receiving anticoagulants.ConclusionsThe prevalence of AF is 3%. Here, we report evidence of both undertreatment and overtreatment. Although having an indication, a considerable proportion of patients (27.1%) are not anticoagulated, and among patients with AF without an indication to receive anticoagulation therapy, a considerable proportion (40.9%) are receiving anticoagulants. The AF-React study brings extremely relevant conclusions to Portugal and follows real-world studies in patients with AF in Europe, presenting some data not yet studied.
Additional value of volumetric and texture analysis on FDG PET assessment in paediatric Hodgkin lymphoma: an Italian multicentric study protocol
Authors: Lopci Egesta , Burnelli Roberta , Elia Caterina , Piccardo Arnoldo , Castello Angelo , Borsatti Eugenio , Zucchetta Pietro , Cistaro Angelina , Mascarin Maurizio 
Published: March 2021

IntroductionAssessment of response to therapy in paediatric patients with Hodgkin lymphoma (HL) by 18F-fluorodeoxyglucose positron emission tomography/CT has become a powerful tool for the discrimination of responders from non-responders. The addition of volumetric and texture analyses can be regarded as a valuable help for disease prognostication and biological characterisation. Based on these premises, the Hodgkin Lymphoma Study Group of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) has designed a prospective evaluation of volumetric and texture analysis in the Italian cohort of patients enrolled in the EuroNet-PHL-C2.Methods and analysisThe primary objective is to compare volumetric assessment in patiens with HL at baseline and during the course of therapy with standard visual and semiquantitative analyses. The secondary objective is to identify the impact of volumetric and texture analysis on bulky masses. The tertiary objective is to determine the additional value of multiparametric assessment in patients having a partial response on morphological imaging.The overall cohort of the study is expected to be round 400–500 patients, with approximately half presenting with bulky masses. All PET scans of the Italian cohort will be analysed for volumetric assessment, comprising metabolic tumour volume and total lesion glycolysis at baseline and during the course of therapy. A dedicated software will delineate semiautomatically contours using different threshold methods, and the impact of each segmentation techniques will be evaluated. Bulky will be defined on contiguous lymph node masses ≥200 mL on CT/MRI. All bulky masses will be outlined and analysed by the same software to provide textural features. Morphological assessment will be based on RECIL 2017 for response definition.Ethics and disseminationThe current study has been ethically approved (AIFA/SC/P/27087 approved 09/03/2018; EudraCT 2012-004053-88, EM-04). The results of the different analyses performed during and after study completion the will be actively disseminated through peer-reviewed journals, conference presentations, social media, print media and internet.
Psychosocial stress and musculoskeletal pain among senior workers from nine occupational groups: Cross-sectional findings from the SeniorWorkingLife study
Authors: Vinstrup Jonas , Sundstrup Emil , Andersen Lars L 
Published: March 2021

IntroductionMaintaining good health with advancing age is increasingly important as most European countries experience an increase in retirement age. In order to decrease the risk of premature departure from the workforce, identifying groups at increased risk of musculoskeletal pain and psychosocial stress is essential in designing workplace policies. Therefore, the aim of this study was to investigate the relationship between occupational groups differing in terms of physical demands and skill requirement, and the outcomes of stress and pain.MethodsThis cross-sectional study reports associations of nine different occupational groups with stress and pain among 11 474 senior workers; stratified by occupational group and based on the International Standard Classification of Occupations (ISCO). A large-scale questionnaire survey was dispatched to Danish workers; drawn as a probability sample and merged with national registers. Representative estimates were produced using logistic regression controlling for various confounders, combined with model-assisted weights.ResultsThe prevalence of daily pain and high stress among occupational groups ranged between 20.0%–50.5% and 3.9%–10.0%, respectively. Compared with occupations characterised by being mostly sedentary (ISCO group 1–4), those with primarily physical demanding work (ISCO group 5–9) had higher odds of daily pain (OR 1.53, 95% CI 1.37 to 1.70) and a tendency towards higher stress scores (OR 1.20, 95% CI 0.98 to 1.46). Lastly, female workers experience increased odds of daily pain (OR 1.50, 95% CI 1.35 to 1.66) and high stress (OR 1.56, 95% CI 1.29 to 1.89) compared with male workers.ConclusionsOccupational settings characterised by mainly physical work and low skill requirements are more likely to experience daily pain compared with those entailing mainly sedentary work. Likewise, in this sample of senior workers, women are more likely to experience pain and stress. These results highlights the need for improving occupation-specific and sex-specific guidelines in the prevention of musculoskeletal pain and psychological stress in workplaces.Trial registration numberClinicalTrials identifier:NCT03634410
Effectiveness of a medication adherence management intervention in a community pharmacy setting: a cluster randomised controlled trial
Authors: Torres-Robles Andrea , Benrimoj Shalom I , Gastelurrutia Miguel Angel , Martinez-Martinez Fernando , Peiro Tamara , Perez-Escamilla Beatriz , Rogers Kris , Valverde-Merino Isabel , Varas-Doval Raquel , Garcia-Cardenas Victoria 
Published: March 2021

BackgroundNon-adherence to medications continues to be a burden worldwide, with significant negative consequences. Community pharmacist interventions seem to be effective at improving medication adherence. However, more evidence is needed regarding their impact on disease-specific outcomes. The aim was to evaluate the impact of a community pharmacist-led adherence management intervention on adherence and clinical outcomes in patients with hypertension, asthma and chronic obstructive pulmonary disease (COPD).MethodsA 6-month cluster randomised controlled trial was conducted in Spanish community pharmacies. Patients suffering from hypertension, asthma and COPD were recruited. Patients in the intervention group received a medication adherence management intervention and the control group received usual care. The intervention was based on theoretical frameworks for changing patient behaviour. Medication adherence, disease-specific outcomes (Asthma Control Questionnaire (ACQ) scores, Clinical COPD Questionnaire (CCQ) scores and blood pressure levels) and disease control were evaluated. A multilevel regression model was used to analyse the data.ResultsNinety-eight pharmacies and 1186 patients were recruited, with 1038 patients completing the study. Patients receiving the intervention had an OR of 5.12 (95% CI 3.20 to 8.20, p<0.05) of being adherent after the 6 months. At the end of the study, patients in the intervention group had lower diastolic blood pressure levels (mean difference (MD) −2.88, 95% CI −5.33 to −0.43, p=0.02), lower CCQ scores (MD −0.50, 95% CI −0.82 to −0.18, p<0.05) and lower ACQ scores (MD −0.28, 95% CI −0.56 to 0.00, p<0.05) when compared with the control group.ConclusionsA community pharmacist-led medication adherence intervention was effective at improving medication adherence and clinical outcomes in patients suffering from hypertension, asthma and COPD. Future research should explore the implementation of these interventions in routine practice.Trial registration numberACTRN12618000410257.
Dickkopf 1 impairs the tumor response to PD-1 blockade by inactivating CD8+ T cells in deficient mismatch repair colorectal cancer
Authors: Sui Qiaoqi , Liu Dingxin , Jiang Wu , Tang Jinghua , Kong Lingheng , Han Kai , Liao Leen , Li Yuan , Ou Qingjian , Xiao Binyi , Liu Guochen , Ling Yihong , Chen Jiewei , Liu Zexian , Zuo Zhixiang , Pan Zhizhong , Zhou Penghui , Zheng Jian , Ding Pei-Rong 
Published: March 2021

BackgroundDickkopf 1 (DKK1) is associated with tumor progression. However, whether DKK1 influences the tumor response to programmed cell death protein 1 (PD-1) blockade in colorectal cancers (CRCs) with deficient mismatch repair (dMMR) or microsatellite instability (MSI) has never been clarified.MethodsTumor tissues from 80 patients with dMMR CRC were evaluated for DKK1 expression and immune status via immunohistochemistry. Serum DKK1 was measured in another set of 43 patients who received PD-1 blockade therapy. CT26 cells and dMMR CRC organoids were cocultured with T cells, and CT26-grafted BALB/c mice were also constructed. T-cell cytotoxicity was assessed by apoptosis assays and flow cytometry. The pathway through which DKK1 regulates CD8+ T cells was investigated using RNA sequencing, and chromatin immunoprecipitation and luciferase reporter assays were conducted to determine the downstream transcription factors of DKK1.ResultsElevated DKK1 expression was associated with recurrence and decreased CD8+ T-cell infiltration in dMMR CRCs, and patients with high-serum DKK1 had a poor response to PD-1 blockade. RNA interference or neutralization of DKK1 in CRC cells enhanced CD8+ T-cell cytotoxicity, while DKK1 decreased T-bet expression and activated GSK3β in CD8+ T cells. In addition, E2F1, a downstream transcription factor of GSK3β, directly upregulated T-bet expression. In organoid models, the proportion of apoptotic cells was elevated after individual neutralization of PD-1 or DKK1 and was further increased on combined neutralization of PD-1 and DKK1.ConclusionsDKK1 suppressed the antitumor immune reaction through the GSK3β/E2F1/T-bet axis in CD8+ T cells. Elevated serum DKK1 predicted poor tumor response to PD-1 blockade in dMMR/MSI CRCs, and DKK1 neutralization may restore sensitivity to PD-1 blockade.
Analyses of PD-L1 and Inflammatory Gene Expression Association with Efficacy of Nivolumab ± Ipilimumab in Gastric Cancer/Gastroesophageal Junction Cancer
Authors: Lei Ming , Siemers Nathan O. , Pandya Dimple , Chang Han , Sanchez Teresa , Harbison Christopher , Szabo Peter M. , Janjigian Yelena , Ott Patrick A. , Sharma Padmanee , Bendell Johanna , Evans Thomas R. Jeffry , de Braud Filippo , Chau Ian , Boyd Zachary 
Published: March 2021

AbstractPurpose:In advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC), there is a need to identify biomarkers of response to therapies, such as immune checkpoint inhibitors.Patients and Methods:In post hoc exploratory analyses from CheckMate 032 (GC/GEJC cohort), we evaluated associations between nivolumab ± ipilimumab (NIVO ± IPI) efficacy and programmed death ligand 1 (PD-L1) expression, defined by tumor cells (% TC) or combined positive score (CPS; sum of PD-L1–staining TCs + immune cells, divided by total viable TCs, × 100) using the Dako PD-L1 IHC 28-8 pharmDx assay, or inflammatory gene expression.Results:There was a trend toward increased efficacy (objective response and overall survival) when PD-L1 expression was determined by CPS compared with % TC at higher cutoffs of ≥5 and ≥10 in the pooled analysis of all treatment regimens. In this analysis, 19% and 26% of patients with PD-L1–positive tumors at a CPS cutoff of ≥5 and ≥10, respectively, had an objective response compared with 8% and 9% of patients at the equivalent % TC cutoffs. Longer survival was demonstrated in patients with PD-L1–positive (defined by CPS cutoffs of ≥5 and ≥10) versus PD-L1–negative status. Similar results were observed in the NIVO 1 mg/kg + IPI 3 mg/kg subgroup. Multiple inflammatory gene signatures/transcripts, including a signature consisting of four genes (CD274, CD8A, LAG3, and STAT1), showed associations with response to NIVO ± IPI.Conclusions:This study suggests a greater association of PD-L1 expression by CPS with NIVO ± IPI efficacy compared with % TC PD-L1 expression in patients with GC/GEJC. Inflammatory signatures were also associated with NIVO ± IPI response, warranting further investigation.See related commentary by Moutafi and Rimm, p. 3812
Therapeutic Efficacy of Combined JAK1/2, Pan-PIM, and CDK4/6 Inhibition in Myeloproliferative Neoplasms
Authors: Rampal Raajit K. , Pinzon-Ortiz Maria , Somasundara Amritha Varshini Hanasoge , Durham Benjamin , Koche Richard , Spitzer Barbara , Mowla Shoron , Krishnan Aishwarya , Li Bing , An Wenbin , Derkach Andriy , Devlin Sean , Rong Xianhui , Longmire Tyler , Eisman Shira Esther , Cordner Keith , Whitfield Justin T. , Vanasse Gary , Cao Zhu A. , Levine Ross L. 
Published: March 2021

Abstract

Purpose:
The JAK1/2 inhibitor ruxolitinib has demonstrated significant benefits for patients with myeloproliferative neoplasms (MPN). However, patients often lose response to ruxolitinib or suffer disease progression despite therapy with ruxolitinib. These observations have prompted efforts to devise treatment strategies to improve therapeutic efficacy in combination with ruxolitinib therapy. Activation of JAK–STAT signaling results in dysregulation of key downstream pathways, notably increased expression of cell-cycle mediators including CDC25A and the PIM kinases.

Experimental Design:
Given the involvement of cell-cycle mediators in MPNs, we sought to examine the efficacy of therapy combining ruxolitinib with a CDK4/6 inhibitor (LEE011) and a PIM kinase inhibitor (PIM447). We utilized JAK2-mutant cell lines, murine models, and primary MPN patient samples for these studies.

Results:
Exposure of JAK2-mutant cell lines to the triple combination of ruxolitinib, LEE011, and PIM447 resulted in expected on-target pharmacodynamic effects, as well as increased apoptosis and a decrease in the proportion of cells in S-phase, compared with ruxolitinib. As compared with ruxolitinib monotherapy, combination therapy led to reductions in spleen and liver size, reduction of bone marrow reticulin fibrosis, improved overall survival, and elimination of disease-initiating capacity of treated bone marrow, in murine models of MPN. Finally, the triple combination reduced colony formation capacity of primary MPN patient samples to a greater extent than ruxolitinib.

Conclusions:
The triple combination of ruxolitinib, LEE011, and PIM447 represents a promising therapeutic strategy with the potential to increase therapeutic responses in patients with MPN.
Analysis and Evaluation of Language Models for Word Sense
Disambiguation
Authors: Loureiro Daniel , Rezaee Kiamehr , Pilehvar Mohammad Taher , Camacho-Collados Jose 
Published: March 2021

Abstract
Transformer-based language models have taken many fields in NLP by storm. BERT and its derivatives dominate most of the existing evaluation benchmarks, including those for Word Sense Disambiguation (WSD), thanks to their ability in capturing context-sensitive semantic nuances. However, there is still little knowledge about their capabilities and potential limitations in encoding and recovering word senses. In this article, we provide an in-depth quantitative and qualitative analysis of the celebrated BERT model with respect to lexical ambiguity. One of the main conclusions of our analysis is that BERT can accurately capture high-level sense distinctions, even when a limited number of examples is available for each word sense. Our analysis also reveals that in some cases language models come close to solving coarse-grained noun disambiguation under ideal conditions in terms of availability of training data and computing resources. However, this scenario rarely occurs in real-world settings and, hence, many practical challenges remain even in the coarse-grained setting.We also perform an in-depth comparison of the two main language model based WSD strategies, namely, fine-tuning and feature extraction, finding that the latter approach is more robust with respect to sense bias and it can better exploit limited available training data. In fact, the simple feature extraction strategy of averaging contextualized embeddings proves robust even using only three training sentences per word sense, with minimal improvements obtained by increasing the size of this training data.