bluuebunny/crossref_metadata_2025_split huggingface dataset:
Racial/Ethnic Disparities in Alzheimer’s Disease Risk: Role of Exposure to Ambient Fine Particles
Authors: Younan Diana , Wang Xinhui , Gruenewald Tara , Gatz Margaret , Serre Marc L , Vizuete William , Braskie Meredith N , Woods Nancy F , Kahe Ka , Garcia Lorena , Lurmann Fred , Manson JoAnn E , Chui Helena C , Wallace Robert B , Espeland Mark A , Chen Jiu-Chiuan 
Published: August 2021

Abstract

Background
Whether racial/ethnic disparities in Alzheimer’s disease (AD) risk may be explained by ambient fine particles (PM2.5) has not been studied.

Method
We conducted a prospective, population-based study on a cohort of Black (n = 481) and White (n = 6 004) older women (aged 65–79) without dementia at enrollment (1995–1998). Cox models accounting for competing risk were used to estimate the hazard ratio (HR) for racial/ethnic disparities in AD (1996–2010) defined by Diagnostic and Statistical Manual of Mental Disorders, 4th edition and the association with time-varying annual average PM2.5 (1999–2010) estimated by spatiotemporal model.

Results
Over an average follow-up of 8.3 (±3.5) years with 158 incident cases (21 in Black women), the racial disparities in AD risk (range of adjusted HRBlack women = 1.85–2.41) observed in various models could not be explained by geographic region, age, socioeconomic characteristics, lifestyle factors, cardiovascular risk factors, and hormone therapy assignment. Estimated PM2.5 exposure was higher in Black (14.38 ± 2.21 µg/m3) than in White (12.55 ± 2.76 µg/m3) women, and further adjustment for the association between PM2.5 and AD (adjusted HRPM2.5 = 1.18–1.28) slightly reduced the racial disparities by 2%–6% (HRBlack women = 1.81–2.26). The observed association between PM2.5 and AD risk was ~2 times greater in Black (HRPM2.5 = 2.10–2.60) than in White (HRPM2.5 = 1.07–1.15) women (range of interaction ps: &lt;.01–.01). We found similar results after further adjusting for social engagement (social strain, social support, social activity, living alone), stressful life events, Women’s Health Initiative’s clinic sites, and neighborhood socioeconomic characteristics.

Conclusions
PM2.5 may contribute to racial/ethnic disparities in AD risk and its associated increase in AD risk was stronger among Black women.
Understanding the Benefits of Different Types and Timing of Education for Mental Health: A Sequence Analysis Approach
Authors: Vable Anusha M , Duarte Catherine dP , Wannier S Rae , Chan-Golston Alec M , Cohen Alison K , Glymour M Maria , Ream Robert K , Yen Irene H 
Published: August 2021

Abstract

Objectives
Individuals increasingly experience delays or interruptions in schooling; we evaluate the association between these nontraditional education trajectories and mental health.

Methods
Using year-by-year education data for 7,501 National Longitudinal Survey of Youth 1979 participants, ages 14–48 (262,535 person-years of education data), we applied sequence analysis and a clustering algorithm to identify educational trajectory groups, incorporating both type and timing to credential. Linear regression models, adjusted for early-life confounders, evaluated relationships between educational trajectories and mental health component summary (MCS) scores from the 12-item short form instrument at age 50. We evaluated effect modification by race, gender, and race by gender.

Results
We identified 24 distinct educational trajectories based on highest credential and educational timing. Compared to high school (HS) diplomas, &lt;HS (β = −3.41, 95% CI: −4.74, −2.07) and general educational development credentials predicted poorer MCS (β = −2.07, 95% CI: −3.16, −0.98). The following educational trajectories predicted better MCS: some college immediately after HS (β = 1.52, 95% CI: 0.68, 2.37), Associate degrees after long interruptions (β = 1.73, 95% CI: 0.27, 3.19), and graduate school soon after Bachelor’s completion (β = 1.13, 95% CI: 0.21, 2.06). Compared to White men, Black women especially benefited from educational credentials higher than HS in predicting MCS.

Discussion
Both type and timing of educational credential predicted mental health. Black women’s mental health especially benefited from higher educational credentials.
Truncated O-GalNAc glycans impact on fundamental signaling pathways in pancreatic cancer
Authors: Hofmann Bianca T , Picksak Aeint-Steffen , Kwiatkowski Marcel , Grupp Katharina , Jücker Manfred , Bachmann Kai , Mercanoglu Baris , Izbicki Jakob R , Kahlert Christoph , Bockhorn Maximilian , Güngör Cenap , Ewald Florian , Wolters-Eisfeld Gerrit 
Published: August 2021

Abstract
Truncated O-N-acetylgalactosamine (O-GalNAc) glycosylation is an important feature of pancreatic ductal adenocarcinoma (PDAC), and the expression of truncated O-GalNAc glycans is strongly associated with decreased survival and poor prognosis. It has been proven that aberrant O-GalNAc glycosylation influences PDAC signaling to promote oncogenic properties, but elucidation of the influence of truncated O-GalNAc glycosylation on different signaling molecules has just been started. We herein elucidated the impact of aberrant O-GalNAc glycosylation on two important PDAC signaling pathways, namely, AKT/mTOR and RAS/MAPK. In PDAC cells expressing truncated O-GalNAc glycans, we identified differentially expressed proteins associated with AKT/mTOR and RAS/MAPK pathways using quantitative proteomics. Since AKT, a key-signaling molecule in PDAC, was among the identified proteins, we analyzed AKT and found a strikingly enhanced S473 phosphorylation and identified a previously unknown O-GalNAc modification. Consecutive analysis of COSMC knockdowns in PDAC revealed strong effects on AKT upstream and downstream effector molecules. Interestingly, truncated O-GalNAc glycans could facilitate an mTORC1 inhibitor resistance using AZD8055. In addition, as AKT/mTOR pathway has extensive cross talks with RAS/MAPK pathway, we analyzed the pathways and found it to be negatively regulated. Finally, we found that the expression of epithelial-mesenchymal transition markers, key features of aggressive PDACs cells, are enhanced and truncated O-GalNAc glycans enhance pancreatic cancer cell growth in a xenograft mouse model. Our study demonstrates that truncated O-GalNAc glycans have a strong impact on AKT/mTOR and RAS/MAPK signaling pathways, are modulated by EGF or IGF-1 signaling and should be considered for targeted therapy of these pathways in PDAC.
Biochemical characterization of an inverting S/O-HexNAc-transferase and evidence of S-linked glycosylation in Actinobacteria
Authors: Sharma Yogita , Ahlawat Shimona , Rao Alka 
Published: August 2021

Abstract
Antimicrobial peptides harboring S- and or O-linked glycans are known as glycocins. Glycocins were first discovered and best characterized in Firmicutes. S-glycosylation is an enzymatic process catalyzed by S-glycosyltransferases of the GT2 family. Using a heterologous expression system, here we describe an inverting S/O-HexNAc-transferase (SvGT), encoded by ORF AQF52_3101 of Streptomyces venezuelae ATCC 15439, along with its acceptor substrate (SvC), encoded by ORF AQF52_3099. Using in vitro and in vivo assays, we define the distinct donor specificity, acceptor specificity, regioselectivity, chemoselectivity and Y(G/A/K/Q/E ≠ ΔG)(C/S/T ≠ Y/N)(G/A ≠ P/Q)G as the minimum acceptor sequon of SvGT. Although UDP-GlcNAc served as the donor in the cellular milieu, SvGT could also utilize UDP-Glc and UDP-GalNAc as donors in vitro. Using mass spectrometry and western blotting, we provide evidence that an anti-O-GlcNAc antibody (CTD110.6) cross-reacts with S-GlcNAc and may be used to detect S-GlcNAcylated glycoconjugates directly. With an understanding of enzyme specificities, we finally employed SvGT to generate two proof-of-concept neoglycocins against Listeria monocytogenes. In conclusion, this study provides the first experimental evidence for S-glycosylation in Actinobacteria and the application of its S/O-HexNAc-transferase in glycocin engineering.
No Trademark Protection for Artworks in the Public Domain – A Practical Guide to the Application of Public Order and Morality as Grounds for Refusal
Authors: Senftleben Martin 
Published: August 2021

Abstract
With its 2017 landmark decision in Vigeland, the Court of Justice of the European Free Trade Association States (EFTA Court) has paved the way for the invocation of public order and morality as grounds for refusal when trademark protection is sought for cultural expressions in the public domain. Dealing with an attempt to register artworks of the famous Norwegian sculptor Gustav Vigeland as trademarks, the EFTA Court took this step to safeguard the public domain status of literary and artistic works after the expiry of copyright, shield cultural creations against ‘commercial greed’ and ensure the freedom of the arts.1 Trademark examiners and judges seeking to follow in the footsteps of the EFTA Court, however, may find it difficult to operationalize the Vigeland criteria and put corresponding arguments for refusal into practice. Against this background, the following analysis provides guidelines for the practical application of public order and morality arguments in cultural heritage cases. It describes problems arising from the grant of trademark rights in cultural public domain material (Section I) and the traditional reluctance of trademark offices and courts to rely on public order and morality considerations in this context (Section II). After this statement of the problem, the criteria following from the Vigeland decision will be introduced (Section III) before we explore the practical implementation of the EFTA Court’s morality (Section IV) and public order (Section V) arguments in more detail. The final Section VI summarizes the results of the analysis.
Presence-only habitat suitability models for vulnerable marine ecosystem indicator taxa in the South Pacific have reached their predictive limit
Authors: Stephenson Fabrice , Rowden Ashley A , Anderson Owen F , Pitcher C Roland , Pinkerton Matt H , Petersen Grady , Bowden David A 
Published: August 2021

AbstractVulnerable marine ecosystems (VMEs) are typically fragile and slow to recover, making them likely to be substantially altered by disturbance. In the High Seas, regional fishery management organizations (RFMOs) are required to implement measures to prevent significant adverse impacts on VMEs. The objectives of the present study were to: update distribution models of VME indicator taxa in the South Pacific RFMO Convention Area; evaluate these against newly-collated independent field data to test the reliability of the presence-only habitat suitability models; and assess how well the updated models were able to predict into unsampled space. Ensemble habitat suitability models of 10 VME indicator taxa performed well using the newly collated data (AUC &gt; 0.95, TSS &gt; 0.76, and RMSE &lt; 0.34). There were no obvious patterns of decreasing model performance with decreasing environmental coverage; areas with few samples underpinning model predictions still had AUC &gt; 0.93, TSS &gt; 0.71, and RMSE &lt; 0.43. Despite these encouraging results, we also identify some important inherent issues with presence-only models that have profound implications for their use in management of VMEs. Future modelling efforts for VME management purposes should be based ideally on the use of survey presence-absence data and, preferably, abundance data.
Antimicrobial activity of ceftazidime/avibactam, ceftolozane/tazobactam and comparator agents against Pseudomonas aeruginosa from cystic fibrosis patients
Authors: Sader Helio S , Duncan Leonard R , Doyle Timothy B , Castanheira Mariana 
Published: August 2021

Abstract

Objectives
To evaluate the antimicrobial susceptibility patterns of Pseudomonas aeruginosa isolates collected from the lower respiratory tract of cystic fibrosis (CF) patients.

Methods
We susceptibility tested 273 contemporary P. aeruginosa isolates from 39 hospitals worldwide (17 countries) by the reference broth microdilution method.

Results
Ceftazidime/avibactam [MIC50/90, 2/8 mg/L; 96.0% susceptible (S)] was the most active agent, followed by ceftolozane/tazobactam (MIC50/90, 1/4 mg/L; 90.5% S), ceftazidime (MIC50/90, 2/&gt;32 mg/L; 80.6% S), piperacillin/tazobactam (MIC50/90, 4/128 mg/L; 80.2% S) and tobramycin (MIC50/90, 2/&gt;16 mg/L; 76.6% S). Ceftazidime/avibactam retained activity against P. aeruginosa isolates non-susceptible to meropenem (86.5% S to ceftazidime/avibactam), piperacillin/tazobactam (85.2% S to ceftazidime/avibactam) or ceftazidime (79.2% S to ceftazidime/avibactam). MDR phenotype was observed among 36.3% of isolates, and 88.9% and 73.7% of MDR isolates were susceptible to ceftazidime/avibactam and ceftolozane/tazobactam, respectively. Against isolates non-susceptible to meropenem, piperacillin/tazobactam and ceftazidime, susceptibility rates were 78.9% for ceftazidime/avibactam and 47.4% for ceftolozane/tazobactam. Ceftazidime/avibactam was active against 65.4% of ceftolozane/tazobactam-non-susceptible isolates and ceftolozane/tazobactam was active against 18.2% of ceftazidime/avibactam-non-susceptible isolates.

Conclusions
Ceftazidime/avibactam and ceftolozane/tazobactam exhibited potent and broad-spectrum activity against P. aeruginosa isolated from CF patients worldwide, but higher susceptibility rates for ceftazidime/avibactam compared with ceftolozane/tazobactam were observed among the resistant subsets. Ceftazidime/avibactam and ceftolozane/tazobactam represent valuable options to treat CF pulmonary exacerbations caused by P. aeruginosa.
A qualitative study of provider burnout: do medical scribes hinder or help?
Authors: Corby Sky , Ash Joan S , Mohan Vishnu , Becton James , Solberg Nicholas , Bergstrom Robby , Orwoll Benjamin , Hoekstra Christopher , Gold Jeffrey A 
Published: August 2021

Abstract

Objective
Provider burnout is a crisis in healthcare and leads to medical errors, a decrease in patient satisfaction, and provider turnover. Many feel that the increased use of electronic health records contributes to the rate of burnout. To avoid provider burnout, many organizations are hiring medical scribes. The goal of this study was to identify relevant elements of the provider–scribe relationship (like decreasing documentation burden, extending providers’ careers, and preventing retirement) and describe how and to what extent they may influence provider burnout.

Materials and Methods
Qualitative methods were used to gain a broad view of the complex landscape surrounding scribes. Data were collected in 3 phases between late 2017 and early 2019. Data from 5 site visits, interviews with medical students who had experience as scribes, and discussions at an expert conference were analyzed utilizing an inductive approach.

Results
A total of 184 transcripts were analyzed to identify patterns and themes related to provider burnout. Provider burnout leads to increased provider frustration and exhaustion. Providers reported that medical scribes improve provider job satisfaction and reduce burnout because they reduce the documentation burden. Medical scribes extend providers’ careers and may prevent early retirement. Unfortunately, medical scribes themselves may experience similar forms of burnout.

Conclusion
Our data from providers and managers suggest that medical scribes help to reduce provider burnout. However, scribes are not the only solution for reducing documentation burden and there may be potentially better options for preventing burnout. Interestingly, medical scribes sometimes suffer from burnout themselves, despite their temporary roles.
A comparison of attentional neural network architectures for modeling with electronic medical records
Authors: Finch Anthony , Crowell Alexander , Chang Yung-Chieh , Parameshwarappa Pooja , Martinez Jose , Horberg Michael 
Published: August 2021

Abstract

Objective
Attention networks learn an intelligent weighted averaging mechanism over a series of entities, providing increases to both performance and interpretability. In this article, we propose a novel time-aware transformer-based network and compare it to another leading model with similar characteristics. We also decompose model performance along several critical axes and examine which features contribute most to our model’s performance.

Materials and methods
Using data sets representing patient records obtained between 2017 and 2019 by the Kaiser Permanente Mid-Atlantic States medical system, we construct four attentional models with varying levels of complexity on two targets (patient mortality and hospitalization). We examine how incorporating transfer learning and demographic features contribute to model success. We also test the performance of a model proposed in recent medical modeling literature. We compare these models with out-of-sample data using the area under the receiver-operator characteristic (AUROC) curve and average precision as measures of performance. We also analyze the attentional weights assigned by these models to patient diagnoses.

Results
We found that our model significantly outperformed the alternative on a mortality prediction task (91.96% AUROC against 73.82% AUROC). Our model also outperformed on the hospitalization task, although the models were significantly more competitive in that space (82.41% AUROC against 80.33% AUROC). Furthermore, we found that demographic features and transfer learning features which are frequently omitted from new models proposed in the EMR modeling space contributed significantly to the success of our model.

Discussion
We proposed an original construction of deep learning electronic medical record models which achieved very strong performance. We found that our unique model construction outperformed on several tasks in comparison to a leading literature alternative, even when input data was held constant between them. We obtained further improvements by incorporating several methods that are frequently overlooked in new model proposals, suggesting that it will be useful to explore these options further in the future.
The Algebra of Non-deterministic Programs: Demonic Operations, Orders and Axioms
Authors: Hirsch Robin , Mikulás Szabolcs , Stokes Tim 
Published: August 2021

Abstract
Demonic composition, demonic refinement and demonic union are alternatives to the usual ‘angelic’ composition, angelic refinement (inclusion) and angelic (usual) union defined on binary relations. We first motivate both the angelic and the demonic via an analysis of the behaviour of non-deterministic programs, with the angelic associated with partial correctness and demonic with total correctness, both cases emerging from a richer algebraic model of non-deterministic programs incorporating both aspects. Zareckiĭ has shown that the isomorphism class of algebras of binary relations under angelic composition and inclusion is finitely axiomatized as the class of ordered semigroups. The proof can be used to establish that the same axiomatization applies to binary relations under demonic composition and refinement, and a further modification of the proof can be used to incorporate a zero element representing the empty relation in the angelic case and the full relation in the demonic case. For the signature of angelic composition and union, it is known that no finite axiomatization exists, and we show the analogous result for demonic composition and demonic union by showing that the same axiomatization holds for both. We show that the isomorphism class of algebras of binary relations with the ‘mixed’ signature of demonic composition and angelic inclusion has no finite axiomatization. As a contrast, we show that the isomorphism class of partial algebras of binary relations with the partial operation of constellation product and inclusion (also a ‘mixed’ signature) is finitely axiomatizable.
A systematic literature review of prognostic factors in patients with HR+/HER2− advanced breast cancer in Japan
Authors: Hattori Masaya , Novick Diego , Takaura Kana , Tanizawa Yoshinori , Kawaguchi Tsutomu , Haro Josep Maria , Monistrol-Mula Anna , Onishi Akira , Iwata Hiroji 
Published: August 2021

Abstract

Background
Breast cancer is the most prevalent cancer in women in Japan and the fifth in mortality. This systematic review summarized the evidence for prognostic factors for patients with HR+/HER2− advanced and metastatic breast cancer in Japan.

Methods
MEDLINE and EMBASE were searched with keywords ‘breast neoplasms’ AND ‘Japan’ AND ‘advanced’ or equivalent, and Japan Medical Abstract Society database with ‘breast cancer’ AND ‘advanced/metastatic’ for publications from January 2010 to October 2019. ASCO, ESMO, ABC4 abstracts and WHO website were hand searched. The endpoints of interest were overall survival, progression-free survival, tumour response and post-progression survival. Factors were evaluated based on the consistency in direction and the strength (hazard ratios) of association.

Results
Searches identified 4530 publications, of which 27 were eligible. All were observational studies. Among the endpoints, overall survival was the most commonly assessed (n = 22) and evaluated further. Ki-67 expression, progesterone receptor expression status, tumour grade and lymph node metastases were consistently associated with poor overall survival in univariate analysis but not in multivariate analysis. Short disease-free interval, the number of metastatic organs and liver metastasis were consistently associated with poor overall survival in both of univariate and multivariate analysis. The association was strong for liver metastasis (hazard ratio ≥2.8 in the majority of studies) and moderate for disease-free interval and the number of metastatic organs (hazard ratio 1.3–2.8 in the majority of studies).

Conclusions
Disease-free interval, the number of metastatic organs and liver metastasis were identified as independent prognostic factors for overall survival. These findings may help clinical decision-making to improve outcomes in patients with HR+/HER2− advanced and metastatic breast cancer.
Molecular responses to chilling in a warming climate and their impacts on plant reproductive development and yield
Authors: Penfield Steven , Warner Samuel , Wilkinson Laura 
Published: August 2021

Abstract
Responses to prolonged winter chilling are universal in temperate plants which use seasonal temperature cues in the seed, vegetative, and reproductive phases to align development with the earth’s orbit. Climate change is driving a decline in reliable winter chill and affecting the subtropical extent of cultivation for temperate overwintering crops. Here we explore molecular aspects of plant responses to winter chill including seasonal bud break and flowering, and how variation in the intensity of winter chilling or devernalization can lead to effects on post-chilling plant development, including that of structures necessary for crop yields.