bluuebunny/crossref_metadata_2025_split huggingface dataset:
Three decades of genetic privacy: a metaphoric journey
Authors: Knoppers Bartha Maria , Beauvais Michael J S 
Published: June 2021

Abstract
Debates surrounding genetic privacy have taken on different forms over the past 30 years. Taking genetic privacy to mean an interest that individuals, families, or even communities have with respect to genetic information, we examine the metaphors used in these debates to chronicle the development of genetic privacy. In 1990–2000, we examine claims for ownership and of ‘humanity’ spurred by the launch of the Human Genome Project and related endeavors. In 2000–2010, we analyze the interface of law and ethics with research infrastructures such as biobanks, for which notions of citizenship and ‘public goods’ were central. In 2010–2020, we detail the relational turn of genetic privacy in response of large international research consortia and big data. Although each decade had its leading conceptions of genetic privacy, the subject is neither strictly chronological nor static. We conclude with reflections on the nature of genetic privacy and the necessity to bring together the unique and private genetic self with the human other.
Pharmacokinetic-Pharmacodynamic Model of Vedolizumab for Targeting Endoscopic Remission in Patients With Crohn Disease: Posthoc Analysis of the LOVE-CD Study
Authors: Hanzel Jurij , Dreesen Erwin , Vermeire Séverine , Löwenberg Mark , Hoentjen Frank , Bossuyt Peter , Clasquin Esmé , Baert Filip J , D’Haens Geert R , Mathôt Ron 
Published: June 2021

Abstract

Background
Higher serum concentrations of vedolizumab have been associated with improved outcomes in inflammatory bowel disease. It is unclear how vedolizumab exposure is linked to endoscopic remission in Crohn disease (CD). We aimed to develop a pharmacokinetic-pharmacodynamic model linking vedolizumab exposure to endoscopic remission in CD.

Methods
Data were obtained from the first 110 patients participating in a phase 4 prospective multicenter trial (LOVE-CD; ClinicalTrials.gov identifier: NCT02646683), where vedolizumab was dosed at 300 mg every 8 weeks and serum concentrations and antibodies to vedolizumab were measured before each infusion. Concentration-time profiles were described by a 2-compartment model with parallel linear and nonlinear elimination. A first-order discrete-time Markov model was used to describe the relationship between pharmacokinetic exposure metrics and the probability of endoscopic remission (Simple Endoscopic Score for CD &lt; 4).

Results
Linear clearance was 0.215 L/d, and the volume of distribution of the central compartment was 4.92 L. Linear clearance was higher and vedolizumab exposure was lower in patients with lower serum albumin concentrations, in the presence of antibodies to vedolizumab, and in patients with previous exposure to other biologic therapy. A week 22 vedolizumab concentration of 20.0 mg/L was predicted to yield a 35% probability of achieving endoscopic remission at week 26. Model-based simulations suggested that endoscopic remission rates of 46.5% or 40.0% could be reached with every-4-weeks dosing in patients who were naïve or previously exposed to biologic therapy, respectively.

Conclusions
Model-informed dosing of vedolizumab in CD provides a foundation for future research aiming to maximize endoscopic remission rates.
Posttraumatic Stress in Patients With Inflammatory Bowel Disease: Prevalence and Relationships to Patient-Reported Outcomes
Authors: Taft Tiffany H , Quinton Sarah , Jedel Sharon , Simons Madison , Mutlu Ece A , Hanauer Stephen B 
Published: June 2021

Abstract

Background
Patients with chronic illness are at increased risk for traumatic stress because of medical trauma. Initial studies of posttraumatic stress (PTS) in patients with inflammatory bowel disease (IBD) have found that approximately one-third of patients may experience significant PTS symptoms including flashbacks, nightmares, hypervigilance, disrupted sleep, and low mood. We aim to better characterize PTS in IBD and its relationship with patient outcomes in a large cohort of patients with IBD.

Methods
Adult patients registered with the Crohn’s & Colitis Foundation/University of North Carolina IBD Partners database were invited to complete a supplementary survey between February and July 2020. The Post Traumatic Stress Disorder Checklist-5th edition was administered as a supplemental survey. Additional data from IBD Partners included disease severity, surgery and hospital history, demographics, and health care utilization.

Results
A total of 797 patients participated (452 with Crohn disease, 345 with ulcerative colitis). No impacts on response patterns because of the COVID-19 pandemic were found. Although 5.6% of the sample reported an existing PTS diagnosis because of IBD experiences, 9.6% of participants met the full IBD-related PTS diagnostic criteria per the Post Traumatic Stress Disorder Checklist-5th edition. Female patients, younger patients, those with less educational attainment, non-White patients, and Hispanic patients reported higher levels of PTS symptoms. Patients with higher PTS symptoms were more likely to have been hospitalized, have had surgery, have more severe symptoms, and not be in remission. Increased PTS was also associated with increased anxiety, depression, pain interference, fatigue, and health care utilization.

Conclusions
The present findings support prior research that approximately one-quarter to one-third of patients with IBD report significant symptoms of PTS directly from their disease experiences, and certain demographic groups are at higher risk. In addition, PTS is associated with several IBD outcomes. Patients with higher PTS symptoms are less likely to be in remission and may utilize more outpatient gastrointestinal services. Intervention trials to mitigate PTS symptoms in patients with IBD are warranted.
The effects of spatiotemporal scale on commercial fishery abundance index suitability
Authors: Wang Jintao , Boenish Robert , Chen Xinjun , Tian Siquan , Zhu JiangFeng 
Published: June 2021

Abstract
With consideration of sophisticated modern commercial fisheries, the commonly used metric catch per unit effort (CPUE) may not be a reasonable proxy for generating abundance indices (AIs) for all species. Presumably, spatiotemporal scale is a critical factor that affects the accuracy of local/aggregated AIs derived from spatial modelling approaches, thus it is necessary to evaluate how scale affects scientific estimates of abundance. We explored three commonly utilized AI proxies, including aggregated catch (CatchAI), aggregated effort (EffortAI), and CPUEAI from the perspective of accuracy and spatial representational ability using a neural network (NN) model at different spatiotemporal scales. As a case example, we grouped the Chinese fleet's Northwest Pacific neon flying squid (Ommastrephes bartramii) fishery dataset (2009–2018) at four spatial scales (0.25° × 0.25°, 0.5° × 0.5°, 1° × 1°, 2° × 2°) to construct monthly and annual resolution models. The results showed that for both simulated and real datasets, AIs based on catch data had better accuracy, consistency, and spatial representational ability compared to CPUE and effort-dependent AI models at all spatial scales. Relative to the finest spatial scale, only results from the model with 0.5° × 0.5° resolution preserved enough distributional detail to reflect the known migration route for O. bartramii. Model results exhibited large variation dependent on spatial scale, particularly amongst CPUEAI scenarios. We suggest that scale comparisons among potential proxies should be conducted prior to AIs being used for applications such as population trends in stock assessment.
On the convergence and mesh-independent property of the Barzilai–Borwein method for PDE-constrained optimization
Authors: Azmi Behzad , Kunisch Karl 
Published: June 2021

Abstract
Aiming at optimization problems governed by partial differential equations (PDEs), local R-linear convergence of the Barzilai–Borwein (BB) method for a class of twice continuously Fréchet-differentiable functions is proven. Relying on this result, the mesh-independent principle for the BB-method is investigated. The applicability of the theoretical results is demonstrated for two different types of PDE-constrained optimization problems. Numerical experiments are given, which illustrate the theoretical results.
Notch signaling supports the appearance of follicular helper T cells in the Peyer’s patches concomitantly with the reduction of regulatory T cells
Authors: Yazawa Masaki , Hosokawa Hiroyuki , Koizumi Maria , Hirano Ken-ichi , Imai Jin , Hozumi Katsuto 
Published: June 2021

Abstract
The intracellular fragment of Notch1, a mediator of Notch signaling that is frequently detected in thymic immigrants, is critical for specifying T-cell fate in the thymus, where Delta-like 4 (Dll4) functions as a Notch ligand on the epithelium. However, as such Notch signaling has not been detected in mature T cells, how Notch signaling contributes to their response in secondary lymphoid organs has not yet been fully defined. Here, we detected the marked expression of Dll4 on the stromal cells and the active fragment of Notch1 (Notch1 intracellular domain, N1ICD) in CD4+ T cells in the follicles of Peyer’s patches (PPs). In addition, N1ICD-bearing T cells were found in the T-cell zone of PPs, especially in the transcription factor Foxp3+ regulatory T (Treg) cells, with slight expression of Dll4 on the stromal cells. These fragments disappeared in Dll4-deficient conditions. It was also found that Notch1- and Notch2-deficient T cells preferentially differentiated into Treg cells in PPs, but not CXCR5+PD-1+ follicular helper T (Tfh) cells. Moreover, these phenotypes were also observed in chimeric mice reconstituted with the control and T-cell-specific Notch1/2-deficient bone marrow or Treg cells. These results demonstrated that Dll4-mediated Notch signaling in PPs is required for the efficient appearance of Tfh cells in a Treg cell-prone environment, which is common among the gut-associated lymphoid tissues, and is critical for the generation of Tfh-mediated germinal center B cells.
Military Experience and Elite Decision-Making: Self-Selection, Socialization, and the Vietnam Draft Lottery
Authors: Lupton Danielle L 
Published: June 2021

AbstractScholars across international relations (IR) debate the role military experience plays in elite decision-making. I argue there are two critical problems with this debate. First, it fails to adequately consider the underlying mechanisms linking military service to elite policy preferences. Second, it narrowly focuses on the use of force and largely ignores other ways in which military experience may shape elite behavior. I employ vulnerability to the Vietnam draft lottery to disentangle the impact of two key mechanisms linking military service to elite preferences: self-selection and socialization. I compare the foreign and defense policy roll call votes of Members of Congress (MCs) in the House of Representatives across the 94th–113th Congresses who were eligible for the draft and served in the military to those who were eligible for the draft but did not serve. I find significant differences in the roll call voting behavior between these groups, particularly on issues associated with arming and defense budget restrictions, as well as broader oversight of the military. These effects are heightened for MCs who served on active duty, in the military longer, and in combat, providing strong support for socialization effects. My study carries implications for civil–military relations, elite decision-making, and the study of leaders in IR.
Mechanisms of antibiotic resistance of Clostridioides difficile
Authors: Wickramage Ishani , Spigaglia Patrizia , Sun Xingmin 
Published: June 2021

Abstract
Clostridioides difficile (CD) is one of the top five urgent antibiotic resistance threats in USA. There is a worldwide increase in MDR of CD, with emergence of novel strains which are often more virulent and MDR. Antibiotic resistance in CD is constantly evolving with acquisition of novel resistance mechanisms, which can be transferred between different species of bacteria and among different CD strains present in the clinical setting, community, and environment. Therefore, understanding the antibiotic resistance mechanisms of CD is important to guide optimal antibiotic stewardship policies and to identify novel therapeutic targets to combat CD as well as other bacteria. Epidemiology of CD is driven by the evolution of antibiotic resistance. Prevalence of different CD strains and their characteristic resistomes show distinct global geographical patterns. Understanding epidemiologically driven and strain-specific characteristics of antibiotic resistance is important for effective epidemiological surveillance of antibiotic resistance and to curb the inter-strain and -species spread of the CD resistome. CD has developed resistance to antibiotics with diverse mechanisms such as drug alteration, modification of the antibiotic target site and extrusion of drugs via efflux pumps. In this review, we summarized the most recent advancements in the understanding of mechanisms of antibiotic resistance in CD and analysed the antibiotic resistance factors present in genomes of a few representative well known, epidemic and MDR CD strains found predominantly in different regions of the world.
Interpretable disease prediction using heterogeneous patient records with self-attentive fusion encoder
Authors: Kwak Heeyoung , Chang Jooyoung , Choe Byeongjin , Park Sangmin , Jung Kyomin 
Published: June 2021

Abstract

Objective
We propose an interpretable disease prediction model that efficiently fuses multiple types of patient records using a self-attentive fusion encoder. We assessed the model performance in predicting cardiovascular disease events, given the records of a general patient population.

Materials and Methods
We extracted 798111 ses and 67 623 controls from the sample cohort database and nationwide healthcare claims data of South Korea. Among the information provided, our model used the sequential records of medical codes and patient characteristics, such as demographic profiles and the most recent health examination results. These two types of patient records were combined in our self-attentive fusion module, whereas previously dominant methods aggregated them using a simple concatenation. The prediction performance was compared to state-of-the-art recurrent neural network-based approaches and other widely used machine learning approaches.

Results
Our model outperformed all the other compared methods in predicting cardiovascular disease events. It achieved an area under the curve of 0.839, while the other compared methods achieved between 0.74111 d 0.830. Moreover, our model consistently outperformed the other methods in a more challenging setting in which we tested the model’s ability to draw an inference from more nonobvious, diverse factors.

Discussion
We also interpreted the attention weights provided by our model as the relative importance of each time step in the sequence. We showed that our model reveals the informative parts of the patients’ history by measuring the attention weights.

Conclusion
We suggest an interpretable disease prediction model that efficiently fuses heterogeneous patient records and demonstrates superior disease prediction performance.
Isotope analysis reveals dietary overlap among sympatric canids
Authors: Webster Sarah C , Chamberlain Michael J , Hinton Joseph W , Beasley James C 
Published: June 2021

Abstract
When colonizing new regions, invading species might compete strongly with phylogenetically related species native to the regions they are colonizing, eventually leading to coexistence or displacement. In the southeast of the United States, recently established coyotes (Canis latrans) compete with red fox (Vulpes vulpes) and gray fox (Urocyon cinereoargenteus), although it remains unclear if competition is leading to resource partitioning or displacement by species. Using nitrogen and carbon stable isotopes, we tested the hypothesis that coyotes compete with foxes for food resources, with canids partitioning those resources to mitigate competition. We compared diets of canids in the southeast to those in the Plains region of the United States, a region where all three species historically have coexisted. We analyzed 217 hair samples from both regions pre-1960, prior to coyote colonization of the southeast, and post-2000, after coyotes were ubiquitous there, to assess differences in diet among species for both regions (southeast versus Plains and time periods, pre- versus postcolonization by coyotes). Modeling revealed significant dietary overlap among historical and contemporary populations in the southeast. Historically, all species partitioned resources in the Plains. Contemporarily, red fox and coyotes co-occurring in the Plains overlapped in diet; however, gray fox diet did not overlap with those of red fox and coyotes. Absence of partitioning in diet among co-occurring canids in the southeast indicates that interspecific competition could be strong in the region. Competition among canid populations in the southeast could lead to further resource partitioning among species that promotes coexistence or competitive exclusion of smaller fox species where coyote populations are abundant.
Association of the COVID-19 Pandemic With Patterns of Statewide Cancer Services
Authors: Yabroff K Robin , Wu Xiao-Cheng , Negoita Serban , Stevens Jennifer , Coyle Linda , Zhao Jingxuan , Mumphrey Brent J , Jemal Ahmedin , Ward Kevin C 
Published: June 2021

Abstract
The coronavirus disease 2019 (COVID-19) pandemic led to delayed medical care in the United States. We examined changes in patterns of cancer diagnosis and surgical treatment between January 1 and December 31 in 2020 and 2019 with real-time electronic pathology report data from population-based Surveillance, Epidemiology, and End Results cancer registries from Georgia and Louisiana. During 2020, there were 29 905 fewer pathology reports than in 2019, representing a 10.2% decline. Declines were observed in all age groups, including children and adolescents younger than 18 years. The nadir was early April 2020, with 42.8% fewer reports than in April 2019. Numbers of reports through December 2020 never consistently exceeded those in 2019 after first declines. Patterns were similar by age group and cancer site. Findings suggest substantial delays in diagnosis and treatment services for cancers during the pandemic. Ongoing evaluation can inform public health efforts to minimize any lasting adverse effects of the pandemic on cancer diagnosis, stage, treatment, and survival.
Nondiscrimination in Standard Essential Patents; ND Prong V. Art. 102(C) TFEU
Authors: Botta Marco 
Published: June 2021

Abstract
The article analyses the meaning of the nondiscriminatory principle in disputes concerning Standard Essential Patents (SEPs) under EU competition and contract law (that is, ND prong). The article reviews the economics literature, looking at the welfare effect of price discrimination and the interpretation of the ND prong provided by a number of economists. Secondly, the article analyses the case law of the EU Court of Justice on Art. 102(c) TFEU and recent rulings by the German and British courts concerning the scope of the application of the ND prong. A strategy of discrimination in regard to royalty rates may be sanctioned, both under competition and contract law. However, Art. 102(c) requires a higher burden of proof than contract law. As a consequence, it is unsurprising that no case of royalty rate discrimination has ever been sanctioned in Europe as an abuse of dominance. While courts and economists generally agree that the ND prong is applicable only when licensees are “similarly situated,” to date, there is no common understanding of the meaning of this expression. In particular, it is unclear whether, and to what extent, licensees are “similarly situated” if they are not competitors in the downstream market.
Can Understory Plant Composition and Richness Help Designate Riparian Management Zones in Mesic Headwater Forests of the Northeastern United States?
Authors: Jayasuriya Maneesha T , Stella John C , Germain René H 
Published: June 2021

AbstractRiparian buffers implemented to minimize sediment, nutrients, and disturbance impacts on streams during forest operations vary greatly in the degree to which ecological criteria are used in their design. Because most forest operations are concentrated around headwater streams, our primary research objective was to identify a floristically based riparian boundary for headwater streams using plant species composition and indicator species to classify riparian environments distinct from the surrounding upland forest. Within three forested regions of the Northeast US, understory vegetation plots were sampled along perpendicular transects extending from the stream bank into the upland forest. At all sites, species richness was highest adjacent to the stream, decreasing exponentially within 6–12 m from the channel. Species composition closest to the stream was significantly different from all other lateral distances, but identified riparian indicator species were of limited practical use across all sites. However, changes in species richness can serve to identify a riparian area extent up to 6–12 m from headwater streams.
The Statewide Economic Impact of Child Care–Associated Viral Acute Gastroenteritis Infections
Authors: Hayashi Michael A L , Eisenberg Joseph N S , Martin Emily T , Hashikawa Andrew N 
Published: June 2021

AbstractIntroductionMore than 65% of children aged ≤5 years in the United States require out-of-home child care. Child care attendance has been associated with an elevated risk of respiratory illness and acute gastroenteritis (AGE). While child care–associated respiratory disease cases are more numerous, AGE is associated with more severe symptoms and more than double the number of absences from child care. In addition, viral pathogens such as norovirus, rotavirus, and adenovirus are highly infectious and may be spread to parents and other household members. As a result, child care–associated viral AGE may incur substantial economic costs due to healthcare service usage and lost productivity.MethodsWe used surveillance data from a network of child care centers in Washtenaw County, Michigan, as well as a household transmission model to estimate the annual cost of child care–associated viral AGE in the state of Michigan.ResultsWe estimated that child care–associated viral AGE in Michigan costs between $15 million and $31 million annually, primarily due to lost productivity.ConclusionsThe economic burden of child care–associated infections is considerable. Effective targeted interventions are needed to mitigate this impact.