bluuebunny/crossref_metadata_2025_split huggingface dataset:
Exome sequencing of bulked segregants identified a novel TaMKK3-A allele linked to the wheat ERA8 ABA-hypersensitive germination phenotype
Authors: Martinez Shantel A. , Shorinola Oluwayesi , Conselman Samantha , See Deven , Skinner Daniel Z. , Uauy Cristobal , Steber Camille M. 
Published: January 2020

Abstract
Key message
Using bulked segregant analysis of exome sequence, we fine-mapped the ABA-hypersensitive mutant ERA8 in a wheat backcross population to the TaMKK3-A locus of chromosome 4A.

Abstract
Preharvest sprouting (PHS) is the germination of mature grain on the mother plant when it rains before harvest. The ENHANCED RESPONSE TO ABA8 (ERA8) mutant increases seed dormancy and, consequently, PHS tolerance in soft white wheat ‘Zak.’ ERA8 was mapped to chromosome 4A in a Zak/‘ZakERA8’ backcross population using bulked segregant analysis of exome sequenced DNA (BSA-exome-seq). ERA8 was fine-mapped relative to mutagen-induced SNPs to a 4.6 Mb region containing 70 genes. In the backcross population, the ERA8 ABA-hypersensitive phenotype was strongly linked to a missense mutation in TaMKK3-A-G1093A (LOD 16.5), a gene associated with natural PHS tolerance in barley and wheat. The map position of ERA8 was confirmed in an ‘Otis’/ZakERA8 but not in a ‘Louise’/ZakERA8 mapping population. This is likely because Otis carries the same natural PHS susceptible MKK3-A-A660S allele as Zak, whereas Louise carries the PHS-tolerant MKK3-A-C660R allele. Thus, the variation for grain dormancy and PHS tolerance in the Louise/ZakERA8 population likely resulted from segregation of other loci rather than segregation for PHS tolerance at the MKK3 locus. This inadvertent complementation test suggests that the MKK3-A-G1093A mutation causes the ERA8 phenotype. Moreover, MKK3 was a known ABA signaling gene in the 70-gene 4.6 Mb ERA8 interval. None of these 70 genes showed the differential regulation in wild-type Zak versus ERA8 expected of a promoter mutation. Thus, the working model is that the ERA8 phenotype results from the MKK3-A-G1093A mutation.
Sample preparation of formalin-fixed paraffin-embedded tissue sections for MALDI-mass spectrometry imaging
Authors: Hermann Juliane , Noels Heidi , Theelen Wendy , Lellig Michaela , Orth-Alampour Setareh , Boor Peter , Jankowski Vera , Jankowski Joachim 
Published: January 2020

AbstractMatrix-assisted laser desorption/ionization (MALDI) mass spectrometry imaging (MALDI MSI) has become a powerful tool with a high potential relevance for the analysis of biomolecules in tissue samples in the context of diseases like cancer and cardiovascular or cardiorenal diseases. In recent years, significant progress has been made in the technology of MALDI MSI. However, a more systematic optimization of sample preparation would likely achieve an increase in the molecular information derived from MALDI MSI. Therefore, we have employed a systematic approach to develop, establish and validate an optimized “standard operating protocol” (SOP) for sample preparation in MALDI MSI of formalin-fixed paraffin-embedded (FFPE) tissue sample analyses within this study. The optimized parameters regarding the impact on the resulting signal-to-noise (S/N) ratio were as follows: (i) trypsin concentration, solvents, deposition method, and incubation time; (ii) tissue washing procedures and drying processes; and (iii) spray flow rate, number of layers of trypsin deposition, and grid size. The protocol was evaluated on interday variability and its applicability for analyzing the mouse kidney, aorta, and heart FFPE tissue samples. In conclusion, an optimized SOP for MALDI MSI of FFPE tissue sections was developed to generate high sensitivity, to enhance spatial resolution and reproducibility, and to increase its applicability for various tissue types. This optimized SOP will further increase the molecular information content and intensify the use of MSI in future basic research and diagnostic applications.
The past, present, and future status of multimodality treatment for resectable/borderline resectable pancreatic ductal adenocarcinoma
Authors: Sakaguchi Tatsuma , Satoi Sohei , Yamamoto Tomohisa , Yamaki So , Sekimoto Mitsugu 
Published: January 2020

AbstractA multimodal approach to treating pancreatic ductal adenocarcinoma (PDAC) is now widely accepted. Improvements in radiological assessment have enabled us to define resectability in detail. Multimodality treatment is essential for patients, especially for those with PDAC in the borderline resectable (BR) stage. Even for disease in a resectable (R) stage, adjuvant and neoadjuvant therapies have demonstrated beneficial outcomes in several trials and analyses. Thus, there is growing interest in optimization of the perioperative therapeutic strategy. We discuss the transition of resectability criteria and the global standard of adjuvant and neoadjuvant treatments for patients with R/BR-PDAC.
Clinical pathways of epileptic seizures and status epilepticus: results from a survey in Italy
Authors: Zaccara Gaetano , Citerio Giuseppe , Del Gaudio Alfredo , Ferlisi Monica , Pugliese Francesco Rocco , Toni Danilo 
Published: January 2020

Summary
Objective
Patients with seizures or status epilepticus (SE) access the hospital through emergency departments and may be admitted into different wards according to the level of care required. Clinicians with different expertise are in charge of taking critical therapeutic decisions. To date, very few studies have investigated the stage at which these patients are referred to neurologists or epileptologists and how guideline recommendations are applied in clinical practice.

Methods
A survey was used to investigate how patients with epileptic seizures or SE are managed in emergency and in subsequent hospital pathways in Italy.

Results
One hundred and seventy-seven physicians (mainly neurologists) from all parts of Italy filled in a questionnaire. Less than half of the participants (35%) answered that, in their hospital, patients with epilepsy were managed by epileptologists. The percentages were lower for patients presenting with acute seizures (21%) or SE (16%). Diagnostic, therapeutic, and assistance pathways (PDTA) for patients presenting with seizure(s) or SE were available for both conditions in about 50% of cases, while, in the rest of the hospitals, participants indicated informal agreements (about 25% of cases) or lack of any agreement (about 25% of cases) between clinicians. Professionals more often involved in PDTA were epileptologists/neurologists, emergency physicians, and intensivists. More than half ot the participants (55%) thought that organizational issues are the most important criticalities for such patients and need to be improved (61%).

Significance
There is a high variability in hospital clinical pathways for epilepsy in Italy.
Consensus statement of the Italian society of colorectal surgery (SICCR): management and treatment of hemorrhoidal disease
Authors: Gallo G. , Martellucci J. , Sturiale A. , Clerico G. , Milito G. , Marino F. , Cocorullo G. , Giordano P. , Mistrangelo M. , Trompetto M. 
Published: January 2020

AbstractHemorrhoidal disease (HD) is the most common proctological disease in the Western countries. However, its real prevalence is underestimated due to the frequent self-medication.The aim of this consensus statement is to provide evidence-based data to allow an individualized and appropriate management and treatment of HD. The strategy used to search for evidence was based on application of electronic sources such as MEDLINE, PubMed, Cochrane Review Library, CINAHL, and EMBASE.These guidelines are inclusive and not prescriptive.The recommendations were defined and graded based on the current levels of evidence and in accordance with the criteria adopted by American College of Chest Physicians. The recommendations were graded A, B, and C.
Adolf Lorenz und Tomáš Garrigue Masaryk – eine außergewöhnliche Begegnung
Authors: Holzer Gerold , Kokešová Helena 
Published: January 2020

ZusammenfassungAdolf Lorenz, der Begründer der Orthopädie in Österreich und Vater des späteren Nobelpreisträgers Konrad Lorenz, und der Gründer und erste Präsident der tschechoslowakischen Republik, Tomáš G. Masaryk, standen in Kontakt miteinander. In den siebziger und achtziger Jahren des 19. Jahrhunderts studierten beide an der Universität Wien: der um vier Jahre ältere Masaryk Philosophie und Lorenz Medizin. Die ersten Treffen fanden im Seziersaal des Anatomischen Institutes statt. Ihnen beiden gelangen (wissenschaftliche) Karrieren und sie wurden prominente Persönlichkeiten. Fast 40 Jahre nach der ersten zufälligen Begegnung erinnerte sich Lorenz an seinen ehemaligen Schüler, inzwischen Präsident der tschechoslowakischen Republik, und nahm mit ihm Briefkontakt auf. Die im Masaryk-Institut in Prag aufbewahrte Korrespondenz soll hier vorgestellt werden.
Bi-objective load balancing multiple allocation hub location: a compromise programming approach
Authors: Monemi Rahimeh Neamatian , Gelareh Shahin , Nagih Anass , Jones Dylan 
Published: January 2020

AbstractIn this paper we address unbalanced spatial distribution of hub-level flows in an optimal hub-and-spoke network structure of median-type models. Our study is based on a rather general variant of the multiple allocation hub location problems with fixed setup costs for hub nodes and hub edges in both capacitated and uncapacitated variants wherein the number of hub nodes traversed along origin-destination pairs is not constrained to one or two as in the classical models.. From the perspective of an infrastructure owner, we want to make sure that there exists a choice of design for the hub-level sub-network (hubs and hub edges) that considers both objectives of minimizing cost of transportation and balancing spatial distribution of flow across the hub-level network. We propose a bi-objective (transportation cost and hub-level flow variance) mixed integer non-linear programming formulation and handle the bi-objective model via a compromise programming framework. We exploit the structure of the problem and propose a second-order conic reformulation of the model along with a very efficient matheuristics algorithm for larger size instances.
Faster horn diagnosis - a performance comparison of abductive reasoning algorithms
Authors: Koitz-Hristov Roxane , Wotawa Franz 
Published: January 2020

AbstractAbductive inference derives explanations for encountered anomalies and thus embodies a natural approach for diagnostic reasoning. Yet its computational complexity, which is inherent to the expressiveness of the underlying theory, remains a disadvantage. Even when restricting the representation to Horn formulae the problem is NP-complete. Hence, finding procedures that can efficiently solve abductive diagnosis problems is of particular interest from a research as well as practical point of view. In this paper, we aim at providing guidance on choosing an algorithm or tool when confronted with the issue of computing explanations in propositional logic-based abduction. Our focus lies on Horn representations, which provide a suitable language to describe most diagnostic scenarios. We illustrate abduction via two contrasting problem formulations: direct proof methods and conflict-driven techniques. While the former is based on determining logical consequences, the later searches for suitable refutations involving possible causes. To reveal runtime performance trends we conducted a case study, in which we compared publicly available general purpose tools, established Horn reasoning engines, as well as new variations of known methods as a means for abduction.
High risk of breast cancer in women with biallelic pathogenic variants in CHEK2
Authors: Rainville Irene , Hatcher Shanell , Rosenthal Eric , Larson Katie , Bernhisel Ryan , Meek Stephanie , Gorringe Heidi , Mundt Erin , Manley Susan 
Published: January 2020

Abstract
Purpose
Compared to breast cancer risk genes such as BRCA2, ATM, PALB2, and NBN, no defined phenotype is currently associated with biallelic pathogenic variants (PVs) in CHEK2. This study compared the prevalence of breast and other cancers in women with monoallelic and biallelic CHEK2 PVs.

Methods
CHEK2 PV carriers were identified through commercial hereditary cancer panel testing (09/2013–07/2019). We compared cancer histories of 6473 monoallelic carriers to 31 biallelic carriers. Breast cancer risks were estimated using multivariate logistic regression and are reported as odds ratios (OR) with 95% confidence intervals (CI).

Results
Breast cancer frequency was higher among biallelic CHEK2 PV carriers (80.6%, 25/31) than monoallelic carriers (41.2%, 2668/6473; p < 0.0001). Biallelic carriers were more likely to be diagnosed at or before age 50 (61.3%, 19/31) and to have a second breast cancer diagnosis (22.6%, 7/31) compared to monoallelic carriers (23.9%, 1548/6473; p < 0.0001 and 8.1%, 523/6473; p = 0.0107, respectively). Proportionally more biallelic carriers also had any cancer diagnosis and > 1 primary diagnosis. Compared to women with no PVs, biallelic PV carriers had a higher risk of developing ductal invasive breast cancer (OR 8.69, 95% CI 3.69–20.47) and ductal carcinoma in situ (OR 4.98, 95% CI 2.00–12.35) than monoallelic carriers (OR 2.02, 95% CI 1.90–2.15 and OR 1.82, 95% CI 1.66–2.00, respectively).

Conclusions
These data suggest that biallelic CHEK2 PV carriers have a higher risk for breast cancer, are more likely to be diagnosed younger, and to have multiple primary breast cancers compared to monoallelic carriers. Biallelic carriers also appear to have a higher risk of cancer overall. Therefore, more aggressive management may be appropriate for women with biallelic PVs in CHEK2 compared with current recommendations for monoallelic carriers.
A Cognitive Model of Pathological Worry in Children and Adolescents: A Systematic Review
Authors: Songco Annabel , Hudson Jennifer L. , Fox Elaine 
Published: January 2020

AbstractWorry is common in children and adolescents, yet some youth experience excessive worries that persist over time and cause significant distress. Whilst the literature on worry and generalised anxiety disorder (GAD) in adults is well established, relatively less is known about the cognitive mechanisms underlying child and adolescent worry. An influential cognitive model of adult pathological worry (Hirsch and Matthews in Behav Res Therapy 50:636–646, 10.1016/j.brat.2012.06.007, 2012) proposes that negative information-processing biases, reduced executive functions, and verbal worry are critical in the aetiology of GAD in adults. The current systematic review investigated whether this cognitive model of worry could be extended to understand child and adolescent worry. Following a systematic search of the literature and screening for eligibility, 30 studies were identified. Evidence indicates that negative information-processing biases and reduced executive functions play an important role in worry and GAD in children and adolescents. However, evidence that children and adolescents experience verbal worry is inconclusive. Building upon Hirsch and Matthews' cognitive model (Behav Res Therapy 50:636–646, 10.1016/j.brat.2012.06.007, 2012), we propose a model of child and adolescent worry to provide a guiding framework for future research. We conclude that cognitive models of worry should incorporate a developmental framework in order to provide greater insight into the mechanisms uniquely associated with worry in children and adolescents and help to identify the cognitive processes to target for early interventions and treatments.
Regarding ‘Leibniz Equivalence’
Authors: Roberts Bryan W. 
Published: January 2020

AbstractLeibniz Equivalence is a principle of applied mathematics that is widely assumed in both general relativity textbooks and in the philosophical literature on Einstein’s hole argument. In this article, I clarify an ambiguity in the statement of this Leibniz Equivalence, and argue that the relevant expression of it for the hole argument is strictly false. I then show that the hole argument still succeeds as a refutation of manifold substantivalism; however, recent proposals that the hole argument is undermined by principles of representational equivalence do not fare so well.
Epistemological and ethical understandings of access and allocation in Earth System Governance: a 10-year review of the literature
Authors: Kalfagianni Agni , Meisch Simon 
Published: January 2020

Abstract“Access and allocation” is one of the five analytical problems identified as key for analysing earth system governance in the first Earth System Governance Science and Implementation Plan officially published in 2009. Ten years later and with a new Science and Implementation Plan in place, it is time to take stock. Therefore, this paper addresses the question: What does a decadal review of the Earth System Governance literature tell us about how to conceptualize and define access and allocation, what ethical norms and epistemologies underlie access and allocation research, and what does Earth System Governance scholarship reveal about the interplay between access and allocation and other norms? We find that: (a) there is a relatively small body of the Earth System Governance literature on access and allocation, albeit growing; (b) this literature is largely empirical and dispersed across a variety of topics; and (c) there is a diversity of ethical norms and principles emphasized in Earth System Governance scholarship, but the dynamics between different forms of access and related implications for allocation are relatively underexplored. In light of these findings and with a new Earth System Governance Science and Implementation Plan in place, this paper highlights key areas for further research and development.
Evaluation of the effect of the elective blastocyst-stage embryo transfer and freezing strategy on the abandonment of frozen embryos under the Taiwan National Assisted Reproduction Act
Authors: Lan Kuo-Chung , Tseng Ya-Jung , Su Yi-Ru , Lin Tzu-Yu , Lin Yi-Chi 
Published: January 2020

Abstract
Purpose
To evaluate the relationship between elective blastocyst transfer, freezing strategy, and the abandonment of frozen embryos with a storage time limit of 10 years as specified in the National Assisted Reproduction Act of Taiwan.

Methods
This two-phase retrospective cohort study was conducted at a single tertiary center, Kaohsiung Chang Gung Memorial Hospital (KCGMH), in 2019. Participants were selected from a data registry containing 4167 fresh IVF cycles, including phase 1 cycles from 1999 to 2009 and phase 2 cycles from 2010 to 2014, at KCGMH.

Results
In phase 1, embryo abandonment was associated with the production of more mature oocytes and embryos, the freezing of more embryos, young female age, blastocyst transfer, and positive pregnancy results. After adjustment for confounding factors, only positive pregnancy results (adjusted odds ratio [aOR] 4.38, 95% confidence interval [CI] 3.17, 6.04), the freezing of ≥ 2 embryos (aOR 3.68, 95% CI 3.10, 4.38), the production of ≥ 6 embryos (aOR 1.68, 95% CI 1.03, 2.73), and the use blastocyst transfer (aOR 2.46, 95% CI 1.64, 3.69) remained significantly associated with embryo abandonment. The factors associated with embryo abandonment or possible abandonment were similar in phase 2.

Conclusion
For elective blastocyst stage transfer and a freezing strategy performed according to the Taiwan National Assisted Reproduction Act, a young female age ≤ 35 with positive pregnancy status due to the original IVF treatment, the production of ≥ 6 embryos, and the cryopreservation of ≥ 2 blastocysts may increase the likelihood of abandoning embryos in the future.
A Dilemma for Privacy as Control
Authors: Lundgren Björn 
Published: January 2020

AbstractAlthough popular, control accounts of privacy suffer from various counterexamples. In this article, it is argued that two such counterexamples—while individually resolvable—can be combined to yield a dilemma for control accounts of privacy. Furthermore, it is argued that it is implausible that control accounts of privacy can defend against this dilemma. Thus, it is concluded that we ought not define privacy in terms of control. Lastly, it is argued that since the concept of privacy is the object of the right to privacy if the former cannot be defined in terms of control, neither can the latter.
Ailing Hearts and Troubled Minds: An Historical and Narratological Study on Illness Narratives by Physicians with Cardiac Disease
Authors: Wistrand Jonatan 
Published: January 2020

AbstractA number of studies show that when doctors become ill, there is often ambiguity in the division of roles and responsibilities in the medical encounter. Yet little is known about how the dilemma of the sick doctor has changed over time. This article explores the experience of illness among physicians by applying an historical, narratological approach to three doctor’s narratives about personal cases of cardiac disease: Max Pinner’s from the 1940s, Robert Seaver’s from the 1980s, and John Mulligan’s from 2015. Drawing on Erving Goffman’s principles of social interaction, I argue that part of the challenge in the analysed narratives is because when doctors seek medical attention for themselves, the ensuing medical ‘drama’ suffers. I compare the three narratives to argue that the experience of becoming a patient while simultaneously remaining a doctor is a challenge that has changed over time. In Pinner’s narrative, the patient identity is both undesirable and inaccessible; in Seaver’s, role ambivalence between doctor and patient is the most salient feature; for Mulligan, his personal rather than professional experience of illness is the overarching theme of the narrative. Finally, I suggest that an awareness of how the medical drama often changes when doctors are patients might prove beneficial both for the doctor-patients and providers of medical care.
Field-Theoretic Thermodynamic Uncertainty Relation
Authors: Niggemann Oliver , Seifert Udo 
Published: January 2020

AbstractWe propose a field-theoretic thermodynamic uncertainty relation as an extension of the one derived so far for a Markovian dynamics on a discrete set of states and for overdamped Langevin equations. We first formulate a framework which describes quantities like current, entropy production and diffusivity in the case of a generic field theory. We will then apply this general setting to the one-dimensional Kardar–Parisi–Zhang equation, a paradigmatic example of a non-linear field-theoretic Langevin equation. In particular, we will treat the dimensionless Kardar–Parisi–Zhang equation with an effective coupling parameter measuring the strength of the non-linearity. It will be shown that a field-theoretic thermodynamic uncertainty relation holds up to second order in a perturbation expansion with respect to a small effective coupling constant. The calculations show that the field-theoretic variant of the thermodynamic uncertainty relation is not saturated for the case of the Kardar-Parisi-Zhang equation due to an excess term stemming from its non-linearity.
Denn as a highlighting-sensitive particle
Authors: Theiler Nadine 
Published: January 2020

AbstractThis paper develops an account of the German discourse particle denn that captures the meaning contribution of this particle in polar questions, wh-questions, and certain conditional antecedents in a unified way. It is shown that the behavior of denn exhibits an asymmetry between polar and wh-interrogatives, which can be captured by treating the particle as sensitive to the property highlighted by its containing clause, in the sense of Roelofsen and Farkas (Language 91(2):359–414, 2015). In addition, the paper argues that highlighting-sensitivity should be incorporated in the account of another discourse particle, German überhaupt, and discusses how the proposed account of discourse particle denn may be extended to also cover the use of denn as a causal conjunction.