bluuebunny/crossref_metadata_2025_split huggingface dataset:
Omics phenotyping in heart failure: the next frontier
Authors: Bayes-Genis Antoni , Liu Peter P , Lanfear David E , de Boer Rudolf A , González Arantxa , Thum Thomas , Emdin Michele , Januzzi James L 
Published: March 2020

Abstract
This state-of-the-art review aims to provide an up-to-date look at breakthrough omic technologies that are helping to unravel heart failure (HF) disease mechanisms and heterogeneity. Genomics, transcriptomics, proteomics, and metabolomics in HF are reviewed in depth. In addition, there is a thorough, expert discussion regarding the value of omics in identifying novel disease pathways, advancing understanding of disease mechanisms, differentiating HF phenotypes, yielding biomarkers for diagnosis or prognosis, or identifying new therapeutic targets in HF. The combination of multiple omics technologies may create a more comprehensive picture of the factors and physiology involved in HF than achieved by either one alone and provides a rich resource for predictive phenotype modelling. However, the successful translation of omics tools as solutions to clinical HF requires that the observations are robust and reproducible and can be validated across multiple independent populations to ensure confidence in clinical decision-making.
New strategies for profiling and characterization of human milk oligosaccharides
Authors: Porfirio Sara , Archer-Hartmann Stephanie , Moreau G Brett , Ramakrishnan Girija , Haque Rashidul , Kirkpatrick Beth D , Petri William A , Azadi Parastoo 
Published: March 2020

AbstractHuman breast milk is an incredibly rich and complex biofluid composed of proteins, lipids and complex carbohydrates, including a diverse repertoire of free human milk oligosaccharides (HMOs). Strikingly, HMOs are not digested by the infant but function as prebiotics for bacterial strains associated with numerous benefits. Considering the broad variety of beneficial effects of HMOs, and the vast number of factors that affect breast milk composition, the analysis of HMO diversity and complexity is of utmost relevance. Using human milk samples from a cohort of Bangladeshi mothers participating in a study on malnutrition and stunting in children, we have characterized breast milk oligosaccharide composition by means of permethylation followed by liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-MS/MS) analysis. This approach identified over 100 different glycoforms and showed a wide diversity of milk composition, with a predominance of fucosylated and sialylated HMOs over nonmodified HMOs. We observed that these samples contain on average 80 HMOs, with the highest permethylated masses detected being &gt;5000 mass units. Here we report an easily implemented method developed for the separation, characterization and relative quantitation of large arrays of HMOs, including higher molecular weight sialylated HMOs. Our ultimate goal is to create a simple, high-throughput method, which can be used for full characterization of sialylated and/or fucosylated HMOs. These results demonstrate how current analytical techniques can be applied to characterize human milk composition, providing new tools to help the scientific community shed new light on the impact of HMOs during infant development.
When soft budget constraints promote innovation: Kornai meets Schumpeter in Japan
Authors: Jerneck Max 
Published: March 2020

AbstractThe article examines János Kornai’s influential argument that “soft budget constraints” impede innovation, and finds that under certain conditions, they may promote it instead. Kornai’s concept is derived from his analysis of socialism. In capitalism, soft budget constraints can promote innovation if competition is enforced and finance is well regulated. This argument is developed using the same Schumpeterian foundation as Kornai, illustrated empirically with the case of innovation in post-war Japan. Implications are relevant for innovation and industrial policy in general.
Systematic review of mutations associated with resistance to the new and repurposedMycobacterium tuberculosisdrugs bedaquiline, clofazimine, linezolid, delamanid and pretomanid
Authors: Kadura Suha , King Nicholas , Nakhoul Maria , Zhu Hongya , Theron Grant , Köser Claudio U , Farhat Maha 
Published: March 2020

AbstractBackgroundImproved genetic understanding of Mycobacterium tuberculosis (MTB) resistance to novel and repurposed anti-tubercular agents can aid the development of rapid molecular diagnostics.MethodsAdhering to PRISMA guidelines, in March 2018, we performed a systematic review of studies implicating mutations in resistance through sequencing and phenotyping before and/or after spontaneous resistance evolution, as well as allelic exchange experiments. We focused on the novel drugs bedaquiline, delamanid, pretomanid and the repurposed drugs clofazimine and linezolid. A database of 1373 diverse control MTB whole genomes, isolated from patients not exposed to these drugs, was used to further assess genotype–phenotype associations.ResultsOf 2112 papers, 54 met the inclusion criteria. These studies characterized 277 mutations in the genes atpE, mmpR, pepQ, Rv1979c, fgd1, fbiABC and ddn and their association with resistance to one or more of the five drugs. The most frequent mutations for bedaquiline, clofazimine, linezolid, delamanid and pretomanid resistance were atpE A63P, mmpR frameshifts at nucleotides 192–198, rplC C154R, ddn W88* and ddn S11*, respectively. Frameshifts in the mmpR homopolymer region nucleotides 192–198 were identified in 52/1373 (4%) of the control isolates without prior exposure to bedaquiline or clofazimine. Of isolates resistant to one or more of the five drugs, 59/519 (11%) lacked a mutation explaining phenotypic resistance.ConclusionsThis systematic review supports the use of molecular methods for linezolid resistance detection. Resistance mechanisms involving non-essential genes show a diversity of mutations that will challenge molecular diagnosis of bedaquiline and nitroimidazole resistance. Combined phenotypic and genotypic surveillance is needed for these drugs in the short term.
Bevacizumab for Newly Diagnosed Ovarian Cancers: Best Candidates Among High-Risk Disease Patients (ICON-7)
Authors: Colomban Olivier , Tod Michel , Peron Julien , Perren Timothy J , Leary Alexandra , Cook Adrian D , Sajous Christophe , Freyer Gilles , You Benoit 
Published: March 2020

Abstract
Bevacizumab is approved as a maintenance treatment in first-line setting in advanced-stage III-IV ovarian cancers, because GOG-0218 and ICON-7 phase III trials demonstrated progression-free survival benefits. However, only the subgroup of patients with high-risk diseases (stage IV, and incompletely resected stage III) derived an overall survival (OS) gain in the ICON-7 trial (4.8 months). The modeled CA-125 elimination rate constant K (KELIM) parameter, based on the longitudinal CA-125 kinetics during the first 100 days of chemotherapy, is a potential indicator of the tumor primary chemo-sensitivity. In the ICON-7 trial dataset, the OS of patients within the low- and high-risk disease groups was assessed according to treatment arms and KELIM. Among the patients with high-risk diseases, those with favorable standardized KELIM of at least 1.0 (n = 214, 46.7%) had no survival benefit from bevacizumab, whereas those with unfavorable KELIM less than 1.0 (n = 244, 53.2%) derived the highest OS benefit (absolute difference = 9.1 months, 2-sided log-rank P = .10; Cox hazard ratio = 0.78, 95% confidence interval = 0.58 to 1.04, 2-sided P = .09).
Initiative and Military Effectiveness: Evidence from the Yom Kippur War
Authors: Grauer Ryan , Quackenbush Stephen L 
Published: March 2020

AbstractScholars investigating the sources of military capability have located sources of effectiveness in the structure of the international system, the characteristics of states, and features of the armed forces engaged in battle. They also point toward the likely influence of individual-level variables, but such claims tend to lack theoretical and empirical justification. We advance the literature by investigating whether individual initiative—that is, actions taken by soldiers and junior officers to achieve their commander's intent while in the absence of orders, when existing orders no longer fit the situation, or when unforeseen opportunities or threats arise—systematically conditions armed forces’ performance on the battlefield. We develop a theory connecting individual initiative with military effectiveness, highlighting the role of “problem-solving” in facilitating the use of men and materiel in battle. We then assess the empirical validity of our claim through an examination of a uniquely informative episode in military history: Israel's fight on the Sinai front during the first three days of the 1973 Yom Kippur War. The case allows us to hold constant a wide range of potentially confounding variables and, to the best of our knowledge, conduct the first systematic investigation of the impact of individual initiative on the performance of units engaged in combat actions. Our findings suggest individual initiative does have systematic effects on armed forces’ effectiveness in combat. Implications and directions for future research on the development and use of military capabilities are briefly considered.
Pituicytoma associated with Cushing’s disease: a case report and literature review
Authors: rumeh Assem S A l , Bafaqeeh Mohamed , khairan Syed J Allahu , Al shakweer Wafa 
Published: March 2020

Abstract
Pituicytoma is a rare tumor that has been recently recognized and described, where only few reported cases of pituicytoma associated with Cushing’s disease. We describe a case of a 47 years old female with a history of high cortisol levels and a diagnosis of Cushing’s disease was made. Brain magnetic resonance imaging showed lesion in pituitary gland compatible with microadenoma and tumor resection was carried out. The histopathological findings were of a pituicytoma with positive thyroid transcription factor-1 immunostain.
The Discourse Functions of Overspecified Anaphoric Expressions in Biblical Hebrew Narrative: Genesis 12-24 as a Test Case
Authors: Bergström Ulf 
Published: March 2020

Abstract
In Biblical Hebrew, as in other languages, anaphoric reference is often overspecified; that is, an anaphoric noun (lexical anaphora) is used in a place where the inflection of the verb (inflectional anaphora) would be a sufficient indicator as to who is being referred to. The present study investigates the function of overspecified subject referents in Biblical Hebrew narrative discourse. It is found that overspecification can be associated with three main textual phenomena, namely, events of general relevance, subject referent initiative, and various textual discontinuities. The function of indicating subject referent initiative lies behind many of the occurrences of lexical anaphora at the beginning of episodic units, but it may also occur within episodes. The different functions of overspecification and inflectional anaphora arise as a result of the different mental processes triggered by lexical and deictic anaphora, whereby the former evokes general, contextindependent knowledge about the referent and impedes the access to the information contained in the previous clause, whereas the latter makes it immediately available.
Lexical Root vs. Substantive Root: The Status of the Hebrew Alphabet As A Precursory System for Menaḥem Ben Saruq's Root Concept
Authors: Charlap Luba R 
Published: March 2020

Abstract
Menaḥem ben Saruq (Spain, tenth century) is considered to be the first scholar to write a dictionary of Biblical Hebrew - called the Maḥberet - on Spanish soil. His role in the development of Hebrew grammar, however, has not been given pride of place in the scholarly literature. Renewed interest in his theory arose only in the late twentieth century. As some scholars have noted, Menaḥem was the first to reveal the three-consonantal basis of Hebrew roots. This article will continue to establish the basis for this concept, while further elaborating on several emphases in his teaching, especially in the context of the distinction between the radical and the servile letters and their subdivision, which, in our view, led Menaḥem to formulate his root concept. Following our analysis, we note a difference between the ‘lexical root’ concept, by which he arranged the entries in his Maḥberet, and the ‘substantive root’ concept on which he based his innovation. A parallel idea can be seen in the theory of Yusuf Ibn Nūḥ, who set forth the jawhar concept, which means the basic entity of a word on the abstract level (as opposed to a word-based morphology), as Geoffrey Khan has shown. The article concludes with a clarification of the difference between Menaḥem's theory and that of Judah Ḥayyūj. Despite the enormous development made by Menaḥem, he was not able to offer a coherent morphological system, as Ḥayyūj did.
Near-perihelion activity of comet 67P/Churyumov–Gerasimenko. A first attempt of non-static analysis
Authors: Skorov Yu , Keller H U , Mottola S , Hartogh P 
Published: March 2020

ABSTRACT
The observed rate of water production of comet 67P/Churyumov–Gerasimenko near its perihelion can be approximated by a very steep power function of the heliocentric distance. Widely used thermophysical models based on a static dust layer on top of the icy/refractory matrix are poorly consistent with these observations. We analyse published model results and demonstrate that thermophysical models with a uniform and static ice free layer do not reproduce the observed steep water production rates of 67P near perihelion. Based on transient thermal modeling we conclude that the accelerated gas activity can be explained assuming that the active area fraction near the south pole is increased. The deeper penetration of the heat wave during polar day (no sunset) can activate sublimation through thicker inert dust layers. This can also lead to removal of thicker dust layers and consequently to an expansion of the active area.
Full of Orions: a 200-pc mapping of the interstellar medium in the redshift-3 lensed dusty star-forming galaxy SDP.81
Authors: Rybak Matus , Hodge J A , Vegetti S , van der Werf P , Andreani P , Graziani L , McKean J P 
Published: March 2020

ABSTRACT
We present a sub-kpc resolved study of the interstellar medium properties in SDP.81, a $z$ = 3.042 strongly gravitationally lensed, dusty star-forming galaxy, based on high-resolution, multiband ALMA observations of the far-infrared (FIR) continuum, CO ladder, and the [C ii] line. Using a visibility-plane lens modelling code, we achieve a median source-plane resolution of ∼200 pc. We use photon-dominated region (PDR) models to infer the physical conditions – far-ultraviolet (FUV) field strength, density, and PDR surface temperature – of the star-forming gas on 200-pc scales, finding a FUV field strength of ∼103−104G0, gas density of ∼105 cm−3, and cloud surface temperatures up to 1500 K, similar to those in the Orion Trapezium region. The [C ii] emission is significantly more extended than that FIR continuum: ∼50 per cent of [C ii] emission arises outside the FIR-bright region. The resolved [C ii]/FIR ratio varies by almost 2 dex across the source, down to ∼2 × 10−4 in the star-forming clumps. The observed [C ii]/FIR deficit trend is consistent with thermal saturation of the C+ fine-structure-level occupancy at high gas temperatures. We make the source-plane reconstructions of all emission lines and continuum data publicly available.
Mass calibration of the CODEX cluster sample using SPIDERS spectroscopy – II. The X-ray luminosity–mass relation
Authors: Capasso R , Mohr J J , Saro A , Biviano A , Clerc N , Finoguenov A , Klein M , Grandis S , Collins C , Damsted S , Kirkpatrick C , Kukkola A 
Published: March 2020

ABSTRACT
We perform the calibration of the X-ray luminosity–mass scaling relation on a sample of 344 CODEX clusters with z &lt; 0.66 using the dynamics of their member galaxies. Spectroscopic follow-up measurements have been obtained from the SPIDERS survey, leading to a sample of 6658 red member galaxies. We use the Jeans equation to calculate halo masses, assuming an NFW mass profile and analysing a broad range of anisotropy profiles. With a scaling relation of the form $L_{\rm {X}} \propto \text{A}_{\rm {X}}M_{\text{200c}}^{\text{B}_{\rm {X}}} E(z)^2 (1+z)^{\gamma _{\rm {X}}}$, we find best-fitting parameters $\text{A}_{\rm {X}}=0.62^{+0.05}_{-0.06} (\pm 0.06)\times 10^{44}\, \mathrm{erg\, s^{-1}}$, $\text{B}_{\rm {X}}=2.35^{+0.21}_{-0.18}(\pm 0.09)$, $\gamma _{\rm {X}}=-2.77^{+1.06}_{-1.05}(\pm 0.79)$, where we include systematic uncertainties in parentheses and for a pivot mass and redshift of $3\times 10^{14}\, \mathrm{M}_\odot$ and 0.16, respectively. We compare our constraints with previous results, and we combine our sample with the SPT SZE-selected cluster subsample observed with XMM–Newton  extending the validity of our results to a wider range of redshifts and cluster masses.
Nihil Obstat: Lewis’s Compatibilist Account of Abilities
Authors: Beebee Helen , Svedberg Maria , Whittle Ann 
Published: March 2020

AbstractIn an outline of a paper found amongst his philosophical papers and correspondence after his untimely death in 2001—“Nihil Obstat: An Analysis of Ability,” reproduced in this volume—David Lewis sketched a new compatibilist account of abilities, according to which someone is able to A if and only if there is no obstacle to their A-ing, where an obstacle is a ‘robust preventer’ of their A-ing. In this paper, we provide some background context for Lewis’s outline, a section-by-section commentary, and a general discussion of the account’s main features.
Early specializations for mimicry and defense in a Jurassic stick insect
Authors: Yang Hongru , Shi Chaofan , Engel Michael S , Zhao Zhipeng , Ren Dong , Gao Taiping 
Published: March 2020

Abstract
Mimicry and secondary defense are staples among predator–prey interactions. Among insects, the stick and leaf insects are masters of camouflage. Nonetheless, a meager understanding of their origin and early mimetic evolution persists. Here, we report the earliest mimetic and defensive strategies of a stick insect from the Middle Jurassic of China, Aclistophasma echinulatum gen. et sp. nov., exquisitely preserving abdominal extensions and femoral spines. The distribution of these characteristics mapped onto the phylogeny of Phasmatodea reveals that abdominal extensions and femoral spines developed multiple times during the evolution of stick insects, and indicates that the origin of abdominal extensions predates other modifications, while tergal extensions predate other expansions of the body, such as those of the sterna and pleura, as well as defensive femoral spines. The new fossil provides clues into early antipredator defensive strategies, allows inferences as to the potential environment and predators, and reveals the mimetic and defensive mechanisms of stick insects from 165 million years ago.
Rapidly enlarging malignant abdominal PEComa with hepatic metastasis: a promising initial response to sirolimus following surgical excision of primary tumor
Authors: Uhlenhopp Dustin J , West Jacob , Heckart Jonathan , Campbell Ruth , Elhaddad Abdelaziz 
Published: March 2020

Abstract
Intra-abdominal perivascular epithelioid cell tumors (PEComas) are rare mesenchymal tumors. Although no effective therapies have been agreed upon, mTOR inhibitors are currently being investigated as a potential therapy for this extremely rare tumor. We present a case of a 64-year-old male found to have a large intra-abdominal PEComa with multiple metastatic lesions in the liver. Patient underwent surgical resection of the primary lesion in the abdomen and sigmoid colon followed by adjuvant therapy with the mTOR inhibitor, sirolimus. Initial response was noted with a decrease in size and number of lesions found in the patient’s liver. After 8 months of therapy, restaging imaging showed disease progression in the liver lesions. Patient subsequently failed treatments with pazopanib, investigational therapy TAK-228 (Sapanisertib) and nivolumab and ipilimumab. Overall the patient died after 22 months of disease. PEComas generally follow a benign course. This case is a much rarer entity given the malignant features/outcome.
The knowledge needs for Canadian paediatric emergency physicians in the diagnosis and management of tropical diseases: A national physician survey
Authors: Wan Melissa Mengyan , Doan Quynh , Kissoon Niranjan 
Published: March 2020

Abstract

Objectives
To assess the knowledge gaps and need for continuing medical education (CME) resources for Canadian paediatric emergency department (PED) physician management of common tropical diseases.

Methods
A cross-sectional survey study of Canadian PED was performed from May to July 2017 using the Pediatric Emergency Research Canada (PERC) database.

Results
The response rate was 56.4% (133/236). The mean performance on the case-based vignettes identifying clinical presentation of tropical illnesses ranged from 59.9% to 76.0%, with only 15.8% (n=21) to 31.1% (n=42) of participants scoring maximum points. Those who ‘always’ asked about fever performed better than those who only ‘sometimes’ asked (40.4% versus 23.8%). For management cases, the majority of the participants (59.4% to 89.5%) were able to interpret investigations; however, many were unsure of subsequent actions relating to initial treatment, discharge instructions, and reporting requirements. Many would consult infectious diseases (87.8% to 99.3%). Fifty-three per cent of the participants reported a low comfort level in diagnosing or managing these patients. They rated the importance of CME materials with a median of 50/100, via various modalities such as case studies (71.9%), emphasizing a need for PED-specific content.

Conclusion
This study identified a knowledge gap in the recognition and management of pediatric tropical diseases by Canadian PED physicians. There is a need for formal CME materials to supplement physician practice.
Public Agency Strategies, Collaborative Contracting, and Medicaid Managed Care
Authors: Saidel Judith R , Searing Elizabeth A M 
Published: March 2020

AbstractThe nature of the interactions between the organizational entities involved in contracting receives less attention than the efficiency of the procurement and distribution of those services. This is particularly true in periods of policy turbulence, where tensions are high and environments unstable. This study builds on earlier theoretical contributions by cataloging almost 100 different strategies in interviews with state agencies and related policy experts, then distilling important traits and modifying earlier analytical constructs to reflect the empirical findings. The result is a new understanding of the range of relationships and extent of collaboration in contracting interactions at different points in the policy process. This study contributes to the literature not only through the elicitation and nature of these contracting strategies but also by contributing to the theoretical underpinnings of both collaboration in contracting and how such relationships provide a means of navigating periods of policy turbulence.