bluuebunny/crossref_metadata_2025_split huggingface dataset:
Somatic Mutations Predict Acute Myeloid Leukemia Years Before Diagnosis
Authors: Desai Pinkal , Mencia-Trinchant Nuria , Savenkov Oleksandr , Simon Michael S. , Cheang Gloria , Lee Sangmin , Samuels Michael , Ritchie Ellen K , Guzman Monica L. , Ballman Karla V , Roboz Gail J. , Hassane Duane C. 
Published: December 2017

ABSTRACTBackgroundSomatic mutations observed in clonal hematopoiesis are associated with increased age and risk of hematological malignancies. However, the limited number of acute myeloid leukemia (AML) patients in studies of clonal hematopoiesis thus far has precluded determination of the spectrum of mutations leading to AML and their impact on risk and time to diagnosis.MethodsThe relationship between baseline mutations and subsequent AML was determined in a case-control study design. 212 women eventually diagnosed with AML (median time: 9.8 years) were identified from the Women’s Health Initiative cohort alongside 212 matched AML-free controls. Deep sequencing of 67 genes was performed on DNA isolated from peripheral blood to detect subclonal mutations.ResultsThe presence of any mutation was associated with increased odds of eventual AML (odds ratio [OR] 4.0; 95% confidence interval [CI], 2.5-6.3). These odds were further elevated with mutations in IDH1/2 (OR 8.4; 95% CI, 1.4-51.9), TP53 (OR 54.2; 95% CI, 2.9-1017.7), or spliceosome genes (OR 5.6; 95% CI, 1.5-20.6). Eventual AML diagnosis occurred in all or most participants with mutations in TP53 (N=23/23) or IDH1/2 (N=15/16). Mutations indicated sooner AML diagnosis (median 8.0 vs. 11.9 years; P < 0.001) with TP53 mutations demonstrating increased odds of AML within 5 years (OR 3.6; 95% CI, 1.4-9.1).ConclusionsMutations are present in peripheral blood of AML patients a decade prior to AML diagnosis with mutations in TP53 producing especially rapid presentation. Strategies for monitoring of high-risk populations are needed and clinical trials of potential early interventions can be considered.
Structural characterization of a novel monotreme-specific protein with antimicrobial activity from the milk of the platypus
Authors: Newman Janet , Sharp Julie A. , Enjapoori Ashwantha Kumar , Bentley John , Nicholas Kevin R. , Adams Timothy E. , Peat Thomas S. 
Published: December 2017

Monotreme lactation protein (MLP) is a recently identified protein with antimicrobial activity. It is present in the milk of monotremes and is unique to this lineage. To characterize MLP and to gain insight into the potential role of this protein in the evolution of lactation, the crystal structure of duck-billed platypus (Ornithorhynchus anatinus) MLP was determined at 1.82 Å resolution. This is the first structure to be reported for this novel, mammalian antibacterial protein. MLP was expressed as a FLAG epitope-tagged protein in mammalian cells and crystallized readily, with at least three space groups being observed (P1,C2 andP21). A 1.82 Å resolution native data set was collected from a crystal in space groupP1, with unit-cell parametersa= 51.2,b= 59.7,c= 63.1 Å, α = 80.15, β = 82.98, γ = 89.27°. The structure was solved by SAD phasing using a protein crystal derivatized with mercury in space groupC2, with unit-cell parametersa= 92.7,b = 73.2,c= 56.5 Å, β = 90.28°. MLP comprises a monomer of 12 helices and two short β-strands, with much of the N-terminus composed of loop regions. The crystal structure of MLP reveals no three-dimensional similarity to any known structures and reveals a heretofore unseen fold, supporting the idea that monotremes may be a rich source for the identification of novel proteins. It is hypothesized that MLP in monotreme milk has evolved to specifically support the unusual lactation strategy of this lineage and may have played a central role in the evolution of these mammals.
Double moderated mediation models: problems and (part) remedies
Authors: Chryssochoidis George 
Published: December 2017

PurposeResearchers in management regularly face modelling issues that involve double-moderated mediation models. Here, the author illustrates how to conceptualise, specify and empirically estimate mediation effects when having to simultaneously account for continuous (Likert type) and nominal (i.e. group) moderator variables. Researchers’ estimates of the mediation effects suffer serious bias because of the effects of unaccounted confounders. This is an issue that plagues management research, and this study aims to show how to address these valid reservations for its focus models. In aiming to inform a wider management audience, the study deliberately uses the rich context of a focus case as this allows the author to clarify the nuances that management researchers face applying double-moderated mediation models. Specifically, the study’s focus case is on professionals’ willingness to implement a new government policy. The study also combines traditional and Bayesian statistical approaches and explains the differences in estimation and interpretation that are associated with the Bayesian approach. Explaining, and exemplifying the use of, the models, the author focuses on how one can substantially increase the robustness of the methods used in management research and can considerably improve the quality of the generated theoretical insights. The study also clarifies important assumptions and solutions.Design/methodology/approachThe study uses a doubled moderated mediation Bayesian approach, and draws the sample data from a population of 5,199 professionals, all members of either the Dutch Association of Psychologists or the Dutch Association for Psychiatry. The data collection process resulted in 1,307 questionnaires being returned, a response rate of 25 per cent. All the items were measured using a Likert scale, ranging from “strongly disagree” to “strongly agree”, unless stated otherwise.FindingsExplaining, and exemplifying the use of, the models the study focuses on how one can substantially increase the robustness of the methods used in management research and can considerably improve the quality of the generated theoretical insights.Originality/valueThis is an original approach exemplified for wider use by management researchers.
Intraspecific aggression and the colony structure of the invasive antMyrmica rubra
Authors: CHEN WEN , O'SULLIVAN ÁINE , ADAMS ELDRIDGE S. 
Published: December 2017

1. Patterns of aggression between ants from different nests influence colony and population structure. Several species of invasive ants lack colony boundaries over large expanses, forming ‘supercolonies’ with many nests among which workers can move without encountering aggression.2. Bioassays of aggression were used to determine the colony structure of the invasive antMyrmica rubra(L.) at eight sites in Massachusetts, the state where the species was first discovered in North America. To improve the ability to distinguish systematic patterns from background variability in aggressiveness, a repeated‐measures design was used and replicate assays for each pair of nests were conducted.3. Aggressive responses showed that populations at all sites consisted of multiple distinct colonies. Patterns of aggression were repeatable and transitive, with few exceptions. Colonies were identified as clusters of nests whose workers showed little to no aggression towards one another but were aggressive towards conspecifics from more distant nests.4. The degree of aggression varied considerably among different colony pairs but did not depend in any consistent way on the distance of separation or on whether colonies were neighbours.5. Territories of neighbouring colonies abutted, indicating that they were restricted by intraspecific competition. Mapped territories ranged in size from 0.03 to 1.2 ha, but colonies at the study sites have not undergone the enormous expansions seen in introduced populations of some other species of invasive ants, and neighbouring colonies compete locally.
Epidemiology of cancers in Lahore, Pakistan, among children, adolescents and adults, 2010–2012: a cross-sectional study part 2
Authors: Badar Farhana , Mahmood Shahid 
Published: December 2017

ObjectivesTo estimate the cancer incidence by age group for the Lahore district population within the Punjab Cancer Registry (PCR), Pakistan. The average annual population of Lahore was 9.8 million in 2010–2012. This is a sequel to a study published earlier.DesignA cross-sectional study.SettingThe registry has 19 centres in Lahore reporting their data to the coordinating office located within the Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC), Lahore, Pakistan.ParticipantsData existing in the PCR database, based on a confirmed diagnosis of cancer from 1 January 2010 to 31 December 2012, among the Lahore residents, were reviewed.Outcome measuresCancer counts and the age-standardised incidence rates (ASIR) per 100 000 population were computed by gender, cancer site/type and age group (0–14, 15–19 and ≥20 years).ResultsBetween 2010 and 2012, of the 15 840 new cancers diagnosed, 57% were in females. The ASIRs in age groups 0–14, 15–19 and ≥20 years, among females, were: 6.1, 8.4 and 170.7, respectively, and among males, 9.3, 12.2 and 104.5, respectively. The common diagnoses in children, adolescents and adults were: (1) among females: leukaemia: 2.2; bone tumour: 1.4 and breast cancer: 79.2, respectively, and (2) among males: leukaemia: 3.6; bone tumour: 2.4 and prostate cancer: 10.7, respectively.ConclusionsThe ASIR was higher in adult women than in men, but it was lower in girls and young women than their corresponding male counterparts. Leukaemia was the most common diagnosis in children and bone tumour in adolescents, regardless of gender. Among women, breast cancer and, in men, prostate cancer, were the leading cancer types, in adults. These estimates could be used for the expansion of health coverage in the region including setting-up low cost, diagnostic tests for early detection of cancers.
Crowd medical services in the English Football League: remodelling the team for the 21st century using a realist approach
Authors: Leary Alison , Kemp Anthony , Greenwood Peter , Hart Nick , Agnew James , Barrett John , Punshon Geoffrey 
Published: December 2017

ObjectivesTo evaluate the new model of providing care based on demand. This included reconfiguration of the workforce to manage workforce supply challenges and meet demand without compromising the quality of care.DesignCurrently the Sports Ground Safety Authority recommends the provision of crowd medical cover at English Football League stadia. The guidance on provision of services has focused on extreme circumstances such as the Hillsborough disaster in 1989, while the majority of demand on present-day services is from patients with minor injuries, exacerbations of injuries and pre-existing conditions. A new model of care was introduced in the 2009/2010 season to better meet demand. A realist approach was taken. Data on each episode of care were collected over 14 consecutive football league seasons at Millwall FC divided into two periods, preimplementation of changes and postimplementation of changes. Data on workforce retention and volunteer satisfaction were also collected.SettingThe data were obtained from one professional football league team (Millwall FC) located in London, UK.Primary and secondary outcomesThe primary outcome was to examine the demand for crowd medical services. The secondary outcome was to remodel the service to meet these demands.ResultsIn total, 981 episodes of care were recorded over the evaluation period of 14 years. The groups presenting, demographic and type of presentation did not change over the evaluation. First aiders were involved in 87.7% of episodes of care, nurses in 44.4% and doctors 17.8%. There was a downward trend in referrals to hospital. Workforce feedback was positive.ConclusionsThe new workforce model has met increased service demands while reducing the number of referrals to acute care. It involves the first aid workforce in more complex care and key decision-making and provides a flexible registered healthcare professional team to optimise the skill mix of the team.
Using a retrospective cross-sectional study to analyse unintentional fatal drowning in Australia: ICD-10 coding-based methodologies verses actual deaths
Authors: Peden Amy E , Franklin Richard C , Mahony Alison J , Scarr Justin , Barnsley Paul D 
Published: December 2017

ObjectivesFatal drowning estimates using a single underlying cause of death (UCoD) may under-represent the number of drowning deaths. This study explores how data vary by International Classification of Diseases (ICD)-10 coding combinations and the use of multiple underlying causes of death using a national register of drowning deaths.DesignAn analysis of ICD-10 external cause codes of unintentional drowning deaths for the period 2007–2011 as extracted from an Australian total population unintentional drowning database developed by Royal Life Saving Society—Australia (the Database). The study analysed results against three reporting methodologies: primary drowning codes (W65-74), drowning-related codes, plus cases where drowning was identified but not the UCoD.SettingAustralia, 2007–2011.ParticipantsUnintentional fatal drowning cases.ResultsThe Database recorded 1428 drowning deaths. 866 (60.6%) had an UCoD of W65-74 (accidental drowning), 249 (17.2%) cases had an UCoD of either T75.1 (0.2%), V90 (5.5%), V92 (3.5%), X38 (2.4%) or Y21 (5.9%) and 53 (3.7%) lacked ICD coding. Children (aged 0–17 years) were closely aligned (73.9%); however, watercraft (29.2%) and non-aquatic transport (13.0%) were not. When the UCoD and all subsequent causes are used, 67.2% of cases include W65-74 codes. 91.6% of all cases had a drowning code (T75.1, V90, V92, W65-74, X38 and Y21) at any level.ConclusionDefining drowning with the codes W65-74 and using only the UCoD captures 61% of all drowning deaths in Australia. This is unevenly distributed with adults, watercraft and non-aquatic transport-related drowning deaths under-represented. Using a wider inclusion of ICD codes, which are drowning-related and multiple causes of death minimises this under-representation. A narrow approach to counting drowning deaths will negatively impact the design of policy, advocacy and programme planning for prevention.
How is defensive medicine understood and experienced in a primary care setting? A qualitative focus group study among Danish general practitioners
Authors: Assing Hvidt Elisabeth , Lykkegaard Jesper , Pedersen Line Bjørnskov , Pedersen Kjeld Møller , Munck Anders , Andersen Merethe Kousgaard 
Published: December 2017

ObjectivesRecent years have witnessed a progressive increase in defensive medicine (DM) in several Western welfare countries. In Danish primary and secondary care, documentation on the extent of DM is lacking. Before investigating the extent of DM, we wanted to explore how the phenomenon is understood and experienced in the context of general practice in Denmark. The objective of the study was to describe the phenomenon of DM as understood and experienced by Danish general practitioners (GPs).DesignA qualitative methodology was employed and data were generated through six focus group interviews with three to eight GPs per group (n=28) recruited from the Region of Southern Denmark. Data were analysed using a thematic content analysis inspired by a hermeneutic-phenomenological focus on understanding and meaning.ResultsDM is understood as unnecessary and meaningless medical actions, carried out mainly because of external demands that run counter to the GP’s professionalism. Several sources of pressure to act defensively were identified by the GPs: the system’s pressure to meet external regulations, demands from consumerist patients and a culture among GPs and peers of infallibility and zero-risk tolerance.ConclusionsGPs understand DM as unnecessary and meaningless actions driven by external demands instead of a focus on the patient’s problem. GPs consider defensive actions to be carried out as a result of succumbing to various sources of pressure deriving from the system, the patients, the GPs themselves and peers.
Influence of hypoxia on endothelin-1 binding sites in neonatal porcine pulmonary vasculature
Authors: Noguchi Yasuzo , Hislop Alison A. , Haworth Sheila G. 
Published: December 2017

Pages H669–H678: Yasuzo Noguchi, Alison A. Hislop, and Sheila G. Haworth. “Influence of hypoxia on endothelin-1 binding sites in neonatal porcine pulmonary vasculature.” On page H671, Fig. 1 should appear as below (part of the x-axis in A was inadvertently masked by B). (See PDF)
Letters to the Editor
Authors: Efimov Igor R. 
Published: December 2017

The following is an abstract of the article discussed in the subsequent letter:  Choi, Bum-Rak, and Guy Salama. Optical mapping of atrioventricular node reveals a conduction barrier between atrial and nodal cells. Am. J. Physiol. 274 ( Heart Circ. Physiol. 43): H829–H845, 1998.—The mechanisms responsible for atrioventricular (AV) delay remain unclear, in part due to the inability to map electrical activity by conventional microelectrode techniques. In this study, voltage-sensitive dyes and imaging techniques were refined to detect action potentials (APs) from the small cells comprising the AV node and to map activation from the “compact” node. Optical APs (124) were recorded from 5 × 5 mm (∼0.5-mm depth) AV zones of perfused rabbit hearts stained with a voltage-sensitive dye. Signals from the node exhibited a set of three spikes; the first and third ( peaks Iand III) were coincident with atrial (A) and ventricular (V) electrograms, respectively. The second spike ( peak II)represented the firing of midnodal (N) and/or lower nodal (NH) cell APs as indicated by their small amplitude, propagation pattern, location determined from superimposition of activation maps and histological sections of the node region, dependence on depth of focus, and insensitivity to tetrodotoxin (TTX). AV delays consisted of τ1 (49.5 ± 6.59 ms, 300-ms cycle length), the interval between peaks I and II (perhaps AN to N cells), and τ2 (57.57 ± 5.15 ms), the interval between peaks II and III (N to V cells). The conductance time across the node was 10.33 ± 3.21 ms, indicating an apparent conduction velocity (ΘN) of 0.162 ± 0.02 m/s ( n = 9) that was insensitive to TTX. In contrast, τ1 correlated with changes in AV node delays (measured with surface electrodes) caused by changes in heart rate or perfusion with acetylcholine. The data provide the first maps of activation across the AV node and demonstrate that ΘN is faster than previously presumed. These findings are inconsistent with theories of decremental conduction and prove the existence of a conduction barrier between the atrium and the AV node that is an important determinant of AV node delay.
Selective effects of bumetanide on chloride transport in bullfrog cornea
Authors: Candia O. A. , Schoen H. F. 
Published: December 2017

Page F297: O. A. Candia and H. F. Schoen. “Selective effects of bumetanide on chloride transport in bullfrog cornea.”The values for oxygen consumption (means ± SE) as given in the abstract and in Table 4 are 100 times larger than the correct values. In the abstract, line 6 from the bottom should read “from 3.52 ± 0.14 to 2.97 ± 0.19 μl/h ·cm2.” Table 4 (page F300) should be (See PDF)
Mechanism of increased potassium secretion in potassium loading and sodium deprivation
Authors: Hayslett John P. , Myketey Nadia , Binder Henry J. , Aronson Peter S. 
Published: December 2017

Chronic K loading and Na deficiency increase the capacity of colonic cells to secrete K and are characterized by increases in Na-K-ATPase activity and, as recently shown by our laboratory, the area of basolateral membrane. The present experiments were performed in rat colon to evaluate the quantitative and qualitative changes that occur in the enzyme after induction of K adaptation. Changes in specific binding of [3Hlouabain to a plasma membrane-rich fraction of colonic mucosal cells correlated directly with changes in enzyme activity. In Na-deficient animals the number of ouabain-binding sites increased from 63.6 in controls to 111.2 pmol/mg protein, while the KD for ouabain was unchanged. The Km for ATP was not altered in experimental animals, although Vmax rose twofold. Further studies showed no change in the activity of adenylate cyclase, a marker enzyme for basolateral membrane, in the plasma membrane-rich fraction from experimental cells, although Na-K-ATPase activity increased significantly. These data indicate that increased Na-K-ATPase activity in K-adapted colonic cells reflects an absolute increase in number of pump sites, due, at least in part, to an increase in area of basolateral cell membrane. In addition, in sodium-deprived animals the present data suggest an increase in the density of K pumps in basolateral cell membrane. Na-K-ATPase; ouabain binding; K adaptation; colonic mucosal cells; kinetics of Na-K-ATPase Submitted on January 15, 1980 Accepted on April 25, 1980
Letters to the Editor
Authors: Mitzner Wayne , Wagner Elizabeth 
Published: December 2017

The following is the abstract of the article discussed in the subsequent letter: Yuan, Huichin, Edward P. Ingenito, and Béla Suki. Dynamic properties of lung parenchyma: mechanical contributions of fiber network and interstitial cells. J. Appl. Physiol. 83(5): 1420–1431, 1997.—We investigated the contributions of the connective tissue fiber network and interstitial cells to parenchymal mechanics in a surfactant-free system. In eight strips of uniform dimension from guinea pig lung, we assessed the storage (G′) and loss (G") moduli by using pseudo-random length oscillations containing a specially designed set of seven frequencies from 0.07 to 2.4 Hz at baseline, during methacholine (MCh) challenge, and after death of the interstitial cells. Measurements were made at mean forces of 0.5 and 1 g and strain amplitudes of 5, 10, and 15% and were repeated 12 h later in the same, but nonviable samples. The results were interpreted using a linear viscoelastic model incorporating both tissue damping (G) and stiffness (H). The G′ and G" increased linearly with the logarithm of frequency, and both G and H showed negative strain amplitude and positive mean force dependence. After MCh challenge, the G′ and G" spectra were elevated uniformly, and G and H increased by <15%. Tissue stiffness, strain amplitude, and mean force dependence were virtually identical in the viable and nonviable samples. The G and hence energy dissipation were ∼10% smaller in the nonviable samples due to absence of actin-myosin cross-bridge cycling. We conclude that the connective tissue network may also dominate parenchymal mechanics in the intact lung, which can be influenced by the tone or contraction of interstitial cells.