bluuebunny/crossref_metadata_2025_split huggingface dataset:
Six Key Traits of Fungi: Their Evolutionary Origins and Genetic Bases
Authors: Nagy László G. , Tóth Renáta , Kiss Enikő , Slot Jason , Gácser Attila , Kovács Gábor M. 
Published: August 2017

ABSTRACTThe fungal lineage is one of the three large eukaryotic lineages that dominate terrestrial ecosystems. They share a common ancestor with animals in the eukaryotic supergroup Opisthokonta and have a deeper common ancestry with plants, yet several phenotypes, such as morphological, physiological, or nutritional traits, make them unique among all living organisms. This article provides an overview of some of the most important fungal traits, how they evolve, and what major genes and gene families contribute to their development. The traits highlighted here represent just a sample of the characteristics that have evolved in fungi, including polarized multicellular growth, fruiting body development, dimorphism, secondary metabolism, wood decay, and mycorrhizae. However, a great number of other important traits also underlie the evolution of the taxonomically and phenotypically hyperdiverse fungal kingdom, which could fill up a volume on its own. After reviewing the evolution of these six well-studied traits in fungi, we discuss how the recurrent evolution of phenotypic similarity, that is, convergent evolution in the broad sense, has shaped their phylogenetic distribution in extant species.
Accuracy of 11 formulae to guide umbilical arterial catheter tip placement in newborn infants
Authors: Lean Wei Ling , Dawson Jennifer A , Davis Peter G , Theda Christiane , Thio Marta 
Published: August 2017

BackgroundUmbilical arterial catheter (UAC) insertion is a common procedure in the neonatal intensive care unit (NICU). Correct placement of the tip of the UAC at first attempt minimises handling of the infant and reduces the risk of infection and complications. We aimed to determine the accuracy of 11 published formulae to guide UAC placement.MethodsThis was a one-year prospective observational study in a tertiary NICU. Clinicians used their preferred formula for UAC insertion, with X-rays performed immediately post-procedure to check the tip position. Birth weight and measurements included in the 11 formulae were recorded within 48 hours. The gold standard insertion distance was defined as the distance from the abdominal wall to the mid-descending aorta, at T8 level on X-ray (range T6–T10). Insertion length using the 11 formulae was calculated and compared with this gold standard distance.ResultsOne hundred and three infants were included, with median (IQR) gestational age and weight of 28 (26–33.5) weeks and 980 (780–2045) g, respectively. The predicted value of the 11 formulae to place the UAC in correct position ranged from 51.0% to 73.8%. Formulae that involved direct body part measurements showed the highest predicted success rates, smallest mean difference from T8 and narrowest limits of agreement using the Bland-Altman method.ConclusionSuccess rates for accurate UAC placement are highest when formulae that involve body measurements are used. However, even the most accurate method would result in more than 25% of UACs needing manipulation to achieve an optimal position.
Assessing the use of BreatheSmart® mobile technology in adult patients with asthma: a remote observational study
Authors: Melvin Emilie , Cushing Anna , Tam Anne , Kitada Ruri , Manice Melissa 
Published: August 2017

IntroductionNon-adherence to asthma daily controller medications is a common problem, reported to be responsible for 60% of asthma-related hospitalisations. The mean level of adherence for asthma medications is estimated to be as low as 22%. Therefore, objective measurements of adherence to medicine are necessary. This virtual observational study is designed to measure the usability of an electronic monitoring device platform that measures adherence. Understanding how patients use the BreatheSmart mobile technology at home is essential to assess its feasibility as a solution to improve medication adherence. We anticipate this approach can be applied to real-world environments as a cost-effective solution to improve medication adherence.Methods and analysisThis is a virtual 6-month observational study of 100 adults (≥18 years) with an asthma diagnosis, using inhaled corticosteroids for at least 3 months. Participants will be recruited in the USA through ad placements online. All participants receive wireless Bluetooth-enabled inhaler sensors that track medication usage and an mSpirometerTMcapable of clinical-grade lung function measurements, and download the BreatheSmart mobile application that transmits data to a secure server. All analyses are based on an intention-to-treat. Usability is assessed by patient questionnaires and question sessions. Simple paired t-test is used to assess significant change in Asthma Control Test score, quality of life (EuroQol-5D questionnaire) and lung function.Ethics and disseminationNo ethical or safety concerns pertain to the collection of these data. Results of this research are planned to be published as soon as available.Trial registration numberNCT03103880.
Managing diabetes at high altitude: personal experience with support from a Multidisciplinary Physical Activity and Diabetes Clinic
Authors: Malcolm Gary , Rilstone Sian , Sivasubramaniyam Sivasujan , Jairam Carol , Chew Stephen , Oliver Nick , Hill Neil E 
Published: August 2017

ObjectivePhysical activity is important for well-being but can be challenging for people with diabetes. Data informing support of specialist activities such as climbing and high-altitude trekking are limited. A 42-year-old man with type 1 diabetes (duration 30 years) attended a Multidisciplinary Physical Activity and Diabetes Clinic planning to climb Mont Blanc during the summer and trek to Everest Base Camp in the autumn. His aims were to complete these adventures without his diabetes impacting on their success.MethodsWe report the information provided that enabled him to safely facilitate his objectives, in particular, the requirement for frequent checking of blood glucose levels, the effects of altitude on insulin dose requirements, and recognition that acute mountain sickness may mimic the symptoms of hypoglycaemia and vice versa. Real-time continuous glucose monitoring was made available for his treks.ResultsThe effects of high altitude on blood glucose results and glycaemic variability while treated on multiple daily injections of insulin are reported. In addition, we present a first-person account of his experience and lessons learnt from managing diabetes at high altitude.ConclusionsA dedicated Multidisciplinary Physical Activity and Diabetes Clinic delivering individualised, evidence-based, patient-focused advice on the effects of altitude on blood glucose levels, and provision of real-time continuous glucose monitoring enabled uneventful completion of a trek to Everest Base Camp in a person with type 1 diabetes.
A study of intensity, fatigue and precision in two specific interval trainings in young tennis players: high-intensity interval training versus intermittent interval training
Authors: Suárez Rodríguez David , del Valle Soto Miguel 
Published: August 2017

BackgroundThe aim of this study is to find the differences between two specific interval exercises. We begin with the hypothesis that the use of microintervals of work and rest allow for greater intensity of play and a reduction in fatigue.MethodsThirteen competition-level male tennis players took part in two interval training exercises comprising nine 2 min series, which consisted of hitting the ball with cross-court forehand and backhand shots, behind the service box. One was a high-intensity interval training (HIIT), made up of periods of continuous work lasting 2 min, and the other was intermittent interval training (IIT), this time with intermittent 2 min intervals, alternating periods of work with rest periods. Average heart rate (HR) and lactate levels were registered in order to observe the physiological intensity of the two exercises, along with the Borg Scale results for perceived exertion and the number of shots and errors in order to determine the intensity achieved and the degree of fatigue throughout the exercise.ResultsThere were no significant differences in the average heart rate, lactate or the Borg Scale. Significant differences were registered, on the other hand, with a greater number of shots in the first two HIIT series (series 1 p>0.009; series 2 p>0.056), but not in the third. The number of errors was significantly lower in all the IIT series (series 1 p<0.035; series 2 p<0.010; series 3 p<0.001).ConclusionOur study suggests that high-intensity intermittent training allows for greater intensity of play in relation to the real time spent on the exercise, reduced fatigue levels and the maintaining of greater precision in specific tennis-related exercises.
Adjuvant treatment of anogenital warts with systemic interferon: a systematic review and meta-analysis
Authors: Westfechtel Lukas , Werner Ricardo Niklas , Dressler Corinna , Gaskins Matthew , Nast Alexander 
Published: August 2017

BackgroundInterferons are natural messenger proteins that are used to treat various disease entities. Due to their immunomodulating, antiviral and antiproliferative effects, the systemic administration of interferons after ablative treatment for anogenital warts (AGWs) has been advocated to increase clearance and decrease recurrence rates. However, studies investigating the efficacy of adjuvant systemic interferon have yielded inconsistent results. The objective of this systematic review and meta-analysis was to comprehensively assess and evaluate the available evidence from randomised controlled trials.MethodsA literature search was conducted in Cochrane Central Register of Controlled Trials, Embase and MEDLINE. Available data were classified according to the interferon type and dosage. Pooled effect estimates were calculated for predefined outcomes. The Cochrane Collaboration’s risk of bias tool was used to assess the included trials and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to evaluate our confidence in the effect estimates.ResultsTwelve trials were identified that met the inclusion criteria and assessed immunocompetent patients with external AGW. Compared with placebo, adjuvant alpha-, beta- and gamma-interferon were generally not significantly superior in terms of complete clearance over the short, intermediate or long term, nor with regard to intermediate- or long-term recurrence. However, the low-dose subgroup of adjuvant alpha-interferon was significantly superior compared with placebo regarding intermediate-term complete clearance and recurrence. Further data were available for the comparison of different dosages of alpha- and beta-interferon and for comparisons of the three interferon types. No significant differences were seen in these comparisons regarding efficacy. Data on quality of life were not available.ConclusionsThe GRADE quality of the evidence ranged from ‘very low’ to ‘high’. The significantly higher efficacy of low-dose alpha-interferon compared with placebo was based on a single trial, and our confidence in the effect estimates rated as ‘low’. Overall, we found no reliable evidence favouring the systemic use of interferon after ablative treatment of AGW.
Short-term arrival strategies for endurance exercise performance at moderate altitude
Authors: Foss Joshua L. , Constantini Keren , Mickleborough Timothy D. , Chapman Robert F. 
Published: August 2017

For sea level-based endurance athletes who compete at moderate and high altitudes, many are not logistically able to arrive at altitude weeks before the event to fully acclimatize. For those who can only arrive at altitude the night before competition, we asked if there is a physiological and performance advantage in reducing altitude exposure time to 2 h before competition. On three separate visits, 10 cyclists completed overnight laboratory exposures of: 1) a 14-h exposure to normobaric hypoxia (16.2% O2, simulating 2,500 m; 14H), 2) a 12-h exposure to normoxia, then a 2-h hypoxic exposure (2H), and 3) a 14-h exposure to normoxia (CON). Immediately following each exposure, subjects completed a 20-km cycle ergometry time trial in normoxia (CON) or 16.2% O2(14H and 2H). Measures of plasma volume changes, sleep quality, ventilatory acclimatization, perceived exertion, oxygen uptake, and 20-km time were collected. No significant differences were observed in performance measures or perceived exertion between hypoxic trials. Plasma volume loss was significantly greater during 14H than 2H and CON. No differences in ventilatory acclimatization or sleep quality were observed between trials. Although some divergent 20-km performance responses were observed between 14H and 2H, they were not explained by the physiological measures completed. The data suggest that endurance athletes who are logistically restricted from arriving at altitude more than the evening before competition would not gain an advantage by delaying their arrival until a few hours before the competition, although unique individual responses may ultimately influence optimal arrival strategy.NEW & NOTEWORTHY For athletes who cannot arrive at altitude multiple days before an endurance competition to properly acclimatize, this study asked if shortening hypoxic exposure time to 2 h before a competition was more advantageous than arrival at altitude the evening before competition. Our data suggest that athletes who cannot arrive at altitude with adequate time for complete acclimatization can choose the short-term arrival strategy that best fits with the logistics of their travel.
Combination Therapy with Bispecific Antibodies and PD-1 Blockade Enhances the Antitumor Potency of T Cells
Authors: Chang Chien-Hsing , Wang Yang , Li Rongxiu , Rossi Diane L. , Liu Donglin , Rossi Edmund A. , Cardillo Thomas M. , Goldenberg David M. 
Published: August 2017

Abstract
The DOCK-AND-LOCK (DNL) method is a platform technology that combines recombinant engineering and site-specific conjugation to create multispecific, multivalent antibodies of defined composition with retained bioactivity. We have applied DNL to generate a novel class of trivalent bispecific antibodies (bsAb), each comprising an anti-CD3 scFv covalently conjugated to a stabilized dimer of different antitumor Fabs. Here, we report the further characterization of two such constructs, (E1)-3s and (14)-3s, which activate T cells and target Trop-2– and CEACAM5-expressing cancer cells, respectively. (E1)-3s and (14)-3s, in the presence of human T cells, killed target cells grown as monolayers at subnanomolar concentrations, with a similar potency observed for drug-resistant cells. Antitumor efficacy was demonstrated for (E1)-3s coadministered with human peripheral blood mononuclear cells (PBMC) in NOD/SCID mice harboring xenografts of MDA-MB-231, a triple-negative breast cancer line constitutively expressing Trop-2 and PD-L1. Growth inhibition was observed following treatment with (E1)-3s or (14)-3s combined with human PBMC in 3D spheroids generated from target cell lines to mimic the in vivo behavior and microenvironment of these tumors. Moreover, addition of an antagonistic anti–PD-1 antibody increased cell death in 3D spheroids and extended survival of MDA-MB-231-bearing mice. These preclinical results emphasize the potential of combining T-cell–redirecting bsAbs with antagonists or agonists that mitigate T-cell inhibition within the tumor microenvironment to improve immunotherapy of solid cancers in patients. They also support the use of 3D spheroids as a predictive alternative to in vivo models for evaluating T-cell functions. Cancer Res; 77(19); 5384–94. ©2017 AACR.
Therapeutic Targeting of the CBP/p300 Bromodomain Blocks the Growth of Castration-Resistant Prostate Cancer
Authors: Jin Lingyan , Garcia Jesse , Chan Emily , de la Cruz Cecile , Segal Ehud , Merchant Mark , Kharbanda Samir , Raisner Ryan , Haverty Peter M. , Modrusan Zora , Ly Justin , Choo Edna , Kaufman Susan , Beresini Maureen H. , Romero F. Anthony , Magnuson Steven , Gascoigne Karen E. 
Published: August 2017

Abstract
Resistance invariably develops to antiandrogen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here, we report that the transcriptional coactivator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth in vitro and in vivo. Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression. Our findings offer a preclinical proof of concept for small-molecule therapies to target the CBP/p300 bromodomain as a strategy to treat castration-resistant prostate cancer. Cancer Res; 77(20); 5564–75. ©2017 AACR.
PAI-1 (Plasminogen Activator Inhibitor-1) Expression Renders Alternatively Activated Human Macrophages Proteolytically Quiescent
Authors: Hohensinner Philipp J. , Baumgartner Johanna , Kral-Pointner Julia B. , Uhrin Pavel , Ebenbauer Benjamin , Thaler Barbara , Doberer Konstantin , Stojkovic Stefan , Demyanets Svitlana , Fischer Michael B. , Huber Kurt , Schabbauer Gernot , Speidl Walter S. , Wojta Johann 
Published: August 2017

Objective—
Macrophages are versatile immune cells capable of polarizing into functional subsets depending on environmental stimulation. In atherosclerotic lesions, proinflammatory polarized macrophages are associated with symptomatic plaques, whereas Th2 (T-helper cell type 2) cytokine–polarized macrophages are inversely related with disease progression. To establish a functional cause for these observations, we analyzed extracellular matrix degradation phenotypes in polarized macrophages.

Approach and Results—

We provide evidence that proinflammatory polarized macrophages rely on membrane-bound proteases including MMP-14 (matrix metalloproteinase-14) and the serine protease uPA (urokinase plasminogen activator) together with its receptor uPAR for extracellular matrix degradation. In contrast, Th2 cytokine alternatively primed macrophages do not show different proteolytic activity in comparison to unpolarized macrophages and lack increased localization of MMP-14 and uPA receptor to the cell membrane. Nonetheless, they express the highest amount of the serine protease uPA. However, uPA activity is blocked by similarly increased expression of its inhibitor PAI-1 (plasminogen activator inhibitor 1). When inhibiting PAI-1 or when analyzing macrophages deficient in PAI-1, Th2 cytokine–polarized macrophages display the same matrix degradation capability as proinflammatory-primed macrophages. Within atherosclerotic lesions, macrophages positive for the alternative activation marker CD206 express high levels of PAI-1. In addition, to test changed tissue remodeling capacities of alternatively activated macrophages, we used a bleomycin lung injury model in mice reconstituted with PAI-1
−/−
bone marrow. These results supported an enhanced remodeling phenotype displayed by increased fibrosis and elevated MMP activity in the lung after PAI-1 loss.

Conclusions—
We were able to demonstrate matrix degradation dependent on membrane-bound proteases in proinflammatory stimulated macrophages and a forced proteolytical quiescence in alternatively polarized macrophages by the expression of PAI-1.
Paradigm of Biased PAR1 (Protease-Activated Receptor-1) Activation and Inhibition in Endothelial Cells Dissected by Phosphoproteomics
Authors: van den Eshof Bart L. , Hoogendijk Arie J. , Simpson Pelle J. , van Alphen Floris P.J. , Zanivan Sara , Mertens Koen , Meijer Alexander B. , van den Biggelaar Maartje 
Published: August 2017

Objective—
Thrombin is the key serine protease of the coagulation cascade and mediates cellular responses by activation of PARs (protease-activated receptors). The predominant thrombin receptor is PAR1, and in endothelial cells (ECs), thrombin dynamically regulates a plethora of phosphorylation events. However, it has remained unclear whether thrombin signaling is exclusively mediated through PAR1. Furthermore, mechanistic insight into activation and inhibition of PAR1-mediated EC signaling is lacking. In addition, signaling networks of biased PAR1 activation after differential cleavage of the PAR1 N terminus have remained an unresolved issue.

Approach and Results—
Here, we used a quantitative phosphoproteomics approach to show that classical and peptide activation of PAR1 induce highly similar signaling, that low thrombin concentrations initiate only limited phosphoregulation, and that the PAR1 inhibitors vorapaxar and parmodulin-2 demonstrate distinct antagonistic properties. Subsequent analysis of the thrombin-regulated phosphosites in the presence of PAR1 inhibitors revealed that biased activation of PAR1 is not solely linked to a specific G-protein downstream of PAR1. In addition, we showed that only the canonical thrombin PAR1 tethered ligand induces extensive early phosphoregulation in ECs.

Conclusions—
Our study provides detailed insight in the signaling mechanisms downstream of PAR1. Our data demonstrate that thrombin-induced EC phosphoregulation is mediated exclusively through PAR1, that thrombin and thrombin–tethered ligand peptide induce similar phosphoregulation, and that only canonical PAR1 cleavage by thrombin generates a tethered ligand that potently induces early signaling. Furthermore, platelet PAR1 inhibitors directly affect EC signaling, indicating that it will be a challenge to design a PAR1 antagonist that will target only those pathways responsible for tissue pathology.
On the Role of Situational Stressors in the Disruption of Global Neural Network Stability during Problem Solving
Authors: Liu Mengting , Amey Rachel C. , Forbes Chad E. 
Published: August 2017

Abstract
When individuals are placed in stressful situations, they are likely to exhibit deficits in cognitive capacity over and above situational demands. Despite this, individuals may still persevere and ultimately succeed in these situations. Little is known, however, about neural network properties that instantiate success or failure in both neutral and stressful situations, particularly with respect to regions integral for problem-solving processes that are necessary for optimal performance on more complex tasks. In this study, we outline how hidden Markov modeling based on multivoxel pattern analysis can be used to quantify unique brain states underlying complex network interactions that yield either successful or unsuccessful problem solving in more neutral or stressful situations. We provide evidence that brain network stability and states underlying synchronous interactions in regions integral for problem-solving processes are key predictors of whether individuals succeed or fail in stressful situations. Findings also suggested that individuals utilize discriminate neural patterns in successfully solving problems in stressful or neutral situations. Findings overall highlight how hidden Markov modeling can provide myriad possibilities for quantifying and better understanding the role of global network interactions in the problem-solving process and how the said interactions predict success or failure in different contexts.