bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of elevated H+ and Pi on the contractile mechanics of skeletal muscle fibres from young and old men: implications for muscle fatigue in humans
Authors: Sundberg Christopher W. , Hunter Sandra K. , Trappe Scott W. , Smith Carolyn S. , Fitts Robert H. 
Published: May 2018

Key points
The mechanisms responsible for the loss in muscle power and increased fatigability with ageing are unresolved.
We show that the contractile mechanics of fibres from the vastus lateralis of old men were well‐preserved compared to those of young men, but the selective loss of fast myosin heavy chain II muscle was strongly associated with age‐related decrements in whole‐muscle strength and power.
We reveal that the combination of acidosis (H+) and inorganic phosphate (Pi) is an important mediator of muscle fatigue in humans by inhibiting the low‐ to high‐force state of the cross‐bridge cycle and peak power, but the depressive effects of these ions on cross‐bridge function were similar in fibres from young and old men.
These findings suggest that the age‐related loss in muscle power is primarily determined by the atrophy of fast fibres, but the age‐related increased fatigability cannot be explained by an increased sensitivity of the cross‐bridge to H+ and Pi.
AbstractThe present study aimed to identify the mechanisms responsible for the loss in muscle power and increased fatigability with ageing by integrating measures of whole‐muscle function with single fibre contractile mechanics. After adjusting for the 22% smaller muscle mass in old (73–89 years, n = 6) compared to young men (20–29 years, n = 6), isometric torque and power output of the knee extensors were, respectively, 38% and 53% lower with age. Fatigability was ∼2.7‐fold greater with age and strongly associated with reductions in the electrically‐evoked contractile properties. To test whether cross‐bridge mechanisms could explain age‐related decrements in knee extensor function, we exposed myofibres (n = 254) from the vastus lateralis to conditions mimicking quiescent muscle and fatiguing levels of acidosis (H+) (pH 6.2) and inorganic phosphate (Pi) (30 mm). The fatigue‐mimicking condition caused marked reductions in force, shortening velocity and power and inhibited the low‐ to high‐force state of the cross‐bridge cycle, confirming findings from non‐human studies that these ions act synergistically to impair cross‐bridge function. Other than severe age‐related atrophy of fast fibres (−55%), contractile function and the depressive effects of the fatigue‐mimicking condition did not differ in fibres from young and old men. The selective loss of fast myosin heavy chain II muscle was strongly associated with the age‐related decrease in isometric torque (r = 0.785) and power (r = 0.861). These data suggest that the age‐related loss in muscle strength and power are primarily determined by the atrophy of fast fibres, but the age‐related increased fatigability cannot be explained by an increased sensitivity of the cross‐bridge to H+ and Pi.
Increased Usage of Antiseptics Is Associated with Reduced Susceptibility in Clinical Isolates of
Staphylococcus aureus
Authors: Hardy Katherine , Sunnucks Katie , Gil Hannah , Shabir Sahida , Trampari Eleftheria , Hawkey Peter , Webber Mark 
Published: May 2018

ABSTRACT

Hospital-acquired infection is a major cause of morbidity and mortality, and regimes to prevent infection are crucial in infection control. These include the decolonization of vulnerable patients with methicillin-resistant
Staphylococcus aureus
(MRSA) carriage using antiseptics, including chlorhexidine and octenidine. Concern has been raised, however, regarding the possible development of biocide resistance. In this study, we assembled a panel of
S. aureus
isolates, including isolates collected before the development of chlorhexidine and octenidine and isolates, from a major hospital trust in the United Kingdom during a period when the decolonization regimes were altered. We observed significant increases in the MIC and minimum bactericidal concentration (MBC) of chlorhexidine in isolates from periods of high usage of chlorhexidine. Isolates with increased MICs and MBCs of octenidine rapidly emerged after octenidine was introduced in the trust. There was no apparent cross-resistance between the two biocidal agents. A combination of variable-number tandem repeat (VNTR) analysis, PCR for
qac
genes, and whole-genome sequencing was used to type isolates and examine possible mechanisms of resistance. There was no expansion of a single strain associated with decreased biocide tolerance, and biocide susceptibility did not correlate with carriage of
qac
efflux pump genes. Mutations within the NorA or NorB efflux pumps, previously associated with chlorhexidine export, were identified, however, suggesting that this may be an important mechanism of biocide tolerance. We present evidence that isolates are evolving in the face of biocide challenge in patients and that changes in decolonization regimes are reflected in changes in susceptibility of isolates.

IMPORTANCE
Infection in hospitals remains a major cause of death and disease. One way in which we combat this is by decolonizing at-risk patients from carriage of bacteria which can cause disease such as MRSA. This is done with antiseptics, including chlorhexidine and octenidine. There is concern, however, that bacteria may be able to become resistant to these antiseptics. In this study, we looked at isolates of MRSA and found that there was a correlation between the use of antiseptics and increased resistance in the isolates. We also suggest that the mechanism by which these more tolerant isolates may become resistant to antiseptics is that of changing a transport pump that exports these agents. This information suggests that we need to study the impact of antiseptics on clinically important bacteria more closely.
Lower gastrointestinal symptoms are associated with worse glycemic control and quality of life in type 1 diabetes mellitus
Authors: Leeds John S , Hadjivassiliou Marios , Tesfaye Solomon , Sanders David S 
Published: May 2018

ObjectivesLower gastrointestinal symptoms are not well characterized in people with type 1 diabetes, and the effects on quality of life and glycemic control are unknown. This study aimed to determine the prevalence of lower gastrointestinal symptoms and the effects on glycemic control and quality of life, and to investigate for underlying causes.Research design and methodsThis is a prospective, cohort study in secondary care. Patients with type 1 diabetes completed a gastrointestinal symptom questionnaire and the Short Form 36 V.2 quality of life questionnaire and had their hemoglobin A1c measured. Patients with diarrhea were offered reassessment and investigation as per the national guidelines. Controls without diabetes were used to compare symptom prevalence and quality of life scores.Results706 with type 1 diabetes (mean age 41.9 years) and 604 controls (mean age 41.9 years) were enrolled. Gastrointestinal symptoms were significantly more frequent in type 1 diabetes compared with controls, in particular constipation (OR 2.4), diarrhea (OR 2.5), alternating bowel habit (OR 2.1), abdominal pain (OR 1.4), floating stools (OR 2.7), bloating (OR 1.4) and flatulence (OR 1.3) (all p<0.05). Previous pancreatitis was more frequent in type 1 diabetes (OR 4.6), but other gastrointestinal conditions were not. Gastrointestinal symptoms were associated with poorer glycemic control (p<0.01) and worse quality of life particularly in those with diarrhea. Investigation of those with diarrhea, including those with alternating bowel habit, (n=105), identified a cause in 72.3% with subsequent change in management.ConclusionsGastrointestinal symptoms are twice as common in type 1 diabetes and associated with poorer quality of life and glycemic control. Investigation of diarrhea in people with type 1 diabetes leads to a high yield of treatable conditions and a change in management in about three-quarters.
Understanding patient preference for physician attire: a cross-sectional observational study of 10 academic medical centres in the USA
Authors: Petrilli Christopher M , Saint Sanjay , Jennings Joseph J , Caruso Andrew , Kuhn Latoya , Snyder Ashley , Chopra Vineet 
Published: May 2018

ObjectiveSeveral large studies have shown that improving the patient experience is associated with higher reported patient satisfaction, increased adherence to treatment and clinical outcomes. Whether physician attire can affect the patient experience—and how this influences satisfaction—is unknown. Therefore, we performed a national, cross-sectional study to examine patient perceptions, expectations and preferences regarding physicians dress.Setting10 academic hospitals in the USA.ParticipantsConvenience sample of 4062 patients recruited from 1 June 2015 to 31 October 2016.Primary and secondary outcomes measuresWe conducted a questionnaire-based study of patients across 10 academic hospitals in the USA. The questionnaire included photographs of a male and female physician dressed in seven different forms of attire. Patients were asked to rate the provider pictured in various clinical settings. Preference for attire was calculated as the composite of responses across five domains (knowledgeable, trustworthy, caring, approachable and comfortable) via a standardised instrument. Secondary outcome measures included variation in preferences by respondent characteristics (eg, gender), context of care (eg, inpatient vs outpatient) and geographical region.ResultsOf 4062 patient responses, 53% indicated that physician attire was important to them during care. Over one-third agreed that it influenced their satisfaction with care. Compared with all other forms of attire, formal attire with a white coat was most highly rated (p=0.001 vs scrubs with white coat; p<0.001 all other comparisons). Important differences in preferences for attire by clinical context and respondent characteristics were noted. For example, respondents≥65 years preferred formal attire with white coats (p<0.001) while scrubs were most preferred for surgeons.ConclusionsPatients have important expectations and perceptions for physician dress that vary by context and region. Nuanced policies addressing physician dress code to improve patient satisfaction appear important.
Free to move or trapped in your group: Mathematical modeling of information overload and coordination in crowded populations
Authors: Ciallella Alessandro , Cirillo Emilio N. M. , Curşeu Petru L. , Muntean Adrian 
Published: May 2018

We present modeling strategies that describe the motion and interaction of groups of pedestrians in obscured spaces. We start off with an approach based on balance equations in terms of measures and then we exploit the descriptive power of a probabilistic cellular automaton model. Based on a variation of the simple symmetric random walk on the square lattice, we test the interplay between population size and an interpersonal attraction parameter for the evacuation of confined and darkened spaces. We argue that information overload and coordination costs associated with information processing in small groups are two key processes that influence the evacuation rate. Our results show that substantial computational resources are necessary to compensate for incomplete information — the more individuals in (information processing) groups the higher the exit rate for low population size. For simple social systems, it is likely that the individual representations are not redundant and large group sizes ensure that this non-redundant information is actually available to a substantial number of individuals. For complex social systems, information redundancy makes information evaluation and transfer inefficient and, as such, group size becomes a drawback rather than a benefit. The effect of group sizes on outgoing fluxes, evacuation times and wall effects is carefully studied with a Monte Carlo framework accounting also for the presence of an internal obstacle.
Combined c-Met/Trk Inhibition Overcomes Resistance to CDK4/6 Inhibitors in Glioblastoma
Authors: Olmez Inan , Zhang Ying , Manigat Laryssa , Benamar Mouadh , Brenneman Breanna , Nakano Ichiro , Godlewski Jakub , Bronisz Agnieszka , Lee Jeongwu , Abbas Tarek , Abounader Roger , Purow Benjamin 
Published: May 2018

Abstract
Glioblastoma (GBM) is the most common primary brain malignancy and carries an extremely poor prognosis. Recent molecular studies revealed the CDK4/6-Rb-E2F axis and receptor tyrosine kinase (RTK) signaling to be deregulated in most GBM, creating an opportunity to develop more effective therapies by targeting both pathways. Using a phospho-RTK protein array, we found that both c-Met and TrkA-B pathways were significantly activated upon CDK4/6 inhibition in GBM cells. We therefore investigated the efficacy of combined CDK4/6 and c-Met/TrkA-B inhibition against GBM. We show that both c-Met and TrkA-B pathways transactivate each other, and targeting both pathways simultaneously results in more efficient pathway suppression. Mechanistically, inhibition of CDK4/6 drove NF-κB–mediated upregulation of hepatocyte growth factor, brain-derived neurotrophic factor, and nerve growth factor that in turn activated both c-Met and TrkA-B pathways. Combining the CDK4/6 inhibitor abemaciclib with the c-Met/Trk inhibitor altiratinib or the corresponding siRNAs induced apoptosis, leading to significant synergy against GBM. Collectively, these findings demonstrate that the activation of c-Met/TrkA-B pathways is a novel mechanism involved in therapeutic resistance of GBM to CDK4/6 inhibition and that dual inhibition of c-Met/Trk with CDK4/6 should be considered in future clinical trials.
Significance: CDK4/6 inhibition in glioblastoma activates the c-Met and TrkA-B pathways mediated by NF-κB and can be reversed by a dual c-Met/Trk inhibitor. Cancer Res; 78(15); 4360–9. ©2018 AACR.
FGFR1-Activated Translation of WNT Pathway Components with Structured 5′ UTRs Is Vulnerable to Inhibition of EIF4A-Dependent Translation Initiation
Authors: Nguyen Tuan M. , Kabotyanski Elena B. , Dou Yongchao , Reineke Lucas C. , Zhang Peng , Zhang Xiang H.-F. , Malovannaya Anna , Jung Sung Yun , Mo Qianxing , Roarty Kevin P. , Chen Yiwen , Zhang Bing , Neilson Joel R. , Lloyd Richard E. , Perou Charles M. , Ellis Matthew J. , Rosen Jeffrey M. 
Published: May 2018

Abstract
Cooperativity between WNT and FGF signaling is well documented in embryonic development and cancer progression, but the molecular mechanisms underlying this cross-talk remain elusive. In this study, we interrogated the dynamics of RNA levels, ribosome occupancy, and protein expression as a function of inducible FGF signaling in mouse mammary glands with constitutive WNT hyperactivation. Multiomics correlation analysis revealed a substantial discrepancy between RNA and ribosome occupancy levels versus protein levels. However, this discrepancy decreased as cells became premalignant and dynamically responded to FGF signaling, implicating the importance of stringent gene regulation in nontransformed cells. Analysis of individual genes demonstrated that acute FGF hyperactivation increased translation of many stem cell self-renewal regulators, including WNT signaling components, and decreased translation of genes regulating cellular senescence. WNT pathway components translationally upregulated by FGF signaling had long and structured 5′ UTRs with a high frequency of polypurine sequences, several of which harbored (CGG)4 motifs that can fold into either stable G-quadruplexes or other stable secondary structures. The FGF-mediated increase in translation of WNT pathway components was compromised by silvestrol, an inhibitor of EIF4A that clamps EIF4A to polypurine sequences to block 43S scanning and inhibits its RNA-unwinding activity important for translation initiation. Moreover, silvestrol treatment significantly delayed FGF-WNT–driven tumorigenesis. Taken together, these results suggest that FGF signaling selectively enhances translation of structured mRNAs, particularly WNT signaling components, and highlight their vulnerability to inhibitors that target the RNA helicase EIF4A.
Significance: The RNA helicase EIF4A may serve as a therapeutic target for breast cancers that require FGF and WNT signaling. Cancer Res; 78(15); 4229–40. ©2018 AACR.
Drums, Hearts, Bulls, and Dead Gods: The Theology of the Ancient Mesopotamian Kettledrum
Authors: Gabbay Uri 
Published: May 2018

Abstract
The article deals with the theology of the lilis kettledrum, used to accompany prayers in ancient Mesopotamian temple cult. The article analyzes the ritual in which the head of the kettledrum was covered with the hide of a bull and the ancient commentary on this ritual, showing that the ancient understanding of this ritual was that it reflected the primordial battle between the gods Enlil and Enmešara over the rule of the universe. The article connects this myth to other mythical episodes, such as the myths of the Bull of Heaven, Anzu, and Atra-ḫasīs. The analysis of these materials leads to the conclusion that the playing of the kettledrum during the performance of ancient Mesopotamian prayers symbolized the beating heart of the deities to whom the prayers were addressed.
Biology and population growth parameters of the cotton mealybug, Phenacoccus solenopsis Tinsley (Hemiptera: Pseudococcidae), on five host plant species
Authors: Nagrare V.S. , Naikwadi Bhausaheb , Deshmukh Vrushali , Kranthi S. 
Published: May 2018

AbstractThe cotton mealybug,Phenacoccus solenopsisTinsley (Hemiptera: Pseudococcidae), is an invasive pest of cotton, apart from several other important crops, and poses a serious threat to agricultural economy all over the world. Studies on the biology and population growth parameters ofP. solenopsison the five most preferred host plants, namely cotton (Gossypium hirsutumL.) (Malvaceae), China rose (Hibiscus rosa-sinensisL.) (Malvaceae), tomato (Lycopersicon esculentumMill.) (Solanaceae), congress grass (Parthenium hysterophorusL.) (Asteraceae) and okra (Abelmoschus esculentus(L.) Moench) (Malvaceae) were undertaken in the laboratory under controlled temperature and relative humidity. The mean cumulative development time of females was 16.61 days on cotton, 14.16 days on China rose, 14.13 days on okra, 14.00 days on tomato and 13.57 days on congress grass. The longest oviposition period was recorded on cotton (15.20 ± 1.87 days), while it was in the range of 9-10 days in the remaining host plants. Females lived longer (27.40 ± 1.76 days) when reared on cotton, while their life was shortest on tomato (14.60 ± 0.96 days). The highest fecundity was observed on cotton (328.30 ± 23.42), whereas it was found to be in the range 178-212 on the other hosts. The survival frequency from crawler to adult in females was highest on cotton (27.53%), while it was the lowest on tomato (15.87%). The highest net reproductive rate (284.3 females/female/generation), mean length of a generation (31.24 days), and intrinsic rate of increase (0.19 day−1) were recorded on cotton. The finite rate of increase was in the range of 1.18-1.20 (females/female/day) for all the selected host plants. The weekly multiplication rate was highest on China rose and congress grass (3.78), while it was the least on tomato (3.28). The corrected generation time was dissimilar in all the selected host plants, being highest on cotton (31.39 days) and the least on congress grass (27.71 days). The doubling time was shortest on congress grass (3.61 days), while it was longest on tomato (4.11 days). Hence, the host plant species significantly affects population growth ofP. solenopsis.
Creating Cinderella? The Unintended Consequences of the Women Peace and Security Agenda for EU’s Mediation Architecture
Authors: Haastrup Toni 
Published: May 2018

AbstractIn 2000, the United Nations (UN) launched the Women, Peace and Security (WPS) agenda by adopting Security Council Resolution 1325. The agenda, among other things, called for the greater inclusion of women in peace negotiation practices and structures. While the European Union (EU) has made commitments to implementing theWPSagenda, the literature has not yet captured the institutional dynamics of theEUas it seeks to translate theWPSagenda into reality. This article takes stock of this hitherto excluded area of research. It argues that mediation is the ‘Cinderella’ of theEU’s peace and security institution because it has been ignored as a site for the implementation of theWPSagenda with important implications. Using a feminist institutionalist framework, the article shows the ways in which institutional practices of change aimed at including the new perspectives prompted by theWPSagenda lead to unintended gendered consequences.
The EU as a Multi-Mediator: The Case of the Democratic Republic of Congo
Authors: Davis Laura 
Published: May 2018

AbstractIn the 1990s, the Democratic Republic of Congo (DRC) experienced complex wars involving local, national and regional combatants and conflict drivers, which formally ended in 2002. Violence continued and the government and rebel groups negotiated a series of peace deals, most recently in 2013. The European Union (EU) has been engaged in theDRCsince the 1990s. This article proposes a model for conceptualizingEUmediation engagement within the conflict and process contexts, and the necessary capabilities for different types ofEUmediation. It uses theDRCcase study to examine how differentEUcapabilities were engaged in various peace processes which addressed multiple layers of a complex situation, and also engaged with other external actors in a multilateral environment. It concludes that theEUcan be conceptualized as a multi-mediator and identifies the necessary capabilities for this.
Synoptic-Scale Control over Modern Rainfall and Flood Patterns in the Levant Drylands with Implications for Past Climates
Authors: Armon Moshe , Dente Elad , Smith James A. , Enzel Yehouda , Morin Efrat 
Published: May 2018

Abstract
Rainfall in the Levant drylands is scarce but can potentially generate high-magnitude flash floods. Rainstorms are caused by distinct synoptic-scale circulation patterns: Mediterranean cyclone (MC), active Red Sea trough (ARST), and subtropical jet stream (STJ) disturbances, also termed tropical plumes (TPs). The unique spatiotemporal characteristics of rainstorms and floods for each circulation pattern were identified. Meteorological reanalyses, quantitative precipitation estimates from weather radars, hydrological data, and indicators of geomorphic changes from remote sensing imagery were used to characterize the chain of hydrometeorological processes leading to distinct flood patterns in the region. Significant differences in the hydrometeorology of these three flood-producing synoptic systems were identified: MC storms draw moisture from the Mediterranean and generate moderate rainfall in the northern part of the region. ARST and TP storms transfer large amounts of moisture from the south, which is converted to rainfall in the hyperarid southernmost parts of the Levant. ARST rainfall is local and intense, whereas TP rainfall is widespread and prolonged due to high precipitation efficiency and large-scale forcing. Thus, TP rainfall generates high-magnitude floods in the largest catchments; integration of numerous basins leads to sediment feeding from the south into the Dead Sea, exhibited in large sediment plumes. Anecdotal observations of the channel with the largest catchment in the region (Nahal HaArava) indicate that TP floods account for noticeable geomorphic changes in the channel. It provides insights into past intervals of increased flash flood frequency characterized by episodes of marked hydrogeomorphic work; such an increase is especially expected during intervals of southerly situated and southwesterly oriented STJs.