bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacotherapy options for pediatric diabetes
Authors: Marcovecchio Maria Loredana , Chiarelli Francesco 
Published: May 2017

Purpose of review
Type 1 diabetes (T1D) and type 2 diabetes (T2D) are frequent conditions during childhood and adolescence. The present review offers an update on current available treatment strategies for T1D and T2D approved for use in children and adolescents.

Recent findings
Insulin remains the main and essential therapeutic strategy in youth with T1D. A second generation of insulin analogues is being evaluated and could help in improving glycemic control. Over the last decades advances in technology have allowed the implementation of insulin pump therapy and continuous glucose monitoring, and are now leading the way towards the development of an artificial pancreas or closed loop system.
Treatment of T2D is based on lifestyle interventions and metformin as the first-line drug to be used. Little evidence is available for other oral hypoglycemic drugs, currently used in adults.

Summary
Although much progress has been made in the field of diabetes management, there are still several unmet goals. One of the main issues is to develop a system allowing more physiological insulin coverage. For both T1D and T2D, there is a strong need of new drugs to be used alone or in combination, mainly in patients struggling to achieve good glycemic control.
Lung Rest During Extracorporeal Membrane Oxygenation for Neonatal Respiratory Failure—Practice Variations and Outcomes
Authors: Alapati Deepthi , Aghai Zubair H. , Hossain Md Jobayer , Dirnberger Daniel R. , Ogino Mark T. , Shaffer Thomas H. 
Published: May 2017

Objective:
Describe practice variations in ventilator strategies used for lung rest during extracorporeal membrane oxygenation for respiratory failure in neonates, and assess the potential impact of various lung rest strategies on the duration of extracorporeal membrane oxygenation and the duration of mechanical ventilation after decannulation.

Data Sources:
Retrospective cohort analysis from the Extracorporeal Life Support Organization registry database during the years 2008–2013.

Study Selection:
All extracorporeal membrane oxygenation runs for infants less than or equal to 30 days of life for pulmonary reasons were included.

Data Extraction:
Ventilator type and ventilator settings used for lung rest at 24 hours after extracorporeal membrane oxygenation initiation were obtained.

Data Synthesis:
A total of 3,040 cases met inclusion criteria. Conventional mechanical ventilation was used for lung rest in 88% of cases and high frequency ventilation was used in 12%. In the conventional mechanical ventilation group, 32% used positive end-expiratory pressure strategy of 4–6 cm H2O (low), 22% used 7–9 cm H2O (mid), and 43% used 10–12 cm H2O (high). High frequency ventilation was associated with an increased mean (sem) hours of extracorporeal membrane oxygenation (150.2 [0.05] vs 125 [0.02]; p < 0.001) and an increased mean (sem) hours of mechanical ventilation after decannulation (135 [0.09] vs 100.2 [0.03]; p = 0.002), compared with conventional mechanical ventilation among survivors. Within the conventional mechanical ventilation group, use of higher positive end-expiratory pressure was associated with a decreased mean (sem) hours of extracorporeal membrane oxygenation (high vs low: 136 [1.06] vs 156 [1.06], p = 0.001; mid vs low: 141 [1.06] vs 156 [1.06]; p = 0.04) but increased duration of mechanical ventilation after decannulation in the high positive end-expiratory pressure group compared with low positive end-expiratory pressure (p = 0.04) among survivors.

Conclusions:
Wide practice variation exists with regard to ventilator settings used for lung rest during neonatal respiratory extracorporeal membrane oxygenation. Use of high frequency ventilation when compared with conventional mechanical ventilation and use of low positive end-expiratory pressure strategy when compared with mid positive end-expiratory pressure and high positive end-expiratory pressure strategy is associated with longer duration of extracorporeal membrane oxygenation. Further research to provide evidence to drive optimization of pulmonary management during neonatal respiratory extracorporeal membrane oxygenation is warranted.
Immune responses to invasive aspergillosis: new understanding and therapeutic opportunities
Authors: Hohl Tobias M. 
Published: May 2017

Purpose of review
Invasive aspergillosis is a worldwide disease that primarily affects immune-compromised patients, agricultural workers with corneal abrasions, individuals with structural lung disease, and patients with primary immune deficiency. The critical function of the immune system is to prevent the germination of airborne conidia into tissue-invasive hyphae. This review covers recent advances that shape our understanding of anti-Aspergillus immunity at the molecular and cellular level.

Recent findings
Host defense against conidia and hyphae occurs via distinct molecular mechanisms that involve intracellular and extracellular killing pathways, as well as cooperation between different myeloid cell subsets. The strength and efficacy of the host response is shaped by the tissue microenvironment. In preclinical models of disease, host immune augmentation strategies have yielded benefits, yet translating these insights into therapeutic strategies in humans remains challenging.

Summary
Although advances in early diagnostic strategies and in antifungal drugs have ameliorated clinical outcomes of invasive aspergillosis, further improvements depend on gaining deeper insight into and translating advances in anti-Aspergillus immunity.
Enterococcus faecalispromotes innate immune suppression and polymicrobial catheter-associated urinary tract infection
Authors: Tien Brenda Yin Qi , Sharon Goh Hwee Mian , Long Chong Kelvin Kian , Bhaduri-Tagore Soumili , Holec Sarah , Dress Regine , Ginhoux Florent , Ingersoll Molly A. , Williams Rohan B. H. , Kline Kimberly A. 
Published: May 2017

AbstractEnterococcus faecalis, a member of the human gastrointestinal microbiota, is an opportunistic pathogen associated with hospital-acquired wound, bloodstream, and urinary tract infections.E. faecaliscan subvert or evade immune-mediated clearance, although the mechanisms are poorly understood. In this study, we examinedE. faecalis-mediated subversion of macrophage activation. We observed thatE. faecalisactively prevents NF-κB signaling in mouse RAW264.7 macrophages in the presence of Toll-like receptor agonists and during polymicrobial infection withEscherichia coli.E. faecalisandE. colico-infection in a mouse model of catheter-associated urinary tract infection (CAUTI) resulted in a suppressed macrophage transcriptional response in the bladder compared toE. coliinfection alone. Finally, we demonstrated that co-inoculation ofE. faecaliswithE. coliinto catheterized bladders significantly augmentedE. coliCAUTI. Taken together, these results support thatE. faecalissuppression of NF-κB-driven responses in macrophages promotes polymicrobial CAUTI pathogenesis.Author SummarySynergistic polymicrobial infections can contribute to both disease severity and persistence.Enterococcus faecalisandEscherichia coliare frequently co-isolated from polymicrobial urinary tract infections. Immunomodulation by co-infecting microbes can result in a more permissive environment for pathogens to establish infection. Presently, we do not yet understand how these microbes overcome host immunity to establish polymicrobial infections. To address this, we investigated how the immunosuppressive function ofE. faecaliscan contribute to acute infection. We defined thatE. faecalisis able to suppress macrophagesin vitro, despite the presence ofE. coli. We also demonstratedE. faecalis’ability to augmentE. colititersin vivoto establish kidney infection. Our findings raise the prospect thatE. faecaliscan alter host immunity to increase susceptibility to other uropathogens.
Active trachoma cases in the Solomon Islands have varied polymicrobial community structures but do not associate with individual non-chlamydial pathogens of the eye
Authors: Butcher Robert M R , Sokana Oliver , Jack Kelvin , Kalae Eric , Sui Leslie , Russell Charles , Houghton Joanna , Palmer Christine , Holland Martin J , Le Mesurier Richard T , Solomon Anthony W , Mabey David C W , Roberts Chrissy h. 
Published: May 2017

AbstractBackgroundSeveral non-chlamydial microbial pathogens are associated with clinical signs of active trachoma in trachoma-endemic communities with a low prevalence of ocular Chlamydia trachomatis (Ct) infection. In the Solomon Islands, the prevalence of Ct among children is low despite the prevalence of active trachoma being moderate. We therefore set out to investigate whether active trachoma was associated with a common non-chlamydial infection or with a dominant polymicrobial community dysbiosis in the Solomon Islands.MethodsWe studied DNA from conjunctival swabs collected from 257 Solomon Islanders with active trachoma and matched controls. Droplet digital PCR was used to test for pathogens suspected to be able to induce follicular conjunctivitis. Polymicrobial community diversity and composition were studied by sequencing of hypervariable regions of the 16S ribosomal ribonucleic acid gene in a subset of 54 cases and 53 controls.ResultsAlthough Ct was associated with active trachoma, the number of infections was low (cases: 3.9%, controls: 0.4%). Estimated prevalence (cases, controls) of each non-chlamydial infection was as follows: S. aureus (1.9%, 1.9%), Adenoviridae (1.2%, 1.2%), coagulase-negative Staphylococcus (5.8%, 4.3%), H. influenzae (7.4%, 11.7%), M. catarrhalis (2.3%, 4.7%) and S. pneumoniae (7.0%, 6.2%). There was no statistically significant association between clinical signs of trachoma and presence or load of any of the non-Ct infections that were assayed. Inter-individual variations in the conjunctival microbiome were characterised by differences in the levels of Corynebacterium, Proprionibacterium, Helicobacter and Paracoccus, but diversity and relative abundance of these specific genera did not differ significantly between cases and controls.DiscussionIt is unlikely that the prevalent trachoma-like follicular conjunctivitis in the Solomon Islands has a dominant bacterial aetiology. Before implementing community-wide azithromycin distribution for trachoma, policy makers should consider that clinical signs of trachoma can be observed in the absence of any detectable azithromycin-susceptible organism.
Morphometric Similarity Networks Detect Microscale Cortical Organisation And Predict Inter-Individual Cognitive Variation
Authors: Seidlitz Jakob , Váša František , Shinn Maxwell , Romero-Garcia Rafael , Whitaker Kirstie J. , Vértes Petra E. , Reardon Paul Kirkpatrick , Clasen Liv , Messinger Adam , Leopold David A. , Fonagy Peter , Dolan Raymond J. , Jones Peter B. , Goodyer Ian M. ,   the NSPN Consortium, Raznahan Armin , Bullmore Edward T. 
Published: May 2017

SummaryMacroscopic cortical networks are important for cognitive function, but it remains challenging to construct anatomically plausible individual structural connectomes from human neuroimaging. We introduce a new technique for cortical network mapping, based on inter-regional similarity of multiple morphometric parameters measured using multimodal MRI. In three cohorts (two human, one macaque), we find that the resulting morphometric similarity networks (MSNs) have a complex topological organisation comprising modules and high-degree hubs. Human MSN modules recapitulate known cortical cytoarchitectonic divisions, and greater inter-regional morphometric similarity was associated with stronger inter-regional co-expression of genes enriched for neuronal terms. Comparing macaque MSNs to tract-tracing data confirmed that morphometric similarity was related to axonal connectivity. Finally, variation in the degree of human MSN nodes accounted for about 40% of between-subject variability in IQ. Morphometric similarity mapping provides a novel, robust and biologically plausible approach to understanding how human cortical networks underpin individual differences in psychological functions.
Fitness, Physical Activity, and Cardiovascular Disease: Longitudinal and Genetic Analyses in the UK Biobank Study
Authors: Tikkanen Emmi , Gustafsson Stefan , Ingelsson Erik 
Published: May 2017

AbstractBackgroundExercise is inversely related with cardiovascular disease (CVD), but large-scale studies of incident CVD events are lacking. Moreover, little is known about genetic determinants of fitness and physical activity, and modifiable effects of exercise in individuals with elevated genetic risk of CVD. Finally, causal analyses of exercise traits are limited.MethodsWe estimated associations of grip strength, physical activity, and cardiorespiratory fitness with CVD and all-cause death in up to 502,635 individuals from the UK Biobank. We also examined these associations in individuals with different genetic burden on coronary heart disease (CHD) and atrial fibrillation (AF). Finally, we performed genome-wide association study (GWAS) of grip strength and physical activity, as well as Mendelian randomization analysis to assess the causal role of grip strength in CHD.FindingsGrip strength, physical activity, and cardiorespiratory fitness showed strong inverse associations with incident cardiovascular events and all-cause death (for composite CVD; HR, 0.78, 95% CI, 0.77-0.80; HR, 0.94, 95% CI, 0.93-0.95, and HR, 0.67, 95% CI, 0.63-0.71, per SD change, respectively). We observed stronger associations of grip strength with CHD and AF for individuals in the lowest tertile of genetic risk (Pinteraction = 0.006, Pinteraction = 0.03, respectively), but the inverse associations were present in each category of genetic risk. We report 27 novel genetic loci associated with grip strength and 2 loci with physical activity, with the strongest associations in FTO (rs56094641, P=3.8×10-24) and SMIM2 (rs9316077, P=1.4×10-8), respectively. By use of Mendelian randomization, we provide evidence that grip strength is causally related to CHD.InterpretationMaintaining physical strength is likely to prevent future cardiovascular events, also in individuals with elevated genetic risk for CVD.FundingNational Institutes of Health (1 R01 HL135313-01), Knut and Alice Wallenberg Foundation (2013.0126), and the Finnish Cultural Foundation.
Interactive Biology Cloud Lab Enables Authentic Inquiry-Based Science Learning at MOOC Scale
Authors: Hossain Zahid , Bumbacher Engin , Brauneis Alison , Diaz Monica , Saltarelli Andy , Blikstein Paulo , Riedel-Kruse Ingmar 
Published: May 2017

AbstractThe Next Generation Science Standards (NGSS) and other national frameworks are calling for much more sophisticated approaches to STEM education, centered around the integration of complex experimentation (including real labs, not just simulations), data collection and analysis, modeling, and data-driven argumentation, i.e., students can behave like real scientists. How to implement such complex approaches in scalable ways is an unsolved challenge - both for presential and distance education. Here we report on the iterative design and large-scale deployment of an open online course with a “biology cloud experimentation lab” (using living cells) that engaged remote learners (> 300 students) in the scientific practices of experimentation, modeling and data analysis to investigate the phototaxis of a microorganism. We demonstrate (1) the robustness and scalability of the cloud lab technology (> 2, 300 experiments run), (2) the design principles and synergistic integration of multiple UI and learning activities and suitable data formats to facilitate NGSS-aligned science activities, and (3) design features that leverages the natural variability of real biology experiments to instigate authentic inquiry. This platform and course content are now suited for large-scale adaptation in formal K-16 education; and we provide recommendations for inquiry-based science learning in general.
Age-related differences in the influence of task-irrelevant information on the neural bases of phonological and semantic processes
Authors: Diaz Michele T. , Johnson Micah A. , Burke Deborah M. , Truong Trong-Kha , Madden David J. 
Published: May 2017

ABSTRACTAlthough aging is often associated with cognitive decline, there is considerable variability among individuals and across domains of cognition. Within language, several indicators of semantic processing show stability throughout the lifespan. However, older adults have increased difficulty with phonological aspects of language, especially in language production. While these behavioral patterns are established, the neurobiology associated with these behaviors are less clear. Previously we have shown that, older adults were slower and less accurate in phonological compared to semantic decisions, and that older adults didn’t exhibit brain-behavior relationships. In the present study, we examined phonological and semantic processes in the presence of task-irrelevant information. Older and younger adults made phonological and semantic decisions about pictures in the presence of either phonologically-related or semantically-related words, which were unrelated to the task. Behavioral results indicated that overall older adults had slower reaction times and lower accuracy compared to younger adults, and that all adults were less efficient when making phonological compared to semantic decisions. Patterns of brain activation for the semantic condition showed that all adults engaged typical left-hemisphere language regions, and that this activation was positively correlated with efficiency. In contrast, the phonological condition elicited activation in bilateral precuneus and cingulate, but only younger adults showed a significant relationship between activation and efficiency. Our results suggest that the relationship between behavior and neural activation when processing phonological information declines with age, but that the core semantic system continues to be engaged throughout the lifespan, even in the presence of task-irrelevant information.
Plant miRNA regulation is environmentally and developmentally-sensitive
Authors: von Born Patrick , Rubio-Somoza Ignacio 
Published: May 2017

AbstractDevelopment and fitness of any organism rely on properly controlled gene expression. This is especially true for plants, as their development is determined by both internal and external cues. MicroRNAs (miRNAs) are embedded in the genetic cascades that integrate and translate those cues into developmental programs. miRNAs negatively regulate their target genes mainly post-transcriptionally through two co-existing mechanisms; mRNA cleavage and translational inhibition. It is unclear whether the efficiency of miRNA-guided regulation is generally influenced by factors like ambient temperature or developmental stage. Here we show that plant miRNA accumulation, as well as miRNAs’ mode of action can be temperature- and development-sensitive. Higher temperatures tend to induce a more pronounced accumulation of mature miRNAs. Both parameters have also an impact on the expression patterns of the core players involved in miRNA performance. We show that efficiency of miRNA-mediated gene silencing declines with age during vegetative development in a temperature-dependent manner. Co-existence of cleavage and translational inhibition was also found to be dependent on temperature and developmental stage. Therefore, each miRNA family specifically regulates their respective targets, while temperature and growth influence the performance of miRNA-dependent regulation in a more general way.
Modifying and reacting to the environmental pH drives bacterial interactions
Authors: Ratzke Christoph , Gore Jeff 
Published: May 2017

AbstractMicrobes usually exist in communities consisting of myriad different but interacting species. These interactions are typically mediated through environmental modifications; microbes change the environment by taking up resources and excreting metabolites, which affects the growth of both themselves and also other microbes. A very common environmental modification is a change of the environmental pH. Here we show that changing and reacting to the pH leads to a feedback loop that can determine the fate of bacterial populations. We find experimentally that these pH changes can decide the fate of bacterial populations; they can either facilitate or inhibit growth, and in extreme cases will cause extinction of the bacterial population. Moreover, modifying the pH can determine the interactions between different species. Understanding how single species change the pH and react to it allowed us to estimate their pairwise interaction outcomes. Those interactions lead to a set of generic interaction motifs—bistability, succession, murder suicide, and mutualism—that may be independent of which environmental parameter is modified and thus reoccur in different microbial systems.
Selection-driven cost-efficiency optimisation of transcripts modulates gene evolutionary rate in bacteria
Authors: Seward Emily A. , Kelly Steven 
Published: May 2017

AbstractBackgroundMost amino acids are encoded by multiple synonymous codons. However synonymous codons are not used equally and this biased codon use varies between different organisms. It has previously been shown that both selection acting to increase codon translational efficiency and selection acting to decrease codon biosynthetic cost contribute to differences in codon bias. However, it is unknown how these two factors interact or how they affect molecular sequence evolution.ResultsThrough analysis of 1,320 bacterial genomes we show that bacterial genes are subject to multi-objective selection-driven optimisation of codon use. Here, selection acts to simultaneously decrease transcript biosynthetic cost and increase transcript translational efficiency, with highly expressed genes under the greatest selection. This optimisation is not simply a consequence of the more translationally efficient codons being less expensive to synthesise. Instead, we show that tRNA gene copy number alters the cost-efficiency trade-off of synonymous codons such that for many species such that selection acting on transcript biosynthetic cost and translational efficiency act in opposition. Finally, we show that genes highly optimised to reduce cost and increase efficiency show reduced rates of synonymous and non-synonymous mutation.ConclusionsThis analysis provides a simple mechanistic explanation for variation in evolutionary rate between genes that depends on selection-driven cost-efficiency optimisation of the transcript. These findings reveal how optimisation of resource allocation to mRNA synthesis is a critical factor that determines both the evolution and composition of genes.