bluuebunny/crossref_metadata_2025 huggingface dataset:
Maneuvering the secondary surface morphology of electrospun poly (vinylidene fluoride) nanofibers by controlling the processing parameters
Authors: Zaarour Bilal , Zhu Lei , Jin Xiangyu
Published: November 2019

Tailoring surface of fibers has been attracting the attention of researchers in different fields and applications. Nowadays, appreciations to the electrospinning technique, polymeric nanofibers are easily producible. The electrospinning process has been prominently investigated and developed during the last decade. The influence of working parameters on the secondary surface morphology of electrospun fibers is very significant. In this study, the effect of processing parameters (applied voltage, flow rate, distance between the tip of the needle and the collector (DTC), diameter of the needle, and rotation speed of the drum collector) on the secondary surface morphology (e.g. porous, grooved, and rough) of electrospun poly (vinylidene fluoride) (PVDF) fibers are studied. The results indicate that the secondary surface morphology of electrospun PVDF fibers can be alerted by maneuvering applied voltage, flow rate, DTC, and rotation speed of the drum collector. However, there is no relationship between the secondary surface morphology of electrospun PVDF fibers and the diameter of the needle. Importantly, fibers with different secondary surface morphologies have the ability to be served in different applications such as energy harvesting, oil cleanup, filtration, and so on. We believe this study can be served as a good reference for generating electrospun fibers with the desired structure by controlling the processing parameters.
Massive Open Online Courses: enhancing caregiver education and support about dementia care towards and at end of life
Authors: Poole Marie , Davis Nuala , Robinson Louise
Published: November 2019

As the ageing population grows globally, the need for informal care—usually provided by family and friends—will continue to increase. Numbers of people with dementia also continue to rise, and much of their care will be provided by relatives. As such, more people who may themselves be older, will take on such caring roles. Consequently, more carers are likely to have education and support needs. Amidst government recognition of the need to provide good quality, person-centred education and support to carers, there are tensions between the potential for such provision to be resource intensive and whether existing services have the capacity to meet the needs of carers. Massive Open Online Courses (MOOCs) are a resource with scope to meet some of these educational and support needs. MOOCs enable flexible learning, are often free, and can be accessed anywhere in the world. Providing supportive dementia care requires carers to have an understanding of the condition, assistance to cope with the responsibilities of caring, and recognition of the importance of their own health and wellbeing as well as the person they support. In response to the needs of family carers of people with advancing dementia identified through a 5 year programme of research, we developed a MOOC—dementia care: living well as dementia progresses. This is an accessible source of relevant and engaging information; which enables carers to learn about advancing dementia, consider their own needs and create an interactive global forum of peer support.
SPDI: data model for variants and applications at NCBI
Authors: Holmes J Bradley , Moyer Eric , Phan Lon , Maglott Donna , Kattman Brandi
Published: November 2019

Motivation

Normalizing sequence variants on a reference, projecting them across congruent sequences and aggregating their diverse representations are critical to the elucidation of the genetic basis of disease and biological function. Inconsistent representation of variants among variant callers, local databases and tools result in discrepancies that complicate analysis. NCBI’s genetic variation resources, dbSNP and ClinVar, require a robust, scalable set of principles to manage asserted sequence variants.

Results

The SPDI data model defines variants as a sequence of four attributes: sequence, position, deletion and insertion, and can be applied to nucleotide and protein variants. NCBI web services convert representations among HGVS, VCF and SPDI and provide two functions to aggregate variants. One, based on the NCBI Variant Overprecision Correction Algorithm, returns a unique, normalized representation termed the ‘Contextual Allele’. The SPDI data model, with its four operations, defines exactly the reference subsequence affected by the variant, even in repeat regions, such as homopolymer and other sequence repeats. The second function projects variants across congruent sequences and depends on an alignment dataset of non-assembly NCBI RefSeq sequences (prefixed NM, NR and NG), as well as inter- and intra-assembly-associated genomic sequences (NCs, NTs and NWs), supporting robust projection of variants across congruent sequences and assembly versions. The variant is projected to all congruent Contextual Alleles. One of these Contextual Alleles, typically the allele based on the latest assembly version, represents the entire set, is designated the unique ‘Canonical Allele’ and is used directly to aggregate variants across congruent sequences.

Availability and implementation

The SPDI services are available for open access at: https://api.ncbi.nlm.nih.gov/variation/v0.

Supplementary information

Supplementary data are available at Bioinformatics online.
Discovery of disease- and drug-specific pathways through community structures of a literature network
Authors: Pham Minh , Wilson Stephen , Govindarajan Harikumar , Lin Chih-Hsu , Lichtarge Olivier
Published: November 2019

Motivation

In light of the massive growth of the scientific literature, text mining is increasingly used to extract biological pathways. Though multiple tools explore individual connections between genes, diseases and drugs, few extensively synthesize pathways for specific diseases and drugs.

Results

Through community detection of a literature network, we extracted 3444 functional gene groups that represented biological pathways for specific diseases and drugs. The network linked Medical Subject Headings (MeSH) terms of genes, diseases and drugs that co-occurred in publications. The resulting communities detected highly associated genes, diseases and drugs. These significantly matched current knowledge of biological pathways and predicted future ones in time-stamped experiments. Likewise, disease- and drug-specific communities also recapitulated known pathways for those given diseases and drugs. Moreover, diseases sharing communities had high comorbidity with each other and drugs sharing communities had many common side effects, consistent with related mechanisms. Indeed, the communities robustly recovered mutual targets for drugs [area under Receiver Operating Characteristic curve (AUROC)=0.75] and shared pathogenic genes for diseases (AUROC=0.82). These data show that literature communities inform not only just known biological processes but also suggest novel disease- and drug-specific mechanisms that may guide disease gene discovery and drug repurposing.

Availability and implementation

Application tools are available at http://meteor.lichtargelab.org.

Supplementary information

Supplementary data are available at Bioinformatics online.
SBML2Modelica: integrating biochemical models within open-standard simulation ecosystems
Authors: Maggioli F , Mancini T , Tronci E
Published: November 2019

Motivation

SBML is the most widespread language for the definition of biochemical models. Although dozens of SBML simulators are available, there is a general lack of support to the integration of SBML models within open-standard general-purpose simulation ecosystems. This hinders co-simulation and integration of SBML models within larger model networks, in order to, e.g. enable in silico clinical trials of drugs, pharmacological protocols, or engineering artefacts such as biomedical devices against Virtual Physiological Human models. Modelica is one of the most popular existing open-standard general-purpose simulation languages, supported by many simulators. Modelica models are especially suited for the definition of complex networks of heterogeneous models from virtually all application domains. Models written in Modelica (and in 100+ other languages) can be readily exported into black-box Functional Mock-Up Units (FMUs), and seamlessly co-simulated and integrated into larger model networks within open-standard language-independent simulation ecosystems.

Results

In order to enable SBML model integration within heterogeneous model networks, we present SBML2Modelica, a software system translating SBML models into well-structured, user-intelligible, easily modifiable Modelica models. SBML2Modelica is SBML Level 3 Version 2—compliant and succeeds on 96.47% of the SBML Test Suite Core (with a few rare, intricate and easily avoidable combinations of constructs unsupported and cleanly signalled to the user). Our experimental campaign on 613 models from the BioModels database (with up to 5438 variables) shows that the major open-source (general-purpose) Modelica and FMU simulators achieve performance comparable to state-of-the-art specialized SBML simulators.

Availability and implementation

SBML2Modelica is written in Java and is freely available for non-commercial use at https://bitbucket.org/mclab/sbml2modelica.
Convergent evolution in calyptrate flowers of Syzygieae (Myrtaceae)
Authors: Vasconcelos Thais N C , Lucas Eve J , Conejero Maria , Giaretta Augusto , Prenner Gerhard
Published: November 2019

Shedding a fused perianth as a calyptra at anthesis is a trait that has evolved independently multiple times in angiosperm evolutionary history. However, calyptras do not correspond to homologous structures in all cases. Here, we describe calyptra development in the evolutionary context of Myrtaceae tribe Syzygieae. We use scanning electron and light microscopy to contrast calyptra development in calyptrate and non-calyptrate species in the group. Results show that calyptras in Syzygieae are not all homologous, but correspond to two ontogenetically distinct structures involving different perianth whorls that resemble each other by convergence: a calycine structure, in which the sepals are fused; and a pseudocalyptra, in which petals fall as a single unit but are not fused. Presence of non-calyptrate flowers is the ancestral state in the tribe, and both calyptra types appeared multiple times in the evolution of the group, with infrequent reversals from the calyptrate to the non-calyptrate state. Results highlight the fact that similar terminology in non-homologous structures can affect even relatively restricted lineages. The recurrent evolution of the calyptra in Syzygieae, with little evidence for reversal, shows that these structures may be advantageous in certain conditions but also correspond to an evolutionary dead-end in the group.
Hydrophilic interaction in solid-phase extraction of antisense oligonucleotides
Authors: Nuckowski Łukasz , Kilanowska Anna , Studzińska Sylwia
Published: November 2019

The presented studies aimed to develop a new and simple extraction method based on hydrophilic interaction for antisense oligonucleotides with different modifications. For this purpose, solid-phase extraction cartridges with unmodified silica were used. All extraction steps were performed by utilizing water, acetonitrile, acetone or their mixtures. The results obtained show that a high content (95%) of organic solvent, used during sample loading, is critical to achieve a successful extraction, while elution with pure water allows effective oligonucleotides desorption. The recovery values were greater than 90% in the case of unmodified DNA, phosphorothioate, 2′-O-(2-methoxyethyl) and 2′-O-methyl oligonucleotides. For the mixture of phosphorothioate oligonucleotide and its two synthetic metabolites, the recovery values for the standard solutions were in the range of 70–75%, while for spiked human plasma, 45–50%. The developed method is simple, may be performed in a short time and requires simple solvents like water or acetonitrile/acetone, thus showing promise as an alternative to chaotropic salt-based or ion pair-based SPE methods.
A Validated Green HPTLC Method for Quantitative Determination of Dapoxetine Hydrochloride and Tadalafil in Bulk and Pharmaceutical Formulations
Authors: Naguib Ibrahim A , Magdy Maimana A , Anwar Basma H , Abdelhamid Nessreen S
Published: November 2019

Dapoxetine hydrochloride (DAP) and Tadalafil (TAD) were separated and determined quantitatively using a validated green high-performance thin layer chromatographic (HPTLC) method in their binary mixtures either as raw materials or in pharmaceutical formulations. The concentration ranges were 0.1–1.6 and 0.2–2.5 μg/band for dapoxetine and tadalafil, respectively, with accuracies of 98.93% ± 0.62 and 99.26% ± 1.39, respectively. Silica gel HPTLC F254 plates were used to carry out the separation. The mobile phase used was a mixture of ethanol–ethyl acetate (1:9 by volume), which is environmentally green and harmless. Densitometric scanning with UV detector was used to detect the separated peaks at 222 nm. ICH guidelines were followed to validate the suggested method, and the results prove that they can be used for regular analysis in quality control laboratories with compatible results.
Early Experience With Meropenem-Vaborbactam for Treatment of Carbapenem-resistant Enterobacteriaceae Infections
Authors: Shields Ryan K , McCreary Erin K , Marini Rachel V , Kline Ellen G , Jones Chelsea E , Hao Binghua , Chen Liang , Kreiswirth Barry N , Doi Yohei , Clancy Cornelius J , Nguyen M Hong
Published: November 2019

Twenty patients with carbapenem-resistant Enterobacteriaceae infections were treated with meropenem-vaborbactam. Thirty-day clinical success and survival rates were 65% (13/20) and 90% (18/20), respectively. Thirty-five percent of patients had microbiologic failures within 90 days. One patient developed a recurrent infection due to meropenem-vaborbactam–nonsusceptible, ompK36 porin mutant Klebsiella pneumoniae.
Aging influences cerebrovascular myogenic reactivity and BK channel function in a sex-specific manner
Authors: Reed Joseph T , Pareek Tanya , Sriramula Srinivas , Pabbidi Mallikarjuna R
Published: November 2019

Aims

The myogenic reactivity of the middle cerebral arteries (MCA) protects the brain by altering the diameter in response to changes in lumen pressure. Large conductance potassium (BK) channels are known to regulate the myogenic reactivity, yet, it is not clear how aging alters the myogenic reactivity via the BK channel in males and females. Thus, we hypothesize that age-associated changes in BK channel subunits modulate the myogenic reactivity in a sex-specific manner.

Methods and results

We used vascular reactivity, patch-clamp, and biochemical methods to measure myogenic reactivity, BK channel function, and expression, respectively in cerebral vessels of adult and aged male and female Sprague Dawley rats. Our results suggest that aging and ovariectomy (OVX) exaggerated the myogenic reactivity of MCA in females but attenuated it in males. Aging induced outward eutrophic remodelling in females but inward hypertrophic remodelling in males. Aging decreased total, Kv, BK channel currents, and spontaneous transient outward currents (STOC) in vascular smooth muscle cells isolated from females, but not in males. Aging increased BKα subunit mRNA and protein both in males and females. However, aging decreased BKβ1 subunit protein and mRNA in females only. In males, BKβ1 mRNA is increased, but protein is decreased. Iberiotoxin-induced MCA constriction is lower in aged females but higher in aged males. Activation of BKα (10 µM NS1619) and BKβ1 (10 µM S-Equol) subunits failed to increase STOCs and were unable to decrease the myogenic reactivity of MCA in aged female but not in aged male rats. OVX decreased, but chronic supplementation of oestradiol restored BK channel expression and function.

Conclusion

Overall our results suggest that aging or OVX-associated downregulation of the BKβ1 expression and function in females results in exaggerated myogenic reactivity of MCA. However, age-associated increase in BK channel function in males attenuated myogenic reactivity of MCA.
Consequences of Overeducation among Career Starters in Germany: A Trap for the Vocationally Trained as well as for University Graduates?
Authors: Schmelzer Paul , Schneider Thorsten
Published: November 2019

Research on the consequences of starting in overeducation often focuses on either secondary or tertiary graduates. We focus on both within one country, Germany. While matching and search models imply the improvement of initial overeducation, human capital theory and stigma associated with overeducation predict entrapment. The strongly skill- and occupation-based labour market for the vocationally trained in Germany mitigates the bridge function of overeducation. As the less standardized tertiary system creates more uncertainties, initial overeducation should be more prevalent and should serve as a bridge to better positions. However, depreciation of human capital and the stigma associated with overeducation oppose the bridge function of overeducation here, too. Using data from the German National Educational Panel Study (NEPS), we compare labour market positions of career starters in overeducation with those not in overeducation in subsequent years using propensity score matching. In the fifth year after labour market entrance, the differences in overeducation between initially overeducated and non-overeducated individuals amounts to 38 percentage points for graduates and 28 for vocationally trained persons. In addition, vocationally trained persons starting in overeducation face higher unemployment risks later on. Our findings challenge the assumption of a bridge function in both educational groups.
Diversity of carotenogenic microalgae in the White Sea polar region
Authors: Chekanov K , Fedorenko T , Kublanovskaya A , Litvinov D , Lobakova E
Published: November 2019

Carotenogenic microalgae are unicellular photosynthetic organisms with the ability to accumulate carotenoids. Carotenoid accumulation is a protective reaction against environmental stress factors, such as bright light, extreme temperatures, etc. It makes the survival of these microorganisms under harsh environmental conditions possible. The diversity of carotenogenic microalgae has been described in detail for Central Europe and North America, as well as for tropical and subtropical latitudes with relatively favorable environmes. However, data about these microorganisms in polar and subpolar latitudes is scarce and restricted to few reports. We isolated several strains of carotenogenic microalgae from the coastal zone of the White Sea, where they were abundant. The obtained microalgae related to four species of Chlorophytes: Haematococcus lacustris, H. rubicundus, Coelastrella aeroterrestrica, and Bracteacoccus aggregatus. The last three species have been reported for polar latitudes for the first time. Most likely, carotenogenic algae in the White Sea coast are abundant due to their high physiological and metabolic plasticity, which is essential for surviving under adverse conditions of the northern regions. Pigment composition of the strains is provided. Their predominant carotenoids were astaxanthin and β-carotene. Further, the obtained strains may be considered as potential producers of natural pigments for biotechnology.
Contrasting environmental factors drive bacterial and eukaryotic community successions in freshly deglaciated soils
Authors: Khan Ajmal , Kong Weidong , Muhammad Said , Wang Fei , Zhang Guoshuai , Kang Shichang
Published: November 2019

Glacier retreats expose deglaciated soils to microbial colonization and succession; however, the differences in drivers of bacterial and eukaryotic succession remain largely elusive. We explored soil bacterial and eukaryotic colonization and yearly community succession along a deglaciation chronosequence (10 years) on the Tibetan Plateau using qPCR, terminal restriction fragment length polymorphism (T-RFLP) and sequencing of clone libraries. The results exhibited that bacteria and eukaryotes rapidly colonized the soils in the first year of deglaciation, thereafter slowly increasing from 107 up to 1010 and 1011 gene copies g−1 soil, respectively. Bacterial and eukaryotic community changes were observed to group into distinct stages, including early (0–2 year old), transition (3–5 year old) and late stages (6–10 year old). Bacterial community succession was dominantly driven by soil factors (47.7%), among which soil moisture played a key role by explaining 26.9% of the variation. In contrast, eukaryotic community succession was dominantly driven by deglaciation age (22.2%). The dominant bacterial lineage was Cyanobacteria, which rapidly decreased from the early to the transition stage. Eukaryotes were dominated by glacier-originated Cercozoa in early stage soils, while green algae Chlorophyta substantially increased in late stage soils. Our findings revealed contrasting environmental factors driving bacterial and eukaryotic community successions.
Fractional Operators Applied to Geophysical Electromagnetics
Authors: Weiss C J , van Bloemen Waanders B G , Antil H
Published: November 2019

A growing body of applied mathematics literature in recent years has focused on the application of fractional calculus to problems of anomalous transport. In these analyses, the anomalous transport (of charge, tracers, fluid, etc.) is presumed attributable to long–range correlations of material properties within an inherently complex, and in some cases self-similar, conducting medium. Rather than considering an exquisitely discretized (and computationally intractable) representation of the medium, the complex and spatially correlated heterogeneity is represented through reformulation of the governing equation for the relevant transport physics such that its coefficients are, instead, smooth but paired with fractional–order space derivatives. Here we apply these concepts to the scalar Helmholtz equation and its use in electromagnetic interrogation of Earth’s interior through the magnetotelluric method. We outline a practical algorithm for solving the Helmholtz equation using spectral methods coupled with finite element discretizations. Execution of this algorithm for the magnetotelluric problem reveals several interesting features observable in field data: long–range correlation of the predicted electromagnetic fields; a power–law relationship between the squared impedance amplitude and squared wavenumber whose slope is a function of the fractional exponent within the governing Helmholtz equation; and, a non–constant apparent resistivity spectrum whose variability arises solely from the fractional exponent. In geologic settings characterized by self–similarity (e.g. fracture systems; thick and richly–textured sedimentary sequences, etc.) we posit that these diagnostics are useful for geologic characterization of features far below the typical resolution limit of electromagnetic methods in geophysics.
Life history changes and fisheries assessment performance: a case study for small yellow croaker
Authors: Lee Qi , Lee Alice , Liu Zunlei , Szuwalski Cody S
Published: November 2019

Many intensely exploited fish stocks have experienced changes in trophic structure and environmental conditions, resulting in non-stationary population processes. We evaluate the ability of assessment methods to estimate quantities used in management (like target biomasses and fishing mortalities) when life history processes are non-stationary and comprehensive data are not available. We use the small yellow croaker (Larimichthys polyactis) fishery in the East China and Yellow Seas as a case study. We simulate age-structured populations with time-varying fishery and life history characteristics similar to that of the small yellow croaker in China based on historical studies that demonstrate changes in life history. We then fit surplus production and statistical catch-at-age models to simulated catch and index data from these populations. Given our assumptions, both estimation models yielded biased quantities important to management. The production model estimated reference points associated with target biomass with less bias than the age-structured model, while the latter outperformed the former when estimating reference points associated with target fishing mortality. The age-structured model also better captured relative population trends and provided flexibility to consider impacts of life history changes over time. We suggest that assessments of similar stocks consider the potential of life history variation impact management quantities.
Effects of stripper configurations on mass transfer and energy consumption of regeneration process
Authors: Chu Fengming , Su Minghui , Yang Guoan
Published: November 2019

The high energy consumption of the regeneration is the main barrier of the CO2 capture system application. The stripper is the primary device for the regeneration process, which involves with the transport process and reactions. It is beneficial for the energy saving to clarify the impacts of the stripper configurations on the heat and mass transfer performance in the stripper. Based on the representative elementary volume method and pseudo-single-liquid model, a novel computational model of heat and mass transfer was developed, in which the H2O transfer process was also taken into account. The simulation results were compared with the experimental data. The effects of the stripper configurations on the heat and mass transfer performance were investigated, and the energy consumption analysis of different strippers under two representative working conditions was carried out. The results show that the height of stripper is dominant in the heat and mass transfer performance, rather than diameter. When the desorbing rate of CO2 is above 50%, the desorbing rate of CO2 increases with the stripper height rising and the specific energy consumption of regeneration process only increases a little.
Reducing the Administrative Demands of the Science Curiosity Scale: A Validation Study
Authors: Motta Matthew , Chapman Dan , Haglin Kathryn , Kahan Dan
Published: November 2019

Science curious people—those who enjoy consuming science-related information—are less likely to hold politically polarized views about contentious science. Consequently, science curiosity is of great interest to scholars across the social sciences. However, measuring science curiosity via the science curiosity scale (SCS) is time intensive; potentially impeding its widespread usage. We present two new methods for reducing SCS administration time. One method presents respondents with a randomly selected subset of items (“Random Subset [RS] Method”). The other asks all respondents a core set of just four items (“Reduced-Form Method;” RF). In three nationally representative surveys, we assess the construct, convergent, and predictive validity of these alternatives. We find both versions to be well validated.
Antigenic Fingerprinting of Respiratory Syncytial Virus (RSV)-A–Infected Hematopoietic Cell Transplant Recipients Reveals Importance of Mucosal Anti–RSV G Antibodies in Control of RSV Infection in Humans
Authors: Fuentes Sandra , Hahn Megan , Chilcote Katarina , Chemaly Roy F , Shah Dimpy P , Ye Xunyan , Avadhanula Vasanthi , Piedra Pedro A , Golding Hana , Khurana Surender
Published: November 2019

Background

Respiratory syncytial virus (RSV) infection causes significant morbidity in hematopoietic cell transplant (HCT) recipients. However, antibody responses that correlate with recovery from RSV disease are not fully understood.

Methods

In this study, antibody repertoire in paired serum and nasal wash samples from acutely RSV-A–infected HCT recipients who recovered early (<14 days of RSV shedding) were compared with late-recovered patients (≥14 days of shedding) using gene fragment phage display libraries and surface plasmon resonance.

Results

Anti-F serum responses were similar between these 2 groups for antibody repertoires, neutralization titers, anti-F binding antibodies (prefusion and postfusion proteins), antibody avidity, and binding to specific antigenic sites. In contrast, nasal washes from early-recovered individuals demonstrated higher binding to F peptide containing p27. While the serum RSV G antibody repertoires in the 2 groups were similar, the strongest difference between early-recovered and late-recovered patients was observed in the titers of nasal wash antibodies, especially binding to the central conserved domain. Most importantly, a significantly higher antibody affinity to RSV G was observed in nasal washes from early-recovered individuals compared with late-recovered HCT recipients.

Conclusions

These findings highlight the importance of mucosal antibodies in resolution of RSV-A infection in the upper respiratory tract.
Evaluation of iron intake in preschool children in a setting with high anemia burden
Authors: Dunn Maria G , Close Ryan M , McKee Steven G , Cordero Ramona , Japa Ingrid F , Lowenthal Elizabeth D
Published: November 2019

Background

Iron deficiency anemia affects millions of children worldwide. Iron intake assessments can inform targeted interventions.

Methods

This cross-sectional study describes diet and hemoglobin levels of children 1–5 y of age in a resource-limited setting in the Dominican Republic. The study team performed meal observations and measurements, dietary questionnaires, and point-of-care hemoglobin testing.

Results

Iron intake and bioavailability were low, with liberal estimates indicating that not more than 40% of subjects consumed the recommended daily allowance for iron. Forty of 80 children had anemia, with 23% demonstrating moderate or severe anemia.

Conclusions

Poor observed iron intake likely contributes to the high prevalence of anemia in this population.
Taking stock of global immunisation coverage progress: the gains, the losses and the journey ahead
Authors: Nnaji C A , Owoyemi A J , Amaechi U A , Wiyeh A B , Ndwandwe D E , Wiysonge C S
Published: November 2019

Despite the enormous benefits of vaccination, global immunisation coverage progress has stalled and remains suboptimal in many countries. In this commentary, we review the recently published update of the World Health Organization and United Nations Children’s Fund Estimates of National Immunization Coverage. We highlight trends in which, despite substantial gains made in improving immunisation coverage at the global level, there remain numerous challenges with reaching and sustaining optimal coverage. We contextualise the trends by exploring plausible supply- and demand-side root causes. Based on these, we stress the need for targeted, context-appropriate strategies for reaching and maintaining optimal immunisation coverage.
Is there a role for tedizolid in the treatment of non-tuberculous mycobacterial disease?
Authors: Ruth Mike Marvin , Koeken Valerie A C M , Pennings Lian J , Svensson Elin M , Wertheim Heiman F L , Hoefsloot Wouter , van Ingen Jakko
Published: November 2019

Background

Pulmonary infections caused by non-tuberculous mycobacteria (NTM) are hard to treat and have low cure rates despite intensive multidrug therapy.

Objectives

To assess the feasibility of tedizolid, a new oxazolidinone, for the treatment of Mycobacterium avium and Mycobacterium abscessus.

Methods

We determined MICs of tedizolid for 113 isolates of NTM. Synergy with key antimycobacterial drugs was assessed using the chequerboard method and calculation of the FIC index (FICI). We performed time–kill kinetics assays of tedizolid alone and combined with amikacin for M. abscessus and with ethambutol for M. avium. Human macrophages were infected with M. abscessus and M. avium and subsequently treated with tedizolid; intracellular and extracellular cfu were quantified over time.

Results

NTM isolates generally had a lower MIC of tedizolid than of linezolid. FICIs were lowest between tedizolid and amikacin for M. abscessus (FICI = 0.75) and between tedizolid and ethambutol for M. avium (FICI = 0.72). Clarithromycin and tedizolid showed initial synergy, which was abrogated by erm(41)-induced macrolide resistance (FICI = 0.53). Tedizolid had a weak bacteriostatic effect on M. abscessus and combination with amikacin slightly prolonged its effect. Tedizolid had concentration-dependent activity against M. avium and its efficacy was enhanced by ethambutol. Both combinations had a concentration-dependent synergistic effect. Tedizolid could inhibit the intracellular bacterial population of both M. avium and M. abscessus.

Conclusions

Tedizolid should be further investigated in pharmacodynamic studies and clinical trials for M. avium complex pulmonary disease. It is less active against M. abscessus, but still promising.
Prognosis of BRCA1/2-negative breast cancer patients with HBOC risk factors compared with sporadic breast cancer patients without HBOC risk factors
Authors: Ryu Jai Min , Nam Seok Jin , Kim Seok Won , Lee Jeong Eon , Chae Byung Joo , Lee Se Kyung , Yu Jonghan
Published: November 2019

Objective

Demands for genetic counseling with BRCA1/2 examination have markedly increased. Accordingly, the incidence of uninformative results on BRCA1/2 mutation status has also increased. Because most patients examined for BRCA1/2 mutation have a high risk of hereditary breast and/or ovarian cancer, many patients suffer psychological distress even when the BRCA1/2 result is negative. We compared oncological outcomes between BRCA1/2-negative breast cancer with high risk of hereditary breast and/or ovarian cancer and sporadic breast cancer without risk of hereditary breast and/or ovarian cancer.

Methods

The criteria for high risk for hereditary breast and/or ovarian cancer were defined as family history of breast and/or ovarian cancer in first- or second-degree relative, early onset breast cancer at <35 years old and bilateral breast cancer. Patients were matched maximally 1:3 into those who identified as negative for BRCA1/2 mutation with risk of hereditary breast and/or ovarian cancer (study group) and those who were not examined for BRCA1/2 mutation without risk for hereditary breast and/or ovarian cancer (control group). Matched variables were pathologic stage, estrogen receptor, progesterone receptor and human epidermal growth factor receptor-2 status.

Results

All matching variables were successfully matched. Median follow-up duration was 57.8 months. There was no significant difference between the groups in disease-free survival (log-rank P = 0.197); however, the study group showed significantly better overall survival and breast cancer-specific survival (both P < 0.0001). We conducted subgroup analysis in the middle-aged group (36–54) and showed no significant difference for disease-free survival (P = 0.072) but significantly better overall survival and breast cancer-specific survival in the study group (P = 0.002 and P < 0.0001).

Conclusions

BRCA1/2-negative breast cancer patients who had hereditary breast and/or ovarian cancer risk factors showed similar disease-free survival and better overall survival and breast cancer-specific survival compared with those with sporadic breast cancer without hereditary breast and/or ovarian cancer risk factors.
Relationship between anastomotic leakage and CT value of the mesorectum in laparoscopic anterior resection for rectal cancer
Authors: Iwama Nozomi , Tsuruta Masashi , Hasegawa Hirotoshi , Okabayashi Koji , Ishida Takashi , Kitagawa Yuko
Published: November 2019

Objective

This study aims to indicate whether the CT value of the mesorectum could be correlated with the incidence of anastomotic leakage (AL) in laparoscopic surgery for rectal cancer.

Methods

The study subjects included 173 patients who underwent laparoscopic anterior resection (LAR) for rectal cancer from September 2005 to 2016 in our institution as well as reliable contrast-enhanced CT preoperatively. Univariate and multivariate analyses were performed to determine the correlation between surgical outcomes, including AL and CT value of the mesorectum.

Results

AL was observed in 30 (17.3%) patients. Amongst short-term surgical outcomes, overall complication showed significant correlation with the CT value of the mesorectum (P = 0.003). In addition, AL was the only factor, which significantly correlated with the CT value of the mesorectum (P = 0.017). By plotting receiver operating characteristic curve, −75 HU was the threshold of the CT value of the mesorectum for predicting AL with an area under the curve of 0.772. Categorized into two groups as per the threshold, low group showed significantly higher incidence of AL (OR, 2.738; 95% CI, 1.105–6.788; P = 0.030) as well as whole complications (OR, 4.431; 95%CI, 1.912–10.266; P = 0.001).

Conclusion

The CT value of the mesorectum may be a helpful preoperative radiological biomarker to predict AL after LAR for rectal cancer.
Preliminary study of improved median filter using adaptively mask size in light microscopic image
Authors: Kim Ji-Youn , Lee Youngjin
Published: November 2019

This study aimed to develop and evaluate an improved median filter (IMF) with an adaptive mask size for light microscope (LM) images. We acquired images of the mouse first molar using a LM at 100× magnification. The images obtained using our proposed IMF were compared with those from a conventional median filter. Several parameters such as the contrast-to-noise ratio, coefficient of variation, no-reference assessments and peak signal-to-noise ratio were employed to evaluate the image quality quantitatively. The results demonstrated that the proposed IMF could effectively de-noise the LM images and preserve the image details, achieving a better performance than the conventional median filter.
Patient-Reported Outcomes for Pediatric Adherence and Self-Management: A Systematic Review
Authors: Plevinsky Jill M , Gutierrez-Colina Ana M , Carmody Julia K , Hommel Kevin A , Crosby Lori E , McGrady Meghan E , Pai Ahna L H , Ramsey Rachelle R , Modi Avani C
Published: November 2019

Objective

Treatment adherence is approximately 50% across pediatric conditions. Patient-reported outcomes (PROs) are the most common method of measuring adherence and self-management across research and clinical contexts. The aim of this systematic review is to evaluate adherence and self-management PROs, including measures of adherence behaviors, adherence barriers, disease management skills, and treatment responsibility.

Methods

Following PRISMA guidelines for systematic reviews, literature searches were performed. Measures meeting inclusion/exclusion criteria were evaluated using Hunsley and Mash’s (2018) criteria for evidence-based assessment across several domains (e.g., internal consistency, interrater reliability, test–retest reliability, content validity, construct validity, validity generalization, treatment sensitivity, and clinical utility). Rating categories were adapted for the present study to include the original categories of adequate, good, and excellent, as well as an additional category of below adequate.

Results

After screening 172 articles, 50 PROs across a variety of pediatric conditions were reviewed and evaluated. Most measures demonstrated at least adequate content validity (n = 44), internal consistency (n = 34), and validity generalization (n = 45). Findings were mixed regarding interrater reliability, test–retest reliability, and treatment sensitivity. Less than half of the measures (n = 22) exhibited adequate, good, or excellent construct validity.

Conclusions

Although use of adherence and self-management PROs is widespread across several pediatric conditions, few PROs achieved good or excellent ratings based on rigorous psychometric standards. Validation and replication studies with larger, more diverse samples are needed. Future research should consider the use of emerging technologies to enhance the feasibility of broad implementation.
Retinopathy-Positive Cerebral Malaria Is Associated With Greater Inflammation, Blood-Brain Barrier Breakdown, and Neuronal Damage Than Retinopathy-Negative Cerebral Malaria
Authors: Villaverde Chandler , Namazzi Ruth , Shabani Estela , Park Gregory S , Datta Dibyadyuti , Hanisch Benjamin , Opoka Robert O , John Chandy C
Published: November 2019

Background

Our prior study findings suggest that Plasmodium falciparum is the cause of disease in both malaria retinopathy-positive (RP) and most retinopathy-negative (RN) cerebral malaria (CM), and that absence of retinopathy and decreased disease severity in RN CM may be due to shorter duration of illness, lower parasite biomass, and decreased var gene expression in RN compared to RP CM. In the present study, we assessed the pathophysiology of RP and RN CM.

Methods

We compared markers of systemic and central nervous system inflammation, oxidative stress, neuronal injury, systemic endothelial activation, angiogenesis, and platelet activation in Ugandan children with RP (n = 167) or RN (n = 87) CM.

Results

RP children had higher plasma C-reactive protein (P = .013), ferritin and erythropoietin (both P < .001) levels, an elevated cerebrospinal fluid (CSF):plasma albumin ratio (P < .001), and higher CSF tau protein levels (P = .049) than RN children. Levels of plasma and CSF proinflammatory and anti-inflammatory cytokines and oxidative stress markers did not differ between RP and RN children. RN children had higher plasma levels of endothelin 1 (P = .003), platelet-derived growth factor (P = .012), and platelet factor 4 (P = .034).

Conclusions

RP and RN CM may represent different phases of CM. RN CM may be driven by early vasospasm and platelet activation, whereas the more advanced RP CM is associated with greater inflammation, increased erythropoietic drive, blood-brain barrier breakdown, and neuronal injury, each of which may contribute to greater disease severity.
High incidence of radiation pneumonitis in lung cancer patients with chronic silicosis treated with radiotherapy
Authors: Shen Tianle , Sheng Liming , Chen Ying , Cheng Lei , Du Xianghui
Published: November 2019

Silica is an independent risk factor for lung cancer in addition to smoking. Chronic silicosis is one of the most common and serious occupational diseases associated with poor prognosis. However, the role of radiotherapy is unclear in patients with chronic silicosis. We conducted a retrospective study to evaluate efficacy and safety in lung cancer patients with chronic silicosis, especially focusing on the incidence of radiation pneumonitis (RP). Lung cancer patients with chronic silicosis who had been treated with radiotherapy from 2005 to 2018 in our hospital were enrolled in this retrospective study. RP was graded according to the National Cancer Institute’s Common Terminology Criteria for Adverse Events (CTCAE), version 3.0. Of the 22 patients, ten (45.5%) developed RP ≥2. Two RP-related deaths (9.1%) occurred within 3 months after radiotherapy. Dosimetric factors V5, V10, V15, V20 and mean lung dose (MLD) were significantly higher in patients who had RP >2 (P < 0.05). The median overall survival times in patients with RP ≤2 and RP>2 were 11.5 months and 7.1 months, respectively. Radiotherapy is associated with excessive and fatal pulmonary toxicity in lung cancer patients with chronic silicosis.
Extracting galaxy merger timescales I: Tracking haloes with WhereWolf and spinning orbits with OrbWeaver
Authors: Poulton Rhys J J , Power Chris , Robotham Aaron S G , Elahi Pascal J
Published: November 2019

Hierarchical models of structure formation predict that dark matter halo assembly histories are characterised by episodic mergers and interactions with other haloes. An accurate description of this process will provide insights into the dynamical evolution of haloes and the galaxies that reside in them. Using large cosmological N-body simulations, we characterise halo orbits to study the interactions between substructure haloes and their hosts, and how different evolutionary histories map to different classes of orbits. We use two new software tools - WhereWolf, which uses halo group catalogues and merger trees to ensure that haloes are tracked accurately in dense environments, and OrbWeaver, which quantifies each halo’s orbital parameters. We demonstrate how WhereWolf improves the accuracy of halo merger trees, and we use OrbWeaver to quantify orbits of haloes. We assess how well analytical prescriptions for the merger timescale from the literature compare to measured merger timescales from our simulations and find that existing prescriptions perform well, provided the ratio of substructure-to-host mass is not too small. In the limit of small substructure-to-host mass ratio, we find that the prescriptions can overestimate the merger timescales substantially, such that haloes are predicted to survive well beyond the end of the simulation. This work highlights the need for a revised analytical prescription for the merger timescale that more accurately accounts for processes such as catastrophic tidal disruption.
Evidence for Non-smooth Quenching in Massive Galaxies at z ∼ 1
Authors: Carleton Timothy , Guo Yicheng , Nayyeri Hooshang , Cooper Michael , Rudnick Gregory , Whitaker Katherine
Published: November 2019

We investigate a large sample of massive galaxies at z ∼ 1 with combined HST broad-band and grism observations to constrain the star-formation histories of these systems as they transition from a star-forming state to quiescence. Among our sample of massive ($M_*>10^{10}~\hbox{${\rm M}_{\odot }$}{}$) galaxies at 0.7 < z < 1.2, dust-corrected Hα and UV star-formation indicators agree with a small dispersion (∼0.2 dex) for galaxies on the main sequence, but diverge and exhibit substantial scatter (∼0.7 dex) once they drop significantly below the star-forming main sequence. Significant Hα emission is present in galaxies with low dust-corrected UV SFR values as well as galaxies classified as quiescent using the UVJ diagram. We compare the observed Hα flux distribution to the expected distribution assuming bursty or smooth star-formation histories, and find that massive galaxies at z ∼ 1 are most consistent with a quick, bursty quenching process. This suggests that mechanisms such as feedback, stochastic gas flows, and minor mergers continue to induce low-level bursty star formation in massive galaxies at moderate redshift, even as they quench.
RNA-Puzzles toolkit: a computational resource of RNA 3D structure benchmark datasets, structure manipulation, and evaluation tools
Authors: Magnus Marcin , Antczak Maciej , Zok Tomasz , Wiedemann Jakub , Lukasiak Piotr , Cao Yang , Bujnicki Janusz M , Westhof Eric , Szachniuk Marta , Miao Zhichao
Published: November 2019

Significant improvements have been made in the efficiency and accuracy of RNA 3D structure prediction methods during the succeeding challenges of RNA-Puzzles, a community-wide effort on the assessment of blind prediction of RNA tertiary structures. The RNA-Puzzles contest has shown, among others, that the development and validation of computational methods for RNA fold prediction strongly depend on the benchmark datasets and the structure comparison algorithms. Yet, there has been no systematic benchmark set or decoy structures available for the 3D structure prediction of RNA, hindering the standardization of comparative tests in the modeling of RNA structure. Furthermore, there has not been a unified set of tools that allows deep and complete RNA structure analysis, and at the same time, that is easy to use. Here, we present RNA-Puzzles toolkit, a computational resource including (i) decoy sets generated by different RNA 3D structure prediction methods (raw, for-evaluation and standardized datasets), (ii) 3D structure normalization, analysis, manipulation, visualization tools (RNA_format, RNA_normalizer, rna-tools) and (iii) 3D structure comparison metric tools (RNAQUA, MCQ4Structures). This resource provides a full list of computational tools as well as a standard RNA 3D structure prediction assessment protocol for the community.