bluuebunny/crossref_metadata_2025 huggingface dataset:
A Nursing Dashboard to Communicate the Evaluation of Program Outcomes
Authors: Opsahl Angela , Horton-Deutsch Sara
Published: December 2018

Background

Schools of nursing pursue accreditation to convey the quality of their program. Communication of their process for continuous quality improvement and ability to produce competent nurse graduates are common program goals.

Purpose

This article describes the implementation of a nursing dashboard as an innovative approach to examine and communicate program outcomes.

Methods

A comprehensive evaluation document in the form of a dashboard was created in a user-friendly format to monitor and convey outcomes to stakeholders. This visual evaluation document was crafted in congruence with a utilization-oriented evaluation model incorporating accreditation standards.

Results

Stakeholders, including alumni, faculty, and students, conveyed satisfaction with the dashboard graphic of program evaluation data. Participant responses were greater than 4.3/5.0 on a Likert scale, indicating satisfaction with the dashboard communication of outcomes.

Conclusions

The nursing dashboard provides an innovative approach to the review of program outcomes with meaningful data for strategic planning and program decisions.
Birth Defects After Exposure to Efavirenz-Based Antiretroviral Therapy at Conception/First Trimester of Pregnancy: A Multicohort Analysis
Authors: Martinez de Tejada Begoña ,   European Pregnancy and Paediatric HIV Cohort Collaboration Study Group
Published: December 2018

Background:

To investigate the association between efavirenz (EFV) use during conception or first trimester (T1) of pregnancy and the occurrence of birth defects.

Setting:

Seven observational studies of pregnant HIV-positive women across 13 European countries and Thailand.

Methods:

Individual-level data were pooled on singleton pregnancies included in participating cohorts in 2002–2015. Birth defects were coded according to ICD-10 and the EUROCAT classification. We performed mixed-effects logistic regression models to assess the association between EFV exposure in utero and likelihood of birth defects.

Results:

We included 24,963 live births from 21,093 women. At conception, 30.2% (7537) women were on a non–EFV-based regimen, 4.8% (1200) on EFV, and 65% (16,226) were unexposed to antiretroviral therapy (ART). There were 412 infants with ≥1 birth defect, a prevalence of 1.65% (95% confidence interval: 1.50 to 1.82). Limb/musculoskeletal and congenital heart defects were the most common defects reported. Birth defects were present in 2.4%, 1.6%, and 1.3% of infants exposed to non-EFV, EFV, and unexposed to ART during conception/T1 (P = 0.135), respectively. The association between exposure to ART during conception/T1 and birth defects remained nonsignificant in adjusted analyses, as did exposure to EFV versus non-EFV (adjusted odds ratio 0.61; 95% confidence interval: 0.36 to 1.03, P = 0.067). Among the 21 birth defects in 19 infants on EFV, no neural tube defects were reported.

Conclusions:

Prevalence of birth defects after exposure to EFV-based compared with non–EFV-based ART in conception/T1 was not statistically different in this multicohort study, and even lower. EFV is at least as safe as other ART drugs currently recommended for antenatal use.
Retention in Care Trajectories of HIV-Positive Individuals Participating in a Universal Test-and-Treat Program in Rural South Africa (ANRS 12249 TasP Trial)
Authors: Gosset Andréa , Protopopescu Camelia , Larmarange Joseph , Orne-Gliemann Joanna , McGrath Nuala , Pillay Deenan , Dabis François , Iwuji Collins , Boyer Sylvie
Published: December 2018

Objective:

To study retention in care (RIC) trajectories and associated factors in patients eligible for antiretroviral therapy (ART) in a universal test-and-treat setting (TasP trial, South Africa, 2012–2016).

Design:

A cluster-randomized trial whereby individuals identified HIV positive after home-based testing were invited to initiate ART immediately (intervention) or following national guidelines (control).

Methods:

Exiting care was defined as ≥3 months late for a clinic appointment, transferring elsewhere, or death. Group-based trajectory modeling was performed to estimate RIC trajectories over 18 months and associated factors in 777 ART-eligible patients.

Results:

Four RIC trajectory groups were identified: (1) group 1 “remained” in care (reference, n = 554, 71.3%), (2) group 2 exited care then “returned” after [median (interquartile range)] 4 (3–9) months (n = 40, 5.2%), (3) group 3 “exited care rapidly” [after 4 (4–6) months, n = 98, 12.6%], and (4) group 4 “exited care later” [after 11 (9–13) months, n = 85, 10.9%]. Group 2 patients were less likely to have initiated ART within 1 month and more likely to be male, young (<29 years), without a regular partner, and to have a CD4 count >350 cells/mm3. Group 3 patients were more likely to be women without social support, newly diagnosed, young, and less likely to have initiated ART within 1 month. Group 4 patients were more likely to be newly diagnosed and aged 39 years or younger.

Conclusions:

High CD4 counts at care initiation were not associated with a higher risk of exiting care. Prompt ART initiation and special support for young and newly diagnosed patients with HIV are needed to maximize RIC.
Nadir CD4 Is Negatively Associated With Antinuclear Antibody Detection in HCV/HIV-Coinfected Patients
Authors: Poizot-Martin Isabelle , Rosenthal Eric , Gilbert Camille , Cano Carla E. , Simon Anne , Lascoux-Combe Caroline , Alric Laurent , Gervais Anne , Neau Didier , Esterle Laure , Salmon Dominique , Sogni Philippe , Wittkop Linda ,   for the ANRS CO13 HEPAVIH Study Group
Published: December 2018

Background:

Hepatitis C virus (HCV) and HIV infections are associated with higher risk of autoimmune diseases and T-cell dysfunction.

Setting:

We evaluate prevalence and factors associated with the presence of autoimmune antinuclear (ANA), anti–smooth muscle actin (aSMA), and anti–liver kidney microsome (aLKM1) antibodies (Ab) in HCV/HIV-coinfected patients during the post–combined antiretroviral therapy era.

Methods:

A cross-sectional observational study nested in the ANRS CO13 HEPAVIH cohort (NCT number: NCT03324633). We selected patients with both ANA testing and T-cell immunophenotyping determination during the cohort follow-up and collected aLKM1 and aSMA data when available. Logistic regression models were built to determine factors associated with the presence of auto-Ab.

Results:

Two hundred twenty-three HCV/HIV-coinfected patients fulfilled selection criteria. Prevalence of ANA and aSMA was 43.5% and 23.2%, respectively, and both were detected in 13.3% of patients. Isolated aSMA were detected in 9.9% and aLKM1 in 2 patients. In multivariable analysis, only a low nadir CD4 T-cell count was significantly associated with ANA detection.

Conclusions:

ANA and aSMA detection remain frequent in HCV/HIV-coinfected patients during the post–combined antiretroviral therapy era, despite fair immune restoration. These results advocate for a close monitoring of ANA before immune checkpoint inhibitor therapy in these patients with greater caution for those with a low nadir CD4 T-cell count.
Antiretroviral Drug Concentrations in Breastmilk, Maternal HIV Viral Load, and HIV Transmission to the Infant: Results From the BAN Study
Authors: Davis Nicole L. , Corbett Amanda , Kaullen Josh , Nelson Julie A. E. , Chasela Charles S. , Sichali Dorothy , Hudgens Michael G. , Miller William C. , Jamieson Denise J. , Kourtis Athena P. ,   on behalf of the BAN Study Team
Published: December 2018

Background:

Concentration of antiretroviral (ARV) drug found in plasma, and amounts of drug excreted into breastmilk, may affect HIV viral load and potentially perinatal HIV transmission.

Methods:

In this cohort study with 2-phase sampling, we included mothers randomized to postpartum maternal ARVs or daily infant nevirapine during 28 weeks of breastfeeding in the Breastfeeding, Antiretrovirals, and Nutrition study. Among these, we included all mothers who transmitted HIV to their infants between 2 and 28 weeks and 15% of mothers who did not (n = 27 and 227, respectively). Spearman correlation coefficients (r2) were used to assess the correlation between maternal plasma and breastmilk ARV concentration. Associations between the median effective drug concentration (EC50) and detectable maternal viral load (plasma: >40 copies per milliliter, breastmilk: >56 copies per milliliter) were assessed using mixed-effects models. Cox models were used to estimate the association between maternal or infant plasma drug concentration and breastmilk HIV transmission from 2 to 28 weeks.

Results:

All ARV compounds exhibited substantial correlations between maternal plasma and breastmilk concentrations (r2: 0.85–0.98, P-value <0.0001). Having plasma drug concentration above the EC50 was associated with lower odds of having detectable HIV RNA [maternal plasma odds ratio (OR) 0.64, 95% confidence interval (CI): 0.45 to 0.91; breastmilk OR 0.22, 95% CI: 0.14 to 0.35] and a reduced rate of breastmilk HIV transmission (hazard ratio 0.40, 95% CI: 0.18 to 0.93). Having breastmilk drug concentration above the EC50 was also associated with lower odds of having detectable maternal HIV RNA (plasma OR 0.62, 95% CI: 0.45 to 0.85; breastmilk OR 0.42, 95% CI: 0.29 to 0.59).

Conclusions:

Ensuring adequate drug concentration is important for viral suppression and preventing breastmilk HIV transmission.
Update on prevention of cytomegalovirus in hematopoietic cell transplantation
Authors: Dadwal Sanjeet S.
Published: December 2018

Purpose of review

Cytomegalovirus infection (CMVi) has been the troll of allogeneic hematopoietic cell transplantation (allo-HCT). Over the last 4 decades various approaches have been adopted to minimize the burden from CMVi. There has been major advancement in the management of CMVi in HCT within the last few years that is poised to change the approaches employed in preventing and managing CMVi. This review will summarize recent advances and potential future development in the management of CMV in HCT.

Recent finding

The major development has been the approval of letermovir for the prevention of CMVi in allo-HCT recipients. Also, with the potential availability of tests that can determine host CMV immunity a risk adapted approach to CMV prevention may become a possibility.

The landscape of CMV prevention is about to change with the approval of a new anti-CMV antiviral that is safe and effective. However, the prophylaxis may lead to late onset CMVi in the context of ongoing risk factors after stopping prophylaxis and measures to counter this shifting epidemiology will need further research; such as extending the prophylaxis in high-risk patients vs. immunotherapy with vaccination and T-cell therapy.
Performance of Anti–Topoisomerase I Antibody Testing by Multiple-Bead, Enzyme-Linked Immunosorbent Assay and Immunodiffusion in a University Setting
Authors: Homer Kate LaRiviere , Warren Jeffrey , Karayev Dmitry , Khanna Puja P. , Young Amber , Nagaraja Vivek , Metzger Allan L. , Khanna Dinesh
Published: December 2018

Background/Objective

The criterion standard for anti–topoisomerase I antibody (anti–topo I antibody) testing in systemic sclerosis (SSc) uses immunodiffusion (ID) techniques, but enzyme-linked immunosorbent assay (ELISA) and multiple-bead technology are often used in current settings to save time and cost. Our aim was to assess the performance of the multiple-bead assay, ELISA, and ID testing methods.

Methods

We conducted a retrospective study of patients at the University of Michigan whose extractable nuclear antigen 10 autoantibody panel tested positive for the anti–topo I antibody by multiple-bead technology during a 1-year period. All samples positive by multiple-bead assay were sent to the RDL Laboratories and reflexed for ELISA, and all anti–topo I antibodies positive by ELISA were further tested by ID. Clinical data were reviewed by a rheumatologist and assessed for presence of SSc. Data were analyzed via frequency tables.

Results

Approximately 9500 extractable nuclear antigen 10 panels were ordered by physicians at the University of Michigan. Of these, 129 patients were positive for the anti–topo I antibody by multiple-bead assay, 51 were positive by multiple-bead assay and ELISA, and 21 were positive by multiple-bead assay, ELISA, and ID. We found that 26.4% of patients positive by multiple-bead assay, 47.1% positive by multiple-bead assay and ELISA, and 95.2% positive by multiple-bead assay, ELISA, and ID had SSc.

Conclusions

Multiple-bead assays have a high rate of false-positive results for the anti–topo I antibody in patients without clinical evidence of SSc. A stepwise approach of confirmation of positive multiple-bead assay results using both ELISA and ID improves the predictive value of antibody testing for the diagnosis of SSc.
A Novel Preservation Solution Containing a JNK Inhibitory Peptide Efficiently Improves Islet Yield for Porcine Islet Isolation
Authors: Noguchi Hirofumi , Miyagi-Shiohira Chika , Nakashima Yoshiki , Ebi Nana , Hamada Eri , Tamaki Yoshihito , Kuwae Kazuho , Kitamura Shinji , Kobayashi Naoya , Saitoh Issei , Watanabe Masami
Published: December 2018

Background

For islet transplantation, pancreas preservation in University of Wisconsin (UW) solution is associated with disadvantages, such as collagenase inhibition, resulting in poor islet yield and islets with poor viability. In this study, we evaluated a novel preservation solution, the extracellular-type c-Jun N-terminal kinase (JNK) inhibitor-containing (EJ) solution.

Methods

The EJ solution has high sodium-low potassium composition with low viscosity compared to UW solution. Moreover, EJ solution contains a recently developed JNK inhibitor from our laboratory.

Results

We first compared the performance of EJ solution with that of UW solution. Islet yield before and after purification was significantly higher in the EJ group than in the UW group. Second, we compared the performance of EJ solution with that of EJ solution without the JNK inhibitor (EJ-J solution). After pancreas preservation in EJ solution, JNK activity was maintained at a relatively low level during islet isolation. Islet yield before and after purification was significantly higher in the EJ group than in the EJ-J group. After islet transplantation into streptozotocin-induced diabetic mice, blood glucose levels reached the normoglycemic range in 61.5% and 7.7% of diabetic mice in the EJ and EJ-J groups, respectively. Moreover, EJ solution exhibited reduced inhibition of collagenase digestion compared with UW solution.

Conclusions

Advantages of EJ solution over UW solution were inhibition of JNK activity and reduced collagenase inhibition. EJ solution may therefore be more suitable for islet isolation than UW solution.
Physics of pre-wetted, lubricated and impregnated surfaces: a review
Authors: Bormashenko Edward
Published: December 2018

Wetting phenomena occurring on pre-wetted flat and rough solid surfaces are reviewed. The wetting of lubricated flat surfaces is strongly correlated with the tribological properties of a solid/lubricant pair. The phenomena taking place on micro- and nano-rough oil-impregnated surfaces have attracted the attention of the scientific community due to their numerous promising applications as omniphobic, self-healing, anti-icing and anti-bacterial interfaces. On the other hand, these phenomena are rich in their physical content. The effects observed on natural and artificial, bioinspired oil-impregnated surfaces are discussed, including electrowetting of oil-impregnated surfaces, enabling low-voltage reversible control of the droplet shape.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology’.
Lessons from nature for green science and technology: an overview and bioinspired superliquiphobic/philic surfaces
Authors: Bhushan Bharat
Published: December 2018

Nature has developed materials, objects and processes that function from the macroscale to the nanoscale. The emerging field of biomimetics allows one to mimic biology or nature to develop nanomaterials, nanodevices and processes which provide desirable properties. The biologically inspired materials and structured surfaces are being explored for various commercial applications. These should have minimum human impact on the environment, leading to eco-friendly or green science and technology. There are a large number of flora and fauna including bacteria, plants, land and aquatic animals, and seashells with properties of commercial interest. The paper presents an overview of the general field of biomimetics followed by a detailed overview of mechanisms, fabrication techniques and characterization of superliquiphobic/philic surfaces and their applications.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology’.
Water condensation and transport on bioinspired triangular patterns with heterogeneous wettability at a low temperature
Authors: Song Dong , Bhushan Bharat
Published: December 2018

Desert beetles and cactus plants collect water from fog in arid regions. The desert beetle uses heterogeneous wettability to transport water to its mouth. A cactus uses conical spines which provide Laplace pressure gradient to transport water to its base. In this study, bioinspired triangular patterns with various wettability and different from the surrounding regions were investigated to transport condensed water from ambient air. A low temperature of 5°C was used to decrease saturated vapour pressure to promote water condensation. Results from this study can be used to enhance the performance of water collection systems.

This article is part of the theme issue ‘Bioinspired materials and surfaces for green science and technology’.
Predicting complex genetic phenotypes using error propagation in weighted networks
Authors: El Mhamdi El Mahdi , Kucharavy Andrei , Guerraoui Rachid , Li Rong
Published: December 2018

Network-biology view of biological systems is a ubiquitous abstraction that emerged in the last two decades to allow a high-level understanding of principles governing them. However, the principles according to which biological systems are organized are still unclear. Here, we investigate if biological networks could be approximated as overlapping, feed-forward networks where the nodes have non-linear activation functions. Such networks have been shown to be universal approximators and their stability has been explored in the context of artificial neural networks. Mathematical formalization of this model followed by numerical simulations based on genomic data allowed us to accurately predict the statistics of gene essentiality in yeast and hence indicate that biological networks might be better understood as a distributed system, comprising potentially unreliable components.
Myeloperoxidase and Eosinophil Peroxidase Inhibit the in vitro Endotoxin Activities of Lipopolysaccharide (LPS) and Lipid A and Increase Survival in an in vivo Mouse LPS LD90 model
Authors: Allen Robert C. , Henery Mary L. , Allen John C. , Hawks Roger J. , Stephens Jackson T.
Published: December 2018

Myeloperoxidase (MPO) and eosinophil peroxidase (EPO) are cationic leukocyte haloperoxidases with potent microbicidal and detoxifying activities. MPO selectively binds and kills specific Gram-positive bacteria (GPB) and all Gram-negative bacteria (GNB) tested. Endotoxin, i.e., lipopolysaccharide (LPS) comprising a toxic Lipid A component, is a characteristic of all GNB. The possibility that haloperoxidases bind to and inhibit the endotoxin of GBN was considered and tested by contacting MPO and EPO with LPS and Lipid A and measuring for inhibition of endotoxin activity using either the in vitro gel or chromogenic Limulus amebocyte lysate (LAL) assays. Contacting MPO and EPO with LPS purified from Escherichia coli O55:B5 and with diphosphoryl Lipid A purified from E. coli F583 inhibited their endotoxin activities in proportion to the natural log of the MPO or EPO concentration. Although MPO is less cationic than EPO, MPO consistently demonstrated inhibition of endotoxin activity that is about threefold superior to EPO. Haloperoxidase enzymatic activity was not required for inhibition, and MPO haloperoxidase action did not increase endotoxin inhibition. MPO and EPO inhibition of LPS endotoxin activity was also measured using a 90% lethal dose (LD90) mouse model studied over a five-day period. Based on Kaplan Meier survival analysis, MPO significantly increased mouse survival in a dose-dependent manner. EPO was less effective. In conclusion, contacting MPO and EPO with LPS and Lipid A inhibits in vitro endotoxin activities, but inhibition is independent of haloperoxidase enzymatic function. MPO significantly increases mouse survival against LPS in an in vivo LD90 endotoxin model.
The bat influenza H17N10 can be neutralized by broadly-neutralizing monoclonal antibodies and its neuraminidase can facilitate viral egress.
Authors: Carnell George , Giotis Efstathios , Grehan Keith , Ferrara Francesca , Mather Stuart , Molesti Eleonora , Scott Simon , Pessi Antonello , Lacek Krzysztof , Temperton Nigel
Published: December 2018

The diversity of subtypes within the Influenza A virus genus has recently expanded with the identification of H17N10 and H18N11 from bats. In order to further study the tropism and zoonotic potential of these viruses, we have successfully produced lentiviral pseudotypes bearing both H17 and N10. These pseudotypes were shown to be efficiently neutralized by the broadly-neutralizing monoclonal antibodies CR9114 and FI6. Our studies also confirm previous reports that H17 does not use sialic acid as its cellular receptor, as pseudotypes bearing the H17 envelope glycoprotein are released into the cell supernatant in the absence of neuraminidase. However, we demonstrate that N10 facilitates heterosubtypic (H5 and H7) influenza hemagglutinin-bearing pseudotype release in the absence of another source of neuraminidase, significantly increasing luciferase pseudotype production titres. Despite this, N10 shows no activity in the enzyme-linked lectin assay used for traditional sialidases. These findings suggest that this protein plays an important role in viral egress, but is perhaps involved in further accessory roles in the bat influenza lifecycle that are yet to be discovered. Thus we show the lentiviral pseudotype system is a useful research tool, and amenable for investigation of bat influenza tropism, restriction and sero-epidemiology, without the constraints or safety issues with producing a replication-competent virus, to which the human population is naive.
High-dimensional Bayesian network inference from systems genetics data using genetic node ordering
Authors: Wang Lingfei , Audenaert Pieter , Michoel Tom
Published: December 2018

Studying the impact of genetic variation on gene regulatory networks is essential to understand the biological mechanisms by which genetic variation causes variation in phenotypes. Bayesian networks provide an elegant statistical approach for multi-trait genetic mapping and modelling causal trait relationships. However, inferring Bayesian gene networks from high-dimensional genetics and genomics data is challenging, because the number of possible networks scales super-exponentially with the number of nodes, and the computational cost of conventional Bayesian network inference methods quickly becomes prohibitive. We propose an alternative method to infer high-quality Bayesian gene networks that easily scales to thousands of genes. Our method first reconstructs a node ordering by conducting pairwise causal inference tests between genes, which then allows to infer a Bayesian network via a series of independent variable selection problems, one for each gene. We demonstrate using simulated and real systems genetics data that this results in a Bayesian network with equal, and sometimes better, likelihood than the conventional methods, while having a significantly higher over-lap with groundtruth networks and being orders of magnitude faster. Moreover our method allows for a unified false discovery rate control across genes and individual edges, and thus a rigorous and easily interpretable way for tuning the sparsity level of the inferred network. Bayesian network inference using pairwise node ordering is a highly efficient approach for reconstructing gene regulatory networks when prior information for the inclusion of edges exists or can be inferred from the available data.
Sensory coding and causal impact of mouse cortex in a visual decision
Authors: Zatka-Haas Peter , Steinmetz Nicholas A. , Carandini Matteo , Harris Kenneth D.
Published: December 2018

Correlates of sensory stimuli and motor actions are found in multiple cortical areas, but such correlates do not indicate whether these areas are causally relevant to task performance. We trained mice to discriminate visual contrast and report their decision by turning a wheel. Widefield calcium imaging and Neuropixels recordings in cortex revealed stimulus-related activity in visual (VIS) and frontal (MOs) areas, and widespread movement-related activity across the whole dorsal cortex. Optogenetic inactivation biased choices only when targeted at VIS and MOs, at times corresponding to peak stimulus decoding. A neurometric model based on summing and subtracting activity in VIS and MOs successfully described behavioral performance and predicted the effect of optogenetic inactivation. Thus, local sensory signals in visual and frontal cortex play a causal role in task performance, while widespread dorsal cortical signals correlating with movement reflect processes that do not play a causal role.
Low Computational-cost Cell Detection Method for Calcium Imaging Data
Authors: Ito Tsubasa , Ota Keisuke , Ueno Kanako , Oisi Yasuhiro , Matsubara Chie , Kobayashi Kenta , Ohkura Masamichi , Nakai Junichi , Murayama Masanori , Aonishi Toru
Published: December 2018

The rapid progress of calcium imaging has reached a point where the activity of tens of thousands of cells can be recorded simultaneously. However, the huge amount of data in such records makes it difficult to carry out cell detection manually. Consequently, because the cell detection is the first step of multicellular data analysis, there is a pressing need for automatic cell detection methods for large-scale image data. Automatic cell detection algorithms have been pioneered by a handful of research groups. Such algorithms, however, assume a conventional field of view (FOV) (i.e. 512 × 512 pixels) and need a significantly higher computational power for a wider FOV to work within a practical period of time. To overcome this issue, we propose a method called low computational-cost cell detection (LCCD), which can complete its processing even on the latest ultra-large FOV data within a practical period of time. We compared it with two previously proposed methods, constrained non-negative matrix factorization (CNMF) and Suite2P. We found that LCCD makes it possible to detect cells from a huge-amount of high-density imaging data within a shorter period of time and with an accuracy comparable to or better than those of CNMF and Suite2P.
Roles matter: Graduate student perceptions of active learning in the STEM courses they take and those they teach
Authors: Wischusen Everett W. , Patrick Lorelei , Howell Leigh Anne
Published: December 2018

Despite many calls to reform undergraduate science, technology, engineering, and math (STEM) education to incorporate active learning into classes, there has been little attention paid to graduate level classrooms or courses taught by graduate students. Here, we set out to understand if and how STEM graduate students' perceptions of active learning change in the classes they take versus those they teach by administering surveys to STEM graduate students at our institution. We found that graduate students had taken relatively few graduate level classes using active learning and they felt that more time should devoted to active learning in the courses they were taking. Teaching assistants felt that they were devoting the right amount of class time to active learning in the classes they taught. Graduate students also felt that they were using teaching methods in the classes they taught that were different from those they thought should be used when teaching undergraduates and were different from how they preferred to learn when taking classes. These findings suggest that graduate students' perceptions of teaching and learning changed based on their role in the classroom, which have implications for graduate level course work and professional development programs.
Single nucleotide variant at the alphaVbeta3 integrin associated to Andes virus infection susceptibility.
Authors: Martinez-Valdebenito Constanza , Angulo Jenniffer , Le Corre N. , Marco Clauda , Vial Cecilia , Miquel JF , Cerda Jaime , Mertz Gregory , Vial Pablo , Lopez-Lastra Marcelo , Ferres Marcela ,   F. Valdivieso, R. Riquelme,ML Rioseco, M. Calvo, F. Vargas, M. Acuña, R. Mansilla, C. Infante
Published: December 2018

Background

ANDV, agent of hantavirus cardiopulmonary syndrome, enters through integrin cell protein. A change from leucine-to-proline at residues 33 in the PSI-domain (L33P) inhibits ANDV recognition. We assessed the association between this human-variant and ANDV infection.

Results

We defined susceptible genotype to “TT” (coding leucine) and protective “CC” (coding proline). TT was in 89.2% (66/74) of a first cohort of ANDV-cases and in 60% (63/105) of exposed close-household contacts who remained unifected (p<0.05). Protective genotype was absent in all 85 ANDV cases in both cohorts and was present at 11.4% in exposed close-household contacts who remained uninfected. Logistic regression modeling to become a case had an OR 6.2-12.6 (p<0.05) in presence of TT and ANDV well-known risk activities. Moreover, OR of 7.3 was obtained when TT condition was analyzed for two groups exposed to the same environmental risk.

Conclusion

Host genetic background has an important role in ANDV-infection susceptibility in the studied population.
The Role of Interleukin-1 cytokine family (IL-1β, IL-37) and interleukin-12 cytokine family (IL-12, IL-35) in eumycetoma infection pathogenesis
Authors: Fahal Ahmed Hassan , Abushouk Amir , Nasr Amre , Masuadi Emad , Allam Gamal , Siddig Emmanuel E.
Published: December 2018

Mycetoma is a neglected tropical disease, endemic in many tropical and subtropical regions, characterised by massive deformity and disability and can be fatal if untreated early and appropriately. Interleukins (IL) -35 and IL-37 are newly discovered cytokines that play an important role in suppressing the immune system. However, the expression of these interleukins in patients with Madurella mycetomatis (M. mycetomatis) induced eumycetoma has not yet been explored. This study aims to determine the levels of the IL-1 family (IL-1β, IL-37) and IL-12 family (IL-12, IL-35) in a group of these patients and the association between these cytokines levels and the patients' demographic characteristics. The present, a case-control study was conducted at the Mycetoma Research Centre, Soba University Hospital, University of Khartoum, Sudan and it included 140 individuals. They were divided into two groups; group I: healthy controls [n = 70; median age 25 years (range 12 to 70 years)]. Group II: mycetoma patients [n = 70 patients; median age 25 (range 13 to 70 years)]. Cytokines levels were measured in sera using enzyme-linked immunosorbent assay (ELISA).

There was no significant correlation between the IL-1β and IL-12 levels and the lesions size and disease duration, whereas levels of IL-37 and IL-35 were significantly correlated with that. The analysis of the risk factors of higher circulatory levels of IL-37 in patients of mycetoma showed a significant negative association with IL-1β cytokine, where a unit increment in IL-1β will decrease the levels of IL-37 by 35.28 pg/ml. The levels of IL-37 among the patients with a duration of mycetoma infection ≤ one year had significantly decreased by an average of 18.45 compared to patients with a mycetoma infection's duration of ≥ 5years (reference group). Furthermore, the risk factors of higher levels of IL-35 in mycetoma patients revealed a significant negative association with IL-12, as a unit increment in IL-12 decreases the levels of IL-35by 8.99 pg/ml (p < 0.001). Levels of IL-35 among the patients with duration of mycetoma infection ≤ one year had significantly decreased (p-value = 0.002) on average by 41.82 compared to patients with a duration of mycetoma infection ≥ five years (reference group). In conclusion, this study indicates that both IL-35 and IL-37 are negatively associated with the levels of IL-1β and IL-12 in eumycetoma mycetoma infection; and high levels of IL-37 and IL-35 may have a negative impact on disease progression.
The economy and environmental attitudes: Does a good economy make citizens care more about the environment?
Authors: Rizio Stephanie Marie , Kashima Yoshihisa
Published: December 2018

The relationship between economic conditions and environmental attitudes has been hotly debated in academic and public discourse. Some contend that economic prosperity strengthens environmental attitudes, while others argue that no such relationship exists. We shed light on the economy-environmental importance relationship by incorporating both nonlinear effects and public perceptions of the economy. Two countries with comparable economic performance and cultural heritage, Australia and Canada, are investigated. Using opinion survey data in a time-series analysis over a 20-year period, we find that GDP per capita has a nonlinear relationship with environmental attitudes in both countries, and the inclusion of perceptions of the economy significantly improves the prediction of environmental attitudes. In both Australia and Canada, a U-shaped relationship is observed; initial improvements in economic conditions tend to worsen environmental attitudes, but past a certain threshold, further economic improvements result in increased environmental concern. Perceptions of the economy too showed analogous trends. In both countries, positive perceptions of the economy were associated with strong environmental attitudes; at least in Canada, negative perceptions of the economy were also positively associated with environmental attitudes. The nonlinear effects of the economy as well as perceptions of the economy helps shed light on the current inconclusive literature on the relationship between the economy and citizens' pro-environmental support. This is an important consideration given the critical importance to the future sustainability of the natural environment.
Use of IFNγ/IL10 ratio for stratification of hydrocortisone therapy in patients with septic shock
Authors: König Rainer , Kolte Amol , Ahlers Olaf , Oswald Marcus , Röll Daniela , Dimopoulos George , Tsangaris Iraklis , Antoniadou Eleni , Bogatsch Holger , Löffler Markus , Sprung Charles L. , Singer Mervyn , Brunkhorst Frank , Oppert Michael , Gerlach Herwig , Claus Ralf A. , Coldewey Sina M. , Briegel Josef , Giamarellos-Bourboulis Evangelos J. , Keh Didier , Bauer Michael
Published: December 2018

Background

Large clinical trials testing hydrocortisone therapy in septic shock have produced conflicting results. Subgroups may however benefit depending on their individual immune response.

Methods

We performed an exploratory analysis of the CORTICUS trial database employing machine learning to a panel of 137 variables collected from 83 patients (60 survivors, 23 non-survivors) including demographic and clinical measures, organ failure scores, leukocyte counts and circulating cytokine levels. The identified biomarker was validated against data collected from patients enrolled into a cohort of the Hellenic Sepsis Study Group (HSSG) (n=162) and two data sets of two other clinical trials.Ex vivostudies were performed on this biomarker to assess a possible mechanistic role.

Results

A low serum IFNγ/IL10 ratio predicted increased survival in the hydrocortisone group whereas a high ratio predicted better survival in the placebo group. Using this ratio for a decision rule, we found significant improvement in survival in the groups of patients being in compliance with the prediction rule (discovery set: OR=3.03 [95% Cl: 1.05-8.75], P=0.031, validation set: OR=2.01 [95% CI: 1.04-3.88], P=0.026). Applying the rule to two further, smaller datasets showed the same tendency. Mechanistic studies revealed that IFNγ/IL10 was negatively associated with pathogen load in spiked human blood. Anin silicoanalysis of published IFNγ and IL10 values in bacteremic and non-bacteremic SIRS patients supported this association between the ratio and pathogen burden.

Conclusion

If confirmed prospectively, the IFNγ/IL10 ratio could be used as a rapidly available theranostic for use of hydrocortisone therapy in septic shock.
The Effect of Compound Kushen Injection on Cancer Cells: Integrated Identification of Candidate Molecular Mechanisms
Authors: Cui Jian , Qu Zhipeng , Harata-Lee Yuka , Shen Hanyuan , Nwe Aung Thazin , Wang Wei , Daniel Kortschak R. , Adelson David L
Published: December 2018

Background

Because Traditional Chinese Medicine (TCM) preparations are often combinations of multiple herbs containing hundreds of compounds, they have been difficult to study. Compound Kushen Injection (CKI) is a complex mixture cancer treatment used in Chinese hospitals for over twenty years.

Purpose

To demonstrate that a systematic analysis of molecular changes resulting from complex mixtures of bioactives from TCM can identify a core set of differentially expressed (DE) genes and a reproducible set of candidate pathways.

Study Design

We used a cancer cell culture model to measure the effect of CKI on cell cycle phases, apoptosis and correlate those phenotypes with CKI induced changes in gene expression.

Methods

We treated cancer cells with CKI in order to generate and analyse high-throughput transcriptome data from two cancer cell lines. We integrated these differential gene expression results with previously reported results.

Results

CKI induced cell-cycle arrest and apoptosis and altered the expression of 363 core candidate genes associated with cell cycle, apoptosis, DNA replication/repair and various cancer pathways. Of these, 7 are clinically relevant to cancer diagnosis or therapy and 14 are cell cycle regulators, and most of these 21 candidates are downregulated by CKI. Comparison of our core candidate genes to a database of plant medicinal compounds and their effects on gene expression identified one-to-one, one-to-many and many-to-many regulatory relationships between compounds in CKI and DE genes.

Conclusions

By identifying promising candidate pathways and genes associated with CKI based on our transcriptome-based analysis, we have shown this approach is useful for the systematic analysis of molecular changes resulting from complex mixtures of bioactives.
VIT1-dependent Fe distribution in seeds is conserved in dicots
Authors: Eroglu Seckin , Karaca Nur , Vogel-Mikus Katarina , Kavčič Anja , Filiz Ertugrul , Tanyolac Bahattin
Published: December 2018

One third of the people suffer from iron (Fe) Fe deficiency. An underlying factor for this malnutrition is insufficient Fe intake from the diet. A major part of the human diet includes seeds of staple crops, which contain Fe that is poorly bioavailable. One reason for the low bioavailability is these seeds store Fe in cellular compartments that also contain antinutrients, such as phytate. Thus, several studies focused on decreasing phytate concentrations. As an alternative approach to increase bioavailable Fe, Fe reserves might be directed to cellular compartments such as plastids that are free of phytate. Previous studies indicated that Fe reserves can be relocalized inside the seed to the desired compartment by genetic modification, provided that a suitable iron transporter protein is used. However, to the best of our knowledge, a Fe transporter localizing to plastids have not been identified in seeds to date. To discover novel Fe transporters, we screened Fe patterns in seeds of distinct plant lineages, hypothesizing Fe hyperaccumulating sites would indicate Fe transporter presence. To this end, metal localizations in seeds of more than twenty species were investigated using histochemical or X-ray based techniques. Results showed that in Rosids, the largest clade of eudicots, Fe reserves were primarily confined in the embryo part of the seeds. Furthermore, inside the embryos, Fe was enriched in the endodermal cell layer, a well-known feature that is mediated by vacuolar Fe transporter, VIT1 in model plantArabidopsis thaliana. This enrichment was well conserved in and beyond Rosid species. Finally, a few seeds showed novel Fe patterns, includingCarica papayawhich concentrated large Fe reserves exclusively in plastids called amyloplasts. Generally, Fe stored in amyloplast is considered bioavailable. Taken together, this study suggests dicot seeds store Fe mainly in the embryo, with a VIT1-dependent enrichment in its endodermal cell layer and indicateCarica papayapossess a strong Fe transporter at the plastid membrane. Once it is identified that might be useful in biofortification, as a novel tool to shift Fe to compartments where it is more bioavailable.
Analysis of Maize Profilin-4 Isoform as an allergen
Authors: Alam Saruar , Hasan Md. Kamrul , Hossain Md. Faruk
Published: December 2018

Profilin is an actin monomer-binding protein that controls the dynamic turnover of actin filaments and is ubiquitously present in different organisms ranging from prokaryotes to higher eukaryotes. Maize (Zea mays) profilin-4 isoform is a pollen-specific protein. Birch profilin isoform is a known allergen but maize profilin is yet to be characterized. Due to the high cultivation rate of maize, the analysis of the properties of maize profilin-4 isoform as an allergen is a demand of time for developing an effective immune therapy. Here, we analyzed the allergenic potency of profilin-4 by studying of its physicochemical properties, including molecular weight (∼14kD) and theoretical pI (4.63). We tested the potential B cell epitope candidates of profilin-4 using different immune-informatics tools housed at IEDB analysis resource. For the B cell epitope prediction, potential antigenic sites on the protein surface were predicted by both propensity scale and machine learning method followed by their mapping of 3D structure prediction. We hereby claim that the profilin-4 is a potential allergen and is able to induce allergic responses. However, the wet lab experiments are needed to validate our claim that’s beyond our scope.
Individualized non-invasive brain stimulation engages the subgenual anterior cingulate and amygdala
Authors: Oathes Desmond J , Zimmerman Jared , Duprat Romain , Cavdaroglu Seda , Scully Morgan , Rosenberg Benjamin , Flounders Matthew , Long Hannah , Elliott Mark , Shandler Gavriella , Shinohara Russell T , Linn Kristin A
Published: December 2018

Brain stimulation is used clinically to treat a variety of neurological and psychiatric conditions. The mechanisms of the clinical effects of these brain-based therapies are presumably dependent on their effects on brain networks. It has been hypothesized that using individualized brain network maps is an optimal strategy for defining network boundaries and topologies. Traditional non-invasive imaging can determine correlations between structural or functional time series. However, they cannot easily establish hierarchies in communication flow as done in non-human animals using invasive methods. In the present study, we interleaved functional MRI recordings with non-invasive transcranial magnetic stimulation in the attempt to map causal communication between the prefrontal cortex and two subcortical structures thought to contribute to affective dysregulation: the subgenual anterior cingulate cortex (sgACC) and the amygdala. In both cases, we found evidence that these brain areas were engaged when TMS was applied to prefrontal sites determined from each participant's previous fMRI scan. Specifically, after transforming individual participant images to within-scan quantiles of evoked TMS response, we modeled the average quantile response within a given region across stimulation sites and individuals to demonstrate that the targets were differentially influenced by TMS. Furthermore, we found that the sgACC distributed brain network, estimated in a separate cohort, was engaged in response to sgACC focused TMS and was partially separable from the proximal default mode network response. The amygdala, but not its distributed network, responded to TMS. Our findings indicate that individual targeting and brain response measurements usefully capture causal circuit mapping to the sgACC and amygdala in humans, setting the stage for approaches to non-invasively modulate subcortical nodes of distributed brain networks in clinical interventions and mechanistic human neuroscience studies.
Mitochondrial cristae biogenesis coordinates with ETC complex IV assembly during Drosophila maturation
Authors: Jiang Yi-fan , Lin Hsiang-ling , Wang Li-jie , Hsu Tian , Fu Chi-yu
Published: December 2018

Mitochondrial cristae contain electron transport chain (ETC) complexes and are distinct from the inner boundary membrane (IBM) in both protein composition and function. While many details of mitochondrial membrane structure are known, the processes governing cristae biogenesis, including the organization of lipid membranes and assembly of proteins encoded by both nuclear and mitochondrial DNA, remain obscure. We followed cristae biogenesis in situ upon Drosophila eclosion using serial-section electron tomography and revealed that the morphogenesis of lamellar cristae coordinates with ETC complex IV assembly. The membrane morphogenesis and gain-of-function were intricately co-evolved during cristae biogenesis. Marf-knockdown flies formed lamellar cristae containing ATP synthase and functional COX. However, OPA1-knockdown flies showed impaired cristae biogenesis. Overall, this study revealed the multilevel coordination of protein-coupled membrane morphogenesis in building functional cristae.
Determinants of cyclization-decyclization kinetics of short DNA with sticky ends
Authors: Jeong Jiyoun , Kim Harold D
Published: December 2018

Cyclization of DNA with sticky ends is commonly used to construct DNA minicircles and to measure DNA bendability. The cyclization probability of short DNA (<150 bp) has a strong length dependence, but how it depends on the rotational positioning of the sticky ends around the helical axis is less clear. To shed light upon the determinants of the cyclization probability of short DNA, we measured cyclization and decyclization rates of ~100-bp DNA with sticky ends over two helical periods using single-molecule Fluorescence Resonance Energy Transfer (FRET). The cyclization rate increases monotonically with length, indicating no excess twisting, while the decyclization rate oscillates with length, higher at half-integer helical turns and lower at integer helical turns. The oscillation profile is kinetically and thermodynamically consistent with a three-state cyclization model in which sticky-ended short DNA first bends into a torsionally-relaxed teardrop, and subsequently transitions to a more stable loop upon terminal base stacking. We also show that the looping probability density (the J factor) extracted from this study is in good agreement with the worm-like chain model near 100 bp. For shorter DNA, we discuss various experimental factors that prevent an accurate measurement of the J factor.