bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of Clinical Judgment in Prelicensure Nursing Students
Authors: Bussard Michelle E.
Published: August 2017

Clinical judgment is an essential end-of-program outcome for prelicensure nursing students. Evaluating progression of clinical judgment when students participate in simulated patient experiences is essential in ensuring that end-of-program and course outcomes are achieved. The purpose of this study was to identify if progression in clinical judgment is evident after students participate in 4 simulated patient experiences as measured by the Lasater Clinical Judgment Rubric.
Gamification of Nursing Education With Digital Badges
Authors: White Meagan , Shellenbarger Teresa
Published: August 2017

Digital badges (DBs) serve as an innovative approach to gamifying nursing education by engaging socially connected, technologically savvy nursing students in learning. Because assessment and credentialing mechanisms are housed and managed online, DBs are designed as visible indicators of accomplishment and skill. This article describes important considerations for faculty when incorporating game-based pedagogies such as DB into nursing education and identifies potential pitfalls with DB use that faculty should consider.
Comparison of Instructional Methods for Screening, Brief Intervention, and Referral to Treatment for Substance Use in Nursing Education
Authors: Knopf-Amelung Sarah , Gotham Heather , Kuofie Araba , Young Pamela , Manney Stinson Ronalda , Lynn Jolene , Barker Kendra , Hildreth Jessica
Published: August 2017

Most nursing programs lack curriculum on substance use. This project evaluated 3 didactic instructional methods for teaching baccalaureate nursing students about screening, brief intervention, and referral to treatment for substance use. In-person, asynchronous narrated slides and interactive online instructional methods were all effective in developing students’ competency; however, active learning methods (in-person and interactive online course) were more effective in changing students’ attitudes about their role in screening and intervening for drug use.
Lipid Deposition on Contact Lenses when Using Contemporary Care Solutions
Authors: Babaei Omali Negar , Lada Mark , Lakkis Carol , Morgan Philip B. , Nichols Jason J. , Subbaraman Lakshman N. , Jones Lyndon W.
Published: August 2017

SIGNIFICANCE

There remains only a small amount of data from human studies demonstrating the effect of contact lens/lens care solution combinations on the deposition of lipids. Therefore, information on the degree to which modern materials deposit lipids when used with contemporary care solutions would be valuable.

PURPOSE

The present study aims to determine the effect of lens care system combinations on levels of total lipid, cholesterol, and cholesteryl esters extracted from three different contact lenses (CLs) when used with four contemporary care systems.

METHODS

Experienced CL wearers were recruited to participate in this study. Combinations of three CLs (etafilcon A [ETA], galyfilcon A [GALY], and senofilcon A [SENO]) and four CL care solutions (Biotrue, ClearCare, OPTI-FREE PureMoist, and RevitaLens Ocutec) were investigated. A total of 791 CLs were analyzed. Subjects were randomized to one lens type and then used all four lens care solutions in random sequence for 10–14 days before the CLs were collected and analyzed for the amount of cholesterol, cholesteryl esters, and total lipids.

RESULTS

The mean range of cholesterol recovered across the different care solutions was 0.34–2.77 μg/lens, 3.48–4.29 μg/lens, and 4.75–6.20 μg/lens for ETA, SENO, and GALY lenses, respectively. Use of OPTI-FREE PureMoist with ETA lenses led to a significantly greater amount of cholesterol being recovered when compared to the use of the other solutions with ETA lenses (P < .05). The mean range of cholesteryl esters recovered across different care solutions was 1.31–2.02 μg/lens, 6.43–7.19 μg/lens, and 7.96–10.13 μg/lens for ETA, SENO, and GALY lenses, respectively. There were no differences in the amount of cholesteryl esters and total lipids extracted for a given lens type when used with any of the four care solutions (P > .05).

CONCLUSIONS

This study did not demonstrate conclusively that any of the solution/CL combinations were superior to any of the other combinations when the amounts of lipid deposition were compared among the tested lenses.
Primary Bone Lymphoma Exhibits a Favorable Prognosis and Distinct Gene Expression Signatures Resembling Diffuse Large B-Cell Lymphoma Derived From Centrocytes in the Germinal Center
Authors: Li Xin , Xu-Monette Zijun Y. , Yi Shuhua , Dabaja Bouthaina S. , Manyam Ganiraju C. , Westin Jason , Fowler Nathan , Miranda Roberto N. , Zhang Mingzhi , Ferry Judith A. , Medeiros L. Jeffrey , Harris Nancy L. , Young Ken H.
Published: August 2017

Primary bone (PB) diffuse large B-cell lymphoma (DLBCL) is rare and has a favorable prognosis, but the underlying biological mechanisms remain unknown. In this study we analyzed the clinicopathologic features of 160 patients with PB-DLBCL in comparison with 499 nonosseous DLBCL. Compared with patients with nonosseous DLBCL and secondary involvement of bone by DLBCL, PB-DLBCL patients less frequently had elderly age, B-symptoms, elevated serum lactate dehydrogenase levels, and high International Prognostic Index at diagnosis, more frequently had germinal center (GC) subtype (approximately 90%) and complete remission, and had significantly better survival. The 5-year progression-free and overall survival rates of PB-DLBCL patients were 80% and 93%, respectively, superior to both GC B-cell–like (GCB) and activated B cell–like subtypes of DLBCL. Further stratifying nonosseous DLBCL cell-of-origin subtypes by clinical factors showed that PB-DLBCL had similar survival rates as the centrocyte-origin (CC) subtype of DLBCL-GCB classified by the B-cell–associated gene signature algorithm. To better understand the favorable outcome of PB-DLBCL patients, gene expression profiling and microRNA profiling were performed in a small subset of PB-DLBCL. The gene expression profiles of PB-DLBCL resembled those of nonosseous DLBCL-GCB-CC, but were distinct from other DLBCL cell-of-origin especially the centroblast-origin (CB) subtype. Compared with DLBCL-GCB-CB, PB-DLBCL and DLBCL-GCB-CC also had much higher levels of miR-125a-3p, miR-34-3p, and miR-155-5p, and significantly lower levels of miR-17-5p and miR-17-3p. These results demonstrated that PB-DLBCL is clinically distinct, and the cell-of-origin of PB-DLBCL stems from centrocytes in the GC, that are biologically attributed for the favorable prognosis of PB-DLBCL.
Improving Timeliness of β-Agonist and Corticosteroid Administration in Patients With Acute Wheezing
Authors: McIver Mandisa , Stoudemire William , Smith-Ramsey Cherrelle , Panigrahi Mousumee , Walsh-Kelly Christine , Rutman Lori E.
Published: August 2017

Objective

Timely delivery of β-agonists and steroids to patients with acute recurrent wheezing is a key component of the National Heart, Lung, and Blood Institute recommended emergency department (ED) asthma care. We conducted an ED improvement initiative to standardize asthma care and improve time to treatments.

Methods

Our multidisciplinary team identified key contributing factors to timeliness, developed key driver diagrams, implemented and refined a management pathway, designed and executed rapid cycle improvements, and implemented interventions. A time series design was used to analyze outcomes with baseline data and continuous monitoring during active intervention steps. The primary outcomes analyzed were the times to first β-agonist and steroid administration. Secondary outcomes included admission rate, ED length of stay, and ED revisits.

Results

Assignment of the Pediatric Asthma Score, our initial pathway step, occurred in most patients within the first several months. Time to first β-agonist administration decreased from the baseline mean of 76 minutes to 27 minutes. Time to steroid administration decreased from the baseline mean of 108 minutes to 49 minutes. Mean monthly admission rate remained at 22% with no special cause variation identified. The ED revisit rate was not negatively impacted and, in most months, was 0%.

Conclusions

By standardizing asthma care in our ED and redesigning care delivery processes, care variation decreased and significant improvements in timeliness of β-agonist and steroid administration occurred.
Prevalence of Disability in Patients With Musculoskeletal Pain and Rheumatic Diseases in a Population From Cuenca, Ecuador
Authors: Guevara-Pacheco Sergio Vicente , Feican-Alvarado Astrid , Delgado-Pauta Jorge , Lliguisaca-Segarra Angelita , Pelaez-Ballestas Ingris
Published: August 2017

Objective

The aim of this study was to determine the prevalence of disability in patients with musculoskeletal pain and rheumatic diseases in Cuenca, Ecuador.

Methods

We performed a cross-sectional analytical study with randomized sampling in 4877 subjects, from urban and rural areas. COPCORD (Community Oriented Program for Control of Rheumatic Diseases)–validated questionnaire was administered house-to-house to identify subjects with nontraumatic musculoskeletal pain and rheumatic diseases. The subjects were assessed by rheumatologists for diagnostic accuracy, and the Health Assessment Questionnaire Disability Index was administered to assess functional capacity. A logistic regression analysis was conducted to determine the association of rheumatic diseases with functional disability.

Results

Functional disability was found in 221 subjects (73.1% women), with mean age 62 (SD, 18.2) years, residing in rural areas (201 [66.5%]), with education of 6.9 (SD, 5.3) years, and of low income (77 [47.2%]). The value of HAQ-DI was a mean of 0.2 (0–2.9). The real prevalence of physical disability was 9.5%. Moderate and severe disability predominated in activities such as kneeling (4.9% and 3.3%), squatting (4.8% and 2.7%), and leaning to pick up objects (3.7% and 0.9%), respectively. Rheumatic diseases associated with physical disabilities were knee osteoarthritis (95 [31.4%]) and hand osteoarthritis (69 [22.8%]), mechanical low-back pain (43 [14.2%]), fibromyalgia (27 [9.5%]), and rheumatoid arthritis (11 [3.6%]; P < 0.001).

Conclusions

Physical disability was associated with older age, female sex, rural residence, lower education, and lower income. Moderate and severe disability predominated in the dimensions of kneeling, squatting, and picking up objects. Rheumatic diseases associated with disability were hand and knee osteoarthritis, back pain, fibromyalgia, and rheumatoid arthritis.

Take Home Message
Relation Between Epicardial Fat and Subclinical Atherosclerosis in Asymptomatic Individuals
Authors: Abazid Rami M. , Smettei Osama A. , Kattea Mohammad Obadah , Sayed Sawsan , Saqqah Hanaa , Widyan Adel M. , Opolski Maksymilian P.
Published: August 2017

Purpose:

Excessive quantity of epicardial adipose tissue (EAT) is considered a risk factor for coronary artery disease (CAD). There are limited data, however, on the relationship between the quality of EAT and CAD. We investigated the association between the density and volume of EAT and subclinical CAD defined by positive coronary artery calcification (CAC), using computed tomography (CT).

Materials and Methods:

We reviewed 609 consecutive CT scans of patients with a mild to moderate risk for CAD to assess the EAT volume, which was measured manually by tracing the parietal pericardial sac on axial images. Fat density was recorded in mean Hounsfield units (HU), and CAC was measured using the Agatston method.

Results:

The mean patients’ age was 50±11 years, and 393 (64.5%) were men. Overall, CAC was present in 135 (22%) patients, of whom 97 (72%) were men and 38 (28%) were women. The mean EAT volume and density were 65±27 cm3 and −87.0±3.4 HU, respectively. Patients with CAC had significantly higher EAT volume (74±27 vs. 62±26 cm3, P<0.001) and lower EAT density (−88±3 vs. −87±3.4 HU, P<0.001) compared with patients without CAC. Multivariate regression analysis showed that both EAT density (hazard ratio, 0.879; 95% confidence interval, 0.817-0.946; P=0.001) and EAT volume >100 cm3 (hazard ratio, 1.693; 95% confidence interval, 1.256-2.999; P=0.029) predicted the presence of CAC.

Conclusions:

Both the quality and quantity of EAT derived from noncontrast CT scan predict subclinical CAD, with lower density and higher volume of epicardial fat associated with higher CACs.
Surgicopathological Quality Control and Protocol Adherence to Lymphadenectomy in the CRITICS Gastric Cancer Trial
Authors: Claassen Yvette H. M. , de Steur Wobbe O. , Hartgrink Henk H. , Dikken Johan L. , van Sandick Johanna W. , van Grieken Nicole C. T. , Cats Annemiek , Trip Anouk K. , Jansen Edwin P. M. , Kranenbarg Willemina M. Meershoek-Klein , Braak Jeffrey P. B. M. , Putter Hein , van Berge Henegouwen Mark I. , Verheij Marcel , van de Velde Cornelis J. H.
Published: August 2017

Objective:

The purpose of this study was to evaluate surgicopathological quality and protocol adherence for lymphadenectomy in the CRITICS trial.

Summary of Background Data:

Surgical quality assurance is a key element in multimodal studies for gastric cancer. In the multicenter CRITICS trial (ChemoRadiotherapy after Induction chemotherapy In Cancer of the Stomach), patients with resectable gastric cancer were randomized for preoperative chemotherapy, followed by gastrectomy with a D1+ lymphadenectomy (removal of stations 1 to 9 and 11), followed by either chemotherapy or chemoradiotherapy.

Methods:

Surgicopathological compliance was defined as removal of ≥15 lymph nodes. Surgical compliance was defined as removal of the indicated lymph node stations. Surgical contamination was defined as removal of lymph node stations that should be left in situ. The Maruyama Index (MI, lower is better), which has proven to be an indicator of surgical quality and is strongly associated with survival, was analyzed.

Results:

Between 2007 and 2015, 788 patients were randomized, of whom 636 patients underwent a gastrectomy with curative intent. Surgicopathological compliance occurred in 72.8% (n = 460) of the patients and improved from 55.0% (2007) to 90.0% (2015). Surgical compliance occurred in 41.1% (n = 256). Surgical contamination occurred in 59.6% (n = 371). Median MI was 1 (range 0 to 136).

Conclusion:

Surgical quality in the CRITICS trial was excellent, with a MI of 1. Surgicopathological compliance improved over the years. This might be explained by the quality assurance program within the study and centralization of gastric cancer surgery in the Netherlands.
Effect of Amantadine on Agitation in Critically Ill Patients With Traumatic Brain Injury
Authors: Gramish Jawaher A. , Kopp Brian J. , Patanwala Asad E.
Published: August 2017

Objective

This study aimed to compare the presence of agitation in traumatic brain injury patients treated with amantadine with those not treated with amantadine in the intensive care unit (ICU).

Methods

This was a retrospective cohort study conduced in a trauma ICU of a tertiary care institution in the United States. Patients who received amantadine were compared with patients who did not receive amantadine. The primary outcome measure was the presence of agitation, defined as the Richmond Agitation Sedation Scale score of +2 or higher. Secondary comparisons included haloperidol use, benzodiazepine use, opioid use, and ICU length of stay.

Results

A total of 139 patients were included in the study cohort (70 patients in the amantadine group, 69 patients in the no-amantadine group). There were more patients who had agitation in the amantadine group (38% vs 14%, P = 0.018). Patients who received amantadine received more opioids in fentanyl equivalents (10.3 [interquartile range {IQR}, 6.3–20.4] μg/kg vs 7.4 [IQR, 2.1–12.6] μg/kg, P = 0.009) and had a longer ICU length of stay (4.5 [IQR, 3–10] days vs 3 [IQR, 2–5] days, P = 0.010). Haloperidol use and benzodiazepine use were similar between groups.

Conclusions

The early use of amantadine after traumatic brain injury may increase the risk of agitation. This could increase opioid consumption and ICU length of stay.
Reversal of Dropped Head Syndrome After the Cessation of Dopaminergic Agonist Treatment in Parkinson Disease
Authors: Mano Tomoo
Published: August 2017

Dropped head (DH) syndrome is a phenomenon of disproportionate neck anteflexion that has been reported in patients with Parkinson disease (PD). Antiparkinsonian medications such as dopaminergic agonists (DAs) have been implicated in the onset of DH episodes. Deep brain stimulation (DBS) is an important therapeutic option after the failure of conventional treatments such as DA therapy in patients with PD. Here, we report the case of a patient with rigid-akinetic parkinsonism who developed DH syndrome after the initiation of DA treatment. Dopaminergic agonist treatment was required to stabilize motor dysfunction during a period of 5 years; yet, the patient experienced no improvements in DH during this time. Thus, we initiated DBS as an alternative therapy and gradually withdrew DA therapy. The patient recovered from long-term DH after the discontinuation of rotigotine treatment. Accordingly, this case highlights DA treatment as a possible cause of DH and the use of DBS to allow the discontinuation of DA treatment while preserving motor function in patients with PD.
Wnt ligand presentation and reception: from the stem cell niche to tissue engineering
Authors: Mills Kate M. , Szczerkowski James L. A. , Habib Shukry J.
Published: August 2017

Stem cells reside in niches where spatially restricted signals maintain a delicate balance between stem cell self-renewal and differentiation. Wnt family proteins are particularly suited for this role as they are modified by lipids, which constrain and spatially regulate their signalling range. In recent years, Wnt/β-catenin signalling has been shown to be essential for the self-renewal of a variety of mammalian stem cells. In this review, we discuss Wnt-responsive stem cells in their niche, and mechanisms by which Wnt ligands are presented to responsive cells. We also highlight recent progress in molecular visualization that has allowed for the monitoring of Wnt signalling within the stem cell compartment and new approaches to recapitulate this niche signallingin vitro. Indeed, new technologies that present Wnt in a localized manner and mimic the three-dimensional microenvironment of stem cells will advance our understanding of Wnt signalling in the stem cell niche. These advances will expand current horizons to exploit Wnt ligands in the rapidly evolving fields of tissue engineering and regenerative medicine.
Utterance-final position and pitch marking aid word learning in school-age children
Authors: Filippi Piera , Laaha Sabine , Fitch W. Tecumseh
Published: August 2017

We investigated the effects of word order and prosody on word learning in school-age children. Third graders viewed photographs belonging to one of three semantic categories while hearing four-word nonsense utterances containing a target word. In thecontrolcondition, all words had the same pitch and, across trials, the position of the target word was varied systematically within each utterance. The only cue to word–meaning mapping was the co-occurrence of target words and referents. This cue was present in all conditions. In theUtterance-finalcondition, the target word always occurred in utterance-final position, and at the same fundamental frequency as all the other words of the utterance. In thePitch peakcondition, the position of the target word was varied systematically within each utterance across trials, and produced with pitch contrasts typical of infant-directed speech (IDS). In thePitch peak + Utterance-finalcondition, the target word always occurred in utterance-final position, and was marked with a pitch contrast typical of IDS. Word learning occurred in all conditions except the control condition. Moreover, learning performance was significantly higher than that observed with simple co-occurrence (controlcondition) only for thePitch peak + Utterance-finalcondition. We conclude that, for school-age children, the combination of words' utterance-final alignment and pitch enhancement boosts word learning.
The impact of weather and storm water management ponds on the transmission of West Nile virus
Authors: Wang Yiyuan , Pons Wendy , Fang Jessica , Zhu Huaiping
Published: August 2017

West Nile virus (WNV) is the most widely distributed arbovirus in the world and the spread is influenced by complex factors including weather conditions and urban environmental settings like storm water management ponds (SWMP). The purpose of this work was to develop an ordinary differential equation model to explore the impacts of SWMP, temperature and precipitation on WNV vector abundance and the transmission of WNV between mosquito and bird populations. The model was used to analyse how weather conditions and SWMP can influence the basic reproduction number. The results found that an excess of precipitation and fiercer intraspecific competition will reduce vector population and the peak value of infectious vectors and birds. This information can be used to identify measures that would be useful to control larval abundance in SWMP and the transmission of WNV.
Resisting the urge to smoke: inhibitory control training in cigarette smokers
Authors: Adams Sally , Mokrysz Claire , Attwood Angela S. , Munafò Marcus R.
Published: August 2017

Impaired response inhibition is an important factor in tobacco dependence. We examined the effects of inhibitory control training (ICT) on inhibition, smoking resistance and cigarette use. Smokers (
n
 = 55) abstained from smoking for 12 h prior to testing. On the test day, participants recorded cigarette use and completed pre-training measures of global and cue-specific (smoking-related) response inhibition. Participants were randomized to either an active or a control ICT group. The active group was required to repeatedly inhibit a response towards smoking cues (100%), while the control group was required to inhibit a response towards smoking and neutral cues with equal frequency (50%). Participants performed post-training measures of response inhibition, smoking resistance and cigarette use. Inhibition data did not indicate time (pre-training, post-training) × group (active training, control training) or time × group × cue (smoking, neutral) interactions. There was weak evidence that smokers in the active group were more likely to resist smoking than those in the control group. Cigarette use data did not indicate a time × group interaction. Our data suggest that ICT may enhance the ability to resist smoking, indicating that training may be a promising adjunct to smoking pharmacotherapy.
Making better decisions in groups
Authors: Bang Dan , Frith Chris D.
Published: August 2017

We review the literature to identify common problems of decision-making in individuals and groups. We are guided by a Bayesian framework to explain the interplay between past experience and new evidence, and the problem of exploring the space of hypotheses about all the possible states that the world could be in and all the possible actions that one could take. There are strong biases, hidden from awareness, that enter into these psychological processes. While biases increase the efficiency of information processing, they often do not lead to the most appropriate action. We highlight the advantages of group decision-making in overcoming biases and searching the hypothesis space for good models of the world and good solutions to problems. Diversity of group members can facilitate these achievements, but diverse groups also face their own problems. We discuss means of managing these pitfalls and make some recommendations on how to make better group decisions.
An investigation into the unusual linkage isomerization and nitrite reduction activity of a novel tris(2-pyridyl) copper complex
Authors: Roger Isolda , Wilson Claire , Senn Hans M. , Sproules Stephen , Symes Mark D.
Published: August 2017

The copper-containing nitrite reductases (CuNIRs) are a class of enzymes that mediate the reduction of nitrite to nitric oxide in biological systems. Metal–ligand complexes that reproduce the salient features of the active site of CuNIRs are therefore of fundamental interest, both for elucidating the possible mode of action of the enzymes and for developing biomimetic catalysts for nitrite reduction. Herein, we describe the synthesis and characterization of a new tris(2-pyridyl) copper complex ([Cu
1
(NO
2
)
2
]) that binds two molecules of nitrite, and displays all three of the common binding modes for

N

O
2

−

, with one nitrite bound in an asymmetric quasi-bidentate κ
2
-ONO manner and the other bound in a monodentate fashion with a linkage isomerism between the κ
1
-ONO and κ
1
-NO
2
binding modes. We use density functional theory to help rationalize the presence of all three of these linkage isomers in one compound, before assessing the redox activity of [Cu
1
(NO
2
)
2
]. These latter studies show that the complex is not a competent nitrite reduction electrocatalyst in non-aqueous solvent, even in the presence of additional proton donors, a finding which may have implications for the design of biomimetic catalysts for nitrite reduction.
Iron-based magnetic molecular imprinted polymers and their application in removal and determination of di-
n
-pentyl phthalate in aqueous media
Authors: Li Jing , Zhou Qingxiang , Yuan Yongyong , Wu Yalin
Published: August 2017

Iron-based magnetic molecular imprinted polymers (Fe@SiO
2
@MIP) were synthesized for highly selective removal and recognition of di-
n
-pentyl phthalate (DnPP) from water. Well-defined core-shell Fe@SiO
2
nanoparticles (less than 70 nm) were decorated on MIPs reticular layers to endow DnPP-MIPs with magnetic property for the first time. Five other phthalic acid esters including dimethyl phthalate, diethyl phthalate, dipropyl phthalate, di-
n
-butyl phthalate and di-iso-octyl phthalate were used to investigate the adsorptive selectivity to DnPP. The designed experiments were carried out to explore the adsorption kinetics, isotherms and thermodynamics and the results demonstrated that the adsorption was a spontaneous, exothermal and physical adsorption process. The materials were proved to be excellent adsorbents in removal of DnPP with an adsorption capacity as high as 194.15 mg g
−1
in optimal condition. Furthermore, a magnetic solid phase extraction with Fe@SiO
2
@MIP coupled to high-performance liquid chromatography method was successfully developed for the determination of DnPP, and the proposed method achieved a good linear range of 0.5–250 µg l
−1
with a correlation coefficient (
R
2
) of 0.999 and low limit of detection (LOD) of 0.31 µg l
−1
. These materials exhibited excellent capacity in removal and highly sensitive identification of DnPP from aqueous environment samples, and opened a valuable direction for developing new adsorbents for the removal and enrichment of important pollutants.
Activity-induced Ca2+signaling in perisynaptic Schwann cells is mediated by P2Y1receptors and regulates muscle fatigue
Authors: Heredia Dante J. , Feng Cheng-Yuan , Hennig Grant W. , Gould Thomas W.
Published: August 2017

Perisynaptic glial cells respond to neural activity by increasing cytosolic levels of calcium, but the functional significance of this pathway is unclear. Terminal/persiynaptic Schwann cells (TPSCs) are a perisynaptic glial cell at the neuromuscular junction. Here, we provide genetic evidence that neural activity-induced intracellular calcium accumulation in neonatal TPSCs is mediated exclusively by P2Y1receptors. InP2ry1mutant mice lacking these responses, postsynaptic, rather than presynaptic, function was altered in response to nerve stimulation. This impairment was correlated with a greater susceptibility to activity-induced muscle fatigue. Interestingly, fatigue inP2ry1mutants was exacerbated by exposure to high potassium to a greater degree than in control mice. High potassium itself increased cytosolic levels of calcium in TPSCs, a response which was also reducedP2ry1mutants. These results suggest that activity-induced calcium responses in perisynaptic glia at the NMJ regulate postsynaptic function and muscle fatigue by influencing the levels of perisynaptic potassium.
Novel metrics for quantifying bacterial genome composition skews
Authors: Joesch-Cohen Lena M. , Robinson Max , Jabbari Neda , Lausted Christopher , Glusman Gustavo
Published: August 2017

Background

Bacterial genomes have characteristic compositional skews, which are differences in nucleotide frequency between the leading and lagging DNA strands across a segment of a genome. It is thought that these strand asymmetries arise as a result of mutational biases and selective constraints, particularly for energy efficiency. Analysis of compositional skews in a diverse set of bacteria provides a comparative context in which mutational and selective environmental constraints can be studied. These analyses typically require finished and well-annotated genomic sequences.

Results

We present three novel metrics for examining genome composition skews; all three metrics can be computed for unfinished or partially-annotated genomes. The first two metrics, (dot-skew and cross-skew) depend on sequence and gene annotation of a single genome, while the third metric (residual skew) highlights unusual genomes by subtracting a GC content-based model of a library of genome sequences. We applied these metrics to all 7738 available bacterial genomes, including partial drafts, and identified outlier species. A number of these outliers (i.e., Borrelia, Ehrlichia, Kinetoplastibacterium, and Phytoplasma) display similar skew patterns despite only distant phylogenetic relationship. While unrelated, some of the outlier bacterial species share lifestyle characteristics, in particular intracellularity and biosynthetic dependence on their hosts.

Conclusions

Our novel metrics appear to reflect the effects of biosynthetic constraints and adaptations to life within one or more hosts on genome composition. We provide results for each analyzed genome, software and interactive visualizations athttp://db.systemsbiology.net/gestalt/skew_metrics.
The somatically generated T cell receptor CDR3α contributes to the MHC allele specificity of the T cell receptor
Authors: Marrack Philippa , Krovi Sai Harsha , Silberman Daniel , White Janice , Kushnir Eleanora , Nakayama Maki , Crook James , Danhorn Thomas , Leach Sonia , Anselment Randy , Scott-Browne James , Gapin Laurent , Kappler John
Published: August 2017

Mature T cells bearing αβ T cell receptors react with foreign antigens bound to alleles of major histocompatibility complex proteins (MHC) that they were exposed to during their development in the thymus, a phenomenon known as positive selection. The structural basis for positive selection has long been debated. Here, using mice expressing one of two different T cell receptor β chains and various MHC alleles, we show that positive selection-induced MHC bias of T cell receptors is affected both by the germline encoded elements of the T cell receptor α and β chain and, surprisingly, dramatically affected by the non germ line encoded CDR3 of the T cell receptor α chain. Thus, in addition to determining specificity for antigen, the non germline encoded elements of T cell receptors may help the proteins cope with the extremely polymorphic nature of major histocompatibility complex products within the species.
The measurement of species selection on evolving characters
Authors: Simpson Carl
Published: August 2017

Many processes can contribute to macroevolutionary change. This fact is the source of the wide variety of macroevolutionary change across time and taxa as well as the bane of pale-obiological research trying to understand how macroevolution works. Here, I present a general framework for understanding the variety of macroevolutionary phenomena. Based on Price’s theorem, this framework provides a simple quantitative means to understand (1) the macroevolutionary processes that are possible and (2) the way those processes interact with each other. The major qualitative features of macroevolution depend first on the number of processes that co-occur and then on the magnitudes and evolutionary directions of those processes. Species selection, the major macroevolutionary process, consists of patterns of differential rates of speciation and extinction. Its macroevolutionary efficacy depends on the presences of sufficient microevolutionary change. Conversely, microevolutionary change is limited in power by the independent evolution of species, and species selection acting across populations of species can amplify or suppress microevolution. Non-trends may result if species selection sufficiently neutralizes microevolution and may yield stable macroevolutionary patterns over many millions of years.
Requirements for coregistration accuracy in on-scalp MEG
Authors: Zetter Rasmus , Iivanainen Joonas , Stenroos Matti , Parkkonen Lauri
Published: August 2017

Recent advances in magnetic sensing has made on-scalp magnetoencephalography (MEG) possible. In particular, optically-pumped magnetometers (OPMs) have reached sensitivity levels that enable their use in MEG. In contrast to the SQUID sensors used in current MEG systems, OPMs do not require cryogenic cooling and can thus be placed within millimetres from the head, enabling the construction of sensor arrays that conform to the shape of an individual’s head. To properly estimate the location of neural sources within the brain, one must accurately know the position and orientation of sensors in relation to the head. With the adaptable on-scalp MEG sensor arrays, this coregistration becomes more challenging than in current SQUID-based MEG systems that use rigid sensor arrays.

Here, we used simulations to quantify how accurately one needs to know the position and orientation of sensors in an on-scalp MEG system. The effects that different types of localisation errors have on forward modelling and source estimates obtained by minimum-norm estimation, dipole fitting, and beamforming are detailed.

We found that sensor position errors generally have a larger effect than orientation errors and that these errors affect the localisation accuracy of superficial sources the most. To obtain similar or higher accuracy than with current SQUID-based MEG systems, RMS sensor position and orientation errors should be < 4 mm and < 10°, respectively.
Large-scale determination and characterization of cell type-specific regulatory elements in the human genome
Authors: Wang Can , Zhang Shihua
Published: August 2017

Histone modifications have been widely elucidated to play vital roles in gene regulation and cell identity. The Roadmap Epigenomics Consortium generated a reference catalogue of several key histone modifications across >100s of human cell types and tissues. Decoding these epigenomes into functional regulatory elements is a challenging task in computational biology. To this end, we adopted a differential chromatin modification analysis framework to comprehensively determine and characterize cell type-specific regulatory elements (CSREs) and their histone modification codes in the human epigenomes of five histone modifications across 127 tissues or cell types. The CSREs show significant relevance with cell type-specific biological functions and diseases and cell identity. Clustering of CSREs with their specificity signals reveals diverse histone codes, demonstrating the diversity of functional roles of CSREs within the same cell or tissue. Last but not least, dynamics of CSREs from close cell types or tissues can give a detailed view of developmental processes such as normal tissue development and cancer occurrence.
Genome-wide Enhancer Maps Differ Significantly in Genomic Distribution, Evolution, and Function
Authors: Benton Mary Lauren , Talipineni Sai Charan , Kostka Dennis , Capra John A.
Published: August 2017

Non-coding gene regulatory enhancers are essential to transcription in mammalian cells. As a result, a large variety of experimental and computational strategies have been developed to identify cis-regulatory enhancer sequences. In practice, most studies consider enhancers identified by only a single method, and the concordance of enhancers identified by different methods has not been comprehensively evaluated. Here, we assess the similarities of enhancer sets identified by ten representative strategies in four biological contexts and evaluate the robustness of downstream conclusions to the choice of identification strategy. All pairs of enhancer sets we evaluated overlap significantly more than expected by chance; however, we also found significant dissimilarity between enhancer sets in their genomic characteristics, evolutionary conservation, and association with functional loci within each context. We find most regions identified as enhancers are supported by only one method. The disagreement is sufficient to influence interpretation of GWAS SNPs and eQTL, and to lead to disparate conclusions about enhancer biology and disease mechanisms. We also find only limited evidence that regions identified by multiple enhancer identification methods are better candidates than those identified by a single method. Our results highlight the inherent complexity of enhancer biology and argue that current approaches have yet to adequately account for enhancer diversity. As a result, we cannot recommend the use of any single enhancer identification strategy in isolation. To facilitate assessment of enhancer diversity on studies’ conclusions, we developed creDB, a database of enhancer annotations designed to integrate into bioinformatics workflows. While our findings highlight a major challenge to mapping the genetic architecture of complex disease and interpreting regulatory variants found in patient genomes, a systematic understanding of similarities and differences in enhancer identification methodology will ultimately enable robust inferences about gene regulatory sequences.
Gaussian decomposition of high-resolution melt curve derivatives for measuring genome-editing efficiency
Authors: Zaboikin Michail , Freter Carl , Srinivasakumar Narasimhachar
Published: August 2017

We describe a method for measuring genome editing efficiency fromin silicoanalysis of high-resolution melt curve data. The melt curve data derived from amplicons of genome-edited or unmodified target sites were processed to remove the background fluorescent signal emanating from free fluorophore and then corrected for temperature-dependent quenching of fluorescence of double-stranded DNA-bound fluorophore. Corrected data were normalized and numerically differentiated to obtain the first derivatives of the melt curves. These were then mathematically modeled as a sum or superposition of minimal number of Gaussian components. Using Gaussian parameters determined by modeling of melt curve derivatives of unedited samples, we were able to model melt curve derivatives from genetically altered target sites where the mutant population could be accommodated using an additional Gaussian component. From this, the proportion contributed by the mutant component in the target region amplicon could be accurately determined. Mutant component computations compared well with the mutant frequency determination from next generation sequencing data. The results were also consistent with our earlier studies that used difference curve areas from high-resolution melt curves for determining the efficiency of genome-editing reagents. The advantage of the described method is that it does not require calibration curves to estimate proportion of mutants in amplicons of genome-edited target sites.
Towards a reliable, automated method of individual alpha frequency (IAF) quantification
Authors: Corcoran Andrew W. , Alday Phillip M. , Schlesewsky Matthias , Bornkessel-Schlesewsky Ina
Published: August 2017

Individual alpha frequency (IAF) is a promising electrophysiological marker of interindividual differences in cognitive function. IAF has been linked with trait-like differences in information processing and general intelligence, and provides an empirical basis for the definition of individualised frequency bands. Despite its widespread application, however, there is little consensus on the optimal method for estimating IAF, and many common approaches are prone to bias and inconsistency. Here, we describe an automated strategy for deriving two of the most prevalent IAF estimators in the literature: peak alpha frequency (PAF) and centre of gravity (CoG). These indices are calculated from resting-state power spectra that have been smoothed using a Savitzky-Golay filter (SGF). We evaluate the performance characteristics of this analysis procedure in both empirical and simulated EEG datasets. Applying the SGF technique to resting-state data fromn= 63 healthy adults furnished 61 PAF, and 62 CoG estimates. The statistical properties of these estimates were consistent with previous reports. Simulation analyses revealed that the SGF routine was able to reliably extract target alpha components, even under relatively noisy spectral conditions. The routine consistently outperformed a simpler method of automated peak detection that did not involve spectral smoothing. The SGF technique is fast, open-source, and available in two popular programming languages (MATLAB and Python), and thus can easily be integrated within the most popular M/EEG toolsets (EEGLAB, FieldTrip and MNE-Python). As such, it affords a convenient tool for improving the reliability and replicability of future IAF-related research.
Evolution of mechanisms that control mating inDrosophilamales
Authors: Ahmed Osama M. , Avila-Herrera Aram , Tun Khin May , Serpa Paula H. , Peng Justin , Parthasarathy Srinivas , Knapp Jon-Michael , Stern David L. , Davis Graeme W. , Pollard Katherine S. , Shah Nirao M.
Published: August 2017

Genetically wired neural mechanisms inhibit mating between species because even naive animals rarely mate with other species. These mechanisms can evolve through changes in expression or function of key genes in specific sensory pathways or central circuits. Gr32a is a gustatory chemoreceptor that, inD. melanogaster, is essential to inhibit interspecies courtship and sense quinine. Similar toD. melanogaster,D. simulansGr32a is expressed in foreleg tarsi, sensorimotor appendages that inhibit interspecies courtship in both species, and it is required to sense quinine. Nevertheless, Gr32a is not required to inhibit interspecies mating byD. simulansmales. However, and similar to its function inD. melanogaster, Ppk25, a member of the Pickpocket family, promotes conspecific courtship inD. simulans. Taken together, we have identified shared as well as distinct evolutionary solutions to chemosensory processing of tastants as well as cues that inhibit or promote courtship in two closely relatedDrosophilaspecies.
Interaction of induced anxiety and verbal working memory: influence of trait anxiety
Authors: Patel Nilam , Stoodley Catherine , Pine Daniel S. , Grillon Christian , Ernst Monique
Published: August 2017

This study examines the influence of trait anxiety on working memory (WM) in safety and threat. Interactions between experimentally induced anxiety and WM performance (on different cognitive loads) have been reported in healthy, nonanxious subjects. Differences in trait anxiety may moderate these interactions. Accordingly, these interactions may be potentiated by high trait anxiety (HTA), or show a resilient pattern that protects cognitive performance. HTA and low trait anxiety (LTA) were defined by a median split of scores on the trait component of the state-trait anxiety inventory. Sustained anxiety was evoked by a probabilistic exposure to an aversive scream, and was measured by eyeblink startle and self-report. WM was tested using an n-back task (1-, 2-, and 3-back). Results revealed that, as expected, the HTA group reported greater anxiety during the task. However, trait anxiety did not impact the modulation of WM performance by induced anxiety. Notably, HTA influenced anxiety-potentiated startle (startle during threat minus startle during safe; APS) differently as a function of memory load. Accordingly, APS decreased with increasing WM load, but HTA antagonized this reduction. The HTA group showed no impairment on the 3-back WM task despite a higher APS. The amplified APS could be associated with the increase in effort-related cognitive arousal. Furthermore, this third replication of the interaction of induced anxiety by load on WM performance testifies to the robustness of the unique interplay between anxiety and WM.
Role of the bed nucleus of the stria terminalis in aversive learning and memory
Authors: Goode Travis D. , Maren Stephen
Published: August 2017

Surviving threats in the environment requires brain circuits for detecting (or anticipating) danger and for coordinating appropriate defensive responses (e.g., increased cardiac output, stress hormone release, and freezing behavior). The bed nucleus of the stria terminalis (BNST) is a critical interface between the “affective forebrain”—including the amygdala, ventral hippocampus, and medial prefrontal cortex—and the hypothalamic and brainstem areas that have been implicated in neuroendocrine, autonomic, and behavioral responses to actual or anticipated threats. However, the precise contribution of the BNST to defensive behavior is unclear, both in terms of the antecedent stimuli that mobilize BNST activity and the consequent defensive reactions. For example, it is well known that the BNST is essential for contextual fear conditioning, but dispensable for fear conditioning to discrete conditioned stimuli (CSs), at least as indexed by freezing behavior. However, recent evidence suggests that there are circumstances in which contextual freezing may persist independent of the BNST. Furthermore, the BNST is involved in the reinstatement (or relapse) of conditioned freezing to extinguished discrete CSs. As such, there are critical gaps in understanding how the BNST contributes to fundamental processes involved in Pavlovian fear conditioning. Here, we attempt to provide an integrative account of BNST function in fear conditioning. We discuss distinctions between unconditioned stress and conditioned fear and the role of BNST circuits in organizing behaviors associated with these states. We propose that the BNST mediates conditioned defensive responses—not based on the modality or duration of the antecedent threat or the duration of the behavioral response to the threat—but rather as consequence the ability of an antecedent stimulus to predict when an aversive outcome will occur (i.e., its temporal predictability). We argue that the BNST is not uniquely mobilized by sustained threats or uniquely involved in organizing sustained fear responses. In contrast, we argue that the BNST is involved in organizing fear responses to stimuli that poorly predictwhendanger will occur, no matter the duration, modality, or complexity of those stimuli. The concepts discussed in this review are critical to understanding the contribution of the human BNST to fear and anxiety disorders.