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Nisin is a broad spectrum bacteriocin used extensively as a food preservative that was identified in Lactococcus lactis nearly a century ago. We show that orally-ingested nisin survives transit through the porcine gastrointestinal tract intact (as evidenced by activity and molecular weight determination) where it impacts both the composition and functioning of the microbiota. Specifically, nisin treatment caused a reversible decrease in Gram positive bacteria, resulting in a reshaping of the Firmicutes and a corresponding relative increase in Gram negative Proteobacteria. These changes were mirrored by the modification in relative abundance of pathways involved in acetate, butyrate (decreased) and propionate (increased) synthesis which correlated with overall reductions in short chain fatty acid levels in stool. These reversible changes that occur as a result of nisin ingestion demonstrate the potential of bacteriocins like nisin to shape mammalian microbiomes and impact on the functionality of the community., (© 2023. The Author(s).)

Thalamoreticular circuitry plays a key role in arousal, attention, cognition, and sleep spindles, and is linked to several brain disorders. A detailed computational model of mouse somatosensory thalamus and thalamic reticular nucleus has been developed to capture the properties of over 14,000 neurons connected by 6 million synapses. The model recreates the biological connectivity of these neurons, and simulations of the model reproduce multiple experimental findings in different brain states. The model shows that inhibitory rebound produces frequency-selective enhancement of thalamic responses during wakefulness. We find that thalamic interactions are responsible for the characteristic waxing and waning of spindle oscillations. In addition, we find that changes in thalamic excitability control spindle frequency and their incidence. The model is made openly available to provide a new tool for studying the function and dysfunction of the thalamoreticular circuitry in various brain states., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Mental Health First Aid (MHFA) training teaches participants how to respond to mental health crises, including suicide. Little is known about the impact of training on participants' observed MHFA behaviours. This exploratory study aimed to compare MHFA-trained Australian and US student pharmacists' performance and suicide assessment language during simulated patient role-play (SPRP) assessments., Methods: Student pharmacists (n = 265) completed MHFA training and participated (n = 81) in SPRPs with simulated patients (SP) who were people with lived experience of mental illness. Each SPRP was marked by three raters (student, tutor and SP). One-way ANOVA, chi-squared tests and independent samples t-tests were used to compare scores and pass/fail rates, where appropriate. Transcribed audio-recordings of suicide assessments underwent discourse analysis. A chi-squared test was conducted to investigate the differences in how suicide assessment language was coded across six discursive frames ('confident'/'timid', 'empathetic'/'apathetic', and 'direct'/'indirect')., Results: Three raters assessed 81 SPRPs, resulting in quantitative analysis of 243 rubrics. There were no significant differences between student pharmacists' mean scores and pass/fail rates across countries. Overall, both cohorts across Australia and the US performed better during the mania scenario, with a low failure rate of 13.9 and 19.0%, respectively. Most students in both countries passed their SPRP assessment; however, 27.8% did not assess for suicide or used indirect language during suicide assessment, despite completing MHFA training. Australian student pharmacists demonstrated, more direct language (76.9% versus 67.9%) and empathy (42.3% versus 32.1%) but less confidence (57.7% versus 60.7%) compared to US student pharmacists, during their suicide assessment; however, these differences were not statistically significant., Conclusions: Findings indicate most MHFA-trained student pharmacists from Australia and the US can provide MHFA during SPRPs, as well as assess for suicide directly, empathetically and confidently. This exploratory study demonstrates the importance of practicing skills post-training and the need for further research exploring participants' hesitance to assess for suicide, despite training completion., (© 2022. The Author(s).)

Introduction: Routine outpatient follow-up visits for surgical patients are a source of strain on health-care resources and patients. With the COVID-19 pandemic adding a new urgency to finding the safest follow-up arrangement, text message follow-up might prove an acceptable alternative to a phone call or an in-person clinic visit., Methods: An open-label, three-arm, parallel randomized trial was conducted. The interventions were traditional in-person appointment, a telephone call, or a text message. The primary outcome was the number of postdischarge complications identified. The secondary outcomes were patient satisfaction with follow-up, future preference, default to follow-up, and preference to receiving medical information by text message., Results: Two hundred eight patients underwent randomization: 50 in the in-person group, 80 in the telephone group, and 78 in the text message group. There was no difference in the number of reported complications: 5 (10%) patients in the in-person group, 7 (9%) patients in the text group, and 11 (14%) patients in the telephone group (P = 0.613). The preferred method of follow-up was by telephone (106, 61.6%). The least preferred was the in-person follow-up (15, 8.7%, P = 0.002), which also had the highest default rate (44%)., Conclusions: There was no evidence that text messages and telephone calls are unsafe and ineffective methods of follow-up. Although most patients are happy to receive results by text message, the majority of patients would prefer a telephone follow-up and are less likely to default by this method. Health-care systems should develop telehealth initiatives when planning health-care services in the wake of the COVID-19 pandemic., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Computer mediated communication has marked differences from the face-to-face context. One major difference is that, in the online context, we often have explicit access to others' opinions and these opinions are often the only informational cues available. We investigate if awareness of opinion congruence, in the absence of any other reference categories, may be sufficient to foster social identification. In a pre-registered experiment (N = 681), we manipulated exposure to opinions, and measured levels of ingroup identification, opinion-based identification and their social influence on activism intentions. Our results demonstrate exposure to others' opinions in an otherwise anonymous context fosters ingroup and opinion-based identification. There was no effect on opinion-based group activism intentions. We conclude that computer mediated contexts have consequences for identification - opinion (in)congruence is becoming more relevant as a source of social categorization. While we did not find this identification had a social influence on activism, we discuss avenues for future research to disentangle the features of opinion-based groups necessary to foster activism., Competing Interests: Declaration of competing interest We have no conflict of interest to disclose., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

We prospectively studied SARS-CoV-2 transmission at schools in an era of variants of concern, offering all close contacts serial viral asymptomatic testing up to 14 days. From the 69 primary cases detected in schools, 392 close contacts were identified and offered asymptomatic testing. A total of 229 (58%) were close school contacts, and of these, 3 tested positive (1.3%), 2 of which were detected through asymptomatic testing. This is in contrast to the 117 household contacts, where 43 (37%) went on to become secondary cases. Routine asymptomatic testing of close contacts should be examined in the context of local testing rates, preventive measures, programmatic costs, and health impacts of asymptomatic transmission. IMPORTANCE There is concern that schools may be a setting where asymptomatic infections might result in significant "silent" transmission of SARS-CoV-2, particularly after the emergence of more transmissible variants of concern. After the programmatic implementation of a strategy of asymptomatic testing of close COVID-19 contacts as part of contact tracing in the school setting, the majority of the secondary cases were still found to have occurred in home or social contacts. However, for the 6.2% of secondary cases that occurred in close school contacts, the majority were detected through asymptomatic testing. The potential added yield of this approach needs to be considered within the overall setting, including consideration of the local epidemiology, ongoing goals of case and contact management, additional costs, logistical challenges for families, and possible health impacts of asymptomatic transmission.

Several studies in Lake Tanganyika have effectively employed traditional methods to explore changes in water quality in open waters; however, coastal monitoring has been restricted and sporadic, relying on costly sample and analytical methods that require skilled technical staff. This study aims in validating citizen science water quality collected data (nitrate, phosphate and turbidity) with those collected and measured by professional scientists in the laboratory. A second objective of the study is to use citizen scientist data to identify the patterns of seasonal and spatial variations in nutrient conditions and forecast potential changes based on expected changes in population and climate (to 2050). The results showed that the concentrations of nitrate and phosphate measured by citizen scientists nearly matched those established by professional scientists, with overall accuracy of 91% and 74%, respectively. For total suspended solids measured by professional and turbidity measured by citizen scientists, results show that, using 14 NTU as a cut-off, citizen scientist measurements of Secchi tube depth to identify lake TSS below 7.0 mg/L showed an accuracy of 88%. In both laboratory and citizen scientist-based studies, all measured water quality variables were significantly higher during the wet season compared to the dry season. Climate factors were discovered to have a major impact on the likelihood of exceeding water quality restrictions in the next decades (2050), which could deteriorate lake conditions. Upscaling citizen science to more communities on the lake and other African Great Lakes would raise environmental awareness, inform management and mitigation activities, and aid long-term decision-making., (© 2022. The Author(s).)

The orexigenic hormone ghrelin has multifaceted roles in health and disease. We have reported that ablation of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), protects against metabolic dysfunction of adipose tissues in aging. Our further observation interestingly revealed that GHS-R deficiency phenocopies the effects of myokine irisin. In this study, we aim to determine whether GHS-R affects the metabolic functions of aging skeletal muscle and whether GHS-R regulates the muscular functions via irisin. We first studied the expression of metabolic signature genes in gastrocnemius muscle of young, middle-aged and old mice. Then, old GHS-R knockout ( Ghsr -/- ) mice and their wild type counterparts were used to assess the impact of GHS-R ablation on the metabolic characteristics of gastrocnemius and soleus muscle. There was an increase of GHS-R expression in skeletal muscle during aging, inversely correlated with the decline of metabolic functions. Remarkedly the muscle of old GHS-R knockout ( Ghsr -/- ) mice exhibited a youthful metabolic profile and better maintenance of oxidative type 2 muscle fibers. Furthermore, old Ghsr -/- mice showed improved treadmill performance, supporting better functionality. Also intriguing to note was the fact that old GHS-R-ablated mice showed increased expression of the irisin precursor FNDC5 in the muscle and elevated plasma irisin levels in circulation, which supports a potential interrelationship between GHS-R and irisin. Overall, our work suggests that GHS-R has deleterious effects on the metabolism of aging muscle, which may be at least partially mediated by myokine irisin.

Objectives: Few studies reported COVID-19 cases in schools during the 2020/21 academic year in a setting of uninterrupted in-person schooling. The main objective was to determine the SARS-CoV-2 seroprevalence among school staff in Vancouver public schools., Design: Cumulative incident COVID-19 cases among all students and school staff based on public health data, with an embedded cross-sectional serosurvey among a school staff sample that was compared to period, age, sex and geographical location-weighted data from blood donors., Setting: Vancouver School District (British Columbia, Canada) from kindergarten to grade 12., Participants: Active school staff enrolled from 3 February to 23 April 2021 with serology testing from 10 February to 15 May 2021., Main Outcome Measures: SARS-CoV-2 seroprevalence among school staff, based on spike (S)-based (unvaccinated staff) or N-based serology testing (vaccinated staff)., Results: Public health data showed the cumulative incidence of COVID-19 among students attending in-person was 9.8 per 1000 students (n=47 280), and 13 per 1000 among school staff (n=7071). In a representative sample of 1689 school staff, 78.2% had classroom responsibilities, and spent a median of 17.6 hours in class per week (IQR: 5.0-25 hours). Although 21.5% (363/1686) of surveyed staff self-reported close contact with a COVID-19 case outside of their household (16.5% contacts were school-based), 5 cases likely acquired the infection at school based on viral testing. Sensitivity/Specificity-adjusted seroprevalence in 1556/1689 staff (92.1%) was 2.3% (95% CI: 1.6% to 3.2%), comparable to a sex, age, date and residency area-weighted seroprevalence of 2.6% (95% CI: 2.2% to 3.1%) among 5417 blood donors., Conclusion: Seroprevalence among staff was comparable to a reference group of blood donors from the same community. These data show that in-person schooling could be safely maintained during the 2020/21 school year with mitigation measures, in a large school district in Vancouver, Canada., Competing Interests: Competing interests: CO'R is an employee of the Vancouver School District, but the District was not involved in the design, analysis, interpretation of the data or the drafting of this manuscript; MS has been an investigator on projects funded by GlaxoSmithKline, Merck, Pfizer, Sanofi-Pasteur, Seqirus, Symvivo and VBI Vaccines. All funds have been paid to his institute, and he has not received any personal payments; the authors declare no relevant conflicts of interest. LifeLabs and Dynacare played no role in the study other than providing a service for the collection of blood samples., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There is substantial evidence of age-related declines in anatomical connectivity during adulthood, with associated alterations in functional connectivity. But the relation of those functional alterations to the structural reductions is unclear. The complexities of both the structural and the functional connectomes make it difficult to determine such relationships. We pursue this question with methods, based on animal research, that specifically target the interhemispheric connections between the visual cortices. We collect t1- and diffusion-weighted imaging data from which we assess the integrity of the white matter interconnecting the bilateral visual cortices. Functional connectivity between the visual cortices is measured with electroencephalography during the presentation of drifting sinusoidal gratings that agree or conflict across hemifields. Our results show age-related reductions in the integrity of the white matter interconnecting the visual cortices, and age-related increases in the difference in functional interhemispheric lagged coherence between agreeing versus disagreeing visual stimuli. We show that integrity of the white matter in the splenium of the corpus callosum predicts the differences in lagged coherence for the agreeing versus disagreeing stimuli; and that this relationship is mediated by age. These results give new insight into the causal relationship between age and functional connectivity., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

The ability to predict formulation behaviour at production scale during formulation design can reduce the time to market and decrease product development costs. However, it is challenging to extrapolate compaction settings for direct compression formulations between tablet press models during scale-up and transfer from R&D to commercial production. The aim of this study was to develop statistical process models to predict tablet tensile strength, porosity and disintegration time from compaction parameters (pre-compression and main compression force, and press speed), for three formulations, with differing deformation characteristics (plastic, brittle and elastic), on three tablet press models (one pilot-scale tablet press (KG RoTab) and two production-scale presses (Fette 1200i and GEA Modul P)). The deformation characteristics of yield pressure and elastic recovery were determined for the model placebo formulations investigated. To facilitate comparison of dwell time settings between tablet press models, the design of experiments (DoE) approach was 9 individual 16-run response surface DoEs (3 formulation × 3 press models), whose results were combined to create a polynomial regression model for each tablet property. These models predicted tablet tensile strength, porosity and disintegration time and enabled the construction of design spaces to produce tablets with specified target properties, for each formulation on each press. The models were successfully validated. This modelling approach provides an understanding of the compaction behaviour of formulations with varying deformation behaviour on development and commercial tablet press models. This understanding can be applied to inform achievable production rates at a commercial scale, during the formulation development.

Aims: Nisin is a bacteriocin with a broad spectrum of activity against Gram-positive bacteria. The aims were to assess nisin activity against Clostridioides difficile in a complex microbial environment and determine the minimum inhibitory concentration at which C. difficile growth is suppressed whilst having minimal impact on the faecal microbiota., Methods and Results: Faecal slurries were prepared from fresh faecal samples and spiked with C. difficile (10 6  CFU per ml). Nisin was added to each fermentation at a range of concentrations from 0 to 500 µM. Following 24 h, 16S rRNA gene sequencing was performed, and the presence of viable C. difficile was assessed. There was no viable C. difficile detected in the presence of 50-500 µM nisin. There was a decrease in the diversity of the microbiota in a nisin dose-dependent manner. Nisin predominantly depleted the relative abundance of the Gram-positive bacteria whilst the relative abundance of Gram-negative bacteria such as Escherichia Shigella and Bacteroides increased., Conclusions: Using an ex vivo model of the colon, this study demonstrates the ability of purified nisin to selectively deplete C. difficile in a faecal microbial environment and establishes the minimum concentration at which this occurs whilst having a minimal impact on the composition of the microbiota., Significance and Impact of the Study: This study opens up the potential to use nisin as a therapeutic for clostridial gut infections., (© 2021 The Authors. Journal of Applied Microbiology published by John Wiley & Sons Ltd on behalf of Society for Applied Microbiology.)

Background: Increasing participation in the Australian National Bowel Cancer Screening Program (NBCSP) is the most efficient and cost-effective way of reducing mortality associated with colorectal cancer by detecting and treating early-stage disease. Currently, only 44% of Australians aged 50-74 years complete the NBCSP. This efficacy trial aims to test whether this SMS intervention is an effective method for increasing participation in the NBCSP. Furthermore, a process evaluation will explore the barriers and facilitators to sending the SMS from general practice., Methods: We will recruit 20 general practices in the western region of Victoria, Australia to participate in a cluster randomised controlled trial. General practices will be randomly allocated with a 1:1 ratio to either a control or intervention group. Established general practice software will be used to identify patients aged 50 to 60 years old who are due to receive a NBCSP kit in the next month. The SMS intervention includes GP endorsement and links to narrative messages about the benefits of and instructions on how to complete the NBCSP kit. It will be sent from intervention general practices to eligible patients prior to receiving the NBCSP kit. We require 1400 eligible patients to provide 80% power with a two-sided 5% significance level to detect a 10% increase in CRC screening participation in the intervention group compared to the control group. Our primary outcome is the difference in the proportion of eligible patients who completed a faecal occult blood test (FOBT) between the intervention and control group for up to 12 months after the SMS was sent, as recorded in their electronic medical record (EMR). A process evaluation using interview data collected from general practice staff (GP, practice managers, nurses) and patients will explore the feasibility and acceptability of sending and receiving a SMS to prompt completing a NBCSP kit., Discussion: This efficacy trial will provide initial trial evidence of the utility of an SMS narrative intervention to increase participation in the NBCSP. The results will inform decisions about the need for and design of a larger, multi-state trial of this SMS intervention to determine its cost-effectiveness and future implementation., Trial Registration: Australian New Zealand Clinical Trials Registry ACTRN12620001020976 . Registered on 17 October 2020., (© 2022. The Author(s).)

The use of 2 H 2 O in tank water to assess protein synthesis rates in fish is a relatively novel methodology that could allow for a better understanding of the effects of particular nutritional and environmental variables on rates of protein accretion. As such, this study involved an assessment and comparison of protein synthesis rates in the muscle of juvenile red drum fed a control diet (nutritionally complete) versus a valine (Val)-deficient diet. Six groups of 12 juvenile red drum, initially weighing ~ 4.5 g/fish, were stocked in six separate 38-L aquaria operating as a recirculating system. Fish were acclimatized to experimental conditions for 2 weeks while being fed the control diet. Just prior to initiating the protein synthesis assay, one aquarium of fish was fed the control diet while a second aquarium of fish was fed the Val-deficient diet. Immediately after consuming the experimental diets, each group of fish was moved to an independent aquarium containing 2 H 2 O, and the fractional synthetic rate (FSR) of protein synthesis was obtained at 12, 24, 36 and 48 h after feeding by collecting two fish per treatment at each time point. This protein synthesis assay procedure was performed in three separate sessions, and considered as replicates over time (n = 3) for fish fed the control or Val-deficient diets immediately before initiating the session. Results indicated that a one-time feeding of a diet deficient in Val significantly reduced protein synthesis rates in the muscle of red drum. In addition, a significant effect of time after feeding was found, where observed FSR values peaked at 12 h after feeding and decreased as time progressed. In conclusion, deuterium methodologies were applicable to red drum, and this approach had the sensitivity to assess differences in protein synthesis rates when dietary perturbations were introduced., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Optimizing processing conditions to achieve a critical quality attribute (CQA) is an integral part of pharmaceutical quality by design (QbD). It identifies combinations of material and processing parameters ensuring that processing conditions achieve a targeted CQA. Optimum processing conditions are formulation and equipment-dependent. Therefore, it is challenging to translate a process design between formulations, pilot-scale and production-scale equipment. In this study, an empirical model was developed to determine optimum processing conditions for direct compression formulations with varying flow properties, across pilot- and production-scale tablet presses. The CQA of interest was tablet weight variability, expressed as percentage relative standard deviation. An experimental design was executed for three model placebo blends with varying flow properties. These blends were compacted on one pilot-scale and two production-scale presses. The process model developed enabled the optimization of processing parameters for each formulation, on each press, with respect to a target tablet weight variability of <1%RSD. The model developed was successfully validated using data for additional placebo and active formulations. Validation formulations were benchmarked to formulations used for model development, employing permeability index values to indicate blend flow.

Despite the fact that horseback riding is a popular sport, there is little information available on horseback riding as a physical activity. The objective of this experiment was to quantify energy expenditure of participants (n=20) during three riding tests: a 45min walk-trot-canter ride (WTC), a reining pattern ride and a cutting simulation ride while wearing a telemetric gas analyzer. Total energy expenditure (tEE), mean and peak metabolic equivalents of task (MET), heart rate (HR), respiratory frequency (RF), relative oxygen consumption (relVO 2 ), and respiratory exchange ratio (RER) were assessed. Mean MET and HR responses were greater (P < .05) for riders during the long trot portion of the WTC (6.19 ± 0.21 MET, 152.14 ± 4.4 bpm) and cutting (4.53±0.21 MET, 146.88 ± 4.4 bpm) vs the overall WTC (3.81 ± 0.16 MET, 131.5 ± 4.2 bpm). When WTC was evaluated by gait, mean MET increased as gait speed increased. As expected, METs were greater (P < .05) for riders during long trot (6.19 ± 0.21 MET) and canter (5.95 ± 0.21 MET) than during the walk (2.01 ± 0.21 MET) or trot (3.2 ± 0.21 MET). Previous horseback riding studies have not reported METs, but the peaks of all three activities in the present study were similar to METs measured during activities like jogging, playing soccer and rugby. Riders engaged in cutting and reining experienced more intense exercise in short durations, while, as expected on the basis of the duration of the activity, WTC provided a greater overall total energy expenditure. These results suggest that it is possible for health benefits to be achieved through accumulated horseback riding exercise, particularly if riding at the more intense gaits., (Copyright © 2021. Published by Elsevier Inc.)

As our understanding of the thalamocortical system deepens, the questions we face become more complex. Their investigation requires the adoption of novel experimental approaches complemented with increasingly sophisticated computational modeling. In this review, we take stock of current data and knowledge about the circuitry of the somatosensory thalamocortical loop in rodents, discussing common principles across modalities and species whenever appropriate. We review the different levels of organization, including the cells, synapses, neuroanatomy, and network connectivity. We provide a complete overview of this system that should be accessible for newcomers to this field while nevertheless being comprehensive enough to serve as a reference for seasoned neuroscientists and computational modelers studying the thalamocortical system. We further highlight key gaps in data and knowledge that constitute pressing targets for future experimental work. Filling these gaps would provide invaluable information for systematically unveiling how this system supports behavioral and cognitive processes., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Carbohydrate-decorated clusters (glycoclusters) centred on a Ru(ii) ion were synthesised and tested for their activity against Pseudomonas aeruginosa biofilm formation. These clusters were designed by conjugating a range of carbohydrate motifs (galactose, glucose, mannose and lactose, as well as galactose with a triethylene glycol spacer) to a btp (2,6-bis(1,2,3-triazol-4-yl)pyridine) scaffold. This scaffold, which possesses a C 2 symmetry, is an excellent ligand for d-metal ions, and thus the formation of the Ru(ii)-centred glycoclusters 7 and 8Gal was achieved from 5 and 6Gal; each possessing four deprotected carbohydrates. Glycocluster 8Gal, which has a flexible spacer between the btp and galactose moieties, showed significant inhibition of P. aeruginosa bacterial biofilm formation. By contrast, glycocluster 7, which lacked the flexible linker, didn't show significant antimicrobial effects and neither does the ligand 6Gal alone. These results are proposed to arise from carbohydrate-lectin interactions with LecA, which are possible for the flexible metal-centred multivalent glycocluster. Metal-centred glycoclusters present a structurally versatile class of antimicrobial agent for P. aeruginosa , of which this is, to the best of our knowledge, the first example., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Whether neuronal populations exhibit zero-lag (in-phase or in-antiphase) functional connectivity is a fundamental question when conceptualizing communication between cell assemblies. It also has profound implications on how we assess such interactions. Given that the brain is a delayed network due to the finite conduction velocity of the electrical impulses traveling across its fibers, the existence of long-distance zero-lag functional connectivity may be considered improbable. However, in this study, using human intracranial recordings we demonstrate that most interhemispheric connectivity between homotopic cerebral regions is zero-lagged and that this type of connectivity is ubiquitous. Volume conduction can be safely discarded as a confounding factor since it is known to drop almost completely within short interelectrode distances (<20 mm) in intracranial recordings. This finding should guide future electrophysiological connectivity studies and highlight the importance of considering the role of zero-lag connectivity in our understanding of communication between cell assemblies., (© 2020 Wiley Periodicals LLC.)

Electroencephalographic (EEG) source reconstruction is a powerful approach that allows anatomical localization of electrophysiological brain activity. Algorithms used to estimate cortical sources require an anatomical model of the head and the brain, generally reconstructed using magnetic resonance imaging (MRI). When such scans are unavailable, a population average can be used for adults, but no average surface template is available for cortical source imaging in infants. To address this issue, we introduce a new series of 13 anatomical models for subjects between zero and 24 months of age. These templates are built from MRI averages and boundary element method (BEM) segmentation of head tissues available as part of the Neurodevelopmental MRI Database. Surfaces separating the pia mater, the gray matter, and the white matter were estimated using the Infant FreeSurfer pipeline. The surface of the skin as well as the outer and inner skull surfaces were extracted using a cube marching algorithm followed by Laplacian smoothing and mesh decimation. We post-processed these meshes to correct topological errors and ensure watertight meshes. Source reconstruction with these templates is demonstrated and validated using 100 high-density EEG recordings from 7-month-old infants. Hopefully, these templates will support future studies on EEG-based neuroimaging and functional connectivity in healthy infants as well as in clinical pediatric populations., Competing Interests: Declarations of Competing Interest None., (Copyright © 2020. Published by Elsevier Inc.)

Aim: Macrophage migration inhibitory factor (MIF) is a pro-inflammatory cytokine, which has been shown to promote disease severity in cystic fibrosis. Methods : In this study, aerosolized drug-loaded nanoparticles containing SCD-19, an inhibitor of MIF's tautomerase enzymatic activity, were developed and characterized. Results: The aerosolized nanoparticles had an optimal droplet size distribution for deep lung deposition, with a high degree of biocompatibility and significant cellular uptake. Conclusion: For the first time, we have developed an aerosolized nano-formulation against MIF's enzymatic activity that achieved a significant reduction in the inflammatory response of macrophages, and inhibited Pseudomonas aeruginosa  biofilm formation on airway epithelial cells. This represents a potential novel adjunctive therapy for the treatment of P. aeruginosa infection in cystic fibrosis.

Among youth with type 1 diabetes mellitus (T1D), older adolescents demonstrate more dysglycemia and less adherence to disease management. Poor disease management during this time of development can continue into adulthood, perpetuating the economic and health burden to the individual, health care system and society. This study aimed to evaluate the effectiveness of an inpatient multidisciplinary approach to treating youth with T1D. All T1D admissions to the 4 week Chronic Illness Management Program (CIMP) between 1 January 2016 and 31 December 2017 were eligible for inclusion. Data related to physiological and psychosocial outcomes were compared between admission and discharge. Follow-up data, including hemoglobin A1c (HbA1c), psychosocial measures, and health care utilization, were collected at 3, 6, and 12 months after discharge to assess sustained changes. Fifty-seven T1D admissions were included in the sample. There was a significant reduction in mean HbA1c from admission (11.1%/98 mmol/mol) to discharge (9.1%/76 mmol/mol). Patients also demonstrated significant improvements in all psychosocial outcome measures. Improvements in HbA1c were sustained at 3 months follow-up; however, average values returned to baseline by 6 months follow-up. In contrast to preadmission history, the majority of the sample reported reduced crisis health care utilization 1 year after discharge. The inpatient setting provides an intensive treatment model for diabetes management that promotes sustainable behavior change 3 months after discharge. While additional community supports are needed for long-term improvement, this program model may benefit patients who have been unable to manage their diabetes with outpatient treatment and therapy alone., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Objectives: Sleepwalkers have consistently shown N3 sleep discontinuity, especially after sleep deprivation. In healthy subjects, sleep spindles activity has been positively correlated to sleep stability. We aimed to compare spindles density during N3 sleep between sleepwalkers and healthy controls., Methods: Two cohorts of 10 and 21 adult sleepwalkers respectively controlled with 10 and 18 healthy volunteers underwent one baseline and one recovery sleep recording after 38h (cohort 1) and 25h (cohort 2) of sleep deprivation. For the two recordings, we performed an automatic detection of spindles (11-16Hz) from EEG signal during N3 sleep, restricted to the first sleep cycle and repeated for all cycles. For better interpretation of results, we extended the analysis to N2 sleep and we also measured the density of slow waves oscillation (SWO) (0.5-4Hz) during the same periods., Results: Compared to controls, sleepwalkers showed significantly lower spindle densities during N3 sleep considering the first sleep cycle (both cohorts) or all cycles (cohort 1). SWO densities did not differ (cohort 1) or were lower (cohort 2) for sleepwalkers. The effect of sleep deprivation did not interact with the effect of group on spindles and SWO densities., Conclusion: This work suggests that the instability of N3 sleep inherent to sleepwalkers may be underpinned by a specific alteration of spindles activity., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Objective: To explore the literature describing the delivery and assessment of Mental Health First Aid (MHFA) training among university students., Data Sources: The databases MEDLINE, PreMEDLINE, CINAHL, EMBASE, ERIC, and PsycINFO were searched to identify publications describing MHFA training and assessment among university students since 2000., Study Selection: All studies, regardless of design, that described the delivery and assessment of MHFA training among university students, at any level, were included in this systematic review., Data Extraction: The discipline and level of students; the version, length, and integration of MHFA training; and the constructs used to assess students post-MHFA training were extracted from each study., Results: Of the initial 1662 records, 12 were included. Eight studies were conducted in Australia, 3 in the United States, and 1 in the United Kingdom. Most students were enrolled in health care or social work degree programs across all years of their program with 4 studies involving pharmacy students. Three studies described integrating compulsory MHFA training for university students. Most studies reported on the delivery of the Standard or Adult version of MHFA training; no study reported on MHFA for Tertiary Students. Post-MHFA training, students were assessed on mental health knowledge, literacy, intentions, confidence, stigma, and skills application. Only 2 studies described assessment methods involving direct observation of behaviors, whereas the rest relied on self-reported measurements., Conclusion: Despite the spread of MHFA to over 25 countries and the availability of tertiary student-specific training, the studies included in this systematic review were conducted in only 3 countries and mainly involved Standard and Adult MHFA training. Most assessments relied on self-reported measures. Future studies involving different versions of MHFA training, and the exploration of novel competency-based assessment methods among a diverse range of students from different countries are warranted., (Copyright © 2020 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.)

When the fourth edition of the Brain Trauma Foundation's Guidelines for the Management of Severe Traumatic Brain Injury were finalized in late 2016, it was known that the results of the RESCUEicp (Trial of Decompressive Craniectomy for Traumatic Intracranial Hypertension) randomized controlled trial of decompressive craniectomy would be public after the guidelines were released. The guideline authors decided to proceed with publication but to update the decompressive craniectomy recommendations later in the spirit of "living guidelines," whereby topics are updated more frequently, and between new editions, when important new evidence is published. The update to the decompressive craniectomy chapter presented here integrates the findings of the RESCUEicp study as well as the recently published 12-mo outcome data from the DECRA (Decompressive Craniectomy in Patients With Severe Traumatic Brain Injury) trial. Incorporation of these publications into the body of evidence led to the generation of 3 new level-IIA recommendations; a fourth previously presented level-IIA recommendation remains valid and has been restated. To increase the utility of the recommendations, we added a new section entitled Incorporating the Evidence into Practice. This summary of expert opinion provides important context and addresses key issues for practitioners, which are intended to help the clinician utilize the available evidence and these recommendations. The full guideline can be found at: https://braintrauma.org/guidelines/guidelines-for-the-management-of-severe-tbi-4th-ed#/., (© Congress of Neurological Surgeons 2020.)

Method: Data from qualitative semi-structured interviews with 19 participants from primary care settings were thematically analysed., Results: Critical elements in providing clinical care in primary care settings were identified at an organisational and provider level. A supportive organisational culture included leadership, a multidisciplinary team approach, community engagement and cultural competency, while provider-related issues included authorisation to prescribe, access to linguistic and cultural mediators and effective relationships with relevant specialist services., Discussion: The research identified practice leadership, organisational culture and a patient focus supported hepatitis B clinical management transitioning from specialist to primary care services.

Sialidosis is an autosomal recessive lysosomal storage disease, belonging to the glycoproteinoses. The disease is caused by deficiency of the sialic acid-cleaving enzyme, sialidase 1 or neuraminidase 1 (NEU1). Patients with sialidosis are classified based on the age of onset and severity of the clinical symptoms into type I (normomorphic) and type II (dysmorphic). Patient-derived skin fibroblasts from both disease types were reprogrammed using the CytoTune™-iPS 2.0 Sendai Reprogramming Kit. iPSCs were characterized for pluripotency, three germ-layer differentiation, normal karyotype and absence of viral components. These cell lines represent a valuable resource to model sialidosis and to screen for therapeutics., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 The Author(s). Published by Elsevier B.V. All rights reserved.)

B7-H3 is actively being explored as an immunotherapy target for pediatric patients with solid tumors using monoclonal antibodies or T cells expressing chimeric antigen receptors (CARs). B7-H3-CARs containing a 41BB costimulatory domain are currently favored by several groups based on preclinical studies. In this study, we initially performed a detailed analysis of T cells expressing B7-H3-CARs with different hinge/transmembrane (CD8α versus CD28) and CD28 or 41BB costimulatory domains (CD8α/CD28, CD8α/41BB, CD28/CD28, CD28/41BB). Only subtle differences in effector function were observed between CAR T cell populations in vitro . However, CD8α/CD28-CAR T cells consistently outperformed other CAR T cell populations in three animal models, resulting in a significant survival advantage. We next explored whether adding 41BB signaling to CD8α/CD28-CAR T cells would further enhance effector function. Surprisingly, incorporating 41BB signaling into the CAR endodomain had detrimental effects, while expressing 41BBL on the surface of CD8α/CD28-CAR T cells enhanced their ability to kill tumor cells in repeat stimulation assays. Furthermore, 41BBL expression enhanced CD8α/CD28-CAR T cell expansion in vivo and improved antitumor activity in one of four evaluated models. Thus, our study highlights the intricate interplay between CAR hinge/transmembrane and costimulatory domains. Based on our study, we selected CD8α/CD28-CAR T cells expressing 41BBL for early phase clinical testing., (© 2020 The Author(s).)

BCOR has been recognized as a recurrently altered gene in a subset of pediatric tumors of the central nervous system (CNS). Here, we describe a novel BCOR-CREBBP fusion event in a case of pediatric infiltrating astrocytoma and further probe the frequency of related fusion events in CNS tumors. We analyzed biopsy samples taken from a 15-year-old male with an aggressive, unresectable and multifocal infiltrating astrocytoma. We performed RNA sequencing (RNA-seq) and targeted DNA sequencing. In the index case, the fused BCOR-CREBBP transcript comprises exons 1-4 of BCOR and exon 31 of CREBBP. The fused gene thus retains the Bcl6 interaction domain of BCOR while eliminating the domain that has been shown to interact with the polycomb group protein PCGF1. The fusion event was validated by FISH and reverse transcriptase PCR. An additional set of 177 pediatric and adult primary CNS tumors were assessed via FISH for BCOR break apart events, all of which were negative. An additional 509 adult lower grade infiltrating gliomas from the publicly available TCGA dataset were screened for BCOR or CREBBP fusions. In this set, one case was found to harbor a CREBBP-GOLGA6L2 fusion and one case a CREBBP-SRRM2 fusion. In a third patient, both BCOR-L3MBTL2 and EP300-BCOR fusions were seen. Of particular interest to this study, EP300 is a paralog of CREBBP and the breakpoint seen involves a similar region of the gene to that of the index case; however, the resultant transcript is predicted to be completely distinct. While this gene fusion may play an oncogenic role through the loss of tumor suppressor functions of BCOR and CREBBP, further screening over larger cohorts and functional validation is needed to determine the degree to which this or similar fusions are recurrent and to elucidate their oncogenic potential.

Introduction. Management of steroid-refractory ulcerative colitis has predominantly involved treatment with systemic cyclosporine A (CyA) and infliximab. Aim. The purpose of this study was to assess the effect of using a colon-targeted delivery system CyA formulation on the composition and functionality of the gut microbiota. Methodology. Ex vivo faecal fermentations from six healthy control subjects were treated with coated minispheres (SmPill) with (+) or without (-) CyA and compared with a non-treated control in a model colon system. In addition, the in vivo effect of the SmPill+CyA formulation was investigated by analysing the gut microbiota in faecal samples collected before the administration of SmPill+CyA and after 7 consecutive days of administration from eight healthy subjects who participated in a pilot study. Results. Analysis of faecal samples by 16S rRNA gene sequencing indicated little variation in the diversity or relative abundance of the microbiota composition before or after treatment with SmPill minispheres with or without CyA ex vivo or with CyA in vivo . Short-chain fatty acid profiles were evaluated using gas chromatography, showing an increase in the concentration of n-butyrate ( P =0.02) and acetate ( P =0.32) in the faecal fermented samples incubated in the presence of SmPill minispheres with or without CyA. This indicated that increased acetate and butyrate production was attributed to a component of the coated minispheres rather than an effect of CyA on the microbiota. Butyrate and acetate levels also increased significantly ( P =0.05 for both) in the faecal samples of healthy individuals following 7 days' treatment with SmPill+CyA in the pilot study. Conclusion. SmPill minispheres with or without CyA at the clinically relevant doses tested here have negligible direct effects on the gut microbiota composition. Butyrate and acetate production increased, however, in the presence of the beads in an ex vivo model system as well as in vivo in healthy subjects. Importantly, this study also demonstrates the relevance and value of using ex vivo colon models to predict the in vivo impact of colon-targeted drugs directly on the gut microbiota.

A comprehensive series of optimization studies including pH, solvent and temperature were completed on the nitrile hydrolyzing Rhodococcus erythropolis bacterium SET1 with the substrate 3-hydroxybutyronitrile. These identified temperature of 25 °C and pH of 7 as the best conditions to retain enantioselectivity and activity. The effect of the addition of organic solvents to the biotransformation mixture was also determined. The results of the study suggested that SET1 is suitable for use in selected organo-aqueous media at specific ratios only. The functional group tolerance of the isolate with unprotected and protected β- aminonitriles, structural analogues of β -hydroxynitriles was also investigated with disappointingly poor isolated yields and selectivity obtained. The isolate was further evaluated with the α- aminonitrile phenylglycinonitrile generating acid in excellent yield and ee (>99 % ( S ) - isomer and 50 % yield). A series of pH studies with this substrate indicated pH 7 to be the optimum pH to avoid product and substrate degradation., Competing Interests: The authors declare no conflict of interest., (© 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.)

Background: Transfusion Practitioner (TP) is a term that describes activities undertaken by a variety of healthcare professionals who play a key role in supporting safe and appropriate blood management/transfusion care for patients. There is significant variation in staff specialty filling the role. To understand which countries have the TP role, and the variations that exist, an international survey was undertaken in 2017., Methods: A survey was developed by the TP Forum Steering Committee (TPFSC) with input from the International Society of Blood Transfusion (ISBT) Clinical Transfusion Working Party. The survey was distributed by the ISBT Office to all ISBT members and promoted via newsletters and social media., Results/discussion: Five hundred and eighty-two responses received from 84 different countries. The TP role exists in 67 countries, 10 countries do not have the TP role, one was unaware of the role, and respondents from six other countries did not answer this question. The most prevalent TP activities reported were policy and procedure development, education, participation in Transfusion Committees and audit activities. Eighty-eight respondents indicated they did not have a TP role, with the main barrier being financial, followed by lack of support for the role. Eight respondents indicated they previously had a TP, and this role was no longer in place due to lack of support for the role, cutbacks and other priorities., Conclusion: This survey provides insights as to where and how the TP functions and provides the TPFSC with valuable information to develop tools to support further development of the role., (© 2020 International Society of Blood Transfusion.)

Purpose: The concept for the contemplation group intervention was derived from motivational interviewing (MI) to support people suffering from an eating disorder who are reluctant to engage with treatment. This evaluation focuses on the contemplation group run by the eating disorder services in the Cardiff and Vale area between 2012 and 2016 to investigate the outcomes for participants and implications for working with people suffering from an eating disorder who are ambivalent about change., Method: Quantitative measures were used to assess eating disorder symptomatology, motivation to change and location within the stages of change model. A brief qualitative evaluation of client experiences was also included., Results: While dropout was high, a number of patients displayed increased readiness for treatment at the end of the group or even started to engage in change-focussed therapy. Participants who completed the group described it as challenging but helpful., Conclusions: This evaluation shows that explorative contemplation of their ambivalence towards their eating disorder and treatment was helpful for the participants of the group and supported them in achieving more clarity and decisiveness regarding whether to engage in treatment or not. Further research is needed to evaluate long-term outcomes for patients who feel ambivalent towards treatment, and to explore what interventions can be used to help them., Evidence Level: Level IV: Evidence obtained from multiple time series with or without the intervention.

Objective: Rates of vaginal breech delivery at term have fallen significantly. We sought to examine rates of preterm vaginal breech delivery and outcomes associated with delivery route. Methods: This retrospective cohort study was carried out at a large tertiary referral center serving an urban population, from 2001 to 2011. The primary objective was to compare outcomes of breech presenting preterm infants according to mode of delivery. The incidence of preterm breech delivery was examined as well as maternal and neonatal outcomes associated with vaginal and abdominal delivery of preterm breech infants. Results: A total of 15% (413/2759) of breech presenting infants delivered prior to 37-week gestation. In extreme prematurity (<28 weeks) the majority (88%; 37/42) of those who presented in labor delivered vaginally, this rate fell to 47% (63/134) after 28 weeks. Infants delivered vaginally after 28 weeks were more likely to have an Apgar <7 at 5 min, than those who had a cesarean delivery (22.5% [16/71] versus 9% [25/278], p  = .002; numbers needed to treat (NNT) = 4). Maternal blood loss >500 ml was more likely in those patients delivered by cesarean section (24.2% [74/305] versus 3.7% [4/108]; p  < .0001; NNT =2). Conclusion: These results demonstrate that vaginal delivery of a preterm breech - presenting infant is a necessary skill for all birth attendants in contemporary practice, particularly prior to 28-week gestation.

Tooth autotransplantation (the movement of a tooth from one site to another in the same person) is a technique with a history dating back many centuries. However, the use of third molars as donor teeth is perhaps less well-recognised and less documented. A review of the current literature was undertaken with particular attention to the use of the third molar as the donor tooth. The selection process, surgical procedure and follow-up pathways were summarised in the review. Appropriate patient selection was found to be a key factor in the success of the technique. Other prognostic factors were also discussed. The findings from the available literature suggest that autotransplantation is a viable and cost-effective technique. However, the literature relating to the use of third molars as donor teeth for autotransplantation is limited and there are currently no evidence-based guidelines or protocols relating to the technique. This paper discusses the literature and protocols the authors implement for autotransplantation of wisdom teeth.

Quality improvement collaboratives (QICs) have long been used to facilitate group learning and implementation of evidence-based interventions (EBIs) in healthcare. However, few studies systematically describe implementation strategies linked to QIC success. To address this gap, we evaluated a QIC on colorectal cancer (CRC) screening in Federally Qualified Health Centers (FQHCs) by aligning standardized implementation strategies with collaborative activities and measuring implementation and effectiveness outcomes. In 2018, the American Cancer Society and North Carolina Community Health Center Association provided funding, in-person/virtual training, facilitation, and audit and feedback with the goal of building FQHC capacity to enact selected implementation strategies. The QIC evaluation plan included a pre-test/post-test single group design and mixed methods data collection. We assessed: 1) adoption, 2) engagement, 3) implementation of QI tools and CRC screening EBIs, and 4) changes in CRC screening rates. A post-collaborative focus group captured participants' perceptions of implementation strategies. Twenty-three percent of North Carolina FQHCs (9/40) participated in the collaborative. Health Center engagement was high although individual participation decreased over time. Teams completed all four QIC tools: aim statements, process maps, gap and root cause analysis, and Plan-Do-Study-Act cycles. FQHCs increased their uptake of evidence-based CRC screening interventions and rates increased 8.0% between 2017 and 2018. Focus group findings provided insights into participants' opinions regarding the feasibility and appropriateness of the implementation strategies and how they influenced outcomes. Results support the collaborative's positive impact on FQHC capacity to implement QI tools and EBIs to improve CRC screening rates., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Alternative sanitation options are needed for effective waste management in low-income countries where centralized, large-scale waste treatment is not easily achievable. A newly designed solar concentrator technology utilizes solar thermal energy to treat feces contained in drums. This pilot study assessed the efficacy of the new design to inactivate microbes in 13 treatment drums under field conditions in Kenya. Three-quarters of the drums contained <1000 E. coli/g of total solids following 6 h of solar thermal treatment and inactivation of thermotolerant C. perfringens spores ranged from <1.8 to >5.0 log 10 . Nearly all (94%) samples collected from treatment drums achieved thermophilic temperatures (>50 °C) during the treatment period, however this alone did not ensure samples met the WHO E. coli guideline; higher, sustained thermophilic temperatures tended to be more effective in reaching this guideline. The newly designed solar concentrator was capable of inactivating thermotolerant, environmentally-stable microorganisms as, or possibly more, efficiently than a previous design. Additional data are needed to better characterize how temperature, time, and other parameters affect the ability of the solar concentrator to inactivate microbes in feces., (Copyright © 2019 Elsevier B.V. All rights reserved.)

The current study's purpose is to explore the influence of peer-perceived creativity (sociometric creativity) on the short-term development of friendships during a summer program for high ability students. Specifically, the two main objectives of our study are: (1) How did students' friendships network and sociometric creativity network evolve in the summer program? (2) How did sociometric creativity influence the friendship formation? The longitudinal study was conducted at the beginning, middle and the end of a 3-week long program for gifted students in Ireland. The sample consisted of Irish gifted students (N = 702, aged 13-18 years, 52% female, over thirty-one classes). Overall, our longitudinal multilevel and multigroup social network analysis shows that gifted adolescents formed reciprocated friendship ties and cohesive peer group structures in the investigated period; similar age and the same gender predicted friendship formation. Regarding the sociometric creativity, they tended to nominate a similar age and same gender student as very creative. Moreover, the sociometric creativity positively influenced adolescents' friendship networks on a dyadic level, indicating that adolescents select friends based on their perception of the other student's creativity. Further results, explanations, and implications are discussed., (© 2019 The Authors. New Directions for Child and Adolescent Development published by Wiley Periodicals, Inc.)

Naïve pluripotent stem cells (PSCs) display a distinctive phenotype when compared to their "primed" counterparts, including, but not limited to, increased potency to differentiate and more robust mitochondrial respiration. The cultivation and maintenance of naïve PSCs have been notoriously challenging, requiring the use of complex cytokine cocktails. NME7 AB is a newly discovered embryonic stem cell growth factor that is expressed exclusively in the first few days of human blastocyst development. It has been previously reported that growing primed induced PSCs (iPSCs) in bFGF-depleted medium with NME7 AB as the only added growth factor facilitates the regression of these cells to their naïve state. Here, we confirm this regression by demonstrating the reactivation of mitochondrial function in the induced naïve-like PSCs and increased ATP production in these cells, as compared to that in primed iPSCs.

Studies have shown that both nicotine and sleep spindles are associated with enhanced memorisation. Further, a few recent studies have shown how cholinergic input through nicotinic and muscarinic receptors can trigger or modulate sleep processes in general, and sleep spindles in particular. To better understand the interaction between nicotine and sleep spindles, we compared in a single blind randomised study the characteristics of sleep spindles in 10 healthy participants recorded for 2 nights, one with a nicotine patch and one with a sham patch. We investigated differences in sleep spindle duration, amplitude, intra-spindle oscillation frequency and density (i.e. spindles per min). We found that under nicotine, spindles are more numerous (average increase: 0.057 spindles per min; 95% confidence interval: [0.025-0.089]; p = .0004), have higher amplitude (average amplification: 0.260 μV; confidence interval: [0.119-0.402]; p = .0032) and last longer (average lengthening: 0.025 s; confidence interval: [0.017-0.032]; p = 2.7e-11). These results suggest that nicotine can increase spindle activity by acting on nicotinic acetylcholine receptors, and offer an attractive hypothesis for common mechanisms that may support memorisation improvements previously reported to be associated with nicotine and sleep spindles., (© 2018 European Sleep Research Society.)

The curation of neuroscience entities is crucial to ongoing efforts in neuroinformatics and computational neuroscience, such as those being deployed in the context of continuing large-scale brain modelling projects. However, manually sifting through thousands of articles for new information about modelled entities is a painstaking and low-reward task. Text mining can be used to help a curator extract relevant information from this literature in a systematic way. We propose the application of text mining methods for the neuroscience literature. Specifically, two computational neuroscientists annotated a corpus of entities pertinent to neuroscience using active learning techniques to enable swift, targeted annotation. We then trained machine learning models to recognise the entities that have been identified. The entities covered are Neuron Types, Brain Regions, Experimental Values, Units, Ion Currents, Channels, and Conductances and Model organisms. We tested a traditional rule-based approach, a conditional random field and a model using deep learning named entity recognition, finding that the deep learning model was superior. Our final results show that we can detect a range of named entities of interest to the neuroscientist with a macro average precision, recall and F1 score of 0.866, 0.817 and 0.837 respectively. The contributions of this work are as follows: 1) We provide a set of Named Entity Recognition (NER) tools that are capable of detecting neuroscience entities with performance above or similar to prior work. 2) We propose a methodology for training NER tools for neuroscience that requires very little training data to get strong performance. This can be adapted for any sub-domain within neuroscience. 3) We provide a small corpus with annotations for multiple entity types, as well as annotation guidelines to help others reproduce our experiments.

Metabolic studies of human pluripotent stem cells (hPSCs) have focused on how the cells produce energy through the catabolic pathway. The less-studied anabolic pathway, by which hPSCs expend energy in the form of adenosine triphosphate (ATP), is not yet fully understood. Compared to fully differentiated somatic cells, hPSCs undergo significant changes not only in their gene expression but also in their production and/or expenditure of ATP. Here, we investigate how hPSCs tightly control their energy homeostasis by studying the main energy-consuming process, mRNA translation. In addition, change of subcellular organelles regarding energy homeostasis has been investigated. Lysosomes are organelles that play an important role in the elimination of unnecessary cellular materials by digestion and in the recycling system of the cell. We have found that hPSCs control their lysosome numbers in part by regulating lysosomal gene/protein expression. Thus, because the levels of mRNA translation rate are lower in hPSCs than in somatic cells, not only the global translational machinery but also the lysosomal recycling machinery is suppressed in hPSCs. Overall, the results of our study suggest that hPSCs reprogram gene expression and signaling to regulate energy-consuming processes and energy-controlling organelles., (Copyright © 2019. Published by Elsevier Inc.)

Somatosensory thalamocortical (TC) neurons from the ventrobasal (VB) thalamus are central components in the flow of sensory information between the periphery and the cerebral cortex, and participate in the dynamic regulation of thalamocortical states including wakefulness and sleep. This property is reflected at the cellular level by the ability to generate action potentials in two distinct firing modes, called tonic firing and low-threshold bursting. Although the general properties of TC neurons are known, we still lack a detailed characterization of their morphological and electrical properties in the VB thalamus. The aim of this study was to build biophysically-detailed models of VB TC neurons explicitly constrained with experimental data from rats. We recorded the electrical activity of VB neurons (N = 49) and reconstructed morphologies in 3D (N = 50) by applying standardized protocols. After identifying distinct electrical types, we used a multi-objective optimization to fit single neuron electrical models (e-models), which yielded multiple solutions consistent with the experimental data. The models were tested for generalization using electrical stimuli and neuron morphologies not used during fitting. A local sensitivity analysis revealed that the e-models are robust to small parameter changes and that all the parameters were constrained by one or more features. The e-models, when tested in combination with different morphologies, showed that the electrical behavior is substantially preserved when changing dendritic structure and that the e-models were not overfit to a specific morphology. The models and their analysis show that automatic parameter search can be applied to capture complex firing behavior, such as co-existence of tonic firing and low-threshold bursting over a wide range of parameter sets and in combination with different neuron morphologies., Competing Interests: The authors have declared that no competing interests exist.

Nitrilase enzymes (EC 3.5.5.1) are responsible for the direct hydration of nitriles to their corresponding carboxylic acids and ammonia. The utilization of nitrilase enzymes in biocatalysis toward bio-pharmaceuticals and industrial applications facilitates the move towards green chemistry. The body of research presented describes a novel clade-specific touchdown PCR protocol for the detection of novel nitrilase genes. The presented study identified partial sequences of 15 novel nitrilase genes across 7 genera, with partial DNA sequence homology (%) displayed across an additional 16 genera. This research will prove valuable in the screening of microorganisms for the identification of novel clade-specific nitrilase genes, with predicted enantioselective profiles as determined by their clade characterizations., (© 2018 The Authors. MicrobiologyOpen published by John Wiley & Sons Ltd.)