bluuebunny/crossref_metadata_2025 huggingface dataset:
High Prevalence of Developmental Venous Anomaly in Diffuse Intrinsic Pontine Gliomas: A Pediatric Control Study
Authors: Roux Alexandre , Boddaert Nathalie , Grill Jacques , Castel David , Zanello Marc , Zah-Bi Gilles , Chrétien Fabrice , Lefevre Etienne , Ros Volodia Dangouloff , Zerah Michel , Puget Stéphanie , Pallud Johan , Varlet Pascale
Published: July 2019

BACKGROUND

No link has been demonstrated between diffuse intrinsic pontine glioma and developmental venous anomaly in pediatric patients.

OBJECTIVE

To determine the prevalence of developmental venous anomaly in a pediatric cohort of diffuse intrinsic pontine glioma.

METHODS

We performed a retrospective cohort study (1998-2017) of consecutive pediatric patients harboring a diffuse intrinsic pontine glioma (experimental set, n = 162) or a craniopharyngioma (control set, n = 142) in a tertiary pediatric neurosurgical center. The inclusion criteria were the following: age <18 yr at diagnosis; histopathological diagnosis of diffuse intrinsic pontine glioma or craniopharyngioma according to the 2016 World Health Organization classification of tumors of the central nervous system; no previous oncological treatment; and available preoperative magnetic resonance imaging performed with similar acquisition protocol.

RESULTS

We found a significantly higher prevalence of developmental venous anomaly in the experimental set of 162 diffuse intrinsic pontine gliomas (24.1%) than in the control set of 142 craniopharyngiomas (10.6%; P = .001). The prevalence of developmental venous anomalies was not significantly impacted by demographic data (sex, age at diagnosis, and underlying pathological condition), biomolecular analysis (H3-K27M-mutant subgroup, H3.1-K27M-mutant subgroup, and H3.3-K27M-mutant subgroup), or imaging findings (anatomic location, anatomic extension, side, and obstructive hydrocephalus) of the studied diffuse intrinsic pontine gliomas.

CONCLUSION

We report a higher prevalence of developmental venous anomaly in pediatric diffuse intrinsic pontine glioma patients than in control patients, which suggests a potential underlying common predisposition or a causal relationship that will require deeper investigations.
Role of Resistivity Index Analysis in the Prediction of Hemodynamically Significant Venous Sinus Stenosis in Patient With Idiopathic Intracranial Hypertension
Authors: Mohammaden Mahmoud H , Husain Muhammad Rizwan , Brunozzi Denise , Hussein Ahmed E , Atwal Gursant , Charbel Fady T , Alaraj Ali
Published: July 2019

BACKGROUND

The resistivity index (RI) in cerebral venous sinus stenosis (VSS) has not been studied in patients with idiopathic intracranial hypertension (IIH).

OBJECTIVE

To evaluate the role of RI measured by quantitative magnetic resonance venogram (QMRV) as a noninvasive tool in the diagnosis of venous hypertension associated with VSS in IIH.

METHODS

Retrospective evaluation of 13 consecutive IIH patients who underwent venous sinus stenting at our institution between 2013 and 2018.

Patients’ demographics, clinical presentation, cerebral mean venous sinus pressure (MVP), and RI both pre- and poststenting were recorded. The baseline RI was also compared to a control group.

RESULTS

Among 13 patients of IIH, 11 had unilateral VSS in dominant sinus, whereas 2 had bilateral VSS. RI was significantly higher in IIH patients compared to the control group in the superior sagittal (SSS) and transverse sinuses (TS) (0.21 vs 0.11, P = .01 and 0.22 vs 0.13, P = .03, respectively). The MVP (in mm Hg) decreased significantly after venous sinus stenting in the SSS (41.9 to 22.5, P < .001) and TS (39.4 to 19.5, P < .001), which was also associated with a significant reduction of the RI (0.22 vs 0.17, P < .01 in SSS and 0.23 vs 0.17, P = .03 in TS) poststenting.

CONCLUSION

RI calculated using QMRV can serve as a noninvasive tool to aid in the diagnosis of hemodynamically significant VSS. The study had a small sample size, and larger multicenter studies would be required to validate the results further.
Multielectron transportation of polyoxometalate-grafted metalloporphyrin coordination frameworks for selective CO2-to-CH4 photoconversion
Authors: Huang Qing , Liu Jiang , Feng Liang , Wang Qi , Guan Wei , Dong Long-Zhang , Zhang Lei , Yan Li-Kai , Lan Ya-Qian , Zhou Hong-Cai
Published: July 2019

Photocatalytic CO2 reduction into energy carriers is of utmost importance due to the rising concentrations of CO2 and the depleting energy resource. However, the highly selective generation of desirable hydrocarbon fuel, such as methane (CH4), from CO2 remains extremely challenging. Herein, we present two stable polyoxometalate-grafted metalloporphyrin coordination frameworks (POMCFs), which are constructed with reductive Zn-ϵ-Keggin clusters and photosensitive tetrakis(4-carboxylphenyl)porphyrin (H2TCPP) linkers, exhibiting high selectivity (>96%) for CH4 formation in a photocatalytic CO2-reduction system. To our knowledge, the high CH4 selectivity of POMCFs has surpassed all of the reported coordination-framework-based heterogeneous photocatalysts for CO2-to-CH4 conversion. Significantly, the introduction of a Zn-ϵ-keggin cluster with strong reducing ability is the important origin for POMCFs to obtain high photocatalytic selectivity for CH4 formation, considering that eight MoV atoms can theoretically donate eight electrons to fulfill the multielectron reduction process of CO2-to-CH4 transformation.
Understanding the Association Between Spontaneous Quit Attempts and Improved Smoking Cessation Success Rates: A Population Survey in England With 6-Month Follow-up
Authors: Garnett Claire , Shahab Lion , Raupach Tobias , West Robert , Brown Jamie
Published: July 2019

Introduction

Almost half of smoking quit attempts are “spontaneous” (initiated as soon as the decision to quit has been made) and are associated with increased success rates. This study aimed to assess to what extent other factors may account for this association.

Methods

Data were used from respondents to a survey representative of the adult population in England from 2006 to 2016. We included 2018 respondents who were current smokers at baseline and had attempted to quit between baseline and 6-month follow-up. Logistic regression models assessed the association between quit success and spontaneous quit attempts while adjusting for smoking, sociodemographic, and quit attempt characteristics.

Results

Spontaneous quit attempts were associated with greater odds of quit success (OR = 1.31, 95% CI = 1.07 to 1.60) but the association was not significant in the fully adjusted model (ORadj = 1.19, 95% CI = 0.95 to 1.49). In this adjusted model, those who attempted to quit without cutting down first (ORadj = 3.08, 95% CI = 2.46 to 3.88) and were male (ORadj = 1.44, 95% CI = 1.16 to 1.80) had greater odds of success; although a greater number of attempts in the past 6 months, stronger urges to smoke (strong vs. none), higher daily cigarette consumption, and lower social grade (E vs. AB) were associated with lower odds of success (ORadj range = 0.32–0.98, p < .030). Quit attempts made without cutting down first were correlated with spontaneous quit attempts (r = .150, p < .001) and appeared to account for the diminished association between spontaneous quitting and success (ORadj = 1.18, 95% CI = 0.96 to 1.46).

Conclusions

The increased success rate of spontaneous quit attempts appears to be because spontaneous quit attempts are more likely to be made without cutting down first.

Implications

The apparent benefit of spontaneous over planned quit attempts may be attributable to the former being more likely to involve quitting without cutting down first (ie, abrupt cessation) than cutting down first (ie, gradual cessation) and so this may be a more useful target for advice to improve the chances of successful quitting.
Evaluation of a trauma therapy programme within emergency service organizations
Authors: Tehrani N
Published: July 2019

Background

Occupational health practitioners working in emergency services, where employees are exposed to a higher level of physical or psychological trauma, need to be able to access trauma therapy programmes which are economically viable and effective in reducing post-traumatic stress disorder and associated symptoms of anxiety and depression.

Aims

The aim of this review is to provide evidence on benefits of a short-term organizational programme of trauma therapy using NICE (2018) [1] recommended interventions.

Methods

The review examined the pre- and post-therapy clinical scores from 429 emergency service professionals (ESPs) who were employed in five police forces, two fire and two ambulance services. The ESPs in higher risk roles were in a psychological surveillance programme, with those found to be experiencing clinically significant levels of trauma-related symptoms being referred to a psychologist for an assessment which identified the ESPs requiring trauma therapy. At the end of the therapy, the symptoms of the ESPs were re-assessed, and the scores before and after the therapy were compared.

Results

The results showed a significant improvement in the level of symptoms, with 81% of ESPs no longer exhibiting clinically significant trauma symptoms and 6% showing an increase in symptoms. In addition, the clinical results also showed improvements in ESPs’ perceived work capacity and quality of social relationships.

Conclusions

The findings indicate that there are clinical and personal benefits to using an organizationally based short-term model of trauma therapy in an emergency service setting.
The classical monetary theory on bank liquidity and finance
Authors: Le Maux Laurent
Published: July 2019

This article investigates the classical monetary theory on bank liquidity and finance and especially the contribution of Thomas Tooke, John Stuart Mill and John Fullarton at the light of the debate on the Great Recession. These authors show how financial markets and banking system may collapse altogether after a rise of values in certain classes of securities or real estate markets. And they come to the view that competition between commercial banks creates the appearance of market discipline, while the expectation of scarcity in some specific markets leads to a speculative process, which in turn destabilizes the banking system and triggers the need for the lender of last resort.
Noninvasive Diagnosis of Infection Using Plasma Next-Generation Sequencing: A Single-Center Experience
Authors: Rossoff Jenna , Chaudhury Sonali , Soneji Maulin , Patel Sameer J , Kwon Soyang , Armstrong Amy , Muller William J
Published: July 2019

Pediatric patients frequently present with illnesses strongly suggesting infection, but without a clearly identified etiology. Our center has recently added a commercially available plasma metagenomic sequencing assay to its available diagnostic testing. Our experience with the first 100 tests suggests that this technology has good clinical performance with >90% sensitivity.
The Effect of Antiretroviral Therapy Initiation on the Vaginal Microbiome in HIV-Infected Women
Authors: Liu Cindy M , Packman Zoe R , Abraham Alison G , Serwadda David M , Nalugoda Fred , Aziz Maliha , Prodger Jessica L , Kaul Rupert , Kalibbala Sarah , Gray Ronald H , Price Lance B , Quinn Thomas C , Tobian Aaron Ar , Reynolds Steven J
Published: July 2019

Background

The impact of antiretroviral therapy (ART) initiation on the vaginal microbiome is unknown. This is of particular importance among women living in sub-Saharan Africa. Understanding this relationship could help elucidate if and how the host immune system interacts with the vaginal microbiome.

Methods

The vaginal microbiome of HIV-1/HSV-2-coinfected women (n = 92) in Uganda was evaluated from self-collected vaginal swabs 1 month pre-ART and at 4 and 6 months post–ART initiation. The vaginal microbiome was characterized by 16S rRNA gene-based sequencing and quantitative polymerase chain reaction. Vaginal community state types (CSTs) were identified using proportional abundance data. Changes in microbiome composition were assessed with permutational analyses of variance (PerMANOVA).

Results

Five vaginal CSTs were identified, which varied significantly by bacterial load (P < .01): CST-1 was characterized by Lactobacillus iners, CST-2 by Gardnerella, CST-3 by Gardnerella and Prevotella, CST-4 by Lactobacillus crispatus, and CST-5 was highly diverse. Vaginal microbiome composition also did not change significantly after ART initiation (P = .985). Immune reconstitution after ART initiation did not affect vaginal microbiome CST assignment (P = .722) or individual-level changes in bacterial load (log response ratio [interquartile range], –0.50 [–2.75 to 0.38] vs –0.29 [–2.03 to 1.42]; P = .40).

Conclusions

The vaginal microbiome of HIV-infected women was not affected by the initiation of ART or immune reconstitution in this observational study. Further research is needed to explore the long-term effects of ART treatment on the vaginal microbiome.
Epidemiological and Clinical Characteristics of Human Hepegivirus 1 Infection in Patients With Hepatitis C
Authors: Sridhar Siddharth , Yip Cyril C Y , Chew Nicholas F S , Wu Shusheng , Leung Kit-Hang , Chan Jasper F W , Cheng Vincent C C , Yuen Kwok-Yung
Published: July 2019

Background

Transmission of human hepegivirus 1 (HHpgV-1), a novel human pegivirus, is closely associated with hepatitis C virus (HCV). The impact of HHpgV-1 viremia on HCV infection is unknown. This study aimed to (a) evaluate the impact of HHpgV-1 viremia on HCV viral load and liver injury and (b) elucidate the clinical and molecular epidemiology of HHpgV-1 infection.

Methods

Individuals with HHpgV-1 viremia (cases) were identified by screening plasma from 655 HCV-infected adults. HHpgV-1 isolates were sequenced for phylogenetic analysis, and viral load was quantified. Cases were age- and sex-matched to HCV-infected individuals without HHpgV-1 viremia (controls) in a 1:3 ratio. A retrospective case–control analysis was performed to identify differences in HCV viral load and parameters of liver injury.

Results

Among HCV-infected adults, 16/655 (2.4%) had HHpgV-1 viremia. Risk groups for HHpgV-1 infection included intravenous drug users, blood product recipients, tattoo recipients, and men who have sex with men. Viral sequences clustered into 2 distinct HHpgV-1 genogroups. Cases had a higher mean HCV viral load than controls, with difference between means of 0.58 log10 IU/mL (P = .009). Cases were more likely to have an HCV viral load >5 log10 IU/mL (P = .028). Multiple regression demonstrated the impact of HHpgV-1 viral load and infection status on HCV viral load. HHpgV-1 infection was not associated with higher liver function tests, fibrosis scores, or imaging abnormalities.

Conclusions

HHpgV-1 viremia is associated with a higher HCV viral load in co-infected patients. HHpgV-1 infection does not affect progression of HCV-related liver disease.
Impact of the M184V/I Mutation on the Efficacy of Abacavir/Lamivudine/Dolutegravir Therapy in HIV Treatment-Experienced Patients
Authors: Olearo Flaminia , Nguyen Huyen , Bonnet Fabrice , Yerly Sabine , Wandeler Gilles , Stoeckle Marcel , Cavassini Matthias , Scherrer Alexandra , Costagiola Dominique , Schmid Patrick , Günthard Huldrych F , Bernasconi Enos , Boeni Jürg , D’arminio Monforte Antonella , Zazzi Maurizio , Rossetti Barbara , Neau Didier , Bellecave Pantxika , Rijnders Bart , Reiss Peter , Wit Ferdinand , Kouyos Roger , Calmy Alexandra
Published: July 2019

Objective

The impact of the M184V/I mutation on the virological failure (VF) rate in HIV-positive patients with suppressed viremia switching to an abacavir/lamivudine/dolutegravir regimen has been poorly evaluated.

Method

This is an observational study from 5 European HIV cohorts among treatment-experienced adults with ≤50 copies/mL of HIV-1 RNA who switched to abacavir/lamivudine/dolutegravir. Primary outcome was the time to first VF (2 consecutive HIV-1 RNA >50 copies/mL or single HIV-1 RNA >50 copies/mL accompanied by change in antiretroviral therapy [ART]). We also analyzed a composite outcome considering the presence of VF and/or virological blips. We report also the results of an inverse probability weighting analysis on a restricted population with a prior history of VF on any ART regimen to calculate statistics standardized to the disparate sampling population.

Results

We included 1626 patients (median follow-up, 288.5 days; interquartile range, 154–441). Patients with a genotypically documented M184V/I mutation (n = 137) had a lower CD4 nadir and a longer history of antiviral treatment. The incidence of VF was 29.8 cases (11.2–79.4) per 1000 person-years in those with a previously documented M184V/I, and 13.6 cases (8.4–21.8) in patients without documented M184V/I. Propensity score weighting in a restricted population (n = 580) showed that M184V/I was not associated with VF or the composite endpoint (hazard ratio [HR], 1.27; 95% confidence interval [CI], 0.35–4.59 and HR 1.66; 95% CI, 0.81–3.43, respectively).

Conclusions

In ART-experienced patients switching to an abacavir/lamivudine/dolutegravir treatment, we observed few VFs and found no evidence for an impact of previously-acquired M184V/I mutation on this outcome. Additional analyses are required to demonstrate whether these findings will remain robust during a longer follow-up.
Middle Fossa Approach for Facial Nerve Schwannoma Aiming for Functional Improvement: 2-Dimensional Operative Video
Authors: Matsushima Ken , Kohno Michihiro , Izawa Hitoshi , Tanaka Yujiro
Published: July 2019

The treatment paradigm of skull base surgery has been changed from radical tumor resection to maximal tumor removal while giving priority to functional preservation. Facial nerve schwannoma is one of the representative disorders of this type of paradigm shift.
1
This video demonstrates facial nerve schwannoma surgery through the middle fossa approach, aiming for improvement of facial function. A 33-yr-old woman presented with gradually worsening facial palsy (House-Brackmann grade IV), dizziness, and nausea. Neuroimaging revealed a growing tumor involving the geniculate ganglion, and extending to the middle fossa, internal acoustic meatus, and cerebellopontine angle. The nerve-sparing surgery through the left middle fossa approach was performed under detailed neuromonitoring including the evoked facial electromyograms and auditory brainstem response. The facial nerve fibers were involved within the tumor mass and the plane between the tumor and facial nerve could not be identified as seen in most cases of such large facial nerve schwannomas. But sufficient tumor removal with facial nerve preservation was achieved owing to continuous facial monitoring.
2
The patient had no new neurological deficits. Her facial palsy has been gradually improving, now at grade III, without any signs of tumor regrowth during the 10 mo of follow up after the operation. Careful follow up is being continued to survey the possible tumor recurrence. The video was reproduced after informed consent of the patient.
Use of Tubular Retractors for Minimally Invasive Resection of Deep-Seated Cavernomas
Authors: Eichberg Daniel G , Di Long , Shah Ashish H , Ivan Michael E , Komotar Ricardo J , Starke Robert M
Published: July 2019

BACKGROUND

Cavernomas located in subcortical or eloquent locations are difficult lesions to access safely. Tubular retractors, which distribute retraction pressure radially, have been increasingly employed successfully. These retractors may be beneficial in subcortical cavernoma resection.

OBJECTIVE

To review a single institution's case series to determine the safety profile and efficacy of transcortical-transtubular cavernoma resections and to describe our transtubular operative technique.

METHODS

We reviewed a single institution's transcortical-transtubular cavernoma resections using either BrainPath (NICO, Indianapolis, Indiana) or ViewSite Brain Access System (Vycor Medical, Boca Raton, Florida) tubular retractors performed from 2013 to 2018 (n = 20).

RESULTS

Gross total resection was achieved in all patients. When a developmental venous anomaly (DVA) was present, avoidance of DVA resection was achieved in all cases (n = 4). All patients had a supratentorial cavernoma with mean depth below cortical surface of 44.1 mm. Average postoperative clinical follow-up was 20.4 wk. Early neurologic deficit rate was 10% (n = 2); permanent neurologic deficit rate was 0%. One patient (5%) experienced early postoperative seizures (< 1 wk postop). No patients experienced late seizures (> 1 wk follow-up). Engel class 1 seizure control at final clinical follow-up was achieved in 87.5% of patients presenting with preoperative epilepsy.

CONCLUSION

Tubular retractors provide a low-profile, minimally invasive operative corridor for resection of subcortical cavernomas. There were no permanent neurologic complications in our series of 20 cases, and long-term seizure control was achieved in all patients. Thus, tubular retractors appear to be a safe and efficacious tool for resection of subcortical cavernomas.
SX Piscium: A near-contact mass-transferring binary with a possible brown dwarf companion
Authors: Wang Zhi Hua , Zhu Li Ying
Published: July 2019

SX Psc is a short-period Algol-type eclipsing binary whose photometric analysis has long been ignored. Our photometric monitoring of this target covered from 2001 December to 2018 November. Aside from some curves observed at the primary eclipses, the complete four-color light curves in the BVRcIc band were also obtained. Photometric solutions were determined based on the Wilson–Devinney method. It is found that SX Psc is a semidetached binary where the inner Roche lobe of the secondary component has been filled. The filling factor for the primary is about 85% along with an inclination of ${89{^{\circ}_{.}}8}$, indicating that it is a near-contact total eclipsing binary system. Meanwhile, analysis of the O − C curve revealed that the orbital period is increasing continuously at a rate of dP/dt = 4.64(4) × 10−8 d yr−1. This is due to the mass transfers from the secondary to the primary component, which is in accord with the semidetached configuration of this binary star. With the assumption of conservative evolution, the mass transfer rate is estimated as $1.96\times 10^{-8}\, M_{\odot }$ yr−1. By deducting the long-term increasing trend in the O − C diagram, the high-precision data exhibits a cyclic variation, whereas it might be caused by the Applegate mechanism. Moreover, according to the light travel-time effect, there should be a candidate brown dwarf with a mass of no less than $m\,_3 = 0.067\, M_{\odot }$ orbiting the eclipsing binary. This is perhaps a unique case for an Algol-type binary accompanied by a substellar object.
Taking Dimensions of Purpose-Oriented Networks Seriously
Authors: Carboni Julia L , Saz-Carranza Angel , Raab Jörg , Isett Kimberley R
Published: July 2019

Purpose-oriented networks—often referred to as goal-directed networks—are a widely recognized empirical phenomenon in the public administration and management literatures. However, there is no systematic understanding about which characteristics are constitutive for these entities to be present. We use Goetz’s multilevel concept to develop a conceptual framework for purpose-oriented networks that includes four constitutive dimensions: purpose, joint effort, membership, and governance. Then we classify existing literature into this framework. Constitutive dimensions allow scholars to operationalize concepts and develop hypotheses that are testable across a wider range of purpose-oriented networks, better define the external validity of results, and improve the accumulation of knowledge across disciplinary perspectives as well as to point to areas in need of more study. We conclude that the fundamental concepts that constitute purpose-oriented networks are dangerously understudied and are in dire need of systematic, sustained empirical attention.
Nurse-led care is preferred over GP-led care of gout and improves gout outcomes: results of Nottingham Gout Treatment Trial follow-up study
Authors: Fuller Amy , Jenkins Wendy , Doherty Michael , Abhishek Abhishek
Published: July 2019

Objectives

To explore patient satisfaction, gout knowledge, medication adherence and flares among participants receiving nurse-led or general practitioner (GP)-led care of gout in the Nottingham Gout Treatment Trial phase-II (NGTT-II).

Methods

A total of 438 participants of NGTT-II were sent a questionnaire enquiring about gout knowledge, satisfaction with health-care practitioner, urate-lowering treatment being undertaken, and gout flares ⩾1 year after their final visit. Nurse-led care participants were asked about their preference for receiving gout treatment from either a GP or a nurse.

Results

Completed questionnaires were returned by 82% of participants. Participants previously receiving nurse-led care reported greater satisfaction with health-care practitioner (P < 0.001), had better gout knowledge (P = 0.02), were more likely to be taking urate-lowering treatment [adjusted relative risk (95% CI) 1.19 (1.09, 1.30)], and self-reported fewer flares in the previous 12 months [median (inter-quartile range) 0 (0–0) vs 1 (0–3), P < 0.001] than those receiving GP-led care. Of participants receiving nurse-led care, 41–63% indicated preference for receiving gout treatment from a nurse, while only 5–20% indicated preference for receiving treatment from GPs.

Conclusion

The results of this study favour nurse-led care, involving individualized patient education and engagement and a treat-to-target strategy, in terms of patient acceptability, long-term adherence, and flares. Further research is required to evaluate the feasibility of implementing such a model of care in clinical practice.
Methotrexate and interstitial lung disease: controversies and questions. A narrative review of the literature
Authors: Fragoulis George E , Conway Richard , Nikiphorou Elena
Published: July 2019

MTX, which is the anchor-drug for the treatment of RA, has been associated with lung injury and in particular with MTX-related pneumonitis (M-pneu). Although the frequency of M-pneu has been reported to range between 0.3 and 11.6%, more recent studies and meta-analyses have challenged that, suggesting that it is less common than previously thought. M-pneu is considered a hypersensitivity reaction usually occuring early after MTX commencement, and to be dose-independent. Furthermore, it does not seem to be truly related to the development of interstitial lung disease observed in some patients as part of the natural history of RA (RA-ILD). On the other hand, there are data suggesting that clinicians should be cautious when commencing MTX in patients with pre-existing lung disease. However, treatment should not be delayed or limited in progressive RA that could lead to RA-ILD, and MTX remains one of the central players in the treat-to-target approach. In this review, we aimed to summarize the current evidence from observational studies and clinical trials on lung disease in MTX-treated RA patients. We focus the discussion on the lack of association between M-pneu and RA-ILD.
The Limits of Power: Wind Energy, Orkney, and the Post-war British State
Authors: Dudley Marianna
Published: July 2019

This article identifies the environmental components of the limits of industrial nationalization between 1945 and 1956, and with it the spatial dimensions of state power, through a case study of wind power experiments on the Orkney islands. Technocratic and socialist principles drove efforts to supply electricity to all corners of the nation, but material and environmental factors limited success, especially in remote regions. The article considers the materiality of islandness and its effects on the application of national-scale energy policy and emergence of ‘alternative’ energy solutions, in light of James C. Scott’s theory of high modernism as an ideology which emanated from centres of power to rural peripheries. It argues that an environmental lens produces new thinking on the spatial constructions of state in post-war Britain that recognizes the influence of geographical edges as materially and imaginatively capable of disrupting a narrative of one-way power emanating from the centre. Wind joins other natural forces able to exert agency in narratives of technological development and modernism, which augment our understanding of energy, nature, and nation.
The Genetic Links to Anxiety and Depression (GLAD) Study: online recruitment into the largest recontactable study of depression and anxiety
Authors: Davies Molly R. , Kalsi Gursharan , Brailean Anamaria , Cleare Anthony J. , Coleman Jonathan R.I. , Curtis Charles J. , Curzons Susannah C.B. , Davis Katrina A.S. , Goldsmith Kimberley A. , Bennett Megan Hammond , Hotopf Matthew , Hüebel Christopher , Leng Jennifer , Mason Bethany D. , McAtarsney-Kovacs Monika , Monssen Dina , Palaiologou Elisavet , Pariante Carmine , Parikh Shivani , Peel Alicia J. , Rimes Katharine A. , Rogers Henry C. , Skelton Megan , Spaul Anna , Suarez Eddy L.A. , Sykes Bronte L. , White Katie M. , Young Allan H. , Vassos Evangelos , Veale David , Wingrove Janet , Eley Thalia C. , Breen Gerome
Published: July 2019

Background

Anxiety and depression are common, debilitating and costly. These disorders are influenced by multiple risk factors, from genes to psychological vulnerabilities and environmental stressors but research is hampered by a lack of sufficiently large comprehensive studies. We are recruiting 40,000 individuals with lifetime depression or anxiety, with broad assessment of risks to facilitate future research.

Methods

The Genetic Links to Anxiety and Depression (GLAD) Study (www.gladstudy.org.uk) recruits individuals with depression or anxiety into the NIHR Mental Health BioResource. Participants invited to join the study (via media campaigns) provide demographic, environmental and genetic data, and consent for medical record linkage and recontact.

Results

Online recruitment was effective; 41,892 consented and 26,877 participants completed the questionnaire by July 2019. Participants’ questionnaire data identified very high rates recurrent depression, severe anxiety and comorbidity. Participants reported high rates of treatment receipt. The age profile of sample is biased toward young adults, with higher recruitment of females and the better educated, especially at younger ages.

Discussion

This paper describes the study methodology and descriptive data for GLAD, which represents a large, recontactable resource that will enable future research into risks, outcomes and treatment for anxiety and depression.

Highlights

Online recruitment of 40,000 individuals with lifetime depression or anxiety (77 characters)

Detailed online phenotyping combined with genetic and clinical data (66 characters)

The study sample is severe, highly comorbid, with chronic psychopathology (62 characters)

The study protocol enables recall of participants for future research and trials (82 characters)

The views expressed are those of the authors and not necessarily those of the NHS, NIHR, Department of Health or King’s College London
Role of educational attainment, cognitive performance and intelligence in neurodegeneration: a bidirectional Mendelian randomization study
Authors: Grover Sandeep ,   International Age-related Macular Degeneration Consortium (IAMDGC)
Published: July 2019

I examined the potential bi-directional causality between educational attainment (EA) (n = 766,345) and age related macular degeneration (AMD) (cases (n) =16144, controls (n) =17832) using the summary GWAS datasets on individuals with European ancestry. I used datasets on other late-onset neurodegenerative diseases including Alzheimer’s disease (AD) and Parkinson’s disease (PD) as controls to validate the findings. A risky effect of EA on AMD was observed (OR=1.318, 95% CI=1.080 −1.610, P=0.0068) after ruling out potential pleiotropy and absence of reverse causality. I further replicated previously observed protective and risky causal associations of EA with AD and PD.
Bidirectional Mendelian randomization analysis of shared genetic signals between coexisting neurodegenerative disorders to decipher underlying causal pathways
Authors: Grover Sandeep ,   International Age-related Macular Degeneration Consortium (IAMDGC)
Published: July 2019

OBJECTIVE

To investigate whether coexistence of various neurodegenerative disorders is coincidental or biologically connected.

DESIGN

Two sample Mendelian randomization using summary effect estimates

SETTING

Genetic data taken on various neurodegenerative disorders from various cohorts comprising individuals predominantly of European ancestry.

PARTICIPANTS

International Genomics of Alzheimer’s patients (IGAP), project MinE, International Age-related Macular Degeneration Consortium (IAMDGC), International Multiple Sclerosis Genetics Consortium (IMSGC), International Parkinson’s Disease Genomics Consortium (IPDGC)

MAIN OUTCOME MEASURES

Alzheimer’s disease (AD), Amyotrophic lateral sclerosis (ALS), Age related macular degeneration (AMD), Multiple sclerosis (MS) and Parkinson’s disease (PD).

RESULTS

A Bonferroni corrected threshold of P=0.005 was considered to be significant, and P<0.05 was considered suggestive of evidence for a potential association. I observed a risky effect of PD on ALS (OR = 1.126, 95% CI = 1.059-1.198, P = 0.005). Using AD as exposure and PD as outcome, I observed a risky effect of AD on PD using all the MR methods with strongest results using MBE method (OR = 2.072, 95% CI = 1.006-4.028, P = 0.0416). Genetic predisposition to AD was further observed to be a risky for AMD (OR = 1.759, 95% CI = 1.040-1.974, P = 0.0363). On the contrary, AMD was observed to be strongly protective towards MS (OR = 0.861, 95% CI = 0.776-0.955, P = 0.0059).

CONCLUSIONS

My findings are consistent with the previously observed relative occurrence of co-existing neurodegenerative diseases or overlapping symptoms among neurodegenerative diseases.
Tissue mechanics drives epithelialization, goblet cell regeneration, and restoration of a mucociliated epidermis on the surface of embryonic aggregates
Authors: Kim Hye Young , Jackson Timothy R. , Stuckenholz Carsten , Davidson Lance A.
Published: July 2019

Injury, surgery, and disease often disrupt tissues and it is the process of regeneration that aids the restoration of architecture and function. Regeneration can occur through multiple strategies including induction of stem cell expansion, transdifferentiation, or proliferation of differentiated cells. We have uncovered a case of regeneration that restores a mucociliated epithelium from mesenchymal cells. Following disruption of embryonic tissue architecture and assembly of a compact mesenchymal aggregate, regeneration first involves restoration of an epithelium, transitioning from mesenchymal cells at the surface of the aggregate. Cells establish apico-basal polarity within 5 hours and a mucociliated epithelium within 24. Regeneration coincides with nuclear translocation of the putative mechanotransducer YAP1 and a sharp increase in aggregate stiffness, and regeneration can be controlled by altering stiffness. We propose that regeneration of a mucociliated epithelium occurs in response to biophysical cues sensed by newly exposed cells on the surface of a disrupted mesenchymal tissue.
Plasma FABP4 is associated with liver disease recovery during treatment-induced clearance of chronic HCV infection
Authors: Gorin Jean-Baptiste , Malone David F. G. , Strunz Benedikt , Carlsson Tony , Aleman Soo , Björkström Niklas K. , Falconer Karolin , Sandberg Johan K.
Published: July 2019

Direct-acting antivirals (DAAs) have dramatically improved the management of chronic hepatitis C (CHC). In this study, we investigated the effects of hepatitis C virus clearance on markers of systemic inflammation measured in plasma samples from CHC patients before, during and after DAA therapy. We identified a plasma soluble protein profile associated with CHC. Successful DAA therapy rapidly normalised the plasma inflammatory milieu, with the notable exception of soluble (s) CD163, a marker of macrophage activation, which remained elevated after viral clearance and segregated patients with high and low levels of cirrhosis. Patients who received DAA in combination with Ribavirin maintained elevated levels of CXCL10, consistent with an immune-stimulatory role of Ribavirin. As anticipated, DAA-treated patients experienced durable improvement in liver fibrosis measurements. Interestingly, pre-treatment levels of fatty acid-binding protein 4 (FABP4) were inversely associated with reduction of APRI and FIB-4 scores during treatment. Together, these results support the notion of a rapid restoration of many aspects of the inflammatory state in CHC patients in response to DAA therapy. Furthermore, the associations with sCD163 and FABP4 warrants further investigation into the role of macrophages in residual liver disease and fibrosis resolution after viral clearance.
A Wild Yeast Laboratory Activity: From Isolation to Brewing
Authors: Scholes Amanda N. , Pollock Erik D. , Lewis Jeffrey A.
Published: July 2019

Microbial fermentation is a common form of metabolism that has been exploited by humans to great benefit. Industrial fermentation currently produces a myriad of products ranging from biofuels to pharmaceuticals. About one third of the world’s food is fermented, and the brewing of fermented beverages in particular has an ancient and storied history. Because fermentation is so intertwined with our daily lives, the topic is easily relatable to students interested in real-world applications for microbiology. Here, we describe the curriculum for an inquiry-based laboratory course that combines yeast molecular ecology and brewing. The rationale for the course is to compare commercialSaccharomyces cerevisiaeyeast strains, which have been domesticated through thousands of generations of selection, with wild yeast, where there is growing interest in their potentially unique brewing characteristics. Because wild yeast are so easy to isolate, identify, and characterize, this is a great opportunity to present key concepts in molecular ecology and genetics in a way that is relevant and accessible to students. We organized the course around three main modules: isolation and identification of wild yeast, phenotypic characterization of wild and commercial ale yeast strains, and scientific design of a brewing recipe and head-to-head comparison of the performance of a commercial and wild yeast strain in the brewing process. Pre and post assessment showed that students made significant gains in the learning objectives for the course, and students enjoyed connecting microbiology to a real-world application.
Mechanical Properties of DNA Replication
Authors: Sevier Stuart A.
Published: July 2019

Central to the function of cellular life is the reading, storage and replication of DNA. Due to the helical structure of DNA, a complicated topological braiding of new strands follows the duplication of the old strands. Even though this was discovered over 60 years ago, the mathematical and physical questions this presents have largely gone unaddressed. In this letter we construct a simple idealized model of DNA replication using only the most basic mathematical and mechanical elements of DNA replication. The aim of this is to reveal the mechanical balance of braided, replicated DNA against the twist of unreplicated DNA at the heart of the replication process. The addition of topoisomerase action is included presenting a balancing force offering a glimpse into the ways in which cells maintain this balance. Additionally the physical basis for recently observed replication/replication and replication/transcription conflicts are examined showing how gene orientation and size can impact DNA replication.
Use of extracellular polymer substances as additives for improving biogas yield and digestion performance
Authors: Ma Haitong , Guo Chen Yan , Wu Ming , Liu Hui , Wang Zhiwei , Wang Shuangfei
Published: July 2019

To understand how extracellular polymer substances (EPS) as additives promotes methanogenesis, batch tests of methane production potential in anaerobic reactors with the addition of EPS or not were conducted. Research showed that EPS increased remarkably methane production during anaerobic digestion (36.5% increase compared with the control). EPS enriched functional microorganisms such as Firmicutes, Actinobacteria, Synergistetes, and Chloroflexi. Among them, 8.86% OTUs from the important hydrolysis and acidification phyla, which may be an important reason for the enhanced methanogenic capacity of anaerobic granular sludge. Additionally, EPS also improved the abundance of cytochrome c (c-Cyts), accelerating the direct interspecies electron transfer (DIET) between syntrophic bacteria and methanogens, thus enhancing the methane production. Interestingly, the average particle size, volatile suspended solids/total suspended solids (VSS/TSS) and EPS content of anaerobic granular sludge (AnGS) in the EPS reactor were approximately equal to that of the control reactor during the anaerobic digestion, illustrating that EPS could not affect the physicochemical properties of AnGS. Therefore, these results suggested that EPS mainly played a role in the form of conductive materials in the anaerobic digestion process. Compared with conductive materials, EPS as biomass conductive materials was not only environmentally friendly and economical but also no secondary pollution.

Importance

Compared with the reported conductive materials, EPS has the potential of biodegradation, electron transfer and no significant secondary pollution. Besides, there are few studies on the utilization of EPS resources, especially the effect of EPS as an additive on anaerobic digestion performance. To clarify whether EPS as conductive materials or carbon source promotes methanogenesis. Therefore, in this study, we investigated the influence of EPS as an additive on the methanogenic capacity, physical-chemical properties, microbial community structure and metabolic function of anaerobic granular sludge (AnGS), and preliminarily expatiate the influence mechanism of EPS as an additive on methanogenesis. At the meantime, the research is expected to provide new solutions for the improvement of anaerobic digestion performance and disposal of waste mud.
An alternative HIV-1 non-nucleoside Reverse Transcriptase inhibition mechanism: Targeting the p51 subunit
Authors: Chan Kwok-Fong , Su Chinh Tran-To , Krah Alexander , Phua Ser-Xian , Bond Peter J. , Gan Samuel Ken-En
Published: July 2019

HIV drug resistance continues to demand for alternative drug targets. Since Reverse Transcriptase (RT) is unique and critical for the virus life cycle, it is a rational target that is likely to have less off-target effects in humans. Serendipitously, we found two chemical compound scaffolds from the NCI Diversity Set V that inhibited the HIV1- RT catalytic activity. Computational structural analyses and subsequent experimental testing demonstrated that one of the two chemical scaffolds binds to a novel location in the HIV-1 RT p51 subunit, interacting with residue Y183 that has no known association with previously reported drug resistance. This finding leads to the notion of a novel druggable site on p51 for a new class of non-nucleoside RT Inhibitors that may inhibit HIV-1 RT allosterically. Although inhibitory activity was shown experimentally only to be in the hundreds micromolar range, the scaffolds serve as a proof-of-concept of targeting HIV RT p51, with the possibility for medical chemistry methods to be applied to improve the inhibitory activity, towards a functioning drug.
Releasing a preprint is associated with more attention and citations for the peer-reviewed article
Authors: Fu Darwin Y. , Hughey Jacob J.
Published: July 2019

Preprints in biology are gaining popularity, but release of a preprint still precedes only a fraction of peer-reviewed publications. We examined whether having a preprint on bioRxiv was associated with metrics of the corresponding peer-reviewed article. We assembled a dataset of 74,239 articles, 5,405 of which had a preprint, published in 39 journals. Based on log-linear regression and random-effects meta-analysis, articles with a preprint had a 51% higher Altmetric Attention Score and 37% more citations compared to articles without one. These associations were independent of several other article- and author-level variables (e.g., scientific subfield and last author publication age) and unrelated to journal-level variables such as access model and Impact Factor. This observational study can help researchers and publishers make informed decisions about how to incorporate preprints into their work.
Astrocyte senescence in an Alzheimer’s disease mouse model is mediated by TGF-β1 and results in neurotoxicity
Authors: Amram Shoshik , Iram Tal , Lazdon Ekaterina , Vassar Robert , Ben-Porath Ittai , Frenkel Dan
Published: July 2019

Alterations in astrocyte function such as a pro-inflammatory phenotype are associated with Alzheimer’s disease (AD). We had shown impairments in the ability of aged astrocytes isolated from 5xFAD mice to clear and uptake amyloid-β (Aβ) as well as to support neuronal growth. Senescent cells accumulate with age and exhibit a senescence-associated secretory phenotype, which includes secretion of pro-inflammatory cytokines. In this study, we predicted that with age, astrocytes in 5xFAD mice would exhibit a cellular senescence phenotype that could promote neurodegeneration. We found an age-dependent increase in senescent astrocytes adjacent to Aβ plaques in 5xFAD mice. Inhibition of nuclear factor kappa-light-chain-enhancer of activated B cells reduced interelukin-6 secretion by senescent astrocytes and resulted in improved neuronal support. Moreover, senescent astrocytes exhibited an increase in the induction of the TGF-β1-SMAD2/3 pathway, and inhibition of this pathway resulted in a reduction of cellular senescence. We also discovered that soluble Aβ42 induced astrocyte senescence in young naïve mice in a SMAD2/3-dependent manner. Our results suggest an important role of astrocyte senescence in AD and its role in mediating the neurotoxicity properties of astrocytes in AD and related neurodegenerative diseases.
The GATA transcription factor Gaf1 represses tRNA genes, inhibits growth, and extends chronological lifespan downstream of fission yeast TORC1
Authors: Rodríguez-López María , Gonzalez Suam , Hillson Olivia , Tunnacliffe Edward , Codlin Sandra , Tallada Victor A. , Bähler Jürg , Rallis Charalampos
Published: July 2019

Target of Rapamycin Complex 1 (TORC1) signaling promotes growth and ageing. Inhibition of TORC1 leads to a down-regulation of factors that stimulate protein translation, including RNA polymerase III, which in turn contributes to longevity. TORC1-mediated post-transcriptional regulation of protein translation has been well studied, while analogous transcriptional regulation is less well understood. Here we screened fission yeast deletion mutants for resistance to Torin1, which inhibits TORC1 and cell growth. Mutants lacking the GATA transcription factor Gaf1 (gaf1Δ) grew normally even in high doses of Torin1. The gaf1Δ mutants shortened the chronological lifespan of non-dividing cells and diminished the lifespan extension triggered by Torin1 treatment. Expression profiling and genome-wide binding experiments showed that, after TORC1 inhibition, Gaf1 directly up-regulated genes for small-molecule metabolic pathways and indirectly repressed genes for protein translation. Surprisingly, Gaf1 bound to, and down-regulated the tRNA genes, so also functions as a transcription factor for genes transcribed by RNA polymerase III. We conclude that Gaf1 controls the transcription of both coding and tRNA genes to inhibit translation and growth downstream of TORC1.