bluuebunny/crossref_metadata_2025 huggingface dataset:
Strategies for a radical left
Authors: Allen Kieran
Published: July 2018

The current instability in late capitalism has led to a polarisation of politics. There is a growth of both the far right and the radical left. The re-emergence of a radical left is motivated by left reformist aspirations. But the structures of the state and the pressures of global capital make it impossible to satisfy those aspirations by conventional means.

New transition organisations are required which link together those committed to the overthrow of capitalism with those who want genuine reforms. Such organisations need to sink local roots and develop an electoral presence to overcome media-induced marginalisation. Instead of a purely parliamentary focus, there is a need for strategies of ‘people power’ with a particular focus on the mobilisation of organised workers.
Sorting the trash: Micronucleophagy gets selective
Authors: Verlhac Pauline , Reggiori Fulvio
Published: July 2018

During micronucleophagy, the nucleolus is targeted by autophagic degradation, but although nucleolar proteins are recycled, ribosomal DNA is spared. Mostofa et al. (2018. J. Cell Biol. https://doi.org/10.1083/jcb.201706164) reveal that the separation of these two nucleolar components is mediated by the CLIP and cohibin complexes and is vital for cell survival during starvation.
Meta-Research Evidence for Evaluating Therapies
Authors: Fuller Jonathan
Published: July 2018

The new field of meta-research investigates industry bias, publication bias, contradictions between studies, and other trends in medical research. I argue that its findings should be used as meta-evidence for evaluating therapies. ‘Meta-evidence’ is evidence about the support that direct ‘first-order evidence’ provides the hypothesis. I consider three objections to my proposal: the irrelevance objection, the screening-off objection, and the underdetermination objection. I argue that meta-research evidence works by rationally revising our confidence in first-order evidence and, consequently, in the hypothesis—typically, downward.
Representing and Explaining: The Eikonic Conception of Scientific Explanation
Authors: Bokulich Alisa
Published: July 2018

The ontic conception of explanation, according to which explanations are full-bodied things in the world, is fundamentally misguided. I argue instead for what I call the eikonic conception, according to which explanations are the product of an epistemic activity involving representations of the phenomena to be explained. What is explained in the first instance is a particular conceptualization of the explanandum phenomenon, contextualized within a given research program or explanatory project. I conclude that this eikonic conception has a number of benefits, including making better sense of scientific practice and allowing for the full range of normative constraints on explanation.
How to Do Digital Philosophy of Science
Authors: Pence Charles H. , Ramsey Grant
Published: July 2018

Philosophy of science is expanding via the introduction of new digital data and tools for their analysis. The data comprise digitized published books and journal articles, as well as heretofore unpublished material such as images, archival text, notebooks, meeting notes, and programs. The growth in available data is matched by the extensive development of automated analysis tools. The variety of data sources and tools can be overwhelming. In this article, we survey the state of digital work in the philosophy of science, showing what kinds of questions can be answered and how one can go about answering them.
Hierarchical optimization for the efficient parametrization of ODE models
Authors: Loos Carolin , Krause Sabrina , Hasenauer Jan
Published: July 2018

Motivation

Mathematical models are nowadays important tools for analyzing dynamics of cellular processes. The unknown model parameters are usually estimated from experimental data. These data often only provide information about the relative changes between conditions, hence, the observables contain scaling parameters. The unknown scaling parameters and corresponding noise parameters have to be inferred along with the dynamic parameters. The nuisance parameters often increase the dimensionality of the estimation problem substantially and cause convergence problems.

Results

In this manuscript, we propose a hierarchical optimization approach for estimating the parameters for ordinary differential equation (ODE) models from relative data. Our approach restructures the optimization problem into an inner and outer subproblem. These subproblems possess lower dimensions than the original optimization problem, and the inner problem can be solved analytically. We evaluated accuracy, robustness and computational efficiency of the hierarchical approach by studying three signaling pathways. The proposed approach achieved better convergence than the standard approach and required a lower computation time. As the hierarchical optimization approach is widely applicable, it provides a powerful alternative to established approaches.

Availability and implementation

The code is included in the MATLAB toolbox PESTO which is available at http://github.com/ICB-DCM/PESTO

Supplementary information

Supplementary data are available at Bioinformatics online.
BrainImageR: spatiotemporal gene set analysis referencing the human brain
Authors: Linker Sara B , Hsu Jonathan Y , Pfaff Adela , Amatya Debha , Ko Shu-Meng , Voter Sarah , Wong Quinn , Gage Fred H
Published: July 2018

Motivation

Neuronal analyses such as transcriptomics, epigenetics and genome-wide association studies must be assessed in the context of the human brain to generate biologically meaningful inferences. It is often difficult to access primary human brain tissue; therefore, approximations are made using alternative sources such as peripheral tissues or in vitro-derived neurons. Gene sets from these studies are then assessed for their association with the post-mortem human brain. However, most analyses of post-mortem datasets are achieved by building new computational tools each time in-house, which can cause discrepancies from study to study. The field is in need of a user-friendly tool to examine spatiotemporal expression with respect to the postmortem brain. Such a tool will be of use in the molecular interrogation of neurological and psychiatric disorders, with direct advantages for the disease-modeling and human genetics communities.

Results

We have developed brainImageR, an R package that calculates both the spatial and temporal association of a dataset with post-mortem human brain. BrainImageR identifies anatomical regions enriched for candidate gene set expression. It further predicts the developmental time point of the sample, a task that has become increasingly important in the field of in vitro neuronal modeling. These functionalities of brainImageR enable a quick and efficient characterization of a given dataset across normal human brain development.

Availability and implementation

BrainImageR is released under the Creative Commons CC BY-SA 4.0 license and can be accessed directly at brainimager.salk.edu or the R code can be downloaded through github at https://github.com/saralinker/brainImageR.
Resection of a Thoracic Hemangioblastoma in a Patient With Von Hippel-Lindau: 3-Dimensional Operative Video
Authors: Dekker Simone E , Ostergard Thomas A , Glenn Chad A , Shammassian Berje , Cox Efrem , Pace Jonathan A , Yoo Kevin , Alonso Fernando , Bambakidis Nicholas C
Published: July 2018

This 3-dimensional operative video illustrates resection of a thoracic hemangioblastoma in a 30-year-old female with a history of Von Hippel-Lindau disease. The patient presented with right lower extremity numbness and flank pain. Magnetic resonance imaging (MRI) demonstrated an enhancing intradural intramedullary lesion at T 7 consistent with a hemangioblastoma. The patient underwent a thoracic laminectomy with a midline dural opening for tumor resection. This case demonstrates the principles of intradural intramedullary spinal cord tumor resection. In this particular case, internal debulking was untenable owing to the vascular nature of hemangioblastomas. The operative video demonstrates en bloc tumor removal. Postoperative MRI demonstrated gross total resection. The postoperative course was uneventful. The natural history of this disease, treatment options, and potential complications are discussed.
Microsurgical Treatment of Recurrent Conus Medullaris Arteriovenous Malformation: 2-Dimensional Operative Video
Authors: Woodall M Neil , Spetzler Robert F
Published: July 2018

Arteriovenous malformations (AVMs) involving the conus medullaris have a unique angioarchitecture due to their involvement of the arterial basket of the conus medullaris, which represents an arterial anastomotic network between the anterior spinal artery (ASA) and posterior spinal arteries (PSAs) at the level of the conus medullaris.
1
These lesions consist of a combination of a true AVM nidus, which is usually extramedullary, and direct shunts between the ASA, PSAs, and the venous system. Patients may present with radiculopathy, myelopathy, or subarachnoid hemorrhage.
2

A 40-yr-old woman status post T11-L1 laminoplasty for resection of a ruptured conus AVM 6 yr prior presented with routine follow-up angiography suggestive of an arteriovenous fistula. She was counseled regarding treatment options including endovascular embolization and microsurgical ligation or resection, and she elected to proceed with surgical treatment. At the time of surgery, a recurrent AVM was noted. A 2-dimensional intraoperative video illustrates the microsurgical treatment of her recurrent conus AVM. The patient recovered well postoperatively. Spinal angiography demonstrated complete obliteration of the lesion. The patient experienced transient urinary retention that was self-limited but otherwise was without any new neurological deficit. Due to the retrospective nature of this report, informed consent was not required.

Video used with permission from Barrow Neurological Institute, all rights reserved.
Effects of added dietary salt on pig growth performance1,2
Authors: Shawk Dwight J , Goodband Robert D , Tokach Mike D , Dritz Steve S , DeRouchey Joel M , Woodworth Jason C , Lerner Annie B , Williams Hayden E
Published: July 2018

Three studies evaluated the effects of added dietary salt on growth performance of pigs weighing 7 to 10, 11 to 30, and 27 to 65 kg. In experiment 1, 325 pigs were used with 5 pigs per pen and 13 pens per treatment. Pigs were fed a diet (0.39% Na and 0.78% Cl) for 7 d after weaning, then randomly assigned to diets with either 0, 0.20, 0.40, 0.60, or 0.80% added salt for 14 d. All diets were corn-soybean meal-based with 10% dried whey. Calculated Na concentrations were 0.11, 0.19, 0.27, 0.35, and 0.43% and calculated Cl concentrations were 0.23, 0.35, 0.47, 0.59, and 0.70%, respectively. Increasing salt increased (linear, P < 0.05) average daily gain (ADG) and gain to feed ratio (G:F). For ADG, the linear, quadratic polynomial (QP), and broken-line linear (BLL) models were competing with the breakpoint for the BLL at 0.59% salt. For G:F, the BLL reported a breakpoint at 0.33% while the QP indicated maximum G:F at 0.67% added salt. In experiment 2, 300 pigs were used in a 34-d trial with 5 pigs per pen and 12 pens per treatment. Pigs were weaned at 21 d of age and fed a phase 1 diet (0.50% Na and 0.67% Cl) for 11 d and then a phase 2 diet (0.35% Na and 0.59% Cl) for 14 d. Then pens of pigs were randomly assigned to corn-soybean meal-based diets containing 0.20, 0.35, 0.50, 0.65, or 0.80% added salt. Calculated dietary Na concentration were 0.10, 0.16, 0.22, 0.28, and 0.34% and calculated Cl concentrations were 0.23, 0.32, 0.41, 0.50, and 0.59%, respectively. Overall, ADG and G:F increased (quadratic, P < 0.07) with increasing added salt. For ADG, the QP and BLL had similar fit with the breakpoint for BLL at 0.51% added salt. For G:F, the BLL model predicted a break point at 0.35% added salt. In experiment 3, 1,188 pigs were used in a 44-d study with 27 pigs per pen and 11 pens per treatment. Pens of pigs were randomly assigned to corn-soybean meal-based diets containing 0.10, 0.33, 0.55, or 0.75% added salt. Calculated dietary Na concentrations were 0.10, 0.19, 0.28, and 0.36% and calculated Cl concentrations were 0.23, 0.36, 0.49, and 0.61%, respectively. Overall, there was no evidence to indicate that added salt above 0.10% of the diet affected growth. In conclusion, the BLL models suggested to maximize ADG for 7 to 10 and 11 to 30 kg pigs was 0.59% (0.34% Na and 0.58% Cl) and 0.51% added salt (0.22% Na and 0.42% Cl), respectively. There was no evidence that growth of 27 to 65 kg pigs was improved beyond 0.10% added salt (0.11% Na and 0.26% Cl).
Hormetic Effects of Thiophanate-Methyl in Multiple Isolates of Sclerotinia homoeocarpa
Authors: Pradhan Sumit , Miller Lee , Marcillo Vanessa , Koch Alma R. , Graf Grachet Nathalia , Molineros Julio E. , Walker Nathan R. , Melouk Hassan , Garzon Carla D.
Published: July 2018

Twenty-eight isolates of Sclerotinia homoeocarpa, causal agent of dollar spot disease in turf, were assessed for fungicide hormesis at sublethal concentrations of thiophanate-methyl (T-methyl). Each isolate was grown in corn meal agar amended with 11 concentrations of T-methyl (30,500 to 0.047 µg/liter), and the area of mycelial growth was determined relative to the control. Three replicates were used per concentration, and the experiment was repeated three to five times for each isolate. Reference isolates (EC50 > 20 µg/liter), with no prior history of T-methyl exposure, were highly sensitive and not stimulated by low doses. Likewise, no stimulation was observed in two highly sensitive isolates (EC50 > 30 µg/liter) that had been preconditioned by exposure to T-methyl, or in four T-methyl-tolerant isolates. Seventeen (81%) preconditioned T-methyl-tolerant isolates (EC50 = 294 to1,550 µg/liter) had statistically significant growth stimulation, in the range of 2.8 to 19.7% relative to the control. These results support that hormesis (low-dose stimulation, high-dose inhibition) is a common dose response in preconditioned S. homoeocarpa, particularly in response to subtoxic doses of T-methyl.
Assessing Variability in In-Hospital Complication Rates Between Surgical Services for Patients Undergoing Posterior Cervical Decompression and Fusion
Authors: Snyder Daniel J. , Neifert Sean N. , Gal Jonathan S. , Deutsch Brian C. , Rothrock Robert , Hunter Samuel , Caridi John M.
Published: July 2018

Study Design.

A retrospective study was performed including all patients who underwent posterior cervical decompression and fusion (PCDF) by an orthopedic or neurological surgeon at a single institution between January 1, 2006 and November 30, 2016, and all patients who underwent PCDF by a spine surgeon in the National Surgical Quality Improvement Project database between 2007 and 2015. In-hospital complications were compared between surgical specialties.

Objective.

The goal of this study was to determine if in-hospital complication rates differ significantly between surgical services for PCDF patients.

Summary of Background Data.

Orthopedic and neurological surgeons commonly perform PCDF, and differences in surgical opinion and management have been cited between these two specialties in recent literature. This represents a variable that should be evaluated.

Methods.

Cases were preliminarily identified by CPT code and confirmed using the ICD-9 code 81.03 or ICD-10 code M43.22. Cases were separated based on if the primary surgeon was an orthopedic surgeon or a neurological surgeon. The primary outcome variable was in-hospital complication rates; cohorts were compared using bivariate and multivariate analysis.

Results.

A total of 1221 patients at a single institution and 11,116 patients within the National Surgical Quality Improvement Project database underwent PCDF. Patients in the orthopedic surgery service had a higher proportion of bleeding requiring transfusion in both the institutional sample (14.5% vs. 9.08%, P = 0.003) and national sample (11.16% vs. 6.18%, P < 0.0001). In the national sample, orthopedic surgeons were 1.66 times as likely to encounter an in-hospital complication than neurological surgeons (95% CI: 1.44–1.91, P < 0.0001).

Conclusion.

When examining a large institutional sample and an even larger national sample, this study found that orthopedic surgeons were more likely to encounter perioperative bleeding requiring transfusion than neurological surgeons. When in-hospital complications were considered as a whole, in the national sample, orthopedic surgeons are more likely to encounter in-hospital complications than neurological surgeons when performing PCDF.

Level of Evidence: 3
Perioperative Catheter Use as a Risk Factor for Surgical Site Infection After Cervical Surgery
Authors: Tamai Koji , Wang Christopher , Heindel Patrick , Paholpak Permsak , Buser Zorica , Wang Jeffrey C.
Published: July 2018

Study Design.

Retrospective cohort study.

Objective.

To demonstrate the relationship between perioperative use of catheters and the incidence of surgical site infection (SSI) after cervical spine surgery, after adjusting for patient's age, severity of comorbidity, surgical approach, and use of instrumentation.

Summary of Background Data.

Although the association between SSI and the use of arterial catheters (ACs) or central venous catheters (CVCs) is established in cardiac surgery, the relation in the cervical spine was not well elucidated.

Methods.

A private insurance database was analyzed. The incidence of SSI within 1 month postoperatively and the crude odds ratio (cOR) and 95% confidence interval (95% CI) were calculated based on the use of catheters. Subsequently, logistic regression analysis was performed to identify independent factors for SSI. Independent variables of the regression analysis included Charlson comorbidity index with the score of age, the use of CVC, the use of AC, surgical approach (anterior or posterior), and instrumentation (fusion or decompression alone).

Results.

A total of 39,893 patients received cervical surgery between 2007 and 2015. Of these, 1.6% patients experienced an SSI. The incidence of SSI in patients treated with and without AC was 3.2% and 1.3%, respectively (cOR 2.44, 95% CI: 2.05–2.99, P < 0.001). Likewise, incidence of SSI in patients with and without CVC was 5.8% and 1.5%, respectively (cOR 2.61, 95% CI: 2.97–5.55, P < 0.001). Multivariate logistic regression analysis demonstrated that the adjusted OR was 1.66 in CVC use (95% CI: 1.08–2.46, P = 0.016), whereas the AC use was not significant variable (P = 0.086).

Conclusion.

The use of CVC can be a potential risk factor for SSI regardless of age, severity of comorbidity, surgical approach, or presence of instrumentation. Although the essential benefits of catheters are undisputed, our data can bring up the surgeon's attention to appropriate management of the CVC.

Level of Evidence: 3
Does Systemic Administration of Parathyroid Hormone After Noninstrumented Spinal Fusion Surgery Improve Fusion Rates and Fusion Mass in Elderly Patients Compared to Placebo in Patients With Degenerative Lumbar Spondylolisthesis?
Authors: Jespersen Annette Bennedsgaard , Andresen Andreas Duch Kiilerich , Jacobsen Michael Kjær , Andersen Mikkel Ø. , Carreon Leah Y.
Published: July 2018

Study Design.

Prospective, randomized, double-blinded, placebo-controlled clinical trial.

Objective.

To evaluate whether 90-day subcutaneous injections with 20 μg teriparatide increases the volume and quality of the fusion mass compared to placebo based on 12-month postop fine cut computed tomography scans. The secondary objective is to evaluate whether parathyroid hormone (PTH) increases fusion rates compared to placebo.

Summary of Background Data.

Few studies have investigated the effects of PTH on fusion in patients undergoing spinal arthrodesis. Early studies showed a more robust fusion mass with PTH after spinal fusion surgery. But the efficiency of PTH on noninstrumented spinal fusion surgery remains unclear.

Methods.

Patients with degenerative spondylolisthesis scheduled for noninstrumented posterolateral fusion were randomized to receive 90-day subcutaneous injections with 20 μg teriparatide (N = 41) or placebo (N = 46) in a 1:1 fashion. Fusion volume and quality was evaluated using 12-month postoperative fine cut computed tomography scans.

Results.

The two groups were comparable in terms of age, sex, and numbers of levels operated. PTH treatment was well tolerated but provided no additional benefit versus placebo. Fusion rates, the mean volume, and robustness of the fusion mass were similar between the PTH and placebo groups.

Conclusion.

Ninety-day subcutaneous administration of 20 μg teriparatide did not increase fusion volume or improve the quality of the fusion mass in elderly patients compared to placebo after noninstrumented spinal fusion surgery for degenerative spondylolisthesis.

Level of Evidence: 1
Influence of a Preoperative Conference on Surgeons’ Decision-making for Adult Spinal Disorders
Authors: Erken Huseyin Yener , Bae Junseok , Lee Sang-Ho , Seo Jin Suk , Shin Sang Ha
Published: July 2018

Study Design:

This was a prospective clinical study.

Objective:

The aim of this study was to evaluate the influence of a preoperative conference on spine surgeons’ decision-making in the treatment of adult spinal disorders.

Summary and Background Data:

There are several factors that spine surgeons have to consider when determining a surgical plan for the treatment of spinal disorders, which include surgical approach, application of fusion or nonfusion surgery, levels to be treated, treatment of accompanying spinal conditions, the need for further preoperative imaging, and the implant type to be used.

Materials and Methods:

A consecutive series of patients with a variety of adult spinal disorders at a single spine hospital were analyzed. The imaging modalities and clinical examination history of these patients were presented at a daily preoperative conference attended by staff spine surgeons and spine surgery fellows at this spine hospital. The specific surgical plan before the preoperative conference and before the surgery were compared for each patient.

Results:

A total of 506 consecutive patients were reviewed over a 4-month period. Changes in the surgical plan following the preoperative conference occurred in 29 cases (5.7%). Seventeen of these changes were minor modifications in the same surgical level, or inclusion/exclusion of adjacent or other levels in the surgical plan, without changing the planned surgical approach. The surgical approach changed in a total of 12 cases (2.3%). Statistical analysis showed that the surgeons with experience of <10 years and orthopedic surgeons changed their surgical plan more often after the preoperative conference (P<0.05).

Conclusions:

Preoperative conference for the surgical treatment of adult spinal disorders influenced the surgical plan in 5.7% of surgeries. This type of daily preoperative conference seems to have only a minor impact on spine surgeons’ decision-making, but, instead, it could be used to provide training and insight to better a fellow or resident’s education at the spine institution.

Level of Evidence:

Level IV.
Quantifying visual allodynia across migraine subtypes: the Leiden Visual Sensitivity Scale
Authors: Perenboom Matthijs J.L. , Zamanipoor Najafabadi Amir H. , Zielman Ronald , Carpay Johannes A. , Ferrari Michel D.
Published: July 2018

Enhanced sensitivity to light (photophobia) and patterns is common in migraine and can be regarded as visual allodynia. We aimed to develop and validate a questionnaire to easily quantify sensitivity to light and patterns in large populations, and to assess and compare visual allodynia across different migraine subtypes and states. We developed the Leiden Visual Sensitivity Scale (L-VISS), a 9-item scale (score range 0-36 points), based on literature and patient interviews, and examined its construct validity. Furthermore, we assessed ictal and interictal visual sensitivity in episodic migraine with (n = 67) and without (n = 66) aura and chronic migraine with (n = 20) and without (n = 19) aura, and in healthy controls (n = 86). Differences between migraine subtypes and states were tested using a linear mixed model with 3 fixed factors (episodic/chronic, with/without aura, and ictal/interictal). Test–retest reliability and construct validity of L-VISS were good. Leiden Visual Sensitivity Scale scores correlated in the expected direction with light discomfort (Kendall's τ = −0.25) and pattern glare tests (τ = 0.35). Known-group comparisons confirmed its construct validity. Within migraine subtypes, L-VISS scores were higher in migraine with aura versus without aura and in chronic versus episodic migraine. The linear mixed model showed all factors affected the outcome (P < 0.001). The L-VISS is an easy-to-use scale to quantify and monitor the burden of bothersome visual sensitivity to light and patterns in large populations. There are remarkable ictal and interictal differences in visual allodynia across migraine subtypes, possibly reflecting dynamic differences in cortical excitability.
Strategies to Recruit the Next Generation of Nursing Leadership Talent
Authors: Martin Erik R. , Kallmeyer Robert
Published: July 2018

OBJECTIVE

The purpose of this study was to explore how generational differences contribute to challenges in recruiting the next generation of talent into nursing administration roles.

BACKGROUND

The current workforce is aging. Nursing administrative roles, which for the purpose of this study are defined as nurse managers, are increasingly difficult to fill with leaders from upcoming Generations X and Y.

METHODS

A descriptive, nonexperimental study was undertaken using a convenience sample. An electronic survey was distributed to explore the impact a set of interventions would have on recruiting into nursing administration roles. Then differences between generations were analyzed.

RESULTS

Respondents indicated 45% of the interventions have a moderate to high impact on their consideration for a position in administration. Statistical significance between generations was identified on 4 interventions related to work-life harmony.

CONCLUSIONS

Fiscally conservative interventions exist to assist hospital administrators with succession planning among nurse managers. When recruiting Generations X and Y candidates, interventions supporting work-life harmony should be emphasized.
The role of primary care in supporting patients living with and beyond cancer
Authors: Adam Rosalind , Watson Eila
Published: July 2018

Purpose of review

The prevalence of cancer survivors is increasing. Those living with and beyond a cancer diagnosis have a range of physical, psychosocial and practical needs. This review aims to discuss the role of primary care in meeting these needs.

Recent findings

Patients have increased contact with primary care after a cancer diagnosis but the role of the primary care team in the formal delivery of cancer aftercare is not clearly defined and varies depending on setting and context. Research suggests that both patients and health professionals are receptive to greater involvement of primary care, with informational and personal continuity of care, and good co-ordination of care being particularly valued by patients. Recent evidence indicates that shared care between oncologists and primary care physicians can be as effective as and more cost effective than secondary care-led follow-up, and that primary-care nurses could play a role in optimizing survivorship care.

The four pillars of primary care – contact, comprehensiveness, continuity and coordination – are recurring themes in the cancer survivorship literature and emphasize that the traditional core values of general practice lend themselves to innovative interventions to improve the efficiency and efficacy of survivorship care.
Pathophysiological mechanisms of exertional breathlessness in chronic obstructive pulmonary disease and interstitial lung disease
Authors: Jensen Dennis , Schaeffer Michele R. , Guenette Jordan A.
Published: July 2018

Purpose of review

Breathlessness is a common and distressing symptom in patients with chronic obstructive pulmonary disease (COPD) and fibrotic interstitial lung disease (ILD), particularly during exercise. Effective medical management of exertional breathlessness in people living with COPD and fibrotic ILD is challenging for healthcare providers and requires an understanding of its mechanisms. Thus, in this brief review we summarize recent advances in our understanding of the pathophysiological mechanisms of exertional breathlessness in COPD and fibrotic ILD.

Recent findings

The collective results of recent physiological and clinical trials suggest that higher intensity ratings of exertional breathlessness in both COPD and fibrotic ILD compared to healthy control individuals is mechanistically linked to the awareness of greater neural respiratory drive (quantified using inspiratory muscle electromyography) needed to compensate for pathophysiological abnormalities in respiratory mechanics and pulmonary gas exchange efficiency.

Any therapeutic intervention capable of decreasing intrinsic mechanical loading of the respiratory system and/or increasing pulmonary gas exchange efficiency has the potential to decrease the prevalence and severity of activity-related breathlessness and improve related clinical and patient-reported outcomes (e.g., exercise tolerance and health-related quality of life) by decreasing neural respiratory drive in people with COPD and fibrotic ILD.
Aquaporin-4 Serostatus and Visual Outcomes in Clinically Isolated Acute Optic Neuritis
Authors: Carnero Contentti Edgar , De Virgiliis Mariana , Hryb Javier Pablo , Gomez Alejandra , Morales Sergio , Celso Julia , Leguizamón Felisa , Chiganer Edson , Di Pace José Luis , Lessa Carmen , Perassolo Mónica
Published: July 2018

Background:

Aquaporin-4 antibodies (AQP4-Ab) are associated with neuromyelitis optica spectrum disorder (NMOSD) and typically this disorder has a poor visual prognosis as a result of optic neuritis (ON). Our aim was to report the clinical features at onset and final visual outcomes at 6 months of patients with ON who were positive for AQP4-Ab vs. those who were negative for AQP4-Ab.

Methods:

Retrospective cohort study. AQP4-Ab were tested by indirect immunofluorescence in 57 patients with a first episode of ON. All patients initially were referred for consideration of multiple sclerosis ON (MSON), NMOSD, or any other inflammatory central nervous system disorder during follow-up (41.31 ± 24.32 months). Our patients were diagnosed as having NMOSD, MSON, chronic relapsing inflammatory ON, and single isolated ON. Risk factors associated with visual outcomes of ON patients were assessed through an ordinal regression model.

Results:

Positive AQP4-Ab were associated with male sex (P = 0.02), earlier age of onset (P = 0.01), and myelitis relapses (P = 0.04). Seronegative group had fewer recurrences of ON than the seropositive group (35% vs 58%, P = 0.14). Patients that were positive for AQP4-Ab did not have worse visual acuity at baseline and after 6 months. However, poor visual acuity during first attack was associated with a worse visual acuity at 6 months (odds ratio = 2.28, 95% CI [1.58–3.28], P = 0.03).

Conclusions:

At 6 months, positive AQP4-Ab vs negative AQP4-Ab patients no evidence of poorer visual acuity. Lower visual acuity at baseline was associated with poor visual recovery at 6 months.
Two Sides of the Same Coin: The Hippocampus as a Common Neural Substrate for Model-Based Planning and Spatial Memory
Authors: Vikbladh Oliver , Meager Michael R. , King John , Blackmon Karen , Devinsky Orrin , Shohamy Daphna , Burgess Neil , Daw Nathaniel D.
Published: July 2018

Little is known about the neural mechanisms that allow humans and animals to plan actions using knowledge of task contingencies. Emerging theories hypothesize that it involves the same hippocampal mechanisms that support self-localization and memory for locations. Yet, there is limited direct evidence for the link between model-based planning and the hippocampal place map. We addressed this by investigating model-based planning and place memory in healthy controls and epilepsy patients treated using unilateral anterior temporal lobectomy with hippocampal resection. We found that both functions were impaired in the patient group. Specifically, the planning impairment was related to right hippocampal lesion size, controlling for overall lesion size. Furthermore, planning and place memory covaried with one another, but only in neurologically intact controls, consistent with both functions relying on the same structure in the healthy brain. These findings clarify the scope of hippocampal contributions to behavior and the neural mechanism of model-based planning.
The hippocampus and neocortical inhibitory engrams protect against memory interference
Authors: Koolschijn R.S. , Emir U.E. , Pantelides A.C. , Nili H. , Behrens T.E.J. , Barron H.C.
Published: July 2018

Our experiences often overlap with each other, sharing features, stimuli or higher-order information. But despite this overlap, we are able to selectively recall individual memories to guide our decisions and future actions. The neural mechanisms that support such precise memory recall, however, remain unclear. Here, using ultra-high field 7T MRI we reveal two distinct mechanisms that protect memories from interference. The first mechanism involves the hippocampus, where the BOLD signal predicts behavioural measures of memory interference, and contextual representations that aid separation of overlapping memories are organised using a relational code. The second mechanism involves neocortical inhibition: when we reduce the concentration of neocortical GABA using trans-cranial direct current stimulation (tDCS) neocortical memory interference increases in proportion to the reduction in GABA, which in turn predicts behavioural performance. Together these findings suggest that memory interference is mediated by both the hippocampus and neocortex, where the hippocampus aids separation of memories by coding context-dependent relational information, while neocortical inhibition prevents unwanted co-activation between overlapping memories.
A cell cycle-coordinated nuclear compartment for Polymerase II transcription encompasses the earliest gene expression before global genome activation
Authors: Hadzhiev Yavor , Qureshi Haseeb K. , Wheatley Lucy , Cooper Ledean , Jasiulewicz Aleksandra , Nguyen Huy Van , Wragg Joseph , Poovathumkadavil Divyasree , Conic Sascha , Bajan Sarah , Sik Attila , Hutvàgner György , Tora Làszlò , Gambus Agnieszka , Fossey John S. , Müller Ferenc
Published: July 2018

Most metazoan embryos commence development with rapid cleavages without zygotic gene expression and their genome activation is delayed until the mid-blastula transition (MBT). However, a set of genes escape global repression during the extremely fast cell cycles, which lack gap phases and their transcription is activated before the MBT. Here we describe the formation and the spatio-temporal dynamics of a distinct transcription compartment, which encompasses the earliest detectable transcription during the first wave of genome activation. Simultaneous 4D imaging of expression of pri-miR430 and zinc finger genes by a novel, native transcription imaging approach reveals a pair of shared transcription compartments regulated by homolog chromosome organisation. These nuclear compartments carry the majority of nascent RNAs and transcriptionally active Polymerase II, are depleted of compact chromatin and represent the main sites for detectable transcription before MBT. We demonstrate that transcription occurs in the S-phase of the cleavage cycles and that the gradual slowing of these cell cycles are permissive to transcription before global genome activation. We propose that the demonstrated transcription compartment is part of the regulatory architecture of nucleus organisation, and provides a transcriptionally competent, supporting environment to facilitate early escape from the general nuclear repression before global genome activation.
VarSome: The Human Genomic Variant Search Engine
Authors: Kopanos Christos , Tsiolkas Vasilis , Kouris Alexandros , Chapple Charles E. , Aguilera Monica Albarca , Meyer Richard , Massouras Andreas
Published: July 2018

VarSome.com is a search engine, aggregator and impact analysis tool for human genetic variation and a community-driven project aiming at sharing global expertise on human variants.

Availability

VarSome is freely available at http://varsome.com.
NG-meta-profiler: fast processing of metagenomes using NGLess, a domain-specific language
Authors: Coelho Luis Pedro , Alves Renato , Monteiro Paulo , Huerta-Cepas Jaime , Freitas Ana Teresa , Bork Peer
Published: July 2018

NGLess is a domain specific language for describing next-generation sequence processing pipelines. It was developed with the goal of enabling user-friendly computational reproducibility.

Using this framework, we developed NG-meta-profiler, a fast profiler for metagenomes which performs sequence preprocessing, mapping to bundled databases, filtering of the mapping results, and profiling (taxonomic and functional). It is significantly faster than either MOCAT2 or htseq-count and (as it builds on NGLess) its results are perfectly reproducible. These pipelines can easily be customized and extended with other tools.

NGLess and NG-meta-profiler are open source software (under the liberal MIT licence) and can be downloaded from http://ngless.embl.de or installed through bioconda.
High cost of bias: Diminishing marginal returns on NIH grant funding to institutions
Authors: Wahls Wayne P.
Published: July 2018

Scientific output is not a linear function of amounts of federal grant support to individual investigators. As funding per investigator increases beyond a certain point, productivity decreases. This study reports that such diminishing marginal returns also apply for National Institutes of Health (NIH) research project grant funding to institutions. Analyses of data (2006–2015) for a representative cross-section of institutions, whose amounts of funding ranged from $3 million to $440 million per year, revealed robust inverse correlations between funding (per institution, per award, per investigator) and scientific output (publication productivity and citation impact productivity). Interestingly, prestigious institutions had on average 65% higher grant application success rates and 50% larger award sizes, whereas less-prestigious institutions produced 65% more publications and had a 35% higher citation impact per dollar of funding. These findings suggest that implicit biases and social prestige mechanisms (e.g., the Matthew effect) have a powerful impact on where NIH grant dollars go and the net return on taxpayers’ investments. They support evidence-based changes in funding policy geared towards a more equitable, more diverse and more productive distribution of federal support for scientific research. Success rate/productivity metrics developed for this study provide an impartial, empirically based mechanism to do so.
PhyloPi: an affordable, purpose built phylogenetic pipeline for the HIV drug resistance testing facility
Authors: Bester Phillip A , Vries Andrie De , Riekert SJPK , Steegen Kim , Zyl Gert van , Goedhals Dominique
Published: July 2018

Phylogenetic analysis plays a crucial role in quality control in the HIV drug resistance testing laboratory. If previous patient sequence data is available sample swaps can be detected and investigated. As Antiretroviral treatment coverage is increasing in many developing countries, so is the need for HIV drug resistance testing. In countries with multiple languages, transcription errors are easily made with patient identifiers. Here a self-contained blastn integrated phylogenetic pipeline can be especially useful. Even though our pipeline can run on any unix based system, a Raspberry Pi 3 is used here as a very affordable and integrated solution.

The computational capability of this single board computer is demonstrated as well as the utility thereof in the HIV drug resistance laboratory. Benchmarking analysis against a large public database shows excellent time performance with minimal user intervention. This pipeline also contains utilities to find previous sequences as well as phylogenetic analysis and a graphical sequence mapping utility against the pol area of the HIV HXB2 reference genome. Sequence data from the Los Alamos HIV database was analyzed for inter- and intra-patient diversity and logistic regression was conducted on the calculated genetic distances. These findings show that allowable clustering and genetic distance between viral sequences from different patients is very dependent on subtype as well as the area of the viral genome being analyzed.

The Raspberry Pi image for PhyloPi, source code of the pipeline, sequence data, bash-, python- and R-scripts for the logistic regression, benchmarking as well as helper scripts are available at http://scholar.ufs.ac.za:8080/xmlui/handle/11660/7638 and https://github.com/ArmandBester/phylopi.

The PhyloPi image and the source code are published under the GPLv3 license. A demo version of the PhyloPi pipeline is available at http://phylopi.hpc.ufs.ac.za/.
Dispersal-dependent juvenile survival in a sexually dimorphic long-lived bird, the Greater FlamingoPhoenicopterus roseus
Authors: Souchay Guillaume , Barbraud Christophe , Germain Christophe , Béchet Arnaud
Published: July 2018

The viability and dynamics of spatially structured populations depend critically upon dispersal behaviour. Yet, in long lived species with delayed maturity, the fitness consequences of post-fledging dispersal, dispersal from the birthplace after independence and before first breeding attempt, are poorly understood although it is a critical determinant of natal dispersal.

We aimed at estimating sex-specific variations of juvenile survival in a long-lived bird species with sexual size dimorphism, the greater flamingo, as a function of post fledging dispersal destination. Using capture-recapture models, we estimated the survivorship of flamingos ringed in the Camargue (south of France) and wintering in the Mediterranean.

Dispersal probability from France was > 0.66 with important annual variations in preferred dispersal destinations. First-year survival increased along the winter temperature gradient with estimates below 0.50 ± 0.07 in France and above 0.60 ± 0.07 in African wetlands. The survival of flamingos wintering in France dropped by 30–50 % depending on sex between fall and spring of their first year.

In African sites and in Italy, there was no detectable difference of survival between sexes suggesting favorable wintering conditions. Body condition at fledging did not explain variations in first-fall survival within genders. Males wintering in France had a better survival than females.

These results show that sex and post-fledging dispersal destination affect juvenile survival, support theenergetichypothesis predicting an advantage of large body size to cope with cold temperatures and thecompetitionhypothesis, and suggest the existence of sex-specific post fledging dispersal tactics.
Dynamic Measurements of Bovine Serum Albumin Aggregation Using Small Angle Neutron Scattering
Authors: Austerberry James I , Belton Daniel J
Published: July 2018

The rapid and complex nature of protein aggregation makes the identification of aggregation mechanisms and their precursors challenging. Here we demonstrate the novel use of small-angle neutron scattering to perform dynamic real-time measurement and analysis of protein aggregation. Changes in bovine serum albumin monomer population and aggregate size are identified at several isothermal temperatures. Kratky plots indicate that the aggregation of BSA occurs through the partial unfolding of the monomer. Dual population modelling of the scattering data indicates that the protein nucleates and grows through a two stage mechanism; a rapid burst phase and a slower growth phase. Both stages are observed to follow Arrhenius behaviour between 70-80 °C.
Mapping In Vivo O-Glycoproteome Using Site-specific Extraction of O-linked glycopeptides (EXoO)
Authors: Yang Weiming , Ao Minghui , Hu Yingwei , Li Qing Kay , Zhang Hui
Published: July 2018

Protein glycosylation is one of the most abundant post-translational modifications. However, detailed analysis ofin vivoO-linked glycosylation, a major type of protein glycosylation, has been severely impeded by the scarcity of suitable methodologies. Here, we present a chemoenzymatic method for the site-specificextractionofO-linked glycopeptides (EXoO), which enabled the unambiguous mapping of over 3,000 O-linked glycosylation sites and definition of their glycans on over 1,000 proteins in human kidney tissues, T cells and serum. This large-scale localization of O-linked glycosylation sites nearly doubles the number of previously identified sites, demonstrating that EXoO is the most effective method to-date for defining the site-specific O-linked glycoproteome in different types of sample. Detailed structural analysis of the sites identified revealed conserved motifs and topological orientations facing extracellular space, the cell surface, the lumen of the ER and the Golgi. EXoO was also able to reveal significant differences in thein vivoO-linked glycoproteome of tumor and normal kidney tissues pointing to its broader use in clinical diagnostics and therapeutics.
Expansion of a core regulon by transposable elements promotes Arabidopsis chemical diversity and pathogen defense
Authors: Barco Brenden , Kim Yoseph , Clay Nicole K.
Published: July 2018

Plants synthesize hundreds of thousands of ecologically specialized, lineage-specific metabolites through biosynthetic gene duplication and functional specialization. However, the rewiring of duplicated genes into existing regulatory networks remains unclear. We show that the duplicated geneCYP82C2was recruited into the WRKY33 regulon and indole-3-carbonylnitrile (ICN) biosynthetic pathway through exaptation of a retroduplicated LINE retrotransposon (EPCOT3) into a novel enhancer. The stepwise development of a chromatin-accessible WRKY33-binding site onEPCOT3potentiated the regulatory neofunctionalization ofCYP82C2and the evolution of inducible defense metabolite 4-hydroxy-ICN inArabidopsis thaliana.Transposable elements (TEs) have long been recognized to have the potential to rewire regulatory networks; these results establish a more complete understanding of how duplicated genes and TEs contribute in concert to chemical diversity and pathogen defense.