bluuebunny/crossref_metadata_2025 huggingface dataset:
Investigating Multiple-Reported Bacterial Sexually Transmitted Infection Hot Spot Counties in the United States: Ordered Spatial Logistic Regression
Authors: Owusu-Edusei Kwame , Chang Brian A.
Published: November 2019

Purpose

To identify and examine the correlates of multiple bacterial sexually transmitted infection (STI) hot spot counties in the United States.

Methods

We assembled and analyzed 5 years (2008–2012) of cross-sectional STI morbidity data to identify multiple bacterial STI (chlamydia, gonorrhea, and syphilis) hot spot counties using hot spot analysis. Then, we examined the association between the multi-STI hot spots and select multiyear (2008–2012) sociodemographic factors (data obtained from the American Community Survey) using ordered spatial logistic regression analyses.

Results

Of the 2935 counties, the results indicated that 85 counties were hot spots for all 3 STIs (3-STI hot spot counties), 177 were hot spots for 2 STIs (2-STI hot spot counties), and 145 were hot spots for only 1 STI (1-STI hot spot counties). Approximately 93% (79 of 85) of the counties determined to be 3-STI hot spots were found in 4 southern states––Mississippi (n = 25), Arkansas (n = 22), Louisiana (n = 19), and Alabama (n = 13). Counties determined to be 2 STI hot spots were found in 7 southern states––Arkansas, Louisiana, Mississippi, Alabama, Georgia, and North and South Carolina had at least ten 2-STI hot spot counties each. The multi-STI hot spot classes were significantly (P< 0.05) associated with percent black (non-Hispanic), percent Hispanics, percent American Indians, population density, male-female sex ratio, percent aged 25 to 44 years, and violent crime rate.

Conclusions

This study provides information on multiple STI hot spot counties in the United States and the associated sociodemographic factors. Such information can be used to assist planning, designing, and implementing effective integrated bacterial STI prevention and control programs/interventions.
Prevalence of Risk and Protective Factors for Tick Exposure and Tick-Borne Disease Among Residents of Indiana
Authors: Omodior Oghenekaro , Kianersi Sina , Luetke Maya
Published: November 2019

Objective:

To determine the prevalence of risk and protective factors for tick exposure and tick-borne disease (TBD) based on gender and living in urban or rural areas (urbanicity) among a cross section of Indiana adults.

Methods:

Data were collected from 3003 adults (81% response rate) spread across all 92 Indiana counties. Study participants were recruited from existing online panels maintained by Qualtrics. We calculated prevalence ratio (PR) and 95% confidence interval (CI) of 8 primary outcomes for 2 different exposures: (1) gender (male/female) and (2) urbanicity.

Results:

Female participants were 10% less likely to find a tick on themselves than male participants (PR = 0.90; 95% CI, 0.74-0.99) and significantly more likely to worry about their health and safety because of ticks, whereas males avoided the outdoors less because of worry about ticks. Female participants were significantly more likely to adopt various personal protective measures, specifically because of concern for ticks. Female participants were also less likely to have been told by a health care provider that they have a TBD (PR = 0.53; 95% CI, 0.38-0.75). Rural participants were significantly more likely to report seeing a tick at their residential property (PR = 2.40; 95% CI, 2.11-2.76), report finding ticks on themselves (PR = 1.90; 95% CI, 1.68-2.23), and report finding a tick on a child at their residential property within the past 6 months than urban dwellers (PR = 1.37; 95% CI, 1.06-1.77). In addition, we found that 62% of participants have very high trust in government sources of information on TBD and tick prevention.

Conclusions:

In Indiana, the area around people's residences may constitute an important source of tick exposure for humans. Being exposed to ticks is most prevalent in those living in rural areas of Indiana. Finally, risk factors for TBD are higher among males than among females.
The Fragility of Statistically Significant Randomized Controlled Trials in Plastic Surgery
Authors: Chin Brian , Copeland Andrea , Gallo Lucas , Wakeham Scott , Coroneos Christopher J. , Walsh Michael , Thoma Achilleas , Voineskos Sophocles
Published: November 2019

Background:

The fragility index has been proposed as a metric to evaluate the robustness of statistically significant findings in randomized controlled trials. It measures the number of events that a trial result relies on to maintain statistical significance. This study examines the robustness of statistically significant results from randomized controlled trials in the plastic surgery literature.

Methods:

A systematic literature search of the 15 highest impact plastic surgery journals was conducted to identify randomized controlled trials published between 2000 and 2017 that reported a statistically significant dichotomous outcome (p < 0.05). The fragility index of each study was calculated using Fisher’s exact test. Multiple linear regression was used to determine trial characteristics associated with the fragility index.

Results:

The 90 eligible randomized controlled trials had a median sample size of 73.5 patients (25th to 75th percentile, 50 to 115) and a median of 20 events (25th to 75th percentile, 11 to 33.5) for the chosen outcome. The median fragility index was 1 (25th to 75th percentile, 0 to 4), indicating that statistical significance would be lost in half of the randomized controlled trials if a single patient had a change in event status. The fragility index was 0 in 24 of 90 (27 percent) randomized controlled trials, meaning the outcome immediately lost statistical significance on recalculation of the p value using Fisher’s exact test.

Conclusions:

The results of randomized controlled trials in plastic surgery demonstrate substantial fragility, as statistically significant results were found to hinge on a small number of events. The fragility index offers an intuitive and simple metric to complement the p value and determine the confidence in the results of randomized controlled trials.
Extrapelvic Sciatic Nerve Endometriosis, the Role of Magnetic Resonance Imaging: Case Report and Systematic Review
Authors: Lomoro Pascal , Simonetti Igino , Nanni Annalisa , Cassone Rosario , Di Pietto Francesco , Vinci Giorgia , Prevedoni Maria Sole , Romano Stefania , Sammarchi Luigi
Published: November 2019

Endometriosis (EN) is a common gynecological condition characterized by the presence of functional endometrium located outside the uterine cavity. Sciatic nerve (SN) is rarely affected by EN. Magnetic resonance imaging allows a direct visualization of the spinal and SN, and it is the modality of choice for the study of SN involvement in extrapelvic EN. We report a case of an endometrioma located in the right SN with a systematic review of the literature.
Cardiac Outpouchings
Authors: Sharma Arun , Juneja Aparna , Pandey Niraj N. , Ganga Kartik P. , Malhi Amarinder S. , Kumar Sanjeev
Published: November 2019

Cardiac outpouchings pose a diagnostic challenge when encountered in practice, as the signs, symptoms, and initial investigations, such as radiographs and electrocardiogram, are nonspecific. They may remain asymptomatic and be incidentally detected. However, a few may present with progressive shortness of breath, thromboembolic complications, arrhythmias, pressure effects, rupture, or even death. Imaging is of paramount importance in establishing an accurate diagnosis, delineating morphology and extent of the lesion along with its hemodynamic significance, planning management, and in the follow-up.
Anomalies of the Coronary Sinus and Its Tributaries
Authors: Sinha Mumun , Pandey Niraj Nirmal , Sharma Arun
Published: November 2019

Imaging of the coronary sinus and its tributaries has gained increasing significance consequent to the development of an array of electrophysiological and interventional procedures using the cardiac venous system, including ablation for arrhythmias, left ventricular pacing, and in the administration of retrograde cardioplegia. Knowledge of the normal anatomy and the possible anomalies and their clinical significance is imperative to circumvent possible complications. A number of coronary sinus (CS) anomalies, both symptomatic and asymptomatic, have been observed with the widespread use of noninvasive cross-sectional imaging for the imaging of the heart. However, it should be kept in mind that even clinically occult lesions of the CS can cause disastrous complications in specific interventions. Hence, a thorough knowledge of the expected anatomy and the possible anomalies involving the CS along with their clinical significance is imperative for the reporting radiologists and the concerned physicians. In this review, we briefly describe the relevant anatomy and embryology and describe the gamut of anomalies pertaining to the CS and its draining veins on multidetector computed tomography angiography along with their clinical importance.
Defining the surgical critical care research agenda: Results of a gaps analysis from the Critical Care Committee of the American Association for the Surgery of Trauma
Authors: Kim Dennis Y. , Lissauer Matt , Martin Niels , Brasel Karen
Published: November 2019

BACKGROUND

There has been an unprecedented increase in critical care research recently, and there is a need for an organized and systematic approach to surgical critical care research planning. The purpose of this article was to establish a surgical critical care research agenda via a systematic review of the literature and needs assessment.

METHODS

A systematic review of the literature was performed to identify high-impact critical care articles since 1999 on the basis of citation data. Using a standardized data abstraction tool, surgical representation in the literature was analyzed. A needs assessment was performed using a modified Delphi approach in three rounds to obtain consensus among members of the Critical Care Committee of the American Association for the Surgery of Trauma (n = 30) regarding research priorities in surgical critical care.

RESULTS

Of 1,019 articles screened, 645 underwent full-text review, and 276 articles were included in the final analysis. Surgical patients were identified in 177 studies (64.1%), whereas trauma patients were identified in 82 (31.7%). Key categories identified during the first round of the Delphi included end of life care, traumatic brain injury (TBI), delirium, post-intensive care syndrome (PICS), hemodynamic monitoring, and volume/fluid balance. During the second and third rounds, 10 topics were classified as high priority. The three highest ranked topics were: addressing goals of care in the acute care setting (4.44 ± 0.70); improving prognostic indicators in patients with severe TBI (4.38 ± 0.85); and interventions to mitigate PICS (4.22 ± 0.65). There was a strong positive correlation in ratings (R
s value = 0.90, p = 0.001) between rounds 2 and 3.

CONCLUSION

The results of this study highlight the recent surgical critical care research literature and may serve as a platform for future research endeavors in surgical critical care.
Startle and the StartReact Effect: Physiological Mechanisms
Authors: Carlsen Anthony N. , Maslovat Dana
Published: November 2019

It has been well documented that a prepared response can be triggered at short latency following the presentation of a loud acoustic stimulus that evokes a reflexive startle response. Different hypotheses have been proposed for this so-called “StartReact” effect, although there is still much debate surrounding the physiological mechanisms involved in the observed reduction in reaction time (RT). In this review, we outline the various neurophysiological explanations underlying the StartReact effect and summarize the data supporting, and at times opposing, each possibility. Collectively, the experimental results do not unequivocally support a single explanation and we suggest the most parsimonious mechanism may involve a hybrid framework involving a distribution of neural pathways. Specifically, we propose that multiple node networks at the cortical, brainstem, and spinal levels are involved in response preparation and initiation, and the relative contributions of these structures depends on the type of stimulus delivered and the type of movement required. This approach may lead to greater understanding of the pathways involved in response preparation, initiation, and execution for both healthy and motor disordered populations.
Berberine alleviates rotenone-induced cytotoxicity by antioxidation and activation of PI3K/Akt signaling pathway in SH-SY5Y cells
Authors: Deng Han , Jia Yi , Pan Dong , Ma ZeGang
Published: November 2019

Berberine, an isoquinoline alkaloid isolated from traditional Chinese medicine, has been widely studied for its efficacy in the treatment of neurodegenerative diseases. However, berberine-mediated neuroprotection in the pathogenesis of Parkinson’s disease is still uncertain. In this study, the effects of berberine on rotenone-induced neurotoxicity in SH-SY5Y cells were investigated. The results showed that berberine treatment significantly alleviated rotenone-induced decrease in the cell viability in SH-SY5Y cells. Further studies demonstrated that berberine suppressed the production of intracellular reactive oxygen species, restored the mitochondrial transmembrane potential, increased Bcl-2/Bax ratio, and decreased caspase-3 activation that induced by rotenone. Furthermore, berberine also restored the phosphorylation of Akt, which was downregulated by rotenone in SH-SY5Y cells. These results suggest that berberine protects rotenone-treated SH-SY5Y cells by antioxidation and activation of PI3K/Akt signaling pathway.
Altered subcortical emotional salience processing differentiates Parkinson’s patients with and without psychotic symptoms
Authors: Knolle F. , Garofalo S. , Viviani R. , Justicia A. , Ermakova A.O. , Blank H. , Williams G.B. , Arrondo G. , Ramachandra P. , Tudor-Sfetea C. , Bunzeck N. , Duezel E. , Robbins T.W. , Barker R.A. , Murray G.K.
Published: November 2019

Background

Current research does not provide a clear explanation for why some patients with Parkinson’s Disease (PD) develop psychotic symptoms. In the field of schizophrenia research the ‘aberrant salience hypothesis’ of psychosis has been influential. According to the theory, dopaminergic dysregulation leads to the inappropriate attribution of salience to otherwise irrelevant or non-informative stimuli, allowing for the formation of hallucinations and delusions. This theory has not yet been extensively investigated in the context of psychosis in PD.

Methods

We investigated salience processing in 14 PD patients with a history of psychotic symptoms, 23 PD patients without psychotic symptoms and 19 healthy controls. All patients received dopaminergic medication. We examined emotional salience using a visual oddball fMRI paradigm (Bunzeck and Düzel, 2006) that previously has been used to investigate early stages of schizophrenia spectrum psychosis, controlling for resting cerebral blood flow as assessed with arterial spin labelling fMRI.

Results

We found significant differences between patient groups in brain responses to emotional salience. PD patients with psychotic symptoms revealed senhanced brain responses in the striatum, the hippocampus and the amygdala compared to PD patients without psychotic symptoms. PD patients with psychotic symptoms also showed significant correlations between the levels of dopaminergic drugs they were taking and BOLD signalling, as well as psychotic symptom scores. Furthermore, our data provide a first indication for dysfunctional top-down processes, measured in a ‘jumping to conclusions’ bias.

Conclusion

Our study suggests that enhanced signalling in the striatum, hippocampus and amygdala together with deficient top-down cognitive regulations is associated with the development of psychotic symptoms in PD which is similar to that proposed in the ‘aberrant salience hypothesis’ of psychosis in schizophrenia.
Association Between Tuberculosis and Depression on Negative Outcomes of Tuberculosis Treatment: A Systematic Review and Meta-Analysis
Authors: Ruiz-Grosso Paulo , Cachay Rodrigo , de la Flor Adriana , Schwalb Alvaro , Ugarte-Gil Cesar
Published: November 2019

Background

Depression is a common comorbidity of tuberculosis (TB) and is associated with poor adherence to treatment of multiple disorders. We conducted a systematic review to synthesize the existing evidence on the relationship between depression and negative outcomes of TB treatment.

Methods

We systematically reviewed studies that evaluated depressive symptoms (DS) directly or indirectly through psychological distress (PD) and measured negative treatment outcomes of drug-sensitive pulmonary TB, defined as death, loss to follow-up, or non-adherence. Sources included PubMed, Global Health Library, Embase, Scopus and Web of Science from inception to August 2019.

Results

Of the 2,970 studies initially identified, eight articles were eligible for inclusion and two were used for the primary outcome meta-analysis. We found a strong association between DS and negative TB treatment outcomes (OR=4.26; CI95%:2.33-7.79; I2=0%). DS were also associated with loss to follow-up (OR=8.70; CI95%:6.50-11.64; I2=0%) and death (OR=2.85; CI95%:1.52-5.36; I2=0%). Non-adherence was not associated with DS and PD (OR=1.34; CI95%:0.70-2.72; I2=94.36) or PD alone (OR=0.92; CI95%:0.81-1.05; I2=0%).

Conclusions

DS are associated with the negative TB treatment outcomes of death and loss to follow-up. Considerable heterogeneity exists in the definition of depression and outcomes such as non-adherence across the limited number of studies on this topic.
Egocentric Sexual Networks of Men Who Have Sex with Men in the United States: Results from the ARTnet Study
Authors: Weiss Kevin M. , Goodreau Steven M. , Morris Martina , Prasad Pragati , Ramaraju Ramya , Sanchez Travis , Jenness Samuel M.
Published: November 2019

In this paper, we present an overview and descriptive results from the first egocentric network study of MSM from across the United States (U.S.): the ARTnet study. ARTnet was designed to support prevention research for human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs) that are transmitted across partnership networks. ARTnet implemented a population-based egocentric network study design that sampled egos from the target population and asked them to report on the number, attributes, and timing of their sexual partnerships. Such data provide the foundation needed for estimating and simulating stochastic network models that are used for disease projection and intervention planning. ARTnet collected data online from 2017 to 2019, with a final sample of 4904 participants who reported on 16198 sexual partnerships. The analytic aims of the study were to characterize the joint distribution of three network parameters needed for modeling: degree distributions, assortative mixing, and partnership length, with heterogeneity by partnership type (main, casual and one-time), demography, and geography. Participants had an average of 1.19 currently active partnerships (“mean degree”), which was higher for casual partnerships (0.74) than main partnerships (0.45). The mean rate of one-time partnership acquisition was 0.16 per week (8.5 partners per year). Main partnerships lasted 272.5 weeks on average, while casual partnerships lasted 133.0 weeks. There was strong but heterogenous assortative mixing by race/ethnicity for all groups. The mean absolute age difference was 9.5 years, with main partners differing by 6.3 years compared to 10.8 years for casual partners. Our analysis suggests that MSM may be at sustained risk for HIV/STI acquisition and transmission through high network degree of sexual partnerships. The ARTnet network study provides a robust and reproducible foundation for understanding the dynamics of HIV/STI epidemiology among U.S. MSM and supporting the implementation science that seeks to address persistent challenges in HIV/STI prevention.
Predictive approaches to heterogeneous treatment effects: a systematic review
Authors: Rekkas Alexandros , Paulus Jessica K. , Raman Gowri , Wong John B. , Steyerberg Ewout W. , Rijnbeek Peter R. , Kent David M. , van Klaveren David
Published: November 2019

Background

Recent evidence suggests that there is often substantial variation in the benefits and harms across a trial population. We aimed to identify regression modeling approaches that assess heterogeneity of treatment effect within a randomized clinical trial.

Methods

We performed a literature review using a broad search strategy, complemented by suggestions of a technical expert panel.

Results

The approaches are classified into 3 categories: 1) Risk-based methods (11 papers) use only prognostic factors to define patient subgroups, relying on the mathematical dependency of the absolute risk difference on baseline risk; 2) Treatment effect modeling methods (9 papers) use both prognostic factors and treatment effect modifiers to explore characteristics that interact with the effects of therapy on a relative scale. These methods couple data-driven subgroup identification with approaches to prevent overfitting, such as penalization or use of separate data sets for subgroup identification and effect estimation. 3) Optimal treatment regime methods (12 papers) focus primarily on treatment effect modifiers to classify the trial population into those who benefit from treatment and those who do not. Finally, we also identified papers which describe model evaluation methods (4 papers).

Conclusion

Three classes of approaches were identified to assess heterogeneity of treatment effect. Methodological research, including both simulations and empirical evaluations, is required to compare the available methods in different settings and to derive well-informed guidance for their application in RCT analysis.

Key messages

Heterogeneity of treatment effect refers to the non-random variation in the direction or magnitude of a treatment effect for individuals within a population.

A large number of regression-based predictive approaches to the analysis of treatment effect heterogeneity exists, which can be divided into three broad classes based on if they incorporate: prognostic factors (risk-based methods); treatment effect modifiers (optimal treatment regime methods); or both (treatment effect modeling methods).

Simulations and empirical evaluations are required to compare the available methods in different settings and to derive well-informed guidance for their application in RCT analysis.
Quality of care at safety-net hospitals and the impact on pay-for-performance reimbursement
Authors: Sarkar Reith R. , Courtney Patrick T. , Bachand Katie , Sheridan Paige , Riviere Paul , Guss Zachary D. , Lopez Christian R. , Brandel Michael G. , Banegas Matthew P. , Murphy James D.
Published: November 2019

Background

Pay-for-performance reimbursement ties hospital payments to standardized quality of care metrics. The impact of pay-for-performance reimbursement models on safety-net hospitals, which care primarily for uninsured or underinsured patients, remains poorly defined. This study evaluates how standardized quality of care metrics vary by a hospital’s safety-net status, and helps us better understand the potential impact that pay-for-performance reimbursement could have on funding of safety-net hospitals.

Methods

We identified 1,703,865 bladder, breast, cervix, colon, endometrium, gastric, lung, ovary, or rectum cancer patients treated at 1,344 hospitals diagnosed between 2004 and 2015. Safety-net burden was defined for each hospital as the percentage of uninsured or Medicaid patients cared for by that hospital. Hospitals were grouped into low-, medium-, and high-burden hospitals. We evaluated the impact of safety-net burden on concordance with 20 standardized quality of care measures, adjusting for differences in patient age, gender, stage at diagnosis, and comorbidity.

Results

Patients seen at high-burden hospitals were more likely to be young, male, black, Hispanic, and to reside in a low-income and low-educated region. High-burden hospitals had lower adherence to 13 of 20 quality measures compared to low-burden hospitals (all p<0.05). Among the 350 high-burden hospitals, the quality measures were lowest for those caring for the highest fraction of uninsured or Medicaid patients, minority serving hospitals, and those caring for less educated patients (all p<0.001).

Discussion

Cancer care at safety-net hospitals was associated with lower concordance to standardized quality of care measures. Under a pay-for-performance reimbursement model these lower quality of care scores could decrease payments to safety-net hospitals, potentially increasing health disparities for at-risk cancer patients.
Defining predatory journals and responding to the threat they pose: a modified Delphi consensus process
Authors: Cukier Samantha , Lalu Manoj M. , Bryson Gregory L. , Cobey Kelly D. , Grudniewicz Agnes , Moher David
Published: November 2019

Background

Posing as legitimate open access outlets, predatory journals and publishers threaten the integrity of academic publishing by not following publication best practices. Currently, there is no agreed upon definition of predatory journals, making it difficult for funders and academic institutions to generate practical guidance or policy to ensure their members do not publish in these channels.

Methods

We conducted a modified three-round Delphi survey of an international group of academics, funders, policy makers, journal editors, publishers and others, to generate a consensus definition of predatory journals and suggested ways the research community should respond to the problem.

Results

A total of 45 participants completed the survey on predatory journals and publishers. We reached consensus on 18 items out of a total of 33, to be included in a consensus definition of predatory journals and publishers. We came to consensus on educational outreach and policy initiatives on which to focus, including the development of a single checklist to detect predatory journals and publishers, and public funding to support research in this general area. We identified technological solutions to address the problem: a ‘one-stop-shop’ website to consolidate information on the topic and a ‘predatory journal research observatory’ to identify ongoing research and analysis about predatory journals/publishers.

Conclusions

In bringing together an international group of diverse stakeholders, we were able to use a modified Delphi process to inform the development of a definition of predatory journals and publishers. This definition will help institutions, funders and other stakeholders generate practical guidance on avoiding predatory journals and publishers.
Acute ischemic stroke alters the brain’s preference for distinct dynamic connectivity states
Authors: Bonkhoff Anna K. , Espinoza Flor A. , Gazula Harshvardhan , Vergara Victor M. , Hensel Lukas , Michely Jochen , Paul Theresa , Rehme Anne , Volz Lukas J. , Fink Gereon R. , Calhoun Vince D. , Grefkes Christian
Published: November 2019

Acute ischemic stroke disturbs healthy brain organization, prompting subsequent plasticity and reorganization to compensate for loss of specialized neural tissue and function.Staticresting-state functional magnetic resonance imaging (fMRI) studies have already furthered our understanding of cerebral reorganization by estimating stroke-induced changes in network connectivity aggregated over the duration of several minutes. In this study, we utilizeddynamicresting-state fMRI analyses to increase temporal resolution to seconds and explore transient configurations of motor network connectivity in acute stroke. To this end, we collected resting-state fMRI data of 31 acute ischemic stroke patients and 17 age-matched healthy controls. Stroke patients presented with moderate to severe hand motor deficits. By estimating dynamic connectivity within a sliding window framework, we identified three distinct connectivity configurations of motor-related networks. Motor networks were organized into three regional domains, i.e. a cortical, subcortical and cerebellar domain. Temporal connectivity patterns of stroke patients markedly diverged from those of healthy controls depending on the severity of the initial motor impairment. Moderately affected patients (n=18) spent significantly more time in a weakly connected configuration that was characterized by low levels of connectivity, both locally as well as between distant regions. In contrast, severely affected patients (n=13) showed a significant preference for transitions into a spatially segregated connectivity configuration. This configuration featured particularly high levels of local connectivity within the three regional domains as well as anti-correlated connectivity between distant networks across domains. A third connectivity configuration represented an intermediate connectivity pattern compared to the preceding two, and predominantly encompassed decreased inter-hemispheric connectivity between cortical motor networks independent of individual deficit severity. Alterations within this third configuration thus closely resembled previously reported ones originating fromstaticresting-state fMRI studies post-stroke.

In summary, acute ischemic stroke not only prompted changes in connectivity between distinct functional networks, yet also caused severe aberrations in temporal properties of large-scale network interactions depending on the individual deficit severity. These findings offer new vistas on the dynamic neural mechanisms underlying acute neurological symptoms, cortical reorganization and treatment effects in stroke patients.
The Derived-Band Envelope Following Response and its Sensitivity to Sensorineural Hearing Deficits
Authors: Keshishzadeh Sarineh , Garrett Markus , Vasilkov Viacheslav , Verhulst Sarah
Published: November 2019

The envelope following response (EFR) has been proposed as a non-invasive marker of synaptopathy in animal models. However, its amplitude is affected by the spread of basilar-membrane excitation and other coexisting sensorineural hearing deficits. This study aims to (i) improve frequency specificity of the EFR by introducing a derived-band EFR (DBEFR) technique and (ii) investigate the effect of lifetime noise exposure, age and outer-hair-cell (OHC) damage on DBEFR magnitudes. Additionally, we adopt a modelling approach to validate the frequency-specificity of the DBEFR and test how different aspects of sensorineural hearing loss affect peripheral generators. The combined analysis of simulations and experimental data proposes that the DBEFRs extracted from the [2-6]-kHz frequency band is a sensitive and frequency-specific measure of synaptopathy in humans. Individual variability in DBEFR magnitudes among listeners with normal audiograms was explained by their self-reported amount of experienced lifetime noise-exposure and corresponded to amplitude variability predicted by synaptopathy. Older listeners consistently had reduced DBEFR magnitudes in comparison to young normal-hearing listeners, in correspondence to how age-induced synaptopathy affects EFRs and compromises temporal envelope encoding. Lastly, OHC damage was also seen to affect the DBEFR magnitude, hence this marker should be combined with a sensitive marker of OHC-damage to offer a differential diagnosis of synaptopathy in listeners with impaired audiograms.
Identification of a fatty acid-sensitive interaction between mitochondrial uncoupling protein 3 and enoyl-CoA hydratase 1 in skeletal muscle
Authors: Dao Christine K. , Kenaston Alexander , Hirasaka Katsuya , Kohno Shohei , Riley Christopher , Fang Gloria , Fathe Kristin , Solmonson Ashley , Nowinski Sara M. , Pfeiffer Matthew E. , Yang Xianmei , Nikawa Takeshi , Mills Edward M.
Published: November 2019

Skeletal muscle mitochondrial fatty acid (FA) overload in response to chronic overnutrition is a prominent pathophysiological mechanism in obesity-induced metabolic disease. Increased disposal of FAs is therefore an attractive strategy for intervening in obesity and related disorders. Skeletal muscle uncoupling protein 3 (UCP3) activity is associated with increased FA oxidation and antagonizes weight gain in mice on obesogenic diets, but the mechanisms involved are not clear. Here, we show that UCP3 forms a direct, FA-stimulated, mitochondrial matrix-localized complex with the auxiliary unsaturated FA-metabolizing enzyme, Δ3,5-Δ2,4dienoyl-CoA-isomerase (ECH1). Expression studies in C2C12 myoblasts that functionally augments state 4 (uncoupled) respiration and FA oxidation in skeletal myocytes.

Mechanistic studies indicate that ECH1:UCP3 complex formation is likely stimulated by FA import into the mitochondria to enhance uncoupled respiration and unsaturated FA oxidation in mouse skeletal myocytes. In order to characterize the contribution of ECH1-dependent FA metabolism in NST, we generated an ECH1 knockout mouse and found that these mice were severely cold intolerant, despite an up-regulation of UCP3 expression in SKM. These findings illuminate a novel mechanism that links unsaturated FA metabolism with mitochondrial uncoupling and non-shivering thermogenesis in SKM.
Crowdsourcing neuroscience: inter-brain coupling during face-to-face interactions outside the laboratory
Authors: Dikker Suzanne , Michalareas Georgios , Oostrik Matthias , Serafimaki Amalia , Kahraman Hasibe Melda , Struiksma Marijn E. , Poeppel David
Published: November 2019

When we feel connected or engaged during social behavior, are our brains in fact “in sync” in a formal, quantifiable sense? Most studies addressing this question use highly controlled tasks with homogenous subject pools. In an effort to take a more naturalistic approach, we collaborated with art institutions to crowd-source neuroscience data: Over the course of 5 years, we collected electroencephalogram (EEG) data from thousands of museum and festival visitors who volunteered to engage in a 10-minute face-to-face interaction. Pairs of participants with various levels of familiarity sat inside the Mutual Wave Machine—an art/science neurofeedback installation that uses Brain-Computer Interface technology (BCI) to translate real-time correlations of each pair’s EEG activity into light patterns. Because such inter-participant EEG correlations are prone to noise contamination, in subsequent offline analyses we computed inter-brain synchrony using Imaginary Coherence and Projected Power Correlations, two synchrony metrics that are largely immune to instantaneous, noise-driven correlations. When applying these methods to two subsets of recorded data with the most consistent protocols, we found that pairs’ trait empathy, social closeness, engagement, and social behavior (joint action and eye contact) consistently predicted the extent to which their brain activity became synchronized, most prominently in low alpha (∼7-10 Hz) and beta (∼20-22 Hz) oscillations. These findings support an account where shared engagement and joint action drive coupled neural activity and behavior during dynamic, naturalistic social interactions. To our knowledge, this work constitutes a first demonstration that an interdisciplinary, real-world, crowdsourcing neuroscience approach may provide a promising method to collect large, rich datasets pertaining to real-life face-to-face interactions. Additionally, it is a demonstration of how the general public can participate and engage in the scientific process outside of the laboratory. Institutions such as museums, galleries, or any other organization where the public actively engages out of self-motivation, can help facilitate this type of citizen science research, and support the collection of large datasets under scientifically controlled experimental conditions. To further enhance the public interest for the out-of-the-lab experimental approach, the data and results of this study are disseminated through a website tailored to the general public (wp.nyu.edu/mutualwavemachine).
Timing the origin of eukaryotic cellular complexity with ancient duplications
Authors: Vosseberg Julian , van Hooff Jolien J. E. , Marcet-Houben Marina , van Vlimmeren Anne , van Wijk Leny M. , Gabaldón Toni , Snel Berend
Published: November 2019

Eukaryogenesis is one of the most enigmatic evolutionary transitions, during which simple prokaryotic cells gave rise to complex eukaryotic cells. While evolutionary intermediates are lacking, gene duplications allow us to elucidate the order of events by which eukaryotes originated. Here we use a phylogenomics approach to reconstruct successive steps during eukaryogenesis. We found that gene duplications roughly doubled the proto-eukaryotic genome, with families inherited from the Asgard archaea-related host being duplicated most. By relatively timing events using phylogenetic distances we inferred that duplications in cytoskeletal and membrane trafficking families were among the earliest events, whereas most other families expanded primarily after mitochondrial endosymbiosis. Altogether, we demonstrate that the host that engulfed the proto-mitochondrion had some eukaryote-like complexity, which further increased drastically upon mitochondrial acquisition. This scenario bridges the signs of complexity observed in Asgard archaeal genomes to the proposed role of mitochondria in triggering eukaryogenesis.
Histologic safety of transcranial focused ultrasound neuromodulation and magnetic resonance acoustic radiation force imaging in rhesus macaques and sheep
Authors: Gaur Pooja , Casey Kerriann M. , Kubanek Jan , Li Ningrui , Mohammadjavadi Morteza , Saenz Yamil , Glover Gary H. , Bouley Donna M. , Pauly Kim Butts
Published: November 2019

Background

Neuromodulation by transcranial focused ultrasound (FUS) offers the potential to non-invasively treat specific brain regions, with treatment location verified by magnetic resonance acoustic radiation force imaging (MR-ARFI).

Objective

To investigate the safety of these methods prior to widespread clinical use, we report histologic findings in two large animal models following FUS neuromodulation and MR-ARFI.

Methods

Two rhesus macaques and thirteen Dorset sheep were studied. FUS neuromodulation was targeted to the primary visual cortex in rhesus macaques and to subcortical locations, verified by MR-ARFI, in eleven sheep. Both rhesus macaques and five sheep received a single FUS session, whereas six sheep received repeated sessions three to six days apart. The remaining two control sheep did not receive ultrasound but otherwise underwent the same anesthetic and MRI procedures as the eleven experimental sheep. Hematoxylin and eosin-stained sections of brain tissue (harvested zero to eleven days following FUS) were evaluated for tissue damage at FUS and control locations as well as tissue within the path of the FUS beam. TUNEL staining was used to evaluate for the presence of apoptosis in sheep receiving high dose FUS.

Results

No FUS-related pre-mortem histologic findings were observed in the rhesus macaques or in any of the examined sheep. Extravascular red blood cells (RBCs) were present within the meninges of all sheep, regardless of treatment group. Similarly, small aggregates of perivascular RBCs were rarely noted in non-target regions of neural parenchyma of FUS-treated (8/11) and untreated (2/2) sheep. However, no concurrent histologic abnormalities were observed, consistent with RBC extravasation occurring as post-mortem artifact following brain extraction. Sheep within the high dose FUS group were TUNEL-negative at the targeted site of FUS.

Conclusions

The absence of FUS-related histologic findings suggests that the neuromodulation and MR-ARFI protocols evaluated do not cause tissue damage.
First evidence of production of the lantibiotic nisin P
Authors: Garcia-Gutierrez Enriqueta , O’Connor Paula M. , Saalbach Gerhard , Walsh Calum J. , Hegarty James W. , Guinane Caitriona M. , Mayer Melinda J. , Narbad Arjan , Cotter Paul D.
Published: November 2019

Nisin P is a natural nisin variant, the genetic determinants for which were previously identified in the genomes of twoStreptococcusspecies, albeit with no confirmed evidence of production. Here we describeStreptococcus agalactiaeDPC7040, a human fecal isolate, which exhibits antimicrobial activity against a panel of gut and food isolates by virtue of producing nisin P. Nisin P was purified, and its predicted structure was confirmed by nanoLC-MS/MS, with both the fully modified peptide and a variant without rings B and E being identified. Additionally, we compared its spectrum of inhibition and minimum inhibitory concentration (MIC) with that of nisin A and its antimicrobial effect in a fecal fermentation in comparison with nisin A and H. We found that its antimicrobial activity was less potent than nisin A and H, and we propose a link between this reduced activity and the peptide structure.
Relating the strength of density dependence and the spatial distribution of individuals
Authors: Brush Micah , Harte John
Published: November 2019

Spatial patterns in ecology contain useful information about underlying mechanisms and processes. Although there are many summary statistics used to quantify these spatial patterns, there are far fewer models that directly link explicit ecological mechanisms to observed patterns easily derived from available data. We present a model of intraspecific spatial aggregation that quantitatively relates static spatial patterning to negative density dependence. Individuals are placed according to the colonization rule consistent with the Maximum Entropy Theory of Ecology (METE), and die with probability proportional to their abundance raised to a powerα, a parameter indicating the degree of density dependence. Our model shows quantitatively and generally that increasing density dependence randomizes spatial patterning.α= 1 recovers the strongly aggregated METE distribution that is consistent with many ecosystems empirically, and asα →2 our prediction approaches the binomial distribution consistent with random placement. In between our model predicts less aggregation than METE, but more than random placement. We additionally relate our mechanistic parameterαto the statistical aggregation parameterkin the negative binomial distribution, giving it an ecological interpretation in the context of density dependence. We use our model to analyze two contrasting datasets, a 50 ha tropical forest and a 64 m2serpentine grassland plot. For each dataset, we inferαfor individual species as well as a communityαparameter. We find thatαis generally larger in the tightly packed forest than the sparse grassland, and the degree of density dependence increases at smaller scales. These results are consistent with current understanding in both ecosystems, and we infer this underlying density dependence using only empirical spatial patterns. Our model can easily be applied to other datasets where spatially explicit data are available.
Resolvin D-series regulates Phospholipase D both during inflammation and resolution by modulating phagocyte functions
Authors: Ganesan Ramya , Henkels Karen M. , Shah Krushangi , de la Rosa Xavier , Libreros Stephania , Cheemarla Nagarjuna R , Serhan Charles N. , Gomez-Cambronero Julian
Published: November 2019

A successful acute inflammatory response results in the elimination of infectious agents by neutrophils and monocytes, followed by resolution and repair by tissue-resident and recruited macrophages. D-series resolvins are pro-resolving mediators involved in resolution and tissue repair, their intracellular signaling mechanism(s) are of interest. Here, we report that D-series resolvins activate phospholipase D (PLD), a ubiquitously expressed membrane lipase in modulating phagocyte functions. The mechanism for PLD-mediated actions of RvD5 in polarizing macrophages (M1-M2) was found to be two-pronged: (a) RvD5 inhibits post-transcriptional modifications, by miRs and 3’exonulceases that process PLD2 mRNA, thus increasing PLD2 expression and activity; (b) RvD5 enhances PLD2-S6K signaling and Actin expression required for membrane expansion and efferocytosis. In addition, investigating RvD5’s actions in second organ reflow injury, we found that RvD5 did not reduce lung neutrophil myeloperoxidase levels in PLD2-/- mice compared to WT and PLD1-/- mice, pointing to a unique role of PLD2 as the relevant isoform in RvD5-mediated resolution. These results demonstrate that RvD5-PLD2 are attractive targets for therapeutic interventions in vascular inflammation such as I/R injury and cardiovascular diseases.
Measuring three-dimensional dynamics of platelet activation using 3-D quantitative phase imaging
Authors: Lee SangYun , Jang Seongsoo , Park YongKeun
Published: November 2019

Platelets, or thrombocytes, are anucleated tiny blood cells with an indispensable contribution to the hemostatic properties of whole blood, detecting injured sites at the surface of blood vessels and forming blood clots. Here, we quantitatively and non-invasively investigated the morphological and biochemical alterations of individual platelets during activation in the absence of exogenous agents by employing 3-D quantitative phase imaging (QPI). By reconstructing 3-D refractive index (RI) tomograms of individual platelets, we investigated alterations in platelet activation before and after the administration of various platelet agonists. Our results showed that while the integrity of collagen-stimulated platelets was preserved despite the existence of a few degranulated platelets with developed pseudopods, platelets stimulated by thrombin or thrombin receptor-activating peptide (TRAP) exhibited significantly lower cellular concentration and dry mass than did resting platelets. Our work provides a means to systematically investigate drug-respondents of individual platelets in a label-free and quantitative manner, and open a new avenue to the study of the activation of platelets.

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