bluuebunny/crossref_metadata_2025_split huggingface dataset:
Superficial femoral artery blood flow with intermittent pneumatic compression of the lower leg applied during walking exercise and recovery
Authors: Zuj Kathryn A. , Prince Chekema N. , Hughson Richard L. , Peterson Sean D. 
Published: July 2019

The purpose of this study was to determine if muscle blood flow during walking exercise and postexercise recovery can be augmented through the application of intermittent compression of the lower legs applied during the diastolic phase of the cardiac cycle. Results from four conditions were assessed: no compression (NoComp), compression during walking (ExComp), compression during postexercise recovery (RecComp), and compression applied throughout (AllComp). Superficial femoral artery (SFA) blood flow was measured (Doppler ultrasound) during rest and postexercise recovery. Mean arterial blood pressure (MAP, finger photoplethysmography) was used to calculate vascular conductance as VC = SFA flow/MAP. Near infrared spectroscopy measured changes in oxygenated (O2Hb) and deoxygenated hemoglobin concentration throughout the test. Compression during exercise increased SFA blood flow measured over the first 15 s of postexercise recovery (AllComp: 532.2 ± 123.1 mL/min; ExComp: 529.8 ± 99.2 mL/min) compared with NoComp (462.3 ± 87.3 mL/min P < 0.05) and corresponded to increased VC (NoComp: 4.7 ± 0.9 mL·min−1·mmHg−1 versus ExComp: 5.5 ± 1.0 mL·min−1·mmHg−1, P < 0.05). Similarly, compression throughout postexercise recovery also resulted in increased SFA flow (AllComp: 190.5 ± 57.1 mL/min; RecComp: 158.7 ± 49.1 mL/min versus NoComp: 108.8 ± 28.5 mL/min, P < 0.05) and vascular conductance. Muscle contractions during exercise reduced total hemoglobin with O2Hb comprising ~57% of the observed reduction. Compression during exercise augmented this reduction ( P < 0.05) with O2HB again comprising ~55% of the reduction. Total hemoglobin was reduced with compression during postexercise recovery ( P < 0.05) with O2Hb accounting for ~40% of this reduction. Results from this study indicate that intermittent compression applied during walking and during postexercise recovery enhanced vascular conductance during exercise and elevated postexercise SFA blood flow and tissue oxygenation during recovery. NEW & NOTEWORTHY Intermittent compression mimics the mechanical actions of voluntary muscle contraction on venous volume. This study demonstrates that compression applied during the diastolic phase of the cardiac cycle while walking accentuates the actions of the muscle pump resulting in increased immediate postexercise muscle blood flow and vascular conductance. Similarly, compression applied during the recovery period independently increased arterial flow and tissue oxygenation, potentially providing conditions conducive to faster recovery.
Electrical impedance tomography identifies a distinct change in regional phase angle delay pattern in ventilation filling immediately prior to a spontaneous pneumothorax
Authors: Miedema Martijn , Adler Andy , McCall Karen E. , Perkins Elizabeth J. , van Kaam Anton H. , Tingay David G. 
Published: July 2019

Pneumothoraxes are common in preterm infants and are a major cause of morbidity. Early detection and treatment of pneumothoraxes are vital to minimize further respiratory compromise. Electrical impedance tomography (EIT) has been suggested as a method of rapidly detecting pneumothoraxes at the bedside. Our objective was to define the EIT-derived regional phase angle differences in filling characteristics before and during spontaneous pneumothoraxes in preterm lambs. Preterm lambs (124–127-day gestation) were ventilated with high-frequency oscillatory ventilation for 120 min. EIT data and cardiorespiratory parameters were monitored continuously and recorded for 3 min every 15 min. Six animals spontaneously developed a pneumothorax within a gravity-nondependent quadrant of the lung and were included for this analysis. Changes in end-expiratory lung impedance (EELI), ventilation, and phase angle delay were calculated in the four lung quadrants at the onset of the pneumothorax and 15 and 30 min prior. At the onset of the pneumothorax, all animals showed a clear increase in EELI in the affected lung quadrant. Fifteen and thirty minutes before the pneumothorax there was a significant phase angle delay between the nondependent and dependent lung. At 1 min before pneumothorax this phase angle delay was isolated just to the affected quadrant (nondependent). These findings are the first description of the events within the lung at initiation of a pneumothorax, demonstrating distinct predictive changes in air-filling characteristics before the occurrence of pneumothorax. This suggests that EIT may be able to accurately identify the onset of a pneumothorax. NEW & NOTEWORTHY In this article we describe for the first time predictive changes in electrical impedance tomography-based regional filling characteristics of the lung before the onset of a one-sided pneumothorax in six preterm lambs ventilated with high-frequency oscillatory ventilation. This can give clinicians bedside information to change treatment of preterm infants and prevent pneumothorax as life-threatening event from happening.
Time course of the subjective visual vertical during sustained optokinetic and galvanic vestibular stimulation
Authors: Niehof Nynke , Perdreau Florian , Koppen Mathieu , Medendorp W. Pieter 
Published: July 2019

The brain is thought to use rotation cues from both the vestibular and optokinetic system to disambiguate the gravito-inertial force, as measured by the otoliths, into components of linear acceleration and gravity direction relative to the head. Hence, when the head is stationary and upright, an erroneous percept of tilt arises during optokinetic roll stimulation (OKS) or when an artificial canal-like signal is delivered by means of galvanic vestibular stimulation (GVS). It is still unknown how this percept is affected by the combined presence of both cues or how it develops over time. Here, we measured the time course of the subjective visual vertical (SVV), as a proxy of perceived head tilt, in human participants ( n = 16) exposed to constant-current GVS (1 and 2 mA, cathodal and anodal) and constant-velocity OKS (30°/s clockwise and counterclockwise) or their combination. In each trial, participants continuously adjusted the orientation of a visual line, which drifted randomly, to Earth vertical. We found that both GVS and OKS evoke an exponential time course of the SVV. These time courses have different amplitudes and different time constants, 4 and 7 s respectively, and combine linearly when the two stimulations are presented together. We discuss these results in the framework of observer theory and Bayesian state estimation. NEW & NOTEWORTHY While it is known that both roll optokinetic stimuli and galvanic vestibular stimulation affect the percept of vertical, how their effects combine and develop over time is still unclear. Here we show that both effects combined linearly but are characterized by different time constants, which we discuss from a probabilistic perspective.
Sensory and decisional components of endogenous attention are dissociable
Authors: Banerjee Sanjna , Grover Shrey , Ganesh Suhas , Sridharan Devarajan 
Published: July 2019

Endogenous cueing of attention enhances sensory processing of the attended stimulus (perceptual sensitivity) and prioritizes information from the attended location for guiding behavioral decisions (spatial choice bias). Here, we test whether sensitivity and bias effects of endogenous spatial attention are under the control of common or distinct mechanisms. Human observers performed a multialternative visuospatial attention task with probabilistic spatial cues. Observers’ behavioral choices were analyzed with a recently developed multidimensional signal detection model (the m-ADC model). The model effectively decoupled the effects of spatial cueing on sensitivity from those on spatial bias and revealed striking dissociations between them. Sensitivity was highest at the cued location and not significantly different among uncued locations, suggesting a spotlight-like allocation of sensory resources at the cued location. On the other hand, bias varied systematically with cue validity, suggesting a graded allocation of decisional priority across locations. Cueing-induced modulations of sensitivity and bias were uncorrelated within and across subjects. Bias, but not sensitivity, correlated with key metrics of prioritized decision-making, including reaction times and decision optimality indices. In addition, we developed a novel metric, differential risk curvature, for distinguishing bias effects of attention from those of signal expectation. Differential risk curvature correlated selectively with m-ADC model estimates of bias but not with estimates of sensitivity. Our results reveal dissociable effects of endogenous attention on perceptual sensitivity and choice bias in a multialternative choice task and motivate the search for the distinct neural correlates of each. NEW & NOTEWORTHY Attention is often studied as a unitary phenomenon. Yet, attention can both enhance the perception of important stimuli (sensitivity) and prioritize such stimuli for decision-making (bias). Employing a multialternative spatial attention task with probabilistic cueing, we show that attention affects sensitivity and bias through dissociable mechanisms. Specifically, the effects on sensitivity alone match the notion of an attentional “spotlight.” Our behavioral model enables quantifying component processes of attention, and identifying their respective neural correlates.
Cycle-by-cycle analysis of neural oscillations
Authors: Cole Scott , Voytek Bradley 
Published: July 2019

Neural oscillations are widely studied using methods based on the Fourier transform, which models data as sums of sinusoids. This has successfully uncovered numerous links between oscillations and cognition or disease. However, neural data are nonsinusoidal, and these nonsinusoidal features are increasingly linked to a variety of behavioral and cognitive states, pathophysiology, and underlying neuronal circuit properties. We present a new analysis framework, one that is complementary to existing Fourier and Hilbert transform-based approaches, that quantifies oscillatory features in the time domain on a cycle-by-cycle basis. We have released this cycle-by-cycle analysis suite as “bycycle,” a fully documented, open-source Python package with detailed tutorials and troubleshooting cases. This approach performs tests to assess whether an oscillation is present at any given moment and, if so, quantifies each oscillatory cycle by its amplitude, period, and waveform symmetry, the latter of which is missed with the use of conventional approaches. In a series of simulated event-related studies, we show how conventional Fourier and Hilbert transform approaches can conflate event-related changes in oscillation burst duration as increased oscillatory amplitude and as a change in the oscillation frequency, even though those features were unchanged in simulation. Our approach avoids these errors. Furthermore, we validate this approach in simulation and against experimental recordings of patients with Parkinson’s disease, who are known to have nonsinusoidal beta (12–30 Hz) oscillations. NEW & NOTEWORTHY We introduce a fully documented, open-source Python package, bycycle, for analyzing neural oscillations on a cycle-by-cycle basis. This approach is complementary to traditional Fourier and Hilbert transform-based approaches but avoids specific pitfalls. First, bycycle confirms an oscillation is present, to avoid analyzing aperiodic, nonoscillatory data as oscillations. Next, it quantifies nonsinusoidal aspects of oscillations, increasingly linked to neural circuit physiology, behavioral states, and diseases. This approach is tested against simulated and real data.
A novel EEG paradigm to simultaneously and rapidly assess the functioning of auditory and visual pathways
Authors: Backer Kristina C. , Kessler Andrew S. , Lawyer Laurel A. , Corina David P. , Miller Lee M. 
Published: July 2019

Objective assessment of the sensory pathways is crucial for understanding their development across the life span and how they may be affected by neurodevelopmental disorders (e.g., autism spectrum) and neurological pathologies (e.g., stroke, multiple sclerosis, etc.). Quick and passive measurements, for example, using electroencephalography (EEG), are especially important when working with infants and young children and with patient populations having communication deficits (e.g., aphasia). However, many EEG paradigms are limited to measuring activity from one sensory domain at a time, may be time consuming, and target only a subset of possible responses from that particular sensory domain (e.g., only auditory brainstem responses or only auditory P1-N1-P2 evoked potentials). Thus we developed a new multisensory paradigm that enables simultaneous, robust, and rapid (6–12 min) measurements of both auditory and visual EEG activity, including auditory brainstem responses, auditory and visual evoked potentials, as well as auditory and visual steady-state responses. This novel method allows us to examine neural activity at various stations along the auditory and visual hierarchies with an ecologically valid continuous speech stimulus, while an unrelated video is playing. Both the speech stimulus and the video can be customized for any population of interest. Furthermore, by using two simultaneous visual steady-state stimulation rates, we demonstrate the ability of this paradigm to track both parafoveal and peripheral visual processing concurrently. We report results from 25 healthy young adults, which validate this new paradigm.NEW & NOTEWORTHY A novel electroencephalography paradigm enables the rapid, reliable, and noninvasive assessment of neural activity along both auditory and visual pathways concurrently. The paradigm uses an ecologically valid continuous speech stimulus for auditory evaluation and can simultaneously track visual activity to both parafoveal and peripheral visual space. This new methodology may be particularly appealing to researchers and clinicians working with infants and young children and with patient populations with limited communication abilities.
In Vivo ERK1/2 Reporter Predictively Models Response and Resistance to Combined BRAF and MEK Inhibitors in Melanoma
Authors: Sanchez Ileine M. , Purwin Timothy J. , Chervoneva Inna , Erkes Dan A. , Nguyen Mai Q. , Davies Michael A. , Nathanson Katherine L. , Kemper Kristel , Peeper Daniel S. , Aplin Andrew E. 
Published: July 2019

Abstract
Combined BRAF and MEK inhibition is a standard of care in patients with advanced BRAF-mutant melanoma, but acquired resistance remains a challenge that limits response durability. Here, we quantitated in vivo ERK1/2 activity and tumor response associated with resistance to combined BRAF and MEK inhibition in mutant BRAF xenografts. We found that ERK1/2 pathway reactivation preceded the growth of resistant tumors. Moreover, we detected a subset of cells that not only persisted throughout long-term treatment but restored ERK1/2 signaling and grew upon drug removal. Cell lines derived from combination-resistant tumors (CRT) exhibited elevated ERK1/2 phosphorylation, which were sensitive to ERK1/2 inhibition. In some CRTs, we detected a tandem duplication of the BRAF kinase domain. Monitoring ERK1/2 activity in vivo was efficacious in predicting tumor response during intermittent treatment. We observed maintained expression of the mitotic regulator, polo-like kinase 1 (Plk1), in melanoma resistant to BRAF and MEK inhibitors. Plk1 inhibition induced apoptosis in CRTs, leading to slowed growth of BRAF and MEK inhibitor–resistant tumors in vivo. These data demonstrate the utility of in vivo ERK1/2 pathway reporting as a tool to optimize clinical dosing schemes and establish suppression of Plk1 as potential salvage therapy for BRAF inhibitor and MEK inhibitor–resistant melanoma.
Anti-GPRC5D/CD3 Bispecific T-Cell–Redirecting Antibody for the Treatment of Multiple Myeloma
Authors: Kodama Tatsushi , Kochi Yu , Nakai Waka , Mizuno Hideaki , Baba Takeshi , Habu Kiyoshi , Sawada Noriaki , Tsunoda Hiroyuki , Shima Takahiro , Miyawaki Kohta , Kikushige Yoshikane , Mori Yasuo , Miyamoto Toshihiro , Maeda Takahiro , Akashi Koichi 
Published: July 2019

Abstract
Although treatment advances over recent decades have significantly improved survival of patients with multiple myeloma, there is still an unmet medical need for more effective treatments. In this study, we identified G-protein–coupled receptor family C group 5 member D (GPRC5D) expression on the surface of malignant cells involved in multiple myeloma, but except for plasma cells and B cells, not at appreciable levels on normal hematopoietic cells and bone marrow progenitors, including hematopoietic stem cells. In addition, we constructed IgG-based anti-GPRC5D/CD3 bispecific T-cell–redirecting antibodies (GPRC5D TRAB), which suppressed the tumor growth of GPRC5D-positive myeloma cells through the activation of T cells in vitro and in vivo in xenograft models. Collectively, these findings suggest that GPRC5D is an antigen specific to multiple myeloma and a potential target of TRAB therapy.
Acute Kidney Injury following Cardiac Surgery: A Clinical Model
Authors: Billings IV Frederic T. 
Published: July 2019

<b><i>Background:</i></b> Scientists use preclinical models of acute kidney injury (AKI) to decipher mechanisms and develop therapy, but translation of therapies to patients remains poor. Models that better resemble patients, including those within clinical care, should be considered. <b><i>Summary:</i></b> Mice provide many advantages to the study of human disease including an ability to dictate precise experimental conditions. To best isolate and measure phenomena, scientists reduce experimental variability – identical animals, environmental conditions, experimental exposures, and outcome assessments. This technique reduces effect size variability and increases power but dissociates these model organisms from the clinical patients they intend to represent, potentially accounting for the poor translation of findings into patient care. Clinical research, conversely, is often plagued by heterogeneous patients, heterogenous environmental factors, and heterogenous renal insults. A compromise between these 2 extremes – a model of AKI that is more similar to human disease but still provides opportunities for rigorous investigation – should be utilized. Cardiac surgery provides a clinical model for the study of AKI due to mechanism overlap it shares with other clinical conditions (improved generalizability) and characteristics that provide distinct opportunities for research. The high rate of AKI following cardiac surgery and the relative homogeneity (decreased variability) of cardiac surgery subjects, their environment, and renal insults increase power and the opportunity to make discoveries and advance care. Moreover, the elective nature of cardiac surgery provides opportunities to perform detailed baseline assessments and pretreat select patients. <b><i>Key Messages:</i></b> Models that better reflect clinical AKI are needed to decipher mechanisms and develop effective treatments. Cardiac surgery is an important clinical model form for the study of AKI.
HIV Infection and Incidence of Cardiovascular Diseases: An Analysis of a Large Healthcare Database
Authors: Alonso Alvaro , Barnes A. Elise , Guest Jodie L. , Shah Amit , Shao Iris Yuefan , Marconi Vincent 
Published: July 2019

Background

People living with
HIV
(
PLWH
) experience higher risk of myocardial infarction (
MI
) and heart failure (
HF
) compared with uninfected individuals. Risk of other cardiovascular diseases (
CVD
s) in
PLWH
has received less attention.

Methods and Results

We studied 19 798
PLWH
and 59 302 age‐ and sex‐matched uninfected individuals identified from the MarketScan Commercial and Medicare databases in the period 2009 to 2015. Incidence of
CVD
s, including
MI
,
HF
, atrial fibrillation, peripheral artery disease, stroke and any
CVD
‐related hospitalization, were identified using validated algorithms. We used adjusted Cox models to estimate hazard ratios and 95%
CI
s of
CVD
end points and performed probabilistic bias analysis to control for unmeasured confounding by race. After a mean follow‐up of 20 months, patients experienced 154
MI
s, 223
HF
, 93 stroke, 397 atrial fibrillation, 98 peripheral artery disease, and 935
CVD
hospitalizations (rates per 1000 person‐years: 1.2, 1.7, 0.7, 3.0, 0.8, and 7.1, respectively). Hazard ratios (95%
CI
) comparing
PLWH
with uninfected controls were 1.3 (0.9–1.9) for
MI
, 3.2 (2.4–4.2) for
HF
, 2.7 (1.7–4.0) for stroke, 1.2 (1.0–1.5) for atrial fibrillation, 1.1 (0.7–1.7) for peripheral artery disease, and 1.7 (1.5–2.0) for any
CVD
hospitalization. Adjustment for unmeasured confounding led to similar associations (1.2 [0.8–1.8] for
MI
, 2.8 [2.0–3.8] for
HF
, 2.3 [1.5–3.6] for stroke, 1.3 [1.0–1.7] for atrial fibrillation, 0.9 [0.5–1.4] for peripheral artery disease, and 1.6 [1.3–1.9] for
CVD
hospitalization).

Conclusions

In a large health insurance database,
PLWH
have an elevated risk of
CVD
, particularly
HF
and stroke. With the aging of the
HIV
population, developing interventions for cardiovascular health promotion and
CVD
prevention is imperative.
Windkessel Measures Derived From Pressure Waveforms Only: The Framingham Heart Study
Authors: Behnam Vira , Rong Jian , Larson Martin G. , Gotal John D. , Benjamin Emelia J. , Hamburg Naomi M. , Vasan Ramachandran S. , Mitchell Gary F. 
Published: July 2019

Background
Waveform parameters derived from pressure‐only Windkessel models are related to cardiovascular disease risk and could be useful for understanding arterial system function. However, prior reports varied in their adjustment for potential confounders.

Methods and Results

Carotid tonometry waveform data from 2539 participants (mean age 63±11 years, 58% women) of the Framingham Heart Study were used to derive Windkessel measures using pressure and assuming a linear model with fixed diastolic time constant (τ
dias
) and variable asymptotic pressure (P
inf
, median 54.5; 25th, 75th percentiles: 38.4, 64.9 mm Hg) or nonlinear model with inverse pressure‐dependent τ
dias
and fixed P
inf
(20 mm Hg). During follow‐up (median 15.1 years), 459 (18%) participants had a first cardiovascular disease event. In proportional hazards models adjusted for age, sex, total cholesterol, high‐density lipoprotein cholesterol, smoking, antihypertensive medication use, diabetes mellitus, and physician‐acquired systolic blood pressure, only the systolic time constant (τ
sys
) derived from the nonlinear model was related to risk for cardiovascular disease events (hazard ratio=0.91 per 1 SD, 95% CI=0.84–0.99,
P
=0.04). When heart rate was added to the model, τ
sys
(hazard ratio=0.92, CI=0.84–1.00,
P
=0.04) and reservoir pressure amplitude (hazard ratio=1.14, CI=1.01–1.28,
P
=0.04) were related to events. In contrast, measures derived from the linear model were not related to events in models that adjusted for risk factors including systolic blood pressure (
P
>0.31) and heart rate (
P
>0.19).

Conclusions
Our results suggest that pressure‐only Windkessel measures derived by using a nonlinear model may provide incremental risk stratification, although associations were modest and further validation is required.