bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morning exercise mitigates the impact of prolonged sitting on cerebral blood flow in older adults
Authors: Wheeler Michael J. , Dunstan David W. , Smith Brianne , Smith Kurt J. , Scheer Anna , Lewis Jaye , Naylor Louise H. , Heinonen Ilkka , Ellis Kathryn A. , Cerin Ester , Ainslie Philip N. , Green Daniel J. 
Published: February 2019

Preventing declines in cerebral blood flow is important for maintaining optimal brain health with aging. We compared the effects of a morning bout of moderate-intensity exercise, with and without subsequent light-intensity walking breaks from sitting, on cerebral blood velocity over 8 h in older adults. In a randomized crossover trial, overweight/obese older adults ( n = 12, 70 ± 7 yr; 30.4 ± 4.3 kg/m2), completed three acute conditions (6-day washout); SIT: prolonged sitting (8 h, control); EX+SIT: sitting (1 h), moderate-intensity walking (30 min), followed by uninterrupted sitting (6.5 h); and EX + BR: sitting (1 h), moderate-intensity walking (30 min), followed by sitting (6.5 h) interrupted with 3 min of light-intensity walking every 30 min. Bilateral middle cerebral artery velocities (MCAv) were determined using transcranial Doppler at 13 time points across the day. The temporal pattern and average MCAv over 8 h was determined. The pattern of MCAv over 8 h was a negative linear trend in SIT ( P < 0.001), but a positive quadratic trend in EX + SIT ( P < 0.001) and EX + BR ( P < 0.01). Afternoon time points in SIT were lower than baseline within condition ( P ≤ 0.001 for all). A morning dip in MCAv was observed in EX + SIT and EX + BR ( P < 0.05 relative to baseline), but afternoon time points were not significantly lower than baseline. The average MCAv over 8 h was higher in EX + SIT than SIT ( P = 0.007) or EX + BR ( P = 0.024). Uninterrupted sitting should be avoided, and moderate-intensity exercise should be encouraged for the daily maintenance of cerebral blood flow in older adults. The clinical implications of maintaining adequate cerebral blood flow include the delivery of vital oxygen and nutrients to the brain. NEW & NOTEWORTHY This is the first study to measure the combined effects of an exercise bout with breaks in sitting on cerebral blood velocity in older adults. Using frequent recordings over an 8-h period, we have performed a novel analysis of the pattern of cerebral blood velocity, adjusting for concurrent measures of mean arterial pressure and other potential confounders in a linear mixed effects regression.
Diaphragm shear modulus reflects transdiaphragmatic pressure during isovolumetric inspiratory efforts and ventilation against inspiratory loading
Authors: Bachasson Damien , Dres Martin , Niérat Marie-Cécile , Gennisson Jean-Luc , Hogrel Jean-Yves , Doorduin Jonne , Similowski Thomas 
Published: February 2019

The reference method for the assessment of diaphragm function relies on the measurement of transdiaphragmatic pressure (Pdi). Local muscle stiffness measured using ultrafast shear wave elastography (SWE) provides reliable estimates of muscle force in locomotor muscles. This study aimed at investigating whether SWE could be used as a surrogate of Pdi to evaluate diaphragm function. Fifteen healthy volunteers underwent a randomized stepwise inspiratory loading protocol of 0–60% of maximal isovolumetric inspiratory pressure during closed-airways maneuvers and 0–50% during ventilation against an external inspiratory threshold load. During all tasks, Pdi was measured and SWE was used to assess shear modulus of the right hemidiaphragm (SMdi) at the zone of apposition. Pearson correlation coefficients ( r) and repeated-measures correlation coefficients ( R) were computed to determine within-individual and overall relationships between Pdi and SMdi, respectively. During closed-airways maneuvers, mean Pdi correlated to mean SMdi in all participants [ r ranged from 0.77 to 0.96, all P < 0.01; R = 0.82, 95% confidence intervals (0.76, 0.86), P < 0.01]. During ventilation against inspiratory threshold loading, Pdi swing correlated to maximal SMdi in all participants [ r ranged from 0.40 to 0.90, all P < 0.01; R = 0.70, 95% confidence intervals (0.66, 0.73), P < 0.001]. Changes in diaphragm stiffness as assessed by SWE reflect changes in transdiaphragmatic pressure. SWE provides a new opportunity for direct and noninvasive assessment of diaphragm function.NEW & NOTEWORTHY Accurate and specific estimation of diaphragm effort is critical for evaluating and monitoring diaphragm dysfunction. The measurement of transdiaphragmatic pressure requires the use of invasive gastric and esophageal probes. In the present work, we demonstrate that changes in diaphragm stiffness assessed with ultrasound shear wave elastography reflect changes in transdiaphragmatic pressure, therefore offering a new noninvasive method for gauging diaphragm effort.
Nasal high flow reduces minute ventilation during sleep through a decrease of carbon dioxide rebreathing
Authors: Pinkham Maximilian , Burgess Russel , Mündel Toby , Tatkov Stanislav 
Published: February 2019

Nasal high flow (NHF) is an emerging therapy for respiratory support, but knowledge of the mechanisms and applications is limited. It was previously observed that NHF reduces the tidal volume but does not affect the respiratory rate during sleep. The authors hypothesized that the decrease in tidal volume during NHF is due to a reduction in carbon dioxide (CO2) rebreathing from dead space. In nine healthy males, ventilation was measured during sleep using calibrated respiratory inductance plethysmography (RIP). Carbogen gas mixture was entrained into 30 l/min of NHF to obtain three levels of inspired CO2: 0.04% (room air), 1%, and 3%. NHF with room air reduced tidal volume by 81 ml, SD 25 ( P < 0.0001) from a baseline of 415 ml, SD 114, but did not change respiratory rate; tissue CO2and O2remained stable, indicating that gas exchange had been maintained. CO2entrainment increased tidal volume close to baseline with 1% CO2and greater than baseline with 3% CO2by 155 ml, SD 79 ( P = 0.0004), without affecting the respiratory rate. It was calculated that 30 l/min of NHF reduced the rebreathing of CO2from anatomical dead space by 45%, which is equivalent to the 20% reduction in tidal volume that was observed. The study proves that the reduction in tidal volume in response to NHF during sleep is due to the reduced rebreathing of CO2. Entrainment of CO2into the NHF can be used to control ventilation during sleep.NEW & NOTEWORTHY The findings in healthy volunteers during sleep show that nasal high flow (NHF) with a rate of 30 l/min reduces the rebreathing of CO2from anatomical dead space by 45%, resulting in a reduced minute ventilation, while gas exchange is maintained. Entrainment of CO2into the NHF can be used to control ventilation during sleep.
Examining Urban and Rural Differences in How Distance to Care Influences the Initiation and Completion of Treatment among Insured Cervical Cancer Patients
Authors: Spees Lisa P. , Brewster Wendy R. , Varia Mahesh A. , Weinberger Morris , Baggett Christopher , Zhou Xi , Petermann Victoria M. , Wheeler Stephanie B. 
Published: February 2019

Abstract

Background:
Although rural cancer patients encounter substantial barriers to care, they more often report receiving timely care than urban patients. We examined whether geographic distance, a contributor to urban–rural health disparities, differentially influences treatment initiation and completion among insured urban and rural cervical cancer patients.

Methods:
We identified women diagnosed with cervical cancer from 2004 to 2013 from a statewide cancer registry linked to multipayer, insurance claims. Primary outcomes were initiation of guideline-concordant care within 6 weeks of diagnosis and, among stage IB2-IVA cancer patients, completion of concurrent chemoradiotherapy (CCRT) in 56 days. We estimated risk ratios using modified Poisson regressions, stratified by urban/rural status, to examine the association between distance and treatment timing (initiation or completion).

Results:
Among 999 stage IA-IVA patients, 48% initiated guideline-concordant care within 6 weeks of diagnosis, and 37% of 492 stage IB2-IVA cancer patients completed CCRT in 56 days. In urban areas, stage IA-IVA patients who lived ≥15 miles from the nearest treatment facility were less likely to initiate timely treatment compared with those &lt;5 miles [risk ratio (RR): 0.72; 95% confidence intervals (CI), 0.54–0.95]. Among IB2-IVA stage cancer patients, rural women residing ≥15 miles from the nearest radiation facility were more likely to complete CCRT in 56 days (RR: 2.49; 95% CI, 1.12–5.51).

Conclusions:
Geographic distance differentially influences the initiation and completion of treatment among urban and rural cervical cancer patients.

Impact:
Distance was an access barrier for insured cervical cancer patients in urban areas whereas rural patients may require more intensive outreach, support, and resources, even among those living closer to treatment.
Alpha Particle Radium 223 Dichloride in High-risk Osteosarcoma: A Phase I Dose Escalation Trial
Authors: Subbiah Vivek , Anderson Pete M. , Kairemo Kalevi , Hess Kenneth , Huh Winston W. , Ravi Vinod , Daw Najat C. , Somaiah Neeta , Ludwig Joseph A. , Benjamin Robert S. , Chawla Sant , Hong David S. , Meric-Bernstam Funda , Ravizzini Gregory , Kleinerman Eugenie , Macapinlac Homer , Rohren Eric 
Published: February 2019

Abstract

Purpose:
The prognosis of metastatic osteosarcoma continues to be poor. We hypothesized that alpha-emitting, bone-targeting radium 223 dichloride (223RaCl2) can be safely administered to patients with osteosarcoma and that early signals of response or resistance can be assessed by quantitative and qualitative correlative imaging studies and biomarkers.

Patients and Methods:
A 3+3 phase I, dose-escalation trial of 223RaCl2 (50, 75, and 100 kBq/kg) was designed in patients with recurrent/metastatic osteosarcoma aged ≥15 years. Objective measurements included changes in standardized uptake values of positron emission tomography (PET; 18FDG and/or NaF-18) and single-photon emission CT/CT (99mTc-MDP) as well as alkaline phosphatase and bone turnover markers at baseline, midstudy, and the end of the study.

Results:
Among 18 patients enrolled (including 15 males) aged 15–71 years, tumor locations included spine (n = 12, 67%), pelvis (n = 10, 56%), ribs (n = 9, 50%), extremity (n = 7, 39%), and skull (n = 2, 11%). Patients received 1–6 cycles of 223RaCl2; cumulative doses were 6.84-57.81 MBq. NaF PET revealed more sites of metastases than did FDG PET. One patient showed a metabolic response on FDG PET and NaF PET. Four patients had mixed responses, and one patient had a response in a brain metastasis. Bronchopulmonary hemorrhage from Grade 3 thrombocytopenia (N = 1) was a DLT. The median overall survival time was 25 weeks.

Conclusions:
The first evaluation of the safety and efficacy of an alpha particle in high-risk osteosarcoma shows that the recommended phase II dose for 223RaCl2 in osteosarcoma is 100 kBq/kg monthly (twice the dose approved for prostate cancer), with minimal hematologic toxicity, setting the stage for combination therapies.
Impact of Surgical Approach on Patient-Reported Outcomes after Radical Prostatectomy: A Propensity Score-Weighted Analysis from a Multicenter, Prospective, Observational Study (The Pros-IT CNR Study)
Authors: Antonelli Alessandro , Palumbo Carlotta , Noale Marianna , Porreca Angelo , Maggi Stefania , Simeone Claudio , Bassi Pierfrancesco , Bertoni Filippo , Bracarda Sergio , Buglione Michela , Conti Giario Natale , Corvò Renzo , Gacci Mauro , Mirone Vincenzo , Montironi Rodolfo , Triggiani Luca , Tubaro Andrea , Artibani Walter ,   Pros-IT CNR study group
Published: February 2019

<b><i>Background:</i></b> To report health-related quality of life outcomes as assessed by validated patient-reported outcome measures (PROMs) after radical prostatectomy (RP). ­<b><i>Methods:</i></b> This study analyzed patients treated with RP within The PROState cancer monitoring in Italy, from the National Research Council (Pros-IT CNR). Italian versions of Short-Form Heath Survey and university of California los Angeles-prostate cancer index questionnaires were administered. PROMs were physical composite scores, mental composite scores and urinary, bowel, sexual functions and bothers (UF/B, BF/B, SF/B). Baseline unbalances were controlled with propensity scores and stabilized inverse weights; differences in PROMs between different RP approaches were estimated by mixed models. <b><i>Results:</i></b> Of 541 patients treated with RP, 115 (21%) received open RP (ORP), 90 (17%) laparoscopic RP (LRP) and 336 (61%) robot-assisted RP (RARP). At head-to-head ­comparisons, RARP showed higher 12-month UF vs. LRP (interaction treatment * time <i>p</i> = 0.03) and 6-month SF vs. ORP (<i>p</i> &#x3c; 0.001). At 12-month from surgery, 67, 73 and 79% of patients used no pad for urinary loss in ORP, LRP and RARP respectively (no differences for each comparison). Conversely, 16, 27 and 40% of patients declared erections firm enough for sexual intercourse in ORP, LRP and RARP respectively (only significant difference for ORP vs. RARP, <i>p</i> = 0.0004). <b><i>Conclusions:</i></b> Different RP approaches lead to significant variations in urinary and sexual PROMs, with a general trend in favour of RARP. However, their clinical significance seems limited.
Selective Inhibition of PAR4 (Protease-Activated Receptor 4)-Mediated Platelet Activation by a Synthetic Nonanticoagulant Heparin Analog
Authors: Lin Yu-Chuan , Ko Yen-Chun , Hung Shang-Cheng , Lin Ying-Ting , Lee Jia-Hau , Tsai Ju-Ying , Kung Po-Hsiung , Tsai Meng-Chun , Chen Yih-Fung , Wu Chin-Chung 
Published: February 2019

Objective—
PAR4 (protease-activated receptor 4), one of the thrombin receptors in human platelets, has emerged as a promising target for the treatment of arterial thrombotic disease. Previous studies implied that thrombin exosite II, known as a binding site for heparin, may be involved in thrombin-induced PAR4 activation. In the present study, a heparin octasaccharide analog containing the thrombin exosite II–binding domain of heparin was chemically synthesized and investigated for anti-PAR4 effect.

Approach and Results—
PAR4-mediated platelet aggregation was examined using either thrombin in the presence of a PAR1 antagonist or γ-thrombin, which selectively activates PAR4. SCH-28 specifically inhibits PAR4-mediated platelet aggregation, as well as the signaling events downstream of PAR4 in response to thrombin. Moreover, SCH-28 prevents thrombin-induced β-arrestin recruitment to PAR4 but not PAR1 in Chinese Hamster Ovary-K1 cells using a commercial enzymatic complementation assay. Compared with heparin, SCH-28 is more potent in inhibiting PAR4-mediated platelet aggregation but has no significant anticoagulant activity. In an in vitro thrombosis model, SCH-28 reduces thrombus formation under whole blood arterial flow conditions.

Conclusions—
SCH-28, a synthetic small-molecular and nonanticoagulant heparin analog, inhibits thrombin-induced PAR4 activation by interfering with thrombin exosite II, a mechanism of action distinct from other PAR4 inhibitors that target the receptor. The characteristics of SCH-28 provide a new strategy for targeting PAR4 with the potential for the treatment of arterial thrombosis.
Dissociating nNOS (Neuronal NO Synthase)-CAPON (Carboxy-Terminal Postsynaptic Density-95/Discs Large/Zona Occludens-1 Ligand of nNOS) Interaction Promotes Functional Recovery After Stroke via Enhanced Structural Neuroplasticity
Authors: Ni Huan-Yu , Song Yi-Xuan , Lin Yu-Hui , Cao Bo , Wang Dong-Liang , Zhang Yu , Dong Jian , Liang Hai-Ying , Xu Ke , Li Ting-You , Chang Lei , Wu Hai-Yin , Luo Chun-Xia , Zhu Dong-Ya 
Published: February 2019

Background and Purpose—
Stroke is a major public health concern worldwide. Although clinical treatments have improved in the acute period after stroke, long-term therapeutics remain limited to physical rehabilitation in the delayed phase. This study is aimed to determine whether nNOS (neuronal NO synthase)-CAPON (carboxy-terminal postsynaptic density-95/discs large/zona occludens-1 ligand of nNOS) interaction may serve as a new therapeutic target in the delayed phase for stroke recovery.

Methods—
Photothrombotic stroke and transient middle cerebral artery occlusion were induced in mice. Adeno-associated virus (AAV)-cytomegalovirus (CMV)-CAPON-125C-GFP (green fluorescent protein)-3Flag and the other 2 drugs (Tat-CAPON-12C and ZLc-002) were microinjected into the peri-infarct cortex immediately and 4 to 10 days after photothrombotic stroke, respectively. ZLc-002 was also systemically injected 4 to 10 days after transient middle cerebral artery occlusion. Grid-walking task and cylinder task were conducted to assess motor function. Western blotting, immunohistochemistry, Golgi staining, and electrophysiology recordings were performed to uncover the mechanisms.

Results—
Stroke increased nNOS-CAPON association in the peri-infarct cortex in the delayed period. Inhibiting the ischemia-induced nNOS-CAPON association substantially decreased the number of foot faults in the grid-walking task and forelimb asymmetry in the cylinder task, suggesting the promotion of functional recovery from stroke. Moreover, dissociating nNOS-CAPON significantly facilitated dendritic remodeling and synaptic transmission, indicated by increased dendritic spine density, dendritic branching, and length and miniature excitatory postsynaptic current frequency but did not affect stroke-elicited neuronal loss, infarct size, or cerebral edema, suggesting that nNOS-CAPON interaction may function via regulating structural neuroplasticity, rather than neuroprotection. Furthermore, ZLc-002 reversed the transient middle cerebral artery occlusion–induced impairment of motor function.

Conclusions—
Our results reveal that nNOS-CAPON coupling can serve as a novel pharmacological target for functional restoration after stroke.
Evaluating Simulated Microphysics during OLYMPEX Using GPM Satellite Observations
Authors: Conrick Robert , Mass Clifford F. 
Published: February 2019

Abstract
This study evaluates moist physics in the Weather Research and Forecasting (WRF) Model using observations collected during the Olympic Mountains Experiment (OLYMPEX) field campaign by the Global Precipitation Measurement (GPM) satellite, including data from the GPM Microwave Imager (GMI) and Dual-Frequency Precipitation Radar (DPR) instruments. Even though WRF using Thompson et al. microphysics was able to realistically simulate water vapor concentrations approaching the barrier, there was underprediction of cloud water content and rain rates offshore and over western slopes of terrain. We showed that underprediction of rain rate occurred when cloud water was underpredicted, establishing a connection between cloud water and rain-rate deficits. Evaluations of vertical hydrometeor mixing ratio profiles indicated that WRF produced too little cloud water and rainwater content, particularly below 2.5 km, with excessive snow above this altitude. Simulated mixing ratio profiles were less influenced by coastal proximity or midlatitude storm sector than were GMI profiles. Evaluations of different synoptic storm sectors suggested that postfrontal storm sectors were simulated most realistically, while warm sectors had the largest errors. DPR observations confirm the underprediction of rain rates noted by GMI, with no dependence on whether rain occurs over land or water. Finally, WRF underpredicted radar reflectivity below 2 km and overpredicted above 2 km, consistent with GMI vertical mixing ratio profiles.
Future Changes in Monthly Extreme Precipitation in Japan Using Large-Ensemble Regional Climate Simulations
Authors: Hatsuzuka Daisuke , Sato Tomonori 
Published: February 2019

AbstractThis study investigated future changes in monthly extreme precipitation in Japan during summer (June–August). The uncertainties in estimating extreme monthly precipitation were analyzed using large-ensemble regional climate simulations for both present and 4-K warmer climates. The main diagnostics were based on the 100-yr return values of monthly total precipitation PT100 estimated from a best-fit probability distribution. Under the warmer climate, PT100 was projected to increase in approximately 87%, 88%, and 78% of the total number of stations for June, July, and August, respectively, suggesting that once-per-century monthly precipitation will increase as temperature increases over a wide area of Japan, although large regional variations will exist. The western part of Kyushu and the Hokkaido region showed significant and moderately robust increases in PT100 throughout the summer months. In contrast, a considerable and robust increase was projected only in June in the Nansei Islands. The percentage change in PT100 was small in western and eastern Japan, and thus the sign of the change was uncertain. Further analysis indicated that uncertainty in internal variability is more important than uncertainty in the SST scenario for future projections of monthly precipitation extremes.
Evaluation of Low-Cost, Automated Lake Ice Thickness Measurements
Authors: Reed David E. , Desai Ankur R. , Whitaker Emily C. , Nuckles Henry 
Published: February 2019

AbstractClimate change is expected to decrease ice coverage and thickness globally while increasing the variability of ice coverage and thickness on midlatitude lakes. Ice thickness affects physical, biological, and chemical processes as well as safety conditions for scientists and the general public. Measurements of ice thickness that are both temporally frequent and spatially extensive remain a technical challenge. Here new observational methods using repurposed soil moisture sensors that facilitate high spatial–temporal sampling of ice thickness are field tested on Lake Mendota in Wisconsin during the winter 2015/16 season. Spatial variability in ice thickness was high, with differences of 10 cm of ice column thickness over 1.05 km of horizontal distance. When observational data were compared with manual measurements and model output from both the Freshwater Lake (FLake) model and General Lake Model (GLM), ice thickness from sensors matches manual measurements, whereas GLM and FLake results showed a thinner and thicker ice layer, respectively. The FLake-modeled ice column temperature effectively remained at 0°C, not matching observations. We also show that daily ice dynamics follows the expected linear function of ice thickness growth/melt, improving confidence in sensor accuracy under field conditions. We have demonstrated a new method that allows low-cost and high-frequency measurements of ice thickness, which will be needed both to advance winter limnology and to improve on-ice safety.