bluuebunny/crossref_metadata_2025_split huggingface dataset:
pH recovery from a proton load in rat cardiomyocytes: effects of chronic exercise
Authors: Danes Vennetia R. , Anthony Josephine , Rayani Kaveh , Spitzer Kenneth W. , Tibbits Glen F. 
Published: December 2017

The ability of cardiomyocytes to recover from a proton load was examined in the hearts of exercise-trained and sedentary control rats in CO2/[Formula: see text]-free media. Acidosis was created by the NH4Cl prepulse technique, and intracellular pH (pHi) was determined using fluorescence microscopy on carboxy-SNARF-1 AM-loaded isolated cardiomyocytes. CO2-independent pHi buffering capacity (βi) was measured by incrementally reducing the extracellular NH4Cl concentration in steps of 50% from 20 to 1.25 mM. βi increased as pHi decreased in both exercise-trained and sedentary control groups. However, the magnitude of increase in βi as a function of pHi was found to be significantly ( P < 0.001) greater in the exercise-trained group compared with the sedentary control group. The rate of pHi recovery from an imposed proton load was found to not be different between the exercise-trained and control groups. The Na+/H+ exchanger-dependent H+ extrusion rate during the recovery from an imposed proton load, however, was found to be significantly greater in the exercise-trained group compared with the control group. By increasing βi and subsequently the Na+/H+ exchanger-dependent H+ extrusion rate, exercise training may provide cardiomyocytes with the ability to better handle an intracellular excess of H+ generated during hypoxia/ischemic insults and may serve in a cardioprotective role. These data may be predictive of two positive outcomes: 1) increased exercise tolerance by the heart and 2) a protective mechanism that limits the degree of myocardial acidosis and subsequent damage that accompanies ischemia-reperfusion stress. NEW & NOTEWORTHY The enhanced ability to deal with acidosis conferred by exercise training is likely to improve exercise tolerance and outcomes in response to myocardial ischemia-reperfusion injury.
Response inhibition activates distinct motor cortical inhibitory processes
Authors: Cirillo John , Cowie Matthew J. , MacDonald Hayley J. , Byblow Winston D. 
Published: December 2017

We routinely cancel preplanned movements that are no longer required. If stopping is forewarned, proactive processes are engaged to selectively decrease motor cortex excitability. However, without advance information there is a nonselective reduction in motor cortical excitability. In this study we examined modulation of human primary motor cortex inhibitory networks during response inhibition tasks with informative and uninformative cues using paired-pulse transcranial magnetic stimulation. Long- (LICI) and short-interval intracortical inhibition (SICI), indicative of GABAB- and GABAA-receptor mediated inhibition, respectively, were examined from motor evoked potentials obtained in task-relevant and task-irrelevant hand muscles when response inhibition was preceded by informative and uninformative cues. When the participants (10 men and 8 women) were cued to stop only a subcomponent of the bimanual response, the remaining response was delayed, and the extent of delay was greatest in the more reactive context, when cues were uninformative. For LICI, inhibition was reduced in both muscles during all types of response inhibition trials compared with the pre-task resting baseline. When cues were uninformative and left-hand responses were suddenly canceled, task-relevant LICI positively correlated with response times of the responding right hand. In trials where left-hand responding was highly probable or known (informative cues), task-relevant SICI was reduced compared with that when cued to rest, revealing a motor set indicative of responding. These novel findings indicate that the GABAB-receptor-mediated pathway may set a default inhibitory tone according to task context, whereas the GABAA-receptor-mediated pathways are recruited proactively with response certainty. NEW & NOTEWORTHY We examined how informative and uninformative cues that trigger both proactive and reactive processes modulate GABAergic inhibitory networks within human primary motor cortex. We show that GABAB inhibition was released during the task regardless of cue type, whereas GABAA inhibition was reduced when responding was highly probable or known compared with rest. GABAB-receptor-mediated inhibition may set a default inhibitory tone, whereas GABAA circuits may be modulated proactively according to response certainty.
Novel In Vitro Cancer Models for Optimizing Anti-EGFR Therapies
Authors: Napolitano Stefania , Ciardiello Fortunato 
Published: December 2017

Abstract
Preclinical models, which are able to recapitulate the biology and pathology of the original individual cancer, are needed to better investigate mechanisms of response and resistance to anticancer therapies. In this respect, novel in vitro models for metastatic colorectal cancer could be of high value. Clin Cancer Res; 24(4); 727–9. ©2017 AACR.
See related article by Luraghi et al., p. 807
Two Years Follow-Up of Patients with Abnormal Uterine Bleeding after Insertion of the Levonorgestrel-Releasing Intrauterine System
Authors: Cim Numan , Soysal Sunullah , Sayan Sena , Yildizhan Begum , Karaman Erbil , Cetin Orkun , Tolunay Harun Egemen , Yildizhan Recep 
Published: December 2017

<b><i>Aim:</i></b> To evaluate the efficacy and safety of levonorgestrel-releasing intrauterine system (LNG-IUS) in the long-term treatment of heavy menstrual blood loss in women unrelated to intrauterine pathology. <b><i>Methods:</i></b> One hundred and six parous women aged 33–48 years with recurrent heavy menstrual bleeding (HMB) participated in this study. The women were followed up for 24 months and were assessed for intensity of bleeding both for pre- and post-insertion periods. An LNG-IUS was inserted in each patient within 7 days of the start of menstrual flow. The women were followed up at 1, 3, 6, 12, 18, and 24 months following the insertion of the intrauterine device. <b><i>Results:</i></b> One hundred and two women completed the follow-up period and had a significant reduction in the amount of menstrual blood loss. The LNG-IUS was well tolerated by all women. Pre-treatment of the use of the LNG-IUS, endometrial biopsy patterns for irregular proliferative endometrium and for atypical simple hyperplasia were 34/106 (32.08%) and 61/106 (57.55%) respectively and after treatment no abnormal pathologic findings were determined (<i>p</i> &#x3c; 0.001). <b><i>Conclusion:</i></b> Our findings indicate that the LNG-IUS is effective for significantly reducing the amount of menstrual blood loss in women with HMB.
Application of Large-Scale Aptamer-Based Proteomic Profiling to Planned Myocardial Infarctions
Authors: Jacob Jaison , Ngo Debby , Finkel Nancy , Pitts Rebecca , Gleim Scott , Benson Mark D. , Keyes Michelle J. , Farrell Laurie A. , Morgan Thomas , Jennings Lori L. , Gerszten Robert E. 
Published: December 2017

Background:
Emerging proteomic technologies using novel affinity-based reagents allow for efficient multiplexing with high-sample throughput. To identify early biomarkers of myocardial injury, we recently applied an aptamer-based proteomic profiling platform that measures 1129 proteins to samples from patients undergoing septal alcohol ablation for hypertrophic cardiomyopathy, a human model of planned myocardial injury. Here, we examined the scalability of this approach using a markedly expanded platform to study a far broader range of human proteins in the context of myocardial injury.

Methods:
We applied a highly multiplexed, expanded proteomic technique that uses single-stranded DNA aptamers to assay 4783 human proteins (4137 distinct human gene targets) to derivation and validation cohorts of planned myocardial injury, individuals with spontaneous myocardial infarction, and at-risk controls.

Results:

We found 376 target proteins that significantly changed in the blood after planned myocardial injury in a derivation cohort (n=20;
P
<1.05E-05, 1-way repeated measures analysis of variance, Bonferroni threshold). Two hundred forty-seven of these proteins were validated in an independent planned myocardial injury cohort (n=15;
P
<1.33E-04, 1-way repeated measures analysis of variance); >90% were directionally consistent and reached nominal significance in the validation cohort. Among the validated proteins that were increased within 1 hour after planned myocardial injury, 29 were also elevated in patients with spontaneous myocardial infarction (n=63;
P
<6.17E-04). Many of the novel markers identified in our study are intracellular proteins not previously identified in the peripheral circulation or have functional roles relevant to myocardial injury. For example, the cardiac LIM protein, cysteine- and glycine-rich protein 3, is thought to mediate cardiac mechanotransduction and stress responses, whereas the mitochondrial ATP synthase F
0
subunit component is a vasoactive peptide on its release from cells. Last, we performed aptamer-affinity enrichment coupled with mass spectrometry to technically verify aptamer specificity for a subset of the new biomarkers.

Conclusions:
Our results demonstrate the feasibility of large-scale aptamer multiplexing at a level that has not previously been reported and with sample throughput that greatly exceeds other existing proteomic methods. The expanded aptamer-based proteomic platform provides a unique opportunity for biomarker and pathway discovery after myocardial injury.
PINGS (Phone-Based Intervention Under Nurse Guidance After Stroke)
Authors: Sarfo Fred , Treiber Frank , Gebregziabher Mulugeta , Adamu Sheila , Patel Sachin , Nichols Michelle , Awuah Dominic , Sakyi Asumadu , Adu-Darko Nyantakyi , Singh Arti , Tagge Raelle , Carolyn Jenkins , Ovbiagele Bruce 
Published: December 2017

Background and Purpose—
Stroke exacts an immense toll in sub-Saharan Africa where there are few resources, and stroke prevention research is limited. The aim of this study is to test the feasibility and preliminary efficacy of an m-Health technology–enabled, nurse-guided intervention in improving blood pressure (BP) control among Ghanaian stroke patients within 1 month of symptom onset.

Methods—
We conducted a 2-arm cluster pilot randomized controlled trial involving 60 recent stroke survivors encountered within a single tertiary medical system in Ghana. Subjects in the intervention arm (n=30) received a Blue-toothed UA-767Plus BT BP device and smartphone for monitoring and reporting BP measurements and medication intake for 3 months compared with standard of care (n=30). Primary outcome measure was systolic BP <140 mm Hg at month 3; secondary outcomes included medication adherence and autonomous self-regulation. Analysis accounting for clustering was made using generalized linear mixed model by intention to treat.

Results—

Mean±SD age was 55±13 years, 65% male. Systolic BP <140 mm Hg at month 3 was found in 20/30 subjects (66.7%) in the intervention arm versus 14/30 subjects (46.7%) in the control arm (
P
=0.12). Medication possession ratio scores at month 3 were better in the intervention (0.88±0.40) versus control (0.64±0.45) arm (
P
=0.03). One subject in control arm died from a recurrent hemorrhagic stroke.

Conclusions—
It is feasible to conduct an m-Health–based, nurse-guided BP control intervention among recent stroke patients in sub-Saharan Africa. We observed a potential signal of efficacy with the intervention, which will need to be tested in a future large definitive study.

Clinical Trial Registration—

URL:
https://www.clinicaltrials.gov
. Unique identifier: NCT02568137.
Radar Network–Based Detection of Mesocyclones at the German Weather Service
Authors: Hengstebeck Thomas , Wapler Kathrin , Heizenreder Dirk , Joe Paul 
Published: December 2017

AbstractThe radar network of the German Weather Service [Deutscher Wetterdienst (DWD)] provides 3D Doppler data in high spatial and temporal resolution, supporting the identification and tracking of dynamic small-scale weather phenomena. The software framework Polarimetric Radar Algorithms (POLARA) has been developed at DWD to better exploit the capabilities of the existing remote sensing data. The data processing and quality assurance implemented in POLARA include a dual-PRF dealiasing algorithm with error correction. Azimuthal shear information is derived and processed in the mesocyclone detection algorithm (MCD). Low- and midlevel azimuthal shear and track products are available as composite (multiradar) products. Azimuthal shear may be considered as a proxy for rotation. The MCD results and azimuthal shear products are part of the severe weather detection algorithms of DWD and are provided to the forecaster on the NinJo meteorological workstation system. The forecaster analyzes potentially severe cells by combining near-storm environment data with the MCD product as well as with the instantaneous azimuthal shear products (mid- and low level) and their tracks. These products and tracks are used to diagnose threat potential by means of azimuthal shear intensity and track longevity. Feedback from forecasters has shown the utility of the algorithms to analyze and diagnose severe convective cells in Germany and in adjacent Europe. In this paper, the abovementioned algorithms and products are presented in detail and case studies illustrating usability and performance are shown.
Cortical and functional responses to an early protocol of sensory re-education of the hand using audio–tactile interaction
Authors: Mendes Raquel Metzker , Rondinoni Carlo , Fonseca Marisa de Cássia Registro , Barbosa Rafael Inácio , Garrido Salmón Carlos Ernesto , Barbieri Cláudio Henrique , Mazzer Nilton 
Published: December 2017

Introduction Early sensory re-education techniques are important strategies associated with cortical hand area preservation. The aim of this study was to investigate early cortical responses, sensory function outcomes and disability in patients treated with an early protocol of sensory re-education of the hand using an audio-tactile interaction device with a sensor glove model. Methods After surgical repair of median and/or ulnar nerves, participants received either early sensory re-education twice a week with the sensor glove during three months or no specific sensory training. Both groups underwent standard rehabilitation. Patients were assessed at one, three and six months after surgery on training-related cortical responses by functional magnetic resonance imaging, sensory thresholds, discriminative touch and disability using the Disabilities of the Arm, Shoulder and Hand patient-reported questionnaire. Results At six-months, there were no statistically significant differences in sensory function between groups. During functional magnetic resonance imaging, trained patients presented complex cortical responses to auditory stimulation indicating an effective connectivity between the cortical hand map and associative areas. Conclusion Training with the sensor glove model seems to provide some type of early cortical audio-tactile interaction in patients with sensory impairment at the hand after nerve injury. Although no differences were observed between groups related to sensory function and disability at the intermediate phase of peripheral reinnervation, this study suggests that an early sensory intervention by sensory substitution could be an option to enhance the response on cortical reorganization after nerve repair in the hand. Longer follow-up and an adequately powered trial is needed to confirm our findings.
Excess Maternal Thyroxine Alters the Proliferative Activity and Angiogenic Profile of Growth Cartilage of Rats at Birth and Weaning
Authors: Ribeiro Lorena Gabriela Rocha , Silva Juneo Freitas , Ocarino Natália de Melo , Souza Cíntia Almeida de , Melo Eliane Gonçalves de , Serakides Rogéria 
Published: December 2017

Objective The aim of this study was to unravel the mechanisms by which thyroxine affects skeletal growth by evaluating proliferative activity and angiogenic profile of growth cartilage of neonatal and weanling rats. Methods Sixteen adult Wistar rats were equally divided into 2 groups: control and treated with thyroxine during pregnancy and lactation. The weight, measurement of plasma free T4 and thyroids, femurs’ histomorphometric analysis, and proliferative activity and angiogenic profile by immunohistochemical or real-time reverse transcriptase-polymerase chain reaction in growth cartilage was performed. Data were analyzed using Student’s t test. Results The free T4 was significantly higher in the treated rats. However, the height of the follicular epithelium of the thyroid in newborns was significantly lower in the treated group. The excess maternal thyroxine significantly reduced the body weight and length of the femur in the offspring but significantly increased the thickness of trabecular bone and changed the height of the zones of the growth plate. Furthermore, excess maternal thyroxine reduced cell proliferation and vascular endothelial growth factor (VEGF) expression in the growth cartilage of newborn and 20-day-old rats ( P < 0.05). There was also a reduction in the immunohistochemical expression of Tie2 in the cartilaginous epiphysis of the newborns and FLK-1 in the articular cartilage of 20-day-old rats. No significant difference was observed in Ang2 expression. Conclusions The excess maternal thyroxine during pregnancy and lactation reduced endochondral bone growth in the progeny and reduced the proliferation rate and VEGF, Flk-1, and Tie2 expression in the cartilage of growing rats without altering the mRNA expression of Ang1 and Ang2.
Gender Differences in Knee Joint Congruity Quantified from MRI: A Validation Study with Data from Center for Clinical and Basic Research and Osteoarthritis Initiative
Authors: Tummala Sudhakar , Schiphof Dieuwke , Byrjalsen Inger , Dam Erik B. 
Published: December 2017

Objective Gender is a risk factor in the onset of osteoarthritis (OA). The aim of the study was to investigate gender differences in contact area (CA) and congruity index (CI) in the medial tibiofemoral (MTF) joint in 2 different cohorts, quantified automatically from magnetic resonance imaging (MRI). Design The CA and CI markers were validated on 2 different data sets from Center for Clinical and Basic Research (CCBR) and Osteoarthritis Initiative (OAI). The CCBR cohort consisted of 159 subjects and the OAI subcohort consisted of 1,436 subjects. From the MTF joint, the contact area was located and quantified using Euclidean distance transform. Furthermore, the CI was quantified over the contact area by assessing agreement of the first- and second-order general surface features. Then, the gender differences between CA and CI values were evaluated at different stages of radiographic OA. Results Female CAs were significantly higher than male CAs after normalization, male CIs were significantly higher than female CIs after correcting with age and body mass index ( P < 0.05), consistent across the 2 data sets. For the OAI data set, the gender differences were present at all stages of radiographic OA. Conclusion This study demonstrated the gender differences in CA and CI in MTF joints. The higher normalized CA and lower CI values in female knees may be linked with the increased risk of incidence of radiographic OA in females. These differences may help further understand the gender differences and/or to establish gender specific treatment strategies.
Optical Density of Subretinal Fluid as a Predictive Biomarker for Eyes With Chronic Central Serous Retinopathy Treated With Eplerenone
Authors: Joshi Nisarg P. , Adam Murtaza K. , Samara Wasim A. , Shahlaee Abtin , Rahimy Ehsan , Aderman Christopher M. , Hsu Jason , Fineman Mitchell S. , Garg Sunir J. 
Published: December 2017

Purpose: To investigate how the optical density ratio (ODR) of subretinal fluid (SRF) obtained by optical coherence tomography (OCT) in eyes with chronic central serous retinopathy (CSR), defined as symptoms >3 months, treated with eplerenone correlates with treatment response and visual outcomes. Methods: This retrospective, single-center observational study included patients with chronic CSR treated with eplerenone who had at least 6 weeks of follow-up. Eyes with poor-quality OCT scans, shallow SRF precluding sampling of optical density (OD), and macular pathology other than CSR were excluded. Optical density of the vitreous and SRF was measured using ImageJ and used to calculate ODR (ODR = ODSRF/ODVIT). Peak SRF height, foveal SRF height, central macular thickness (CMT), and Snellen visual acuity (VA) were measured. The Mann-Whitney U test was used to compare continuous variables. Pearson correlation coefficient was used to determine the statistical significance of applied linear regressions. Results: Twenty-three eyes of 23 patients met the inclusion criteria. Six (26%) eyes had complete resolution of foveal SRF (resolvers) with eplerenone treatment, and the remainder of patients had worsening or incomplete resolution (nonresolvers). Resolvers had significantly lower baseline logarithm of the minimum angle of resolution (logMAR) VA ( P < .01) than nonresolvers. There was a positive linear correlation between ODR and logMAR VA at baseline ( R2 = 0.208; P = .03) and follow-up ( R2 = 0.206; P = .03). A significant correlation between ODR and percentage change in CMT was found ( R2 = 0.263; P = .01). Linear correlations were not found between ODR and age, peak SRF height, and foveal SRF height (all P > .125). Conclusion: Lower baseline ODR was associated with improved percentage change in CMT and VA in patients treated with eplerenone for chronic CSR. Optical density ratio may represent a novel prognostic biomarker that may help determine which eyes with chronic CSR may respond better to eplerenone.
In silico analysis of natural compounds targeting structural and nonstructural proteins of chikungunya virus
Authors: Jain Jaspreet , Kumari Anchala , Somvanshi Pallavi , Grover Abhinav , Pai Somnath , Sunil Sujatha 
Published: December 2017

Background:Chikungunya fever presents as a high-grade fever during its acute febrile phase and can be prolonged for months as chronic arthritis in affected individuals. Currently, there are no effective drugs or vaccines against this virus. The present study was undertaken to evaluate protein-ligand interactions of all chikungunya virus (CHIKV) proteins with natural compounds from a MolBase library in order to identify potential inhibitors of CHIKV.Methods:Virtual screening of the natural compound library against four non-structural and five structural proteins of CHIKV was performed. Homology models of the viral proteins with unknown structures were created and energy minimized by molecular dynamic simulations. Molecular docking was performed to identify the potential inhibitors for CHIKV. The absorption, distribution, metabolism and excretion (ADME) toxicity parameters for the potential inhibitors were predicted for further prioritization of the compounds.Results:Our analysis predicted three compounds, Catechin-5-O-gallate, Rosmarinic acid and Arjungenin, to interact with CHIKV proteins; two (Catechin-5-O-gallate and Rosmarinic acid) with capsid protein, and one (Arjungenin) with the E3.Conclusion:The compounds identified show promise as potential antivirals, but furtherin vitrostudies are required to test their efficacy against CHIKV.