bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impairment of rat oesophageal muscle contractility associated with experimental non‐erosive oesophageal mucosal damage
Authors: Gadelha Kalinne Kelly Lima , Batista‐Lima Francisco José , de Oliveira Daniel Maia Nogueira , Carvalho Emanuella Feitosa de , Sifrim Daniel , Santos Armênio Aguiar dos , Magalhães Pedro Jorge Caldas 
Published: December 2018

New Findings
What is the central question of this study?
Is the responsiveness of isolated segments of the rat oesophagus to contractile or relaxant stimuli susceptible to acute luminal exposure of the oesophagus to an acid solution that contains pepsin and bile salt?
What is the main finding and its importance?
The study reveals that luminal acidity is an important factor that disrupts barrier function in the oesophagus to allow the diffusion of noxious agents, such as bile acid, that alter the contractile status of the oesophageal body, even in the absence of inflammation.
AbstractWe investigated whether the experimental simulation of duodenogastro‐oesophageal reflux alters the contractile responsiveness of rat oesophageal strips. After 30 min of luminal exposure to a solution at acid pH that contained pepsin and taurodeoxycholic acid, isolated strips of the rat oesophagus and gastro‐oesophageal junction were subjected to contractile or relaxing stimuli. Acid challenge decreased the responsiveness of oesophageal strips to contractile stimulation, especially in oesophageal preparations that were mounted following the circular orientation of the muscularis externa layer. The contractility of longitudinal preparations of the rat oesophagus appeared less susceptible to the deleterious effects of acid challenge. In contrast, the responsiveness of ring‐like preparations from the gastro‐oesophageal junction to contractile stimulation was unaltered by acid challenge. Taurodeoxycholic acid decreased the responsiveness of circular oesophageal preparations to KCl, an effect that was exacerbated by luminal acidity. On the contrary, although the relaxant ability of the rat oesophagus did not change, acid challenge increased the relaxant efficacy of sodium nitroprusside and isoprenaline in strips of the gastro‐oesophageal junction. A significant decrease in transepithelial electrical resistance was seen when the oesophageal mucosa was challenged at pH 1 but not at pH 4. Treatment with alginate blunted the deleterious effects of acid challenge on transepithelial electrical resistance and the responsiveness of oesophageal preparations to KCl. The present findings support the notion that luminal acidity is an important factor that disrupts barrier function in the oesophagus to allow the diffusion of noxious agents, such as bile acid, that alter the contractile status of the oesophagus.
Accumulated or continuous exercise for glycaemic regulation and control: a systematic review with meta-analysis
Authors: Shambrook Philip , Kingsley Michael , Taylor Nicholas , Gordon Brett 
Published: December 2018

ObjectiveTo compare the effectiveness of accumulating exercise in multiple bouts of at least 10 min throughout a day with exercise completed in a single bout (continuous or interval), or no exercise, on glycaemic control and regulation in inactive people without diagnosed glycaemic dysfunction.DesignSystematic review and meta-analysis.Data sourcesSeven electronic databases were searched: CINAHL (EBSCO), Cochrane Library, EMBASE (Ovid), MEDLINE 1948-(Ovid), SCOPUS (Elsevier), SPORTDiscus (EBSCO) and Web of Science (ISI) with no restrictions on date and included all titles indexed up to February 2018.Eligibility criteria for selecting studiesArticles reporting insufficiently active adults (19 to 64 years) without metabolic dysfunction, measuring glycaemic control or regulation following at least 6 weeks of aerobic exercise.ResultsOnly one study compared accumulated exercise to single-bout exercise with no significant effect on fasting glucose (95% CI: −0.04 to 0.24 mmol·L-1) or fasting insulin (95% CI: −1.79 to 9.85 pmol·L-1) reported 48 hours after the final bout. No studies compared accumulated exercise with no-exercise. Compared with no-exercise, single-bout exercise reduces insulin resistance (mean difference (MD): −0.53 pmol·L-1; 95% CI: −0.93 to −0.13). Insulin resistance was clearly reduced with moderate-intensity (−0.68 (−1.28 to −0.09)) but not with high-intensity (−0.38 (−1.20 to 0.44)) exercise. Single-bout exercise was not statistically more beneficial than no-exercise for glycated haemoglobin (HbA1c) (MD: −0.11 %; 95% CI: −0.24 to 0.02) in metabolically healthy individuals.Summary/conclusionThe glycaemic response to accumulated exercise or single-bout exercise might not be different, however exercise intensity might influence the mechanisms generating the response.PROSPERO registration numberCRD42015025042.
Tandem cervical carotid stenting for stenosis with flow diversion embolisation for the treatment of intracranial aneurysms
Authors: Campos Jessica K , Lin Li-Mei , Beaty Narlin B , Bender Matthew T , Jiang Bowen , Zarrin David A , Coon Alexander L 
Published: December 2018

BackgroundAn estimated 2%–3% of the population harbour an intracranial aneurysm. Concomitant atherosclerotic cervical carotid disease is not uncommon. The management of these two entities remains a challenge within the field.Case presentationWe report a single case of concomitant carotid stenosis and two ipsilateral unruptured intracranial aneurysms treated with a single-staged cervical carotid stenting and cerebral aneurysm embolisation with the Pipeline embolisation device.DiscussionNo consensus currently exists to guide endovascular treatment of intracranial aneurysms associated with asymptomatic ipsilateral stenosis. Here, we present a case of asymptomatic moderate carotid stenosis with two ipsilateral intracranial aneurysms and suggest carotid artery stenting takes procedural priority over aneurysm embolisation in single-stage treatment. The rationale for the sequence of neurointerventions is based on the tracking a robust distal access system beyond a stenotic proximal carotid lesion and stabilisation of the ulcerated plaque to avoid thromboembolic complications associated with plaque irritation during aneurysm embolisation. Additional cases and longer follow-up will be needed to further assess the efficacy of this technique.
Broad Spectrum Activity of the Checkpoint Kinase 1 Inhibitor Prexasertib as a Single Agent or Chemopotentiator Across a Range of Preclinical Pediatric Tumor Models
Authors: Lowery Caitlin D. , Dowless Michele , Renschler Matthew , Blosser Wayne , VanWye Alle B. , Stephens Jennifer R. , Iversen Philip W. , Lin Aimee Bence , Beckmann Richard P. , Krytska Kateryna , Cole Kristina A. , Maris John M. , Hawkins Douglas S. , Rubin Brian P. , Kurmasheva Raushan T. , Houghton Peter J. , Gorlick Richard , Kolb E. Anders , Kang Min H. , Reynolds C. Patrick , Erickson Stephen W. , Teicher Beverly A. , Smith Malcolm A. , Stancato Louis F. 
Published: December 2018

Abstract

Purpose:
Checkpoint kinase 1 (CHK1) inhibitors potentiate the DNA-damaging effects of cytotoxic therapies and/or promote elevated levels of replication stress, leading to tumor cell death. Prexasertib (LY2606368) is a CHK1 small-molecule inhibitor under clinical evaluation in multiple adult and pediatric cancers. In this study, prexasertib was tested in a large panel of preclinical models of pediatric solid malignancies alone or in combination with chemotherapy.

Experimental Design:
DNA damage and changes in cell signaling following in vitro prexasertib treatment in pediatric sarcoma cell lines were analyzed by Western blot and high content imaging. Antitumor activity of prexasertib as a single agent or in combination with different chemotherapies was explored in cell line–derived (CDX) and patient-derived xenograft (PDX) mouse models representing nine different pediatric cancer histologies.

Results:
Pediatric sarcoma cell lines were highly sensitive to prexasertib treatment in vitro, resulting in activation of the DNA damage response. Two PDX models of desmoplastic small round cell tumor and one malignant rhabdoid tumor CDX model responded to prexasertib with complete regression. Prexasertib monotherapy also elicited robust responses in mouse models of rhabdomyosarcoma. Concurrent administration with chemotherapy was sufficient to overcome innate resistance or prevent acquired resistance to prexasertib in preclinical models of neuroblastoma, osteosarcoma, and Ewing sarcoma, or alveolar rhabdomyosarcoma, respectively.

Conclusions:
Prexasertib has significant antitumor effects as a monotherapy or in combination with chemotherapy in multiple preclinical models of pediatric cancer. These findings support further investigation of prexasertib in pediatric malignancies.
Rapamycin Prevents Surgery-Induced Immune Dysfunction in Patients with Bladder Cancer
Authors: Svatek Robert S. , Ji Niannian , de Leon Essel , Mukherjee Neelam Z. , Kabra Aashish , Hurez Vincent , Nicolas Marlo , Michalek Joel E. , Javors Martin , Wheeler Karen , Sharp Z. Dave , Livi Carolina B. , Shu Zhen-Ju , Henkes David , Curiel Tyler J. 
Published: December 2018

AbstractThe mechanistic target of rapamycin (mTOR) integrates environmental inputs to regulate cellular growth and metabolism in tumors. However, mTOR also regulates T-cell differentiation and activation, rendering applications of mTOR inhibitors toward treating cancer complex. Preclinical data support distinct biphasic effects of rapamycin, with higher doses directly suppressing tumor cell growth and lower doses enhancing T-cell immunity. To address the translational relevance of these findings, the effects of the mTOR complex 1 (mTORC1) inhibitor, rapamycin, on tumor and T cells were monitored in patients undergoing cystectomy for bladder cancer. MB49 syngeneic murine bladder cancer models were tested to gain mechanistic insights. Surgery-induced T-cell exhaustion in humans and mice and was associated with increased pulmonary metastasis and decreased PD-L1 antibody efficacy in mouse bladder cancer. At 3 mg orally daily, rapamycin concentrations were 2-fold higher in bladder tissues than in blood. Rapamycin significantly inhibited tumor mTORC1, shown by decreased rpS6 phosphorylation in treated versus control patients (P = 0.008). Rapamycin reduced surgery-induced T-cell exhaustion in patients, evidenced by a significant decrease in the prevalence of dysfunctional programmed death-1 (PD-1)–expressing T cells. Grade 3 to 4 adverse event rates were similar between groups, but rapamycin-treated patients had a higher rate of wound complications versus controls. In conclusion, surgery promoted bladder cancer metastasis and decreased the efficacy of postoperative bladder cancer immunotherapy. Low-dose (3 mg daily) oral rapamycin has favorable pharmacodynamic and immune modulating activity in surgical patients and has the potential to decrease surgery-induced immune dysfunction.
Potts Shunt Improves Right Ventricular Function and Coupling With Pulmonary Circulation in Children With Suprasystemic Pulmonary Arterial Hypertension
Authors: Aggarwal Manish , Grady R. Mark , Choudhry Swati , Anwar Shafkat , Eghtesady Pirooz , Singh Gautam K. 
Published: December 2018

Background:
Pulmonary arterial hypertension is a progressive disease with poor outcomes in children. Right ventricular (RV) function is the most important determinant of the prognosis. Novel application of Potts shunt between left pulmonary artery and descending aorta has been introduced in an attempt to improve the survival. However, the effect of Potts shunt creation on RV function, RV-PA coupling, and survival has not been studied.

Methods and Results:

We evaluated the first 12 consecutive pediatric patients (9 male, median age 11.2 years and weight 32.8 kg) who underwent elective Potts shunt placement for suprasystemic pulmonary arterial hypertension between 2013 and 2017 with echocardiographic indices of RV function, RV work, RV-PA coupling, and pulmonary hemodynamics. Of 12 patients, 1 was excluded because of insufficient preshunt data, 2 died, 1 required lung transplant, and 8 survived for a median of 27 months postshunt. In survivors, WHO functional class significantly (
P
=0.01) improved and the majority (5 of 8) came off pulmonary vasodilators at the most recent follow-up. Postshunt RV systolic function improved (
P
=0.03), RV afterload decreased (
P
<0.01), RV work decreased (
P
=0.02), and RV-proximal PA coupling improved (
P
<0.01).

Conclusions:
This proof of concept study shows that Potts shunt allows improvement in functional status and mid-term transplant-free survival in the majority of the recipients by improvement in RV systolic function and RV-PA coupling in children with suprasystemic pulmonary arterial hypertension.
Identifying the Sources of Convective Memory in Cloud-Resolving Simulations
Authors: Colin Maxime , Sherwood Steven , Geoffroy Olivier , Bony Sandrine , Fuchs David 
Published: December 2018

AbstractConvection is often assumed to be controlled by the simultaneous environmental fields. But to what extent does it also remember its past behavior? This study proposes a new framework in which the memory of previous convective-scale behavior, “microstate memory,” is distinguished from macrostate memory, and conducts numerical experiments to reveal these memory types. A suite of idealized, cloud-resolving radiative–convective equilibrium simulations in a 200-km square domain is performed with the Weather Research and Forecasting (WRF) Model. Three deep convective cases are analyzed: unorganized, organized by low-level wind shear, and self-aggregated. The systematic responses to sudden horizontal homogenization of various fields, in various atmospheric layers, designed to eliminate their specific microstructure, are compared in terms of precipitation change and time of recovery to equilibrium. Results imply a substantial role for microstate memory. Across organization types, microstructure in water vapor and temperature has a larger and longer-lasting effect on convection than in winds or hydrometeors. Microstructure in the subcloud layer or the shallow cloud layer has more impact than in the free troposphere. The recovery time scale dramatically increases from unorganized (2–3 h) to organized cases (24 h or more). Longer-time-scale adjustments also occur and appear to involve both small-scale structures and domain-mean fields. These results indicate that most convective microstate memory is stored in low-level thermodynamic structures, potentially involving cold pools and hot thermals. This memory appears strongly enhanced by convective organization. Implications of these results for parameterizing convection are discussed.
A Climatology of Thunderstorms across Europe from a Synthesis of Multiple Data Sources
Authors: Taszarek Mateusz , Allen John , Púčik Tomáš , Groenemeijer Pieter , Czernecki Bartosz , Kolendowicz Leszek , Lagouvardos Kostas , Kotroni Vasiliki , Schulz Wolfgang 
Published: December 2018

AbstractThe climatology of (severe) thunderstorm days is investigated on a pan-European scale for the period of 1979–2017. For this purpose, sounding measurements, surface observations, lightning data from ZEUS (a European-wide lightning detection system) and European Cooperation for Lightning Detection (EUCLID), ERA-Interim, and severe weather reports are compared and their respective strengths and weaknesses are discussed. The research focuses on the annual cycles in thunderstorm activity and their spatial variability. According to all datasets thunderstorms are the most frequent in the central Mediterranean, the Alps, the Balkan Peninsula, and the Carpathians. Proxies for severe thunderstorm environments show similar patterns, but severe weather reports instead have their highest frequency over central Europe. Annual peak thunderstorm activity is in July and August over northern, eastern, and central Europe, contrasting with peaks in May and June over western and southeastern Europe. The Mediterranean, driven by the warm waters, has predominant activity in the fall (western part) and winter (eastern part) while the nearby Iberian Peninsula and eastern Turkey have peaks in April and May. Trend analysis of the mean annual number of days with thunderstorms since 1979 indicates an increase over the Alps and central, southeastern, and eastern Europe with a decrease over the southwest. Multiannual changes refer also to changes in the pattern of the annual cycle. Comparison of different data sources revealed that although lightning data provide the most objective sampling of thunderstorm activity, short operating periods and areas devoid of sensors limit their utility. In contrast, reanalysis complements these disadvantages to provide a longer climatology, but is prone to errors related to modeling thunderstorm occurrence and the numerical simulation itself.
Multiscale Processes Enabling the Longevity and Daytime Persistence of a Nocturnal Mesoscale Convective System
Authors: Chasteen Manda B. , Koch Steven E. , Parsons David B. 
Published: December 2018

Abstract
Nocturnal mesoscale convective systems (MCSs) frequently develop over the Great Plains in the presence of a nocturnal low-level jet (LLJ), which contributes to convective maintenance by providing a source of instability, convergence, and low-level vertical wind shear. Although these nocturnal MCSs often dissipate during the morning, many persist into the following afternoon despite the cessation of the LLJ with the onset of solar heating. The environmental factors enabling the postsunrise persistence of nocturnal convection are currently not well understood. A thorough investigation into the processes supporting the longevity and daytime persistence of an MCS was conducted using routine observations, RAP analyses, and a WRF-ARW simulation. Elevated nocturnal convection developed in response to enhanced frontogenesis, which quickly grew upscale into a severe quasi-linear convective system (QLCS). The western portion of this QLCS reorganized into a bow echo with a pronounced cold pool and ultimately an organized leading-line, trailing-stratiform MCS as it moved into an increasingly unstable environment. Differential advection resulting from the interaction of the nocturnal LLJ with the topography of west Texas established considerable heterogeneity in moisture, CAPE, and CIN, which influenced the structure and evolution of the MCS. An inland-advected moisture plume significantly increased near-surface CAPE during the nighttime over central Texas, while the environment over southeastern Texas abruptly destabilized following the commencement of surface heating and downward moisture transport. The unique topography of the southern plains and the close proximity to the Gulf of Mexico provided an environment conducive to the postsunrise persistence of the organized MCS.
Incorporating UH Occurrence Time to Ensemble-Derived Tornado Probabilities
Authors: Gallo Burkely T. , Clark Adam J. , Smith Bryan T. , Thompson Richard L. , Jirak Israel , Dembek Scott R. 
Published: December 2018

Abstract
Probabilistic ensemble-derived tornado forecasts generated from convection-allowing models often use hourly maximum updraft helicity (UH) alone or in combination with environmental parameters as a proxy for right-moving (RM) supercells. However, when UH occurrence is a condition for tornado probability generation, false alarm areas can occur from UH swaths associated with nocturnal mesoscale convective systems, which climatologically produce fewer tornadoes than RM supercells. This study incorporates UH timing information with the forecast near-storm significant tornado parameter (STP) to calibrate the forecast tornado probability. To generate the probabilistic forecasts, three sets of observed climatological tornado frequencies given an RM supercell and STP value are incorporated with the model output, two of which use UH timing information. One method uses the observed climatological tornado frequency for a given 3-h window to generate the probabilities. Another normalizes the observed climatological tornado frequency by the number of hail, wind, and tornado reports observed in that 3-h window compared to the maximum number of reports in any 3-h window. The final method is independent of when UH occurs and uses the observed climatological tornado frequency encompassing all hours. The normalized probabilities reduce the false alarm area compared to the other methods but have a smaller area under the ROC curve and require a much higher percentile of the STP distribution to be used in probability generation to become reliable. Case studies demonstrate that the normalized probabilities highlight the most likely area for evening RM supercellular tornadoes, decreasing the nocturnal false alarm by assuming a linear convective mode.
Music Therapy and Dance as Gait Rehabilitation in Patients With Parkinson Disease: A Review of Evidence
Authors: Pereira Ana Paula S. , Marinho Victor , Gupta Daya , Magalhães Francisco , Ayres Carla , Teixeira Silmar 
Published: December 2018

Parkinson disease causes several changes in gait, such as postural stability, which consequently induces fall risk factors and loss of quality of life. Alternative forms of treatment through rhythmic and dance stimuli have been used to minimize the Parkinson disease effects, which have been shown to be effective in improving gait and providing social well-being and quality of life in the patient. Aim: This review aims to demonstrate the efficiency of music and dance for gait improvement and symptom alleviation in Parkinson disease. Methodology: Studies that analyzed sound stimuli and dance in gait improvement in Parkinson disease were searched through PubMed, Scopus, Doaj, MEDLINE, and ScienceDirect databases from November 2017 to April 2018 and repeated in September 2018. Results and Discussion: Forty-five studies met the inclusion criteria to synthesize the findings on dance and music performance as a treatment for classical symptoms of Parkinson disease. Five reviews and 40 experimental papers have shown that rhythmic stimulation and dance provide the motor, cognitive, and quality of life benefits for participants with Parkinson disease. Thus, sound stimuli and dance offer satisfactory effects for gait, improving cognitive abilities such as motor control and adjustment and spatial memory. In addition, these new treatment modalities stimulate the elderly population to practice physical exercise, generating well-being and helping self-esteem. Conclusion: Dance and music therapy interventions are noninvasive, simple treatment options, which promote gait and cognition.