bluuebunny/crossref_metadata_2025_split huggingface dataset:
Maturity-Related Differences in Systemic Pulmonary and Localized Fatigue Threshold Among Youth Male Athletes
Authors: Beyer Kyle S. , Stout Jeffrey R. , Redd Michael J. , Baker Kayla M. , Bergstrom Haley C. , Hoffman Jay R. , Fukuda David H. 
Published: September 2018

Purpose: To examine the reliability and the maturity-related differences of fatigue thresholds (FTs) among youth males. Methods: Twenty-nine youth males (11–17 y) completed 2 ramp exercise tests on a cycle ergometer. Systemic FTs were calculated from gas exchange and ventilation variables. Localized FTs were calculated from electromyography and near-infrared spectroscopy of the vastus lateralis. All FTs were determined using the maximal distance method and expressed relative to maximal oxygen consumption. All participants were grouped according to the number of years from peak height velocity into PRE- (< −1.5 y), PERI- (−1.5 to +1.5 y) and POST- (> +1.5 y) peak height velocity. Reliability was assessed with intraclass correlation coefficients, and differences between groups were assessed with analysis of variance and Cohen’s d coefficients. Results: Analysis of variance revealed significant group differences with PRE having significantly greater systemic pulmonary FTs than POST, while localized muscular FTs were significantly greater in PRE when compared with PERI and POST. All FTs exhibited excellent reliability (intraclass correlation coefficient > .75) in all maturity groups. Conclusion: Maturity status appears to influence the onset of FTs among youth male athletes, with FTs occurring later in younger athletes. Furthermore, all FTs were reliable measures regardless of maturity.
Phase II evaluation of anti-MAdCAM antibody PF-00547659 in the treatment of Crohn’s disease: report of the OPERA study
Authors: Sandborn William J , Lee Scott D , Tarabar Dino , Louis Edouard , Klopocka Maria , Klaus Jochen , Reinisch Walter , Hébuterne Xavier , Park Dong-Il , Schreiber Stefan , Nayak Satyaprakash , Ahmad Alaa , Banerjee Anindita , Brown Lisa S , Cataldi Fabio , Gorelick Kenneth J , Cheng John B , Hassan-Zahraee Mina , Clare Robert , D’Haens Geert R 
Published: September 2018

Objective
This phase II, randomised, double-blind, placebo-controlled clinical trial was designed to evaluate the efficacy and safety of PF-00547659, a fully human monoclonal antibody that binds to human mucosal addressin cell adhesion molecule (MAdCAM) to selectively reduce lymphocyte homing to the intestinal tract, in patients with moderate-to-severe Crohn’s disease (CD).

Design
Eligible adults were aged 18–75 years, with active moderate-to-severe CD (Crohn’s Disease Activity Index (CDAI) 220–450), a history of failure or intolerance to antitumour necrosis factor and/or immunosuppressive agents, high-sensitivity C reactive protein >3.0 mg/L and ulcers on colonoscopy. Patients were randomised to PF-00547659 22.5 mg, 75 mg or 225 mg or placebo. The primary endpoint was CDAI 70-point decrease from baseline (CDAI-70) at week 8 or 12.

Results

In all, 265 patients were eligible for study entry. Although CDAI-70 response was not significantly different with placebo versus PF-00547659 treatment at weeks 8 or 12, remission rate was greater in patients with higher baseline C reactive protein (>5 mg/L vs >18.8 mg/L, respectively). Soluble MAdCAM decreased significantly from baseline to week 2 in a dose-related manner and remained low during the study in PF-00547659-treated patients. Circulating β
7
+ CD4+ central memory T-lymphocytes increased at weeks 8 and 12 with PF-00547659 treatment. No safety signal was seen.

Conclusions

Clinical endpoint differences between PF-00547659 and placebo did not reach statistical significance in patients with moderate-to-severe CD. PF-00547659 was pharmacologically active, as shown by a sustained dose-related decrease in soluble MAdCAM and a dose-related increase in circulating β
7
+ central memory T cells.

Trial registration number

NCT01276509
; Results.
Parkinson’s disease: evolution of cognitive impairment and CSF Aβ1–42 profiles in a prospective longitudinal study
Authors: Lerche Stefanie , Wurster Isabel , Röben Benjamin , Machetanz Gerrit , Zimmermann Milan , Bernhard Felix , Stransky Elke , Deuschle Christian , Schulte Claudia , Hansson Oskar , Zetterberg Henrik , Gasser Thomas , Berg Daniela , Maetzler Walter , Brockmann Kathrin 
Published: September 2018

ObjectiveTo evaluate the evolution of cognitive impairment in relation to cerebrospinal fluid (CSF) profiles of amyloid-β (Aβ), total-Tau and phosphorylated-Tau in Parkinson’s disease (PD).MethodsProspective, longitudinal, observational study up to 10 years with follow-up every 2  years. We assessed CSF profiles in 415 patients with sporadic PD (median age 66; 63% men) and 142 healthy controls (median age 62; 43% men).ResultsPatients with PD with low CSF Aβ1–42 levels at baseline were more often cognitively impaired than patients with intermediate and high Aβ1–42 levels. Sixty-seven per cent of the patients with low Aβ1–42 levels at baseline and normal cognition developed cognitive impairment during follow-up, compared with 41% and 37% of patients having intermediate and high CSF Aβ1–42 levels. Kaplan-Meier survival curves and Cox regression revealed that patients with low CSF Aβ1–42 levels at baseline developed cognitive impairment more frequently and earlier during follow-up.ConclusionWe conclude that in patients with sporadic PD, low levels of Aβ1–42 are associated with a higher risk of developing cognitive impairment earlier in the disease process at least in a subgroup of patients.
Assessment of postoperative inflammatory markers and pain in cats after laparoscopy and miniceliotomy ovariectomy
Authors: da Conceição Maria Eduarda Bastos Andrade Moutinho , Uscategui Ricardo Andres Ramirez , Bertolo Paulo Henrique Leal , de Souza Damazio Campos , Rolemberg Daniele dos Santos , de Moraes Paola Castro , Teixeira Pedro Paulo Maia , Dias Luis Gustavo Gosuen Gonçalves 
Published: September 2018

Videosurgery is increasingly used in veterinary medicine. Compared with open surgery, it has been shown to cause minimal pain and promote a more rapid recovery. There are various methods of assessing pain and postoperative inflammation in cats, although their particular behaviours may make these assessments difficult. The aim of this study was to compare levels of postoperative pain and inflammation after laparoscopic ovariectomy with an open minimally invasive technique. Twenty queens were randomly divided into two groups based on the method of haemostasis and surgical technique: (1) laparoscopic ovariectomy using a miniloop (miniloop group (MG)); and (2) minilaparotomy using a Snook hook (control group (CG)). Heart rate (HR), respiratory rate (RR), end tidal CO2(EtCO2) and body temperature were assessed using a multiparametric monitor during anaesthesia and surgery at defined surgical time points (preincision, left ovary manipulation, right ovary manipulation and skin suture). Blood samples (2 mL each) were collected from the jugular vein before surgery and 1, 12, 24, 48 and 72 hours, and 10 days, after endotracheal extubation for blood count analysis and to assess total protein and acute phase proteins (APP). EtCO2and RR were significantly higher in MG patients (P<0.001). HR was higher in the CG group for the duration of surgery (P=0.01). Temperature was significantly lower in MG patients (P<0.001). Pain assessment by dynamic interactive visual analogue scale showed no difference between groups or at specific moments of time within groups. Segmented neutrophil counts increased at 24 hours postoperatively and peaked at 48 and 72 hours in MG (P=0.01). The most important result among APPs was haptoglobin, which peaked at 72 hours in MG patients (P=0.001). Patients undergoing minilaparotomy and laparoscopy showed comparable postoperative pain. However, inflammatory changes such as APPs and neutrophil counts were increased in the laparoscopic group.
Ultrahigh pressure metamorphism and tectonic evolution of southwestern Tianshan orogenic belt, China: a comprehensive review
Authors: Zhang Lifei , Wang Yang , Zhang Lijuan , Lü Zeng 
Published: September 2018

Abstract

Recently, a huge ultrahigh-pressure (UHP) metamorphic belt of oceanic type has been recognized in SW Tianshan, China. Petrological studies show that the UHP metamorphic rocks of SW Tianshan orogenic belt include mafic eclogites and blueschists, pelitic garnet phengite schists, marbles and serpentinites. The well-preserved coesite inclusions are commonly found in eclogites, garnet phengite schists and marbles. Ti-clinohumite and Ti-chondrodite have been identified in UHP metamorphic serpentinites. Based on the
P–T
pseudosection calculation and combined U–Pb zircon dating, the
P–T–t
path has been outlined as four stages: cold subduction to UHP conditions before
c.
320 Ma whose peak ultrahigh pressure is about 30 kbar at 500°C; heating decompression from the
P
max
to the
T
max
stage before 305 Ma whose peak temperature is about 600°C at 22 kbar; then the early cold exhumation from amphibolite eclogite facies to epidote-amphibolite facies metamorphism before 220 Ma; and the last tectonic exhumation from epidote amphibolite facies to greenschist facies metamorphism. Combining with the syn-subduction arc-like 333–326 Ma granitic rocks and 280–260 Ma S-type granites in the coeval low-pressure and high-temperature metamorphic belt, the tectonic evolution of Tianshan UHP metamorphic belt during late Cambrian to early Triassic has been proposed in this paper.
Precise Spatiotemporal Interruption of Regulatory T-cell–Mediated CD8+ T-cell Suppression Leads to Tumor Immunity
Authors: Zhou Xiaoyu , Zhao Shushu , He Yue , Geng Shuang , Shi Yan , Wang Bin 
Published: September 2018

Abstract

Tumors can develop despite the presence of competent host immunity via a complex system of immune evasion. One of the most studied factors originating from the host is immune suppression by regulatory T cells (Treg). Ample laboratory and clinical evidence suggests that Treg ablation leads to robust antitumor immune activation. However, how Tregs specifically achieve their suppression in the context of tumor progression is not entirely clear, particularly with regard to the timing and location where Treg inhibition takes place. In this work, we report that Tregs migrate to tumor-draining lymph nodes (TDLN) and block expression of sphingosine-1-phosphate receptor 1 (S1P1) on CD8+ T cells. This event trapped the CD8+ T cells in the TDLN and served as a facilitating factor for tumor growth. Intriguingly, minimalistic depletion of Tregs in TDLN in a short window following tumor inoculation was sufficient to restore CD8+ T-cell activities, which resulted in significant tumor reduction. Similar treatments outside this time frame had no such effect. Our work therefore reveals a subtle feature in tumor biology whereby Tregs appear to be driven by newly established tumors for a programmed encounter with newly activated CD8+ T cells in TDLN. Our results suggest the possibility that clinical interception of this step can be tested as a new strategy of cancer therapy, with expected high efficacy and low systemic side effects.

Significance:
These findings reveal a strong tumor suppressive effect invoked by minimal blockade of tumor draining lymph node regulatory T cells during early versus late tumorigenesis.
Cyclooxygenase-2 Influences Response to Cotargeting of MEK and CDK4/6 in a Subpopulation of Pancreatic Cancers
Authors: Maust Joel D. , Frankowski-McGregor Christy L. , Bankhead Armand , Simeone Diane M. , Sebolt-Leopold Judith S. 
Published: September 2018

AbstractThe ineffectiveness of chemotherapy in patients with pancreatic cancer highlights a critical unmet need in pancreatic cancer therapy. Two commonly mutated genes in pancreatic cancer, KRAS and CDKN2A, have an incidence exceeding 90%, supporting investigation of dual targeting of MEK and CDK4/6 as a potential therapeutic strategy for this patient population. An in vitro proliferation synergy screen was conducted to evaluate response of a panel of high passage and patient-derived pancreatic cancer models to the combination of trametinib and palbociclib to inhibit MEK and CDK4/6, respectively. Two adenosquamous carcinoma models, L3.6pl and UM59, stood out for their high synergy response. In vivo studies confirmed that this combination treatment approach was highly effective in subcutaneously implanted L3.6pl and UM59 tumor-bearing animals. Both models were refractory to single-agent treatment. Reverse-phase protein array analysis of L3.6pl tumors excised from treated animals revealed strong downregulation of COX-2 expression in response to combination treatment. Expression of COX-2 under a CMV-driven promoter and shRNA knockdown of COX-2 both led to resistance to combination treatment. Our findings suggest that COX-2 may be involved in the improved therapeutic outcome seen in some pancreatic tumors that fail to respond to MEK or CDK4/6 inhibitors alone but respond favorably to their combination.
Cardiac Troponins for the Diagnosis of Acute Myocardial Infarction in Chronic Kidney Disease
Authors: Kraus Daniel , von Jeinsen Beatrice , Tzikas Stergios , Palapies Lars , Zeller Tanja , Bickel Christoph , Fette Georg , Lackner Karl J. , Drechsler Christiane , Neumann Johannes T. , Baldus Stephan , Blankenberg Stefan , Münzel Thomas , Wanner Christoph , Zeiher Andreas M. , Keller Till 
Published: September 2018

Background

Patients with chronic kidney disease (
CKD
) are at high risk of myocardial infarction. Cardiac troponins are the biomarkers of choice for the diagnosis of acute myocardial infarction (
AMI
) without
ST
‐segment elevation (
NSTE
). In patients with
CKD
, troponin levels are often chronically elevated, which reduces their diagnostic utility when
NSTE
‐
AMI
is suspected. The aim of this study was to derive a diagnostic algorithm for serial troponin measurements in patients with
CKD
and suspected
NSTE
‐
AMI
.

Methods and Results

Two cohorts, 1494 patients from a prospective cohort study with high‐sensitivity troponin I (hs‐
cTnI
) measurements and 7059 cases from a clinical registry with high‐sensitivity troponin T (hs‐
cTnT
) measurements, were analyzed. The prospective cohort comprised 280
CKD
patients (estimated glomerular filtration rate <60 mL/min/1.73 m
2
). The registry data set contained 1581
CKD
patients. In both cohorts,
CKD
patients were more likely to have adjudicated
NSTE
‐
AMI
than non‐
CKD
patients. The specificities of hs‐
cTnI
and hs‐
cTnT
to detect
NSTE
‐
AMI
were reduced with
CKD
(0.82 versus 0.91 for hs‐
cTnI
and 0.26 versus 0.73 for hs‐
cTnT
) but could be restored by applying optimized cutoffs to either the first or a second measurement after 3 hours. The best diagnostic performance was achieved with an algorithm that incorporates serial measurements and rules in or out
AMI
in 69% (hs‐
cTnI
) and 55% (hs‐
cTnT
) of CKD patients.

Conclusions

The diagnostic performance of high‐sensitivity cardiac troponins in patients with
CKD
with suspected
NSTE
‐
AMI
is improved by use of an algorithm based on admission troponin and dynamic changes in troponin concentration.
Prognostic Impact of Acute Myocardial Infarction in Patients Presenting With Ventricular Tachyarrhythmias and Aborted Cardiac Arrest
Authors: Behnes Michael , Mashayekhi Kambis , Weiß Christel , Nienaber Christoph , Lang Siegfried , Reiser Linda , Bollow Armin , Taton Gabriel , Reichelt Thomas , Ellguth Dominik , Engelke Niko , Schupp Tobias , Ansari Uzair , El‐Battrawy Ibrahim , Rusnak Jonas , Akin Muharrem , Borggrefe Martin , Akin Ibrahim 
Published: September 2018

Background

The study sought to assess the prognostic impact of acute myocardial infarction (
AMI
) with and without
ST
‐segment–elevation myocardial infarction (
STEMI
and
NSTEMI
) in patients with ventricular tachyarrhythmias and sudden cardiac arrest (
SCA
) on admission.

Methods and Results

A large retrospective registry was used including all consecutive patients presenting with ventricular tachycardia (
VT
), fibrillation (
VF
), and sudden cardiac arrest (
SCA
) on admission from 2002 to 2016.
AMI
versus non‐
AMI
and
STEMI
versus
NSTEMI
were compared applying multivariable Cox regression models and propensity‐score matching for evaluation of the primary prognostic end point defined as long‐term all‐cause mortality at 2.5 years. Secondary end points were 30 days all‐cause mortality, cardiac death at 24 hours, in hospital death, and recurrent percutaneous coronary intervention (re‐
PCI
) at 2.5 years. In 2813 unmatched high‐risk patients with ventricular tachyarrhythmias and
SCA
,
AMI
was present in 29% (10%
STEMI
, 19%
NSTEMI
) with higher rates of
VF
(54% versus 31%) and
SCA
(35% versus 26%), whereas
VT
rates were higher in non‐
AMI
(56% versus 30%) (
P
< 0.05).
AMI
‐related
VT
≥48 hours was associated with higher mortality (log rank
P
= 0.001). Multivariable Cox regression models revealed non‐
AMI
(hazard ratio = 1.458;
P
= 0.001) and
NSTEMI
(hazard ratio = 1.460;
P
= 0.036) associated with increasing long‐term all‐cause mortality at 2.5 years, which was also proven after propensity‐score matching (non‐
AMI
versus
AMI
: 55% versus 43%, log rank
P
= 0.001, hazard ratio = 1.349;
NSTEMI
versus
STEMI
: 45% versus 34%, log rank
P
= 0.047, hazard ratio = 1.372). Secondary end points including 30 days and in‐hospital mortality, as well as re‐
PCI
were higher in non‐
AMI
patients.

Conclusions

In high‐risk patients presenting with ventricular tachyarrhythmias and
SCA
, non‐
AMI
revealed higher mortality than
AMI
, respectively
NSTEMI
than
STEMI
, alongside
AMI
‐related VT ≥48 hours.
Evaluation of Subtropical North Atlantic Ocean Circulation in CMIP5 Models against the Observational Array at 26.5°N and Its Changes under Continued Warming
Authors: Beadling R. L. , Russell J. L. , Stouffer R. J. , Goodman P. J. 
Published: September 2018

AbstractObservationally based metrics derived from the Rapid Climate Change (RAPID) array are used to assess the large-scale ocean circulation in the subtropical North Atlantic simulated in a suite of fully coupled climate models that contributed to phase 5 of the Coupled Model Intercomparison Project (CMIP5). The modeled circulation at 26.5°N is decomposed into four components similar to those RAPID observes to estimate the Atlantic meridional overturning circulation (AMOC): the northward-flowing western boundary current (WBC), the southward transport in the upper midocean, the near-surface Ekman transport, and the southward deep ocean transport. The decadal-mean AMOC and the transports associated with its flow are captured well by CMIP5 models at the start of the twenty-first century. By the end of the century, under representative concentration pathway 8.5 (RCP8.5), averaged across models, the northward transport of waters in the upper WBC is projected to weaken by 7.6 Sv (1 Sv ≡ 106 m3 s−1; −21%). This reduced northward flow is a combined result of a reduction in the subtropical gyre return flow in the upper ocean (−2.9 Sv; −12%) and a weakened net southward transport in the deep ocean (−4.4 Sv; −28%) corresponding to the weakened AMOC. No consistent long-term changes of the Ekman transport are found across models. The reduced southward transport in the upper ocean is associated with a reduction in wind stress curl (WSC) across the North Atlantic subtropical gyre, largely through Sverdrup balance. This reduced WSC and the resulting decrease in the horizontal gyre transport is a robust feature found across the CMIP5 models under increased CO2 forcing.
Prediction of the Madden–Julian Oscillation: A Review
Authors: Kim Hyemi , Vitart Frédéric , Waliser Duane E. 
Published: September 2018

AbstractThere has been an accelerating interest in forecasting the weather and climate within the subseasonal time range. The Madden–Julian oscillation (MJO), an organized envelope of tropical convection, is recognized as one of the leading sources of subseasonal predictability. This review synthesizes the latest progress regarding the MJO predictability and prediction. During the past decade, the MJO prediction skill in dynamical prediction systems has exceeded the skill of empirical predictions. Such improvement has been mainly attributed to more observations and computer resources, advances in theoretical understanding, and improved numerical models aided in part by multinational efforts through field campaigns and multimodel experiments. The state-of-the-art dynamical forecasts have shown MJO prediction skill up to 5 weeks. Prediction skill can be extended by improving the ensemble generation approach tailored for MJO prediction and by averaging multiensembles or multimodels. MJO prediction skill can be influenced by the tropical mean state and low-frequency climate mode variations, as well as by the extratropical circulation. MJO prediction skill is proven to be sensitive to model physics, ocean–atmosphere coupling, and quality of initial conditions, while the impact of the model resolution seems to be marginal. Remaining challenges and recommendations on new research avenues to fully realize the predictability of the MJO are discussed.
Impact of AMSU-A Radiances in a Column Ensemble Kalman Filter
Authors: Mitchell Herschel L. , Houtekamer P. L. , Heilliette Sylvain 
Published: September 2018

Abstract
A column EnKF, based on the Canadian global EnKF and using the RTTOV radiative transfer (RT) model, is employed to investigate issues relating to the EnKF assimilation of Advanced Microwave Sounding Unit-A (AMSU-A) radiance measurements. Experiments are performed with large and small ensembles, with and without localization. Three different descriptions of background temperature error are considered: 1) using analytical vertical modes and hypothetical spectra, 2) using the vertical modes and spectrum of a covariance matrix obtained from the global EnKF after 2 weeks of cycling, and 3) using the vertical modes and spectrum of the static background error covariance matrix employed to initiate a global data assimilation cycle. It is found that the EnKF performs well in some of the experiments with background error description 1, and yields modest error reductions with background error description 3. However, the EnKF is virtually unable to reduce the background error (even when using a large ensemble) with background error description 2. To analyze these results, the different background error descriptions are viewed through the prism of the RT model by comparing the trace of the matrix , where is the RT model and is the background error covariance matrix. Indeed, this comparison is found to explain the difference in the results obtained, which relates to the degree to which deep modes are, or are not, present in the different background error covariances. The results suggest that, after 2 weeks of cycling, the global EnKF has virtually eliminated all background error structures that can be “seen” by the AMSU-A radiances.