bluuebunny/crossref_metadata_2025_split huggingface dataset:
Validation of the Saint George’s Respiratory Questionnaire in Uganda
Authors: Morgan Brooks W , Grigsby Matthew R , Siddharthan Trishul , Kalyesubula Robert , Wise Robert A , Hurst John R , Kirenga Bruce , Checkley William 
Published: July 2018

IntroductionChronic obstructive pulmonary disease (COPD) will soon be the third leading global cause of death and is increasing rapidly in low/middle-income countries. There is a need for local validation of the Saint George’s Respiratory Questionnaire (SGRQ), which can be used to identify those experiencing lifestyle impairment due to their breathing.MethodsThe SGRQ was professionally translated into Luganda and reviewed by our field staff and a local pulmonologist. Participants included a COPD-confirmed clinic sample and COPD-positive and negative members of the community who were enrolled in the Lung Function in Nakaseke and Kampala (LiNK) Study. SGRQs were assembled from all participants, while demographic and spirometry data were additionally collected from LiNK participants.ResultsIn total, 103 questionnaires were included in analysis: 49 with COPD from clinic, 34 community COPD-negative and 20 community COPD-positive. SGRQ score varied by group: 53.5 for clinic, 34.4 for community COPD-positive and 4.1 for community COPD-negative (p<0.001). The cross-validatedcstatistic for SGRQ total score predicting COPD was 0.87 (95% CI 0.75 to 1.00). SGRQ total score was associated with COPD severity (forced expiratory volume in 1 s per cent of predicted), with anrcoefficient of −0.60 (−0.75, −0.39). SGRQ score was associated with dyspnoea (OR 1.05/point; 1.01, 1.09) and cough (1.07; 1.03, 1.11).ConclusionOur Luganda language SGRQ accurately distinguishes between COPD-positive and negative community members in rural Uganda. Scores were correlated with COPD severity and were associated with odds of dyspnoea and cough. We find that it can be successfully used as a respiratory questionnaire for obstructed adults in Uganda.
Differences of in-hospital outcomes within patients undergoing percutaneous coronary intervention at institutions with high versus low procedural volume: a report from the Japanese multicentre percutaneous coronary intervention registry
Authors: Kodaira Masaki , Kuno Toshiki , Numasawa Yohei , Ohki Takahiro , Nakamura Iwao , Ueda Ikuko , Fukuda Keiichi , Kohsaka Shun 
Published: July 2018

ObjectiveWe aimed to determine the relationship between the prevalence of in-hospital complications and annual institutional patient volume in a population of patients undergoing percutaneous coronary intervention (PCI).MethodsClinical data of patients receiving PCI between January 2010 and June 2015 were collected from 14 academic institutions in the Tokyo area and subsequently used for analysis. We employed multivariate hierarchical logistic regression models to determine the effect of institutional volume on several in-hospital outcomes, including in-hospital mortality and procedure-related complications.ResultsA total of 14 437 PCI cases were included and categorised as receiving intervention from either lower-volume (<200 procedures/year, n=6 hospitals) or higher-volume (≥200 procedures/year, n=8 hospitals) institutions. Clinical characteristics differed significantly between the two patient groups. Specifically, patients treated in higher-volume hospitals presented with increased comorbidities and complex coronary lesions. Unadjusted mortality and complication rate in lower-volume and higher-volume hospitals were 1.3% and 1.2% (p=0.0614) and 6.2% and 8.1% (p=0.001), respectively. However, multivariate hierarchical logistic regression models adjusting for differences in the patient characteristics demonstrated that institutional volume was not associated with adverse clinical outcomes.ConclusionsIn conclusion, we observed no significant association between annual institutional volume and in-hospital outcomes within the contemporary PCI multicentre registry.Trial registration numberUMIN R000005598.
Effect of exercise therapy on established and emerging circulating biomarkers in patients with heart failure: a systematic review and meta-analysis
Authors: Pearson Melissa J , King Nicola , Smart Neil A 
Published: July 2018

BackgroundBiomarkers are important in the diagnosis, risk stratification and management of patients with heart failure (HF). The established biomarkers of myocardial stretch, brain natriuretic peptide (BNP) and amino (N) portion of BNP (NT-proBNP) have been extensively studied, and early analyses have demonstrated response to exercise training. Several other biomarkers have been identified over the last decade and may provide valuable and complementary information which may guide treatment strategies, including exercise therapy.MethodsA systematic search of PubMed, EMBASE and Cochrane Trials Register to 31 October 2017 was conducted for exercise-based rehabilitation trials in HF. Randomised and controlled trials that reported biomarkers, BNP, NT-proBNP, soluble ST2, galectin-3, mid-regional atrial natriuretic peptide, mid-regional adrenomedullin and copeptin, were included.ResultsForty-three studies were included in the systematic review, with 27 studies suitable for meta-analyses. Data pooling was only possible for NT-proBNP and BNP. Meta-analyses of conventional training studies demonstrated a statistically significant improvement in NT-proBNP (pmol/L); mean difference (MD) −32.80 (95% CI −56.19 to −9.42), p=0.006 and in BNP (pmol/L); MD −17.17 (95% CI −29.56 to −4.78), p=0.007. Pooled data of non-conventional training failed to demonstrate any statistically significant improvements.ConclusionPooled data indicated a favourable effect of conventional exercise therapy on the established biomarkers, NT-proBNP and BNP; however, this was in contrast to a number of studies that could not be pooled. Limited evidence exists as to the effect of exercise training on emerging biomarkers.
Impact of early treatment with intravenous vasodilators and blood pressure reduction in acute heart failure
Authors: Kitai Takeshi , Tang W H Wilson , Xanthopoulos Andrew , Murai Ryosuke , Yamane Takafumi , Kim Kitae , Oishi Shogo , Akiyama Eiichi , Suzuki Satoshi , Yamamoto Masayoshi , Kida Keisuke , Okumura Takahiro , Kaji Shuichiro , Furukawa Yutaka , Matsue Yuya 
Published: July 2018

ObjectiveAlthough vasodilators are used in acute heart failure (AHF) management, there have been no clear supportive evidence regarding their routine use. Recent European guidelines recommend systolic blood pressure (SBP) reduction in the range of 25% during the first few hours after diagnosis. This study aimed to examine clinical and prognostic significance of early treatment with intravenous vasodilators in relation to their subsequent SBP reduction in hospitalised AHF.MethodsWe performed post hoc analysis of 1670 consecutive patients enrolled in the Registry Focused on Very Early Presentation and Treatment in Emergency Department of Acute Heart Failure. Intravenous vasodilator use within 6 hours of hospital arrival and subsequent SBP changes were analysed. Outcomes were gauged by 1-year mortality and diuretic response (DR), defined as total urine output 6 hours posthospital arrival per 40 mg furosemide-equivalent diuretic use.ResultsOver half of the patients (56.0%) were treated with intravenous vasodilators within the first 6 hours. In this vasodilator-treated cohort, 554 (59.3%) experienced SBP reduction ≤25%, while 381 (40.7%) experienced SBP reduction >25%. In patients experiencing ≤25% drop in SBP, use of vasodilator was associated with greater DR compared with no vasodilators (p<0.001). Moreover, vasodilator treatment with ≤25% drop in SBP was independently associated with lower all-cause mortality compared with those treated without vasodilators (adjusted HR 0.74, 95% CI 0.57 to 0.96, p=0.028).ConclusionsIntravenous vasodilator therapy was associated with greater DR and lower mortality, provided SBP reduction was less than 25%. Our results highlight the importance in early administration of intravenous vasodilators without causing excess SBP reduction in AHF management.Clinical trial registrationURL:http://www.umin.ac.jp/ctr/Unique identifier: UMIN000014105.
Vocal learning in songbirds requires cholinergic signaling in a motor cortex-like nucleus
Authors: Puzerey Pavel A. , Maher Kamal , Prasad Nikil , Goldberg Jesse H. 
Published: July 2018

Cholinergic inputs to cortex modulate plasticity and sensory processing, yet little is known about their role in motor control. Here, we show that cholinergic signaling in a songbird vocal motor cortical area, the robust nucleus of the arcopallium (RA), is required for song learning. Reverse microdialysis of nicotinic and muscarinic receptor antagonists into RA in juvenile birds did not significantly affect syllable timing or acoustic structure during vocal babbling. However, chronic blockade over weeks reduced singing quantity and impaired learning, resulting in an impoverished song with excess variability, abnormal acoustic features, and reduced similarity to tutor song. The demonstration that cholinergic signaling in a motor cortical area is required for song learning motivates the songbird as a tractable model system to identify roles of the basal forebrain cholinergic system in motor control. NEW & NOTEWORTHY Cholinergic inputs to cortex are evolutionarily conserved and implicated in sensory processing and synaptic plasticity. However, functions of cholinergic signals in motor areas are understudied and poorly understood. Here, we show that cholinergic signaling in a songbird vocal motor cortical area is not required for normal vocal variability during babbling but is essential for developmental song learning. Cholinergic modulation of motor cortex is thus required for learning but not for the ability to sing.
Late maturation of backward masking in auditory cortex
Authors: Mattingly Michelle M. , Donell Brittany M. , Rosen Merri J. 
Published: July 2018

Speech perception relies on the accurate resolution of brief, successive sounds that change rapidly over time. Deficits in the perception of such sounds, indicated by a reduced ability to detect signals during auditory backward masking, strongly relate to language processing difficulties in children. Backward masking during normal development has a longer maturational trajectory than many other auditory percepts, implicating the involvement of central auditory neural mechanisms with protracted developmental time courses. Despite the importance of this percept, its neural correlates are not well described at any developmental stage. We therefore measured auditory cortical responses to masked signals in juvenile and adult Mongolian gerbils and quantified the detection ability of individual neurons and neural populations in a manner comparable with psychoacoustic measurements. Perceptually, auditory backward masking manifests as higher thresholds for detection of a short signal followed by a masker than for the same signal in silence. Cortical masking was driven by a combination of suppressed responses to the signal and a reduced dynamic range available for signal detection in the presence of the masker. Both coding elements contributed to greater masked threshold shifts in juveniles compared with adults, but signal-evoked firing suppression was more pronounced in juveniles. Neural threshold shifts were a better match to human psychophysical threshold shifts when quantified with a longer temporal window that included the response to the delayed masker, suggesting that temporally selective listening may contribute to age-related differences in backward masking.NEW & NOTEWORTHY In children, auditory detection of backward masked signals is immature well into adolescence, and detection deficits correlate with problems in speech processing. Our auditory cortical recordings reveal immature backward masking in adolescent animals that mirrors the prolonged development seen in children. This is driven by both signal-evoked suppression and dynamic range reduction. An extended window of analysis suggests that differences in temporally focused listening may contribute to late maturing thresholds for backward masked signals.
Pupil-linked arousal modulates behavior in rats performing a whisker deflection direction discrimination task
Authors: Schriver Brian J. , Bagdasarov Svetlana , Wang Qi 
Published: July 2018

Non-luminance-mediated changes in pupil size have been widely used to index arousal state. Recent animal studies have demonstrated correlations between behavioral state-related pupil dynamics and sensory processing. However, the relationship between pupil-linked arousal and behavior in animals performing perceptual tasks has not been fully elucidated. In the present study, we trained head-fixed rats to discriminate between directions of whisker movements using a Go/No-Go discrimination paradigm while imaging their pupils. Reaction times in this discrimination task were significantly slower than in previously reported detection tasks with similar setup, suggesting that discrimination required an increased cognitive load. We found the pupils dilated for all trials following stimulus presentation. Interestingly, in correct rejection trials, where pupil dilations solely resulted from cognitive processing, dilations were larger for more difficult stimuli. Baseline pupil size before stimulus presentation strongly correlated with behavior, as perceptual sensitivity peaked at intermediate pupil baselines and reaction time was fastest at large baselines. We further explored these relationships by investigating to what extent pupil baseline was predictive of upcoming behavior and found that a Bayesian decoder had significantly greater-than-chance probability in correctly predicting behavioral outcomes. Moreover, the outcome of the previous trial showed a strong correlation with behavior on present trials. Animals were more liberal and faster in responding following hit trials, whereas perceptual sensitivity was greatest following correct rejection trials. Taken together, these results suggest a tight correlation between pupil dynamics, perceptual performance, and reaction time in behaving rats, all of which are modulated by fluctuating arousal state. NEW & NOTEWORTHY In this study, we for the first time demonstrated that head-fixed rats were able to discriminate different directions of whisker movement. Interestingly, we found that the pupil dilated more when discriminating more difficult stimuli, a phenomenon reported in human subjects but not in animals. Baseline pupil size before stimulus presentation was found to strongly correlate with behavior, and a Bayesian decoder had significantly greater-than-chance probability in correctly predicting behavioral outcomes based on the baseline pupil size.
The role of intersegmental dynamics in coordination of the forelimb joints during unperturbed and perturbed skilled locomotion
Authors: Zubair Humza N. , Stout Erik E. , Dounskaia Natalia , Beloozerova Irina N. 
Published: July 2018

Joint coordination during locomotion and how this coordination changes in response to perturbations remains poorly understood. We investigated coordination among forelimb joints during the swing phase of skilled locomotion in the cat. While cats walked on a horizontal ladder, one of the cross-pieces moved before the cat reached it, requiring the cat to alter step size. Direction and timing of the cross-piece displacement were manipulated. We found that the paw was transported in space through body translation and shoulder and elbow rotations, whereas the wrist provided paw orientation required to step on cross-pieces. Kinetic analysis revealed a consistent joint control pattern in all conditions. Although passive interaction and gravitational torques were the main sources of shoulder and elbow motions for most of the movement time, shoulder muscle torque influenced movement of the entire limb at the end of the swing phase, accelerating the shoulder and causing interaction torque that determined elbow motion. At the wrist, muscle and passive torques predominantly compensated for each other. In all perturbed conditions, although all joints and the body slightly contributed to changes in the step length throughout the entire movement, the major adjustment was produced by the shoulder at the movement end. We conclude that joint coordination during the swing phase is produced mainly passively, by exploiting gravity and the limb’s intersegmental dynamics, which may simplify the neural control of locomotion. The use of shoulder musculature at the movement end enables flexible responses to environmental disturbances. NEW & NOTEWORTHY This is the first study to investigate joint control during the swing phase of skilled, accuracy-dependent locomotion in the cat and how this control is altered to adapt to known and unexpected perturbations. We demonstrate that a pattern of joint control that exploits gravitational and interaction torques is used in all conditions and that movement modifications are produced mainly by shoulder muscle torque during the last portion of the movement.
Normal Breast-Derived Epithelial Cells with Luminal and Intrinsic Subtype-Enriched Gene Expression Document Interindividual Differences in Their Differentiation Cascade
Authors: Kumar Brijesh , Prasad Mayuri , Bhat-Nakshatri Poornima , Anjanappa Manjushree , Kalra Maitri , Marino Natascia , Storniolo Anna Maria , Rao Xi , Liu Sheng , Wan Jun , Liu Yunlong , Nakshatri Harikrishna 
Published: July 2018

Abstract
Cell-type origin is one of the factors that determine molecular features of tumors, but resources to validate this concept are scarce because of technical difficulties in propagating major cell types of adult organs. Previous attempts to generate such resources to study breast cancer have yielded predominantly basal-type cell lines. We have created a panel of immortalized cell lines from core breast biopsies of ancestry-mapped healthy women that form ductal structures similar to normal breast in 3D cultures and expressed markers of major cell types, including the luminal-differentiated cell-enriched ERα–FOXA1–GATA3 transcription factor network. We have also created cell lines from PROCR (CD201)+/EpCAM− cells that are likely the “normal” counterpart of the claudin-low subtype of breast cancers. RNA-seq and PAM50-intrinsic subtype clustering identified these cell lines as the “normal” counterparts of luminal A, basal, and normal-like subtypes and validated via immunostaining with basal-enriched KRT14 and luminal-enriched KRT19. We further characterized these cell lines by flow cytometry for distribution patterns of stem/basal, luminal-progenitor, mature/differentiated, multipotent PROCR+ cells, and organogenesis-enriched epithelial/mesenchymal hybrid cells using CD44/CD24, CD49f/EpCAM, CD271/EpCAM, CD201/EpCAM, and ALDEFLUOR assays and E-cadherin/vimentin double staining. These cell lines showed interindividual heterogeneity in stemness/differentiation capabilities and baseline activity of signaling molecules such as NF-κB, AKT2, pERK, and BRD4. These resources can be used to test the emerging concept that genetic variations in regulatory regions contribute to widespread differences in gene expression in “normal” conditions among the general population and can delineate the impact of cell-type origin on tumor progression.
Significance: In addition to providing a valuable resource for the breast cancer research community to investigate cell-type origin of different subtypes of breast cancer, this study highlights interindividual differences in normal breast, emphasizing the need to use "normal" cells from multiple sources as controls to decipher the effects of cancer-specific genomic aberrations. Cancer Res; 78(17); 5107–23. ©2018 AACR.
Targeted Sequencing of Circulating Tumor DNA to Monitor Genetic Variants and Therapeutic Response in Metastatic Colorectal Cancer
Authors: Hsu Hung-Chih , Lapke Nina , Wang Chuang-Wei , Lin Pei-Yi , You Jeng Fu , Yeh Chien Yuh , Tsai Wen-Sy , Hung Hsin Yuan , Chiang Sum-Fu , Chen Hua-Chien , Chen Shu-Jen , Hsu An , Yang Tsai Sheng 
Published: July 2018

Abstract
Substantial improvements have been made in the management of metastatic colorectal cancer (mCRC) in the last two decades, but disease monitoring remains underdeveloped. Circulating tumor DNA (ctDNA) is a promising prognostic and predictive biomarker; however, ctDNA as a marker for mCRC patients is not well established, and there is still no consensus about how to utilize it most cost-effectively. In this study, we aim to investigate plasma ctDNA levels as a biomarker for therapeutic response of mCRC patients. We performed next-generation sequencing (NGS) by using a 12-gene panel to identify genetic variants in 136 tumor tissue and ctDNA samples from 32 mCRC patients. Genetic variants were detected in approximately 70% of samples, and there was a high concordance (85%) between tumor tissue and plasma ctDNA. We observed ctDNA changes in 18 follow-up patients, including the emergence of new variants. Changes in ctDNA levels significantly correlated with tumor shrinkage (P = 0.041), and patients with a ctDNA decrease &gt;80% after treatment had a longer progression-free survival compared with patients with a ctDNA decrease of &lt;80% (HR, 0.22; P = 0.015). The objective response rate among patients with a ctDNA decrease of &gt;80% was better than those with a ctDNA decrease &lt;80% (OR, 0.026; P = 0.007). In conclusion, this study demonstrates that monitoring of genetic ctDNA variants can serve as a valuable biomarker for therapeutic efficacy in mCRC patients, and that using a moderate-sized 12-gene NGS panel may be suitable for such clinical monitoring. Mol Cancer Ther; 17(10); 2238–47. ©2018 AACR.
Henry Whitney Bellows and “A New Catholic Church”
Authors: Willsky-Ciollo Lydia 
Published: July 2018

Abstract
This article examines the evolution of Bellow’s proposal for a newly reformed Unitarian “catholic” church during the 1850s and 1860s. For Bellows in particular, political, cultural, and ecclesiastical matters collided in his efforts to transform a diffuse set of liberal Christian churches in fellowship into a denomination of national, even global, caliber. The creation of this “new catholic church” would, in turn, help to heal an ailing nation. There are two questions driving this narrative. First, how did Bellows arrive at the conclusion that Unitarianism was the future of Christendom, the more “Protestant-Protestantism,” or even more boldly, the “more Catholic-Catholicism?” Secondly, how did Bellows arrive at the conclusion that uniting Christendom under a “catholic” Unitarian banner could unite a fractured country? During the early 1860s, the language of nationalism and catholicity merged in Bellows’ organization of the National Convention.