bluuebunny/crossref_metadata_2025_split huggingface dataset:
Myeloproliferative Neoplasms: A Primer for Radiologists
Authors: Liput Joseph , Smith Daniel A. , Beck Rose , Ramaiya Nikhil H. 
Published: July 2019

Abstract
The myeloproliferative neoplasms (MPNs) are a heterogeneous group of diseases including polycythemia vera, essential thrombocythemia, and primary myelofibrosis. Knowledge of the radiological and clinical features of MPNs and their associated complications is critical for interpreting radiologists. The purpose of this article is to provide a primer to radiologists summarizing the modern understanding of MPNs from an imaging-based perspective, including common disease-related findings and complications related to hematopoietic cell transplant.
Standardized measurement of breathlessness during exercise
Authors: Lewthwaite Hayley , Koch Emily M. , Tracey Lauren , Jensen Dennis 
Published: July 2019

Purpose of review
Exertional breathlessness is common and pervasive across various chronic disease populations. To accurately assess response to intervention and optimize clinical (symptom) management, detailed assessment of exertional breathlessness is imperative. This review provides an update on current approaches to assess exertional breathlessness and presents the need for individualized assessment of breathlessness standardized for the level of exertion.

Recent findings
Breathlessness assessment tools commonly invite people to recall their breathlessness while at rest with reference to activities of daily living. To directly quantify breathlessness, however, requires assessment of the dimensions of breathlessness (e.g., sensory intensity, quality, and unpleasantness) in response to a standardized exercise stimulus. Different exercise stimuli (e.g., self-paced, incremental, and constant work rate exercise tests) have been used to elicit a breathlessness response. Self-paced (e.g., 6-min walk test) and incremental exercise tests assess exercise tolerance or endurance, and are not recommended for assessment of exertional breathlessness. Constant work rate tests, however, including recently validated 3-min constant-rate stair stepping and walking tests, standardize the exercise stimulus to enable the breathlessness response to be directly quantified and monitored over time.

Summary
To adequately guide symptom management and assess intervention efficacy, clinicians and researchers should assess breathlessness with multidimensional assessment tools in response to a standardized and individualized exercise stimulus.
Why treatment efficacy on breathlessness in laboratory but not daily life trials? The importance of standardized exertion
Authors: Ekström Magnus 
Published: July 2019

Purpose of review
Treatments for chronic breathlessness, including opioids and oxygen, have shown efficacy in the controlled laboratory setting, whereas effects have been inconsistent or absent in trials in daily life. This review discusses the lack of standardized exertion as a potential cause of false negative findings for breathlessness in daily life.

Recent findings
The level of breathlessness can be modified by patients by changing their level of physical activity. Effects of opioids and oxygen have been shown at standardized level of exertion (iso-time) but not at the end of symptom-limited (peak) exertion. Trials in daily life reporting no effects on breathlessness did not standardize the exertion or employed insensitive methods, such as the 6-min walk test that should not be used for measuring breathlessness. Novel tests – the 3-min walk and stepping tests have been validated in chronic obstructive pulmonary disease and are responsive for measuring change in breathlessness.

Summary
Breathlessness should be measured at standardized exertion, otherwise treatment effects may be biased or overlooked. Tests for valid measurement of breathlessness in clinical practice and daily life are available and emerging.
Abcg2-Expressing Side Population Cells Contribute to Cardiomyocyte Renewal through Fusion
Authors: Yellamilli Amritha , Ren Yi , McElmurry Ron T. , Lambert Jonathan P. , Gross Polina , Mohsin Sadia , Houser Steven R. , Elrod John W. , Tolar Jakub , Garry Daniel J. , van Berlo Jop H. 
Published: July 2019

ABSTRACTThe adult mammalian heart has a limited regenerative capacity. Therefore, identification of endogenous cells and mechanisms that contribute to cardiac regeneration is essential for the development of targeted regenerative therapies. The side population (SP) phenotype enriches for stem cells throughout the body, and SP cells have been identified in the heart. We generated a novel Abcg2-driven, genetic lineage-tracing mouse model and show efficient labeling of SP cells. Labeled SP cells give rise to terminally differentiated cells in bone marrow and intestines. In the heart, we find that Abcg2-expressing SP cells contribute to cardiomyocyte labeling, which is further enhanced in response to different forms of cardiac injury. We find that cardiac SP cells fuse with preexisting cardiomyocytes, which stimulates cardiomyocyte cell cycle entry and likely proliferation, instead of directly differentiating into cardiomyocytes. Our findings provide evidence that cardiac SP cells contribute to endogenous cardiac regeneration through cardiomyocyte fusion.
A metagene of NRF2 expression is a prognostic biomarker in all stage colorectal cancer
Authors: O’Cathail Séan M. , Wu Chieh-Hsi , Lewis Annabelle , Holmes Chris , Hawkins Maria A , Maughan Tim 
Published: July 2019

ABSTRACTObjectiveNrf2 overexpression confers poor prognosis in some cancers but its role in colorectal cancer (CRC) is unknown. Due to its role as a transcription factor we hypothesise a metagene of NRF2 regulated genes could act as a prognostic biomarker in CRC.DesignUsing known NRF2 regulated genes, we defined an NRF2 metagene to represent the pathway expression using principal component analysis and Cox proportional hazard models. The NRF2 metagene was validated in four independent datasets, including the recently profiled MRC FOCUS randomised controlled trial.Results36 genes comprised the final prognostic metagene in the training set. 1,360 patients were included in the validation analyses. High NRF2 metagene expression is associated with worse disease free survival (DFS) and overall survival (OS) outcomes in stage I/II/III disease and worse OS in stage IV disease. In multivariate analyses, NRF2 expression remained significant when adjusted for known prognostic factors of adjuvant chemotherapy and stage in stage I/II/III disease, as well as BRAF V600E mutation and sidedness in stage IV disease. NRF2 metagene expression exhibits variation within each of the Consensus Molecular Subtypes (CMS) but high expression is particularly enriched in CMS 4.ConclusionWe demonstrate in a large scale analysis that NRF2 expression is a novel biomarker of poor prognosis across all stages of colorectal cancer. Higher expression observed in CMS 4 further refines the molecular taxonomy of colorectal cancer.
tACS entrains neural activity while somatosensory input is blocked
Authors: Vieira Pedro G. , Krause Matthew R. , Pack Christopher C. 
Published: July 2019

AbstractTranscranial alternating current stimulation (tACS) modulates brain activity by passing electrical current through electrodes that are attached to the scalp. Because it is safe and non-invasive, it holds great promise as a tool for basic research and clinical treatment. However, little is known about how tACS ultimately influences neural activity. One hypothesis is that tACS affects neural responses directly, by producing electrical fields that interact with the brain’s endogenous electrical activity. Since the shape and location of these electric fields can be controlled, stimulation could be targeted at brain regions associated with particular behaviors or symptoms. However, an alternative hypothesis is that tACS affects neural activity indirectly, via peripheral sensory afferents. In particular, it has often been hypothesized that tACS acts on nerve fibers in the skin, which in turn provide rhythmic input to central neurons. In this case, there would be little possibility of targeted brain stimulation, as the regions modulated by tACS would depend entirely on the somatosensory pathways originating in the skin around the stimulating electrodes. Here, we directly test these competing hypotheses by recording single-unit activity in the hippocampus and visual cortex of monkeys receiving tACS. We find that tACS entrains neuronal activity in both regions, so that cells fire synchronously with the stimulation. Blocking somatosensory input with a topical anesthetic does not significantly alter these neural entrainment effects. These data are therefore consistent with the direct stimulation hypothesis and suggest that peripheral somatosensory stimulation is not required for tACS to entrain neurons.
Self-body recognition through a mirror: Easing spatial-consistency requirements for rubber hand illusion
Authors: Hasegawa Hikaru , Okamoto Shogo , Ito Ken , Hara Masayuki , Kanayama Noriaki , Yamada Yoji 
Published: July 2019

AbstractTypical experiments to induce the rubber hand illusion (RHI) require experimental participants to gaze at a fake hand while tactile stimuli are provided to both the fake and hidden actual hands in a synchronous manner. However, under such conditions, postural and apparent disagreement between a seen fake hand and hidden actual hand prevents illusory body ownership. Provided that humans recognize mirror images as copies of the real world in spite of their spatial uncertainties or incongruence, the sensory disagreement may be accepted in RHI settings if using a mirror to show a fake hand. The present study performed two experiments to reveal how self-body recognition of a fake hand feature via mirror affects the RHI. These experiments were conducted in an RHI environment involving voluntary hand movements to investigate not only body ownership but also agency. The first experiment (Experiment 1) examined whether illusory ownership of a fake hand seen in a mirror could be induced. Then, we examined whether the RHI using a mirror image allows disagreement in orientation between the rubber and actual hands (Experiment 2). Subjective evaluations using a RHI questionnaire demonstrated that evoked embodiment of the rubber hand was stronger in the presence of a mirror than in the absence of it (Experiment 1) and that participants experienced the RHI even if the actual and rubber hands were incongruent in terms of orientation (45 °; Experiment 2). No significant difference was found in the change of perceived finger location (proprioceptive drift) between these experiments. These findings suggest that the use of a mirror masks subtle spatial incongruency or degrades the contribution of visual cues for spatial recognition and facilitates multisensory integration for bodily illusions.
A time‐series model for estimating temporal variation in phenotypic selection on laying dates in a Dutch great tit population
Authors: Cao Yihan , Visser Marcel E. , Tufto Jarle 
Published: July 2019

Abstract

Temporal and spatial variation in phenotypic selection due to changing environmental conditions is of great interest to evolutionary biologists, but few existing methods estimating its magnitude take into account the temporal autocorrelation.
We use state‐space models (SSMs) to analyse phenotypic selection processes that cannot be observed directly and use Template Model builder (TMB), an R package for computing and maximizing the Laplace approximation of the marginal likelihood for SSM and other complex, nonlinear latent variable model via automatic differentiation. Using a long‐term great tit (Parus major) dataset, we fit several SSMs and conduct model selection based on Akaike information criterion (AIC) to assess the support for fluctuated directional or autocorrelated stabilizing selection on breeding time of the great tit population.
Our results show that there is directional selection on the probability of breeding failure, and stabilizing selection on the mean number of fledglings. This selection for early laying date is consistent with a previous study of the same population. We also estimate the variation and autocorrelation in other parameters of the fitness functions, including the width and height, and found the height and location of annual fitness function are autocorrelated with significant variation, while the width can be assumed to constant over time.
Using TMB to fit SSMs, we are able to estimate additional parameters compared to previous methods, all without requiring a substantial increase in computational resources. Furthermore, our specification of complex nonlinear model structure benefits greatly from the flexibility of model formulation with TMB. Therefore, our approach could be directly applied to estimating even more complicated phenotypic selection processes induced by environmental change for other species.
The prevalence of wholly attributable alcohol conditions in the United Kingdom hospital system: a systematic review, meta‐analysis and meta‐regression
Authors: Roberts Emmert , Morse Rachel , Epstein Sophie , Hotopf Matthew , Leon David , Drummond Colin 
Published: July 2019

ABSTRACTBackground and AimsThe prevalence of alcohol‐related conditions is often reported as higher in hospital in‐patients compared with the general population. However, formal prevalence estimates are commonly derived from small studies which report highly varied results. This systematic review and meta‐analysis, within the UK hospital system, aimed to estimate the pooled prevalence of the 26 ICD‐10 conditions that are wholly attributable to alcohol in in‐patient settings.MethodsWe searched Medline, Embase, PsychINFO and CENTRAL from database inception until 1 May 2018. We included studies of any design that reported the prevalence of one of 26 wholly attributable alcohol conditions defined by the ICD‐10. Studies were required to be conducted in one or more of the constituent nations of the United Kingdom and in an in‐patient setting (general wards, intensive care units, accident and emergency departments or mental health in‐patient units). Estimates were pooled using random‐effects meta‐analysis, and meta‐regression tested study and patient factors contributing to variation. Quality was assessed using the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework.ResultsA total of 124 studies were included, reporting on a total of 1 657 614 patients. The majority of studies reported on harmful use of alcohol and alcohol dependence, for which the pooled prevalence was 19.76% [95% confidence interval (CI) = 15.61–24.26%] and 10.25% (95% CI = 7.06–13.96%), respectively. Mean patient age and type of in‐patient setting were identified as the main sources of variation in prevalence estimates, but not date of data collection. Both estimates were deemed very low quality according to GRADE.ConclusionsAn estimated one in five patients in the UK hospital system use alcohol harmfully, and one in 10 are alcohol‐dependent.
A review of whole brain radiotherapy outcomes in a high epidermal growth factor receptor mutation rate population: Does QUARTZ apply in Asia?
Authors: Ng Ivy Weishan , Tey Jeremy Chee Seong , Chia David Wei Tsau , Yee Choon Meng , Cheo Timothy Song Tao 
Published: July 2019

AbstractAimWhole brain radiotherapy (WBRT) is commonly used to treat brain metastases (BM) from nonsmall cell lung cancer (NSCLC). Its utility is increasingly being questioned after a recent randomized trial (QUARTZ) showed that its omission did not significantly impact the survival or quality of life of their patients recruited from UK and Australian centers. We report the patient characteristics and survival outcomes of our local population in comparison with theirs.MethodsMedical records of patients who received WBRT in two tertiary hospitals over 18 months were reviewed. Characteristics and survival outcomes of patient with NSCLC receiving WBRT for the first time were evaluated. Patients with prior excision of BM or stereotactic radiotherapy were excluded. Treatment details including radiotherapy dose and use of tyrosine kinase inhibitors (TKIs) were recorded.ResultsBetween January 2015 and June 2016, 116 patients with NSCLC received WBRT for their BM. Their median age was 65 years (range, 36‐85) and median follow‐up duration was 110 days (range, 14‐840). A total of 102 (88%) patients had their driver mutation tested of which 59 (58%) were epidermal growth factor receptor (EGFR) mutants. Factors predicting for better survival were female gender (P < .001), EGFR mutant receiving TKIs (P = .013), prescription other than 20 Gray in five fractions (P = .003), and presence of more than four BM (P = .001).ConclusionOur patients appear to be considerably different from those recruited into the QUARTZ trial. Further prospective studies should be done to evaluate the value of WBRT in our population.
The efficacy and safety of tacrolimus as mono‐ and adjunctive therapy for vitiligo: A systematic review of randomised clinical trials
Authors: Arora Charan Jeet , Rafiq Muhammad , Shumack Stephen , Gupta Monisha 
Published: July 2019

AbstractThere is currently no definitive treatment for vitiligo; various modalities include immune modulators phototherapy and skin camouflage. We investigated the efficacy and safety of topical tacrolimus either as monotherapy or combined therapy in the treatment of vitiligo. Electronic systematic search of the literature was carried out using four major databases. Randomised clinical trials (RCTs) that reported the use of topical tacrolimus in the treatment of human vitiligo have been included in a systematic review and meta‐analysis. Meta‐analysis was conducted via RevMan, and risk of bias was assessed through the Cochrane quality assessment tool. The protocol was published through PROSPERO (CRD42018112430). A total of 19 studies including 814 patients were included in our systematic review. The random‐effects‐model meta‐analysis of two studies revealed that the tacrolimus and narrowband ultraviolet B (NB‐UVB) combination therapy rates is better than NB‐UVB alone in inducing >75% repigmentation [RR 1.34 (95% CI: 01.05–1.71), P = 0.02]. Tacrolimus and steroids had similar potency in acheiving >75% repigmentation [RR 1.02 (95% CI: 0.19–5.51), P = 0.98]. Meta‐analysis of two studies revealed that the fractional laser and tacrolimus combination therapy is no better than tacrolimus alone in causing >75% repigmentation [RR 2.11 (95% CI: 0.87–5.09), P = 0.10]. Further investigating tacrolimus as mono‐ or adjuvant therapy for vitiligo is highly recommended. Combining tacrolimus to other treatment options such as steroids, phototherapy and laser may be superior to using tacrolimus alone.
Risk of adult‐onset asthma increases with the number of allergic multimorbidities and decreases with age
Authors: Toppila‐Salmi Sanna , Chanoine Sebastien , Karjalainen Jussi , Pekkanen Juha , Bousquet Jean , Siroux Valérie 
Published: July 2019

AbstractBackgroundThe aim was to study the association between allergic multimorbidity and adult‐onset asthma considering the number of allergic diseases and the age effect.MethodsWe used population‐based data from Finnish national registers including 1205 adults over 30 years of age with recently diagnosed asthma (age range: 30‐93), matched for gender, age, and living region with one or two controls (n = 2050). Allergic rhinitis (AR), allergic conjunctivitis (AC), and allergic dermatitis (AD) were defined from self‐completed questionnaire. Conditional logistic regression adjusted on potential confounders (smoking, growing in countryside, childhood hospitalized infection/pneumonia, parental asthma/allergy, parental smoking, education level, professional training, number of siblings, and birth order) was applied to estimate the asthma risk associated with allergic multimorbidity.ResultsA total of 1118 cases with asthma and 1772 matched controls were included [mean (SD, min‐max) 53 (11, 31‐71) years, 37% men)]. AR, AC, and AD were reported by 50.2%, 39.6%, and 33.8%, respectively, among subjects with asthma and 26.1%, 20.0%, and 23.5%, respectively, among controls. Compared to nonatopics, adult‐onset asthma increased with the number of allergic diseases; adjusted OR for asthma [95% CI] associated with 1, 2, and 3 allergic diseases was 1.95 [1.52‐2.49], 2.87 [2.19‐3.77], and 4.26 [3.07‐5.90], respectively. The association between adult‐onset asthma and ≥ 1 allergic multimorbidity decreased with increasing age (3.52 [2.51‐4.94], 2.44 [1.74‐3.42], and 1.68 [1.04‐2.71]) in subjects < 50 years, 50‐62 years, and > 62 years, respectively (p for age*≥1 allergic multimorbidity interaction, 0.002).ConclusionsAdult‐onset asthma was positively associated with the number of allergic diseases, and this association decreases with age.
Nursing intensity scores did not correlate well with reimbursement claims for infant bronchiolitis
Authors: Heikkilä Paula , Kokko Petra , Lohi Olli , Korppi Matti 
Published: July 2019

AbstractAimWe retrospectively evaluated the hospital reimbursement rates for inpatient bronchiolitis treatment and then compared them to the RAFAELA® nursing intensity scores.MethodsWe selected all 44 bronchiolitis patients treated in the paediatric intensive care unit (PICU) and then for each PICU‐treated patient two patients treated on the ward (n = 88) under 12 months of age in 2010‐2015. The data included medical histories, hospital reimbursement rates using the Nordic Diagnosis Related Groups (NordDRG) or expense categories and the RAFAELA® scores.ResultsReimbursement claims were mostly based on expense categories for PICU admissions and NordDRG categories for ward admissions. The median (range) was €6352 (€1330‐30 554) and €2009 (€768‐6027) per episode for the PICU and ward cases, respectively. The median lengths of hospital stay were 8.5 days (3‐18) and 3 days (1‐8), respectively. Higher RAFAELA® scores were associated with nasal continuous positive airway pressure therapy and mechanical ventilation in the PICU and oxygen supplementation and nasogastric tube feeding on the ward. The correlation coefficients between RAFAELA® scores and hospital reimbursement claims ranged from 0.121‐0.450.ConclusionHospital reimbursement claim for a PICU admission was three times as much as a ward admission and reimbursement claims for bronchiolitis did not match with nursing intensity scores.