bluuebunny/crossref_metadata_2025_split huggingface dataset:
The association between mixed symptoms, irritability and functioning measured using smartphones in bipolar disorder
Authors: Faurholt‐Jepsen M. , Frost M. , Christensen E. M. , Bardram J. E. , Vinberg M. , Kessing L. V. 
Published: March 2019

ObjectiveTo (i) validate patient‐evaluated mixed symptoms and irritability measured using smartphones against clinical evaluations; (ii) investigate associations between mixed symptoms and irritability with stress, quality of life and functioning, respectively, in patients with bipolar disorder.MethodsA total of 84 patients with bipolar disorder used a smartphone‐based system for daily evaluation of mixed symptoms and irritability for nine months. Clinically evaluated symptoms, stress, quality of life and clinically rated functioning were collected multiple times during follow‐up.ResultsPatients presented mild affective symptoms. Patient‐reported mixed symptoms and irritability correlated with clinical evaluations. In analyses including confounding factors there was a statistically significant association between both mixed symptoms and irritability and stress (P < 0.0001) and between irritability and both quality of life and functioning (P < 0.0001) respectively. There was no association between mixed mood and both quality of life and functioning.ConclusionMixed symptoms and irritability can be validly self‐reported using smartphones in patients with bipolar disorder. Mixed symptoms and irritability are associated with increased stress even during full or partial remission. Irritability is associated with decreased quality of life and functioning. The findings emphasize the clinical importance of identifying inter‐episodic symptoms including irritability pointing towards smartphones as a valid tool.
Meta‐analysis of suicide rates among people discharged from non‐psychiatric settings after presentation with suicidal thoughts or behaviours
Authors: Wang M. , Swaraj S. , Chung D. , Stanton C. , Kapur N. , Large M. 
Published: March 2019

ObjectiveTo quantify the suicide rate among people discharged from non‐psychiatric settings after presentations with suicidal thoughts or behaviours.MethodMeta‐analysis of studies reporting suicide deaths among people with suicidal thoughts or behaviours after discharge from emergency departments or the medical or surgical wards of general hospitals.ResultsA total of 115 studies reported 167 cohorts and 3747 suicide deaths among 248 005 patients during 1 263 727 person‐years. The pooled suicide rate postdischarge was 483 suicide deaths per 100 000 person‐years (95% confidence interval (CI) 445–520, prediction interval (PI) 200–770) with high between‐sample heterogeneity (I2 = 92). The suicide rate was highest in the first year postdischarge (851 per 100 000 person‐years) but remained elevated in the long term. Suicide rates were elevated among samples of men (716 per 100 000 person‐years) and older people (799 per 100 000 person‐years) but were lower in samples of younger people (107 per 100 000 person‐years) and among studies published between 2010 and 2018 (329 per 100 000 person‐years).ConclusionsPeople with suicidal thoughts or behaviours who are discharged from non‐psychiatric settings have highly elevated rates of suicide despite a clinically meaningful decline in these suicide rates in recent decades.
The impact of flavors, health risks, secondhand smoke and prices on young adults’ cigarette and e‐cigarette choices: a discrete choice experiment
Authors: Buckell John , Sindelar Jody L. 
Published: March 2019

AbstractAimsTo estimate young adults’ preferences for cigarettes and e‐cigarettes, and how preferences vary by policy‐relevant factors. A related aim was to provide information on potential substitution/complementarity across cigarettes and e‐cigarettes ahead of policy selection.DesignAn online discrete choice experiment (DCE) in which respondents chose their preferred option among cigarettes, two types of e‐cigarettes (disposable/reusable) and ‘none’. Each cigarette‐type was characterized by policy‐relevant attributes: flavors, short‐term health risks to self, secondhand smoke risks and price. A latent class model identified smoking types that respond differently to these.SettingUS tobacco market.ParticipantsA total of 2003 young adults (aged 18–22 years) who ever tried either cigarettes or e‐cigarettes, recruited via the survey platform Qualtrics, matched to the 2015 National Health Interview Survey by age, gender, education and census region.MeasurementsRespondents’ DCE choices.FindingsYoung adults fell into two broad categories. One latent group, termed ‘prefer smoking group’, preferred cigarettes and another, ‘prefer vaping group’, preferred e‐cigarettes. The ‘prefer smoking group’ preferred lower prices and lower health harms more than other attributes. The ‘prefer vaping group’ valued these, although price less intensely, and valued health and fruit/candy flavors more.ConclusionBanning all flavors in cigarettes and e‐cigarettes might improve the health of young adults who ever tried either cigarettes or e‐cigarettes. Young adult ever‐triers might be deterred from smoking by increasing cigarette prices and encouraged to switch to e‐cigarettes by reducing the health harms of e‐cigarettes. Reducing health harms of e‐cigarettes could also make the ‘prefer vaping group’ less likely to quit, resulting in increased health harm.
The natural history of the sleepy lizard, Tiliqua rugosa (Gray, 1825) – Insight from chance observations and long‐term research on a common Australian skink species
Authors: Norval Gerrut , Gardner Michael G. 
Published: March 2019

AbstractIn an effort to better understand the dynamics of the parapatric boundary in South Australia of the ticks Amblyomma limbatum and Bothriocroton hydrosauri the late Professor C. Michael Bull initiated studies into the ecology of sleepy lizards (Tiliqua rugosa), a common host of these parasites. These studies spanned a period of about 40 years and examined aspects such as monogamy, long‐term mate fidelity, social networks, personality, resource use and the transmission of parasites and other pathogens. This review incorporates the results of these studies with other information about this species to provide a comprehensive overview of its natural history, highlighting not only what is known, but also indicates areas that require further study.
Does successful treatment of overactive bladder improve co‐morbidities in patients with nocturia?
Authors: Chin Kai Sin , Rose Georgie E. , Ervin Claire F. , Ong Tee Juan , Whishaw David M. , Bower Wendy F. 
Published: March 2019

ObjectiveTo investigate whether treatment of overactive bladder (OAB), one comorbidity of nocturia, could reduce waking to void and improve other co‐existing symptoms.MethodsA prospective cohort study was conducted at Royal Melbourne Hospital. Participants received 12 weeks of standard treatment, including lifestyle interventions and pharmacotherapy. Outcome measures were nocturia episodes, severity of urinary urgency/incontinence, sleep quality, daytime somnolence, anxiety and depression scores, quality of life and change in blood pressure.ResultsTwenty participants completed the study. Nocturia frequency improved by one void per night. Overactive Bladder Symptom Score, sleep quality, first uninterrupted sleep time and systolic blood pressures improved. There were no significant changes in daytime somnolence, mood or quality of life.ConclusionsIn this pilot study, nocturia and other co‐morbid dysfunctions appeared to improve when the severity of OAB was reduced. Treatment of OAB co‐morbid with nocturia reduces urinary symptoms and may improve sleep parameters and positively impact return to health.
Role of obinutuzumab exposure on clinical outcome of follicular lymphoma treated with first‐line immunochemotherapy
Authors: Jamois Candice , Gibiansky Ekaterina , Gibiansky Leonid , Buchheit Vincent , Sahin Denis , Cartron Guillaume , Marcus Robert , Hiddemann Wolfgang , Seymour John F. , Strefford Jonathan C. , Hargreaves Chantal E. , Meneses‐Lorente Georgina , Frey Nicolas , Fingerle‐Rowson Günter 
Published: March 2019

AimsObinutuzumab (G) is a humanized type II, Fc‐glycoengineered anti‐CD20 monoclonal antibody used in various indications, including patients with previously untreated front‐line follicular lymphoma. We investigated sources of variability in G exposure and association of progression‐free survival (PFS) with average concentration over induction (CmeanIND) in front‐line follicular lymphoma patients treated with G plus chemotherapy (bendamustine, CHOP, or CVP) in the GALLIUM trial.MethodsIndividual exposures (CmeanIND) were obtained from a previously established population pharmacokinetic model updated with GALLIUM data. Multivariate Cox proportional hazard models and univariate Kaplan–Meier plots investigated relationships of PFS with exposure and other potential prognostic factors.ResultsOverall, G exposure was lower in high body‐weight patients and in males, and slightly lower in patients with high baseline tumour burden. Analysis of clinical outcomes showed that variability in G exposure did not impact PFS in G‐bendamustine‐treated patients; PFS was inferior in males and patients with FCGR2a/2b T232 T low‐affinity receptor variant, and superior in patients with FCGR2a/2b I232T variant. In G‐CHOP/CVP arms, PFS improved with increasing CmeanIND (hazard ratio = 1.74 and 0.394 at 5th and 95th percentile compared to median CmeanIND) and was inferior in patients with high baseline tumour size and B symptoms.ConclusionsIt remains unclear whether for G‐CHOP/CVP patients lower G exposure is a consequence of adverse disease biology and/or resistance to chemotherapy backbone (higher clearance in nonresponder patients, as demonstrated for rituximab) rather than being the cause of poorer clinical outcome. A study with >1 dose level of G could help resolve this uncertainty.
Therapeutic gene editing in haematological disorders with CRISPR/Cas9
Authors: Jensen Trine I. , Axelgaard Esben , Bak Rasmus O. 
Published: March 2019

SummaryThe Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)/CRISPR‐associated (Cas)9 platform offers an efficient way of making precise genetic changes to the human genome. This can be employed for disruption, addition and correction of genes, thereby enabling a new class of genetic therapies that can be applied to haematological disorders. Here we review recent technological advances in the CRISPR/Cas9 methodology and applications in haematology for curing monogenic genetic disorders and for engineering novel chimeric antigen receptor (CAR) T cells to treat haematological malignancies. Furthermore, we discuss current challenges for full clinical implementation of CRISPR/Cas9, and reflect on future trajectories of the technology.
Diversity in warning coloration: selective paradox or the norm?
Authors: Briolat Emmanuelle S. , Burdfield‐Steel Emily R. , Paul Sarah C. , Rönkä Katja H. , Seymoure Brett M. , Stankowich Theodore , Stuckert Adam M. M. 
Published: March 2019

ABSTRACTAposematic theory has historically predicted that predators should select for warning signals to converge on a single form, as a result of frequency‐dependent learning. However, widespread variation in warning signals is observed across closely related species, populations and, most problematically for evolutionary biologists, among individuals in the same population. Recent research has yielded an increased awareness of this diversity, challenging the paradigm of signal monomorphy in aposematic animals. Here we provide a comprehensive synthesis of these disparate lines of investigation, identifying within them three broad classes of explanation for variation in aposematic warning signals: genetic mechanisms, differences among predators and predator behaviour, and alternative selection pressures upon the signal. The mechanisms producing warning coloration are also important. Detailed studies of the genetic basis of warning signals in some species, most notably Heliconius butterflies, are beginning to shed light on the genetic architecture facilitating or limiting key processes such as the evolution and maintenance of polymorphisms, hybridisation, and speciation. Work on predator behaviour is changing our perception of the predator community as a single homogenous selective agent, emphasising the dynamic nature of predator–prey interactions. Predator variability in a range of factors (e.g. perceptual abilities, tolerance to chemical defences, and individual motivation), suggests that the role of predators is more complicated than previously appreciated. With complex selection regimes at work, polytypisms and polymorphisms may even occur in Müllerian mimicry systems. Meanwhile, phenotypes are often multifunctional, and thus subject to additional biotic and abiotic selection pressures. Some of these selective pressures, primarily sexual selection and thermoregulation, have received considerable attention, while others, such as disease risk and parental effects, offer promising avenues to explore. As well as reviewing the existing evidence from both empirical studies and theoretical modelling, we highlight hypotheses that could benefit from further investigation in aposematic species. Finally by collating known instances of variation in warning signals, we provide a valuable resource for understanding the taxonomic spread of diversity in aposematic signalling and with which to direct future research. A greater appreciation of the extent of variation in aposematic species, and of the selective pressures and constraints which contribute to this once‐paradoxical phenomenon, yields a new perspective for the field of aposematic signalling.
Mechanisms of human FoxP3+ Treg cell development and function in health and disease
Authors: Attias M , Al-Aubodah T , Piccirillo C A 
Published: March 2019

SummaryRegulatory T (Treg) cells represent an essential component of peripheral tolerance. Given their potently immunosuppressive functions that is orchestrated by the lineage-defining transcription factor forkhead box protein 3 (FoxP3), clinical modulation of these cells in autoimmunity and cancer is a promising therapeutic target. However, recent evidence in mice and humans indicates that Treg cells represent a phenotypically and functionally heterogeneic population. Indeed, both suppressive and non-suppressive Treg cells exist in human blood that are otherwise indistinguishable from one another using classical Treg cell markers such as CD25 and FoxP3. Moreover, murine Treg cells display a degree of plasticity through which they acquire the trafficking pathways needed to home to tissues containing target effector T (Teff) cells. However, this plasticity can also result in Treg cell lineage instability and acquisition of proinflammatory Teff cell functions. Consequently, these dysfunctional CD4+FoxP3+ T cells in human and mouse may fail to maintain peripheral tolerance and instead support immunopathology. The mechanisms driving human Treg cell dysfunction are largely undefined, and obscured by the scarcity of reliable immunophenotypical markers and the disregard paid to Treg cell antigen-specificity in functional assays. Here, we review the mechanisms controlling the stability of the FoxP3+ Treg cell lineage phenotype. Particular attention will be paid to the developmental and functional heterogeneity of human Treg cells, and how abrogating these mechanisms can lead to lineage instability and Treg cell dysfunction in diseases like immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, type 1 diabetes, rheumatoid arthritis and cancer.
Higher rates of rejection in HIV‐infected kidney transplant recipients on ritonavir‐boosted protease inhibitors: 3‐year follow‐up study
Authors: Rollins Brett , Farouk Samira , DeBoccardo Graciela , Lerner Susan , Rana Meenakshi , Huprikar Shirish , Miko Leandra , Delaney Veronica , Florman Sander , Shapiro Ron 
Published: March 2019

AbstractRejection rates in HIV‐infected kidney transplant (KTx) recipients are higher than HIV‐negative recipients. Immunosuppression and highly active antiretroviral therapy (HAART) protocols vary with potentially significant drug‐drug interactions, likely influencing outcomes. This is an IRB‐approved, single‐center, retrospective study of adult HIV‐infected KTx patients between 5/2009 and 12/2014 with 3‐year follow‐up, excluding antibody‐depleting induction. A total of 42 patients were included; median age was 52 years, 81% male, 50% African American, 29% Hispanic, 17% Caucasian. The most common renal failure etiology was hypertensive nephrosclerosis (50%) with 5.8 median years of pre‐transplant dialysis. All patients received IL‐2 receptor antagonist, were maintained on tacrolimus (76%) or cyclosporine (17%), and 40% received ritonavir‐boosted PI‐based HAART (rtv+) regimen. Patient and graft survival at 3 years were 93% and 90%. At 1‐, 2‐, and 3‐year time points, median serum creatinine was 1.49, 1.35, and 1.67; treated biopsy‐proven rejection was 38%, 38%, and 40.5%; and 92% of episodes were acute rejection. At these time points, rejection rates were significantly higher with boosted PI HAART regimens compared to other HAART regimens, 59% vs 24% (P = 0.029), 59% vs 24% (P = 0.029), and 68% vs 24% (P = 0.01). Despite higher rejection rates, HIV‐infected KTx recipients have reasonable outcomes. Given significantly higher rejection rates using rtv+ regimens, alternative HAART regimens should be considered prior to transplantation.
Distribution trends of European dragonflies under climate change
Authors: Termaat Tim , van Strien Arco J. , van Grunsven Roy H. A. , De Knijf Geert , Bjelke Ulf , Burbach Klaus , Conze Klaus‐Jürgen , Goffart Philippe , Hepper David , Kalkman Vincent J. , Motte Grégory , Prins Marijn D. , Prunier Florent , Sparrow David , van den Top Gregory G. , Vanappelghem Cédric , Winterholler Michael , WallisDeVries Michiel F. 
Published: March 2019

AbstractAimPoleward range shifts of species are among the most obvious effects of climate change on biodiversity. As a consequence of these range shifts, species communities are predicted to become increasingly composed of warm‐dwelling species, but this has only been studied for a limited number of taxa, mainly birds, butterflies and plants. As species groups may vary considerably in their adaptation to climate change, it is desirable to expand these studies to other groups, from different ecosystems. Freshwater macroinvertebrates, such as dragonflies (Odonata), have been ranked among the species groups with highest priority. In this paper, we investigate how the occurrence of dragonflies in Europe has changed in recent decades, and if these changes are in parallel with climate change.LocationEurope.MethodsWe use data from 10 European geographical regions to calculate occupancy indices and trends for 99 (69%) of the European species. Next, we combine these regional indices to calculate European indices. To determine if changes in regional dragonfly communities in Europe reflect climatic warming, we calculate Species Temperature Indices (STI), Multi‐species Indicators (MSI) and Community Temperature Indices (CTI).Results55 of 99 considered species increased in occupancy at European level, 32 species remained stable, and none declined. Trends for 12 species are uncertain. MSI of cold‐dwelling and warm‐dwelling species differ in some of the regions, but increased at a similar rate at European level. CTI increased in all regions, except Cyprus. The European CTI increased slightly.Main conclusionsEuropean dragonflies, in general, have expanded their distribution in response to climate change, even though their CTI lags behind the increase in temperature. Furthermore, dragonflies proved to be a suitable species group for monitoring changes in communities, both at regional and continental level.
eGFR and coronary artery calcification in chronic kidney disease
Authors: Hyun Young Youl , Kim Hyang , Oh Kook‐Hwan , Ahn Curie , Park Sue K. , Chae Dong Wan , Oh Yun Kyu , Choi Kyu Hun , Han Seung Hyeok , Kim Yeong Hoon , Lee Kyu‐Beck ,   KNOW‐CKD Study Investigators
Published: March 2019

AbstractBackgroundThe independent association between eGFR and coronary artery calcification (CAC) is complex and not clear. The aim of this study was to investigate the relationship between eGFR calculated from different equations and CAC in predialysis CKD patients in Korea.MethodsIn this cross‐sectional study, we analysed 1533 patients from the KNOW‐CKD cohort. eGFR was calculated by a four‐variable MDRD equation (eGFRMDRD), CKD‐EPI creatinine equations (eGFRCr), CKD‐EPI cystatin C equation (eGFRCys) and CKD‐EPI creatinine‐cystatin equation (eGFRCrCys). Participants were divided into eGFR categories (<30, 30‐59, 60‐89, ≥90 mL/min/1.73 m2). CACS (coronary artery calcium score) was measured using cardiac computed tomography. CAC was defined as CACS >100.ResultsCoronary artery calcification was found in 334 (21.8%) patients and was more prevalent in the lower eGFR groups (P < 0.001). In multivariate Tobit regression, CACS increased gradually as eGFRCrCys decreased (P for trend = 0.034). In multivariate logistic regression, there were gradual associations between lower eGFR and CAC when an eGFRCys or eGFRCrCys was used. The adjusted OR for CAC in the group with eGFR <30 mL/min/1.73 m2 compared to the group with eGFR ≥90 mL/min/1.73 m2 was 2.64 (95% CI, 1.09‐3.60) when eGFRCrCys was used. Of the four eGFR formulas, only adding eGFRCrCys significantly improved CAC prediction models without eGFR (P = 0.046).ConclusionsThere was a gradual and independent association between low eGFR and CAC in a predialysis CKD cohort in Korea. eGFRCrCys predicted CAC better than other equations in this population.