bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development and validation of a self‐report measure of practical barriers to medication adherence: The medication practical barriers to adherence questionnaire (MPRAQ)
Authors: Chan Amy Hai Yan , Vervloet Marcia , Lycett Helen , Brabers Anne , van Dijk Liset , Horne Rob 
Published: January 2021

AimThis study reports the development and validation of a new self‐report measure, the Medication Practical barriers to Adherence Questionnaire (MPRAQ), which assesses practical barriers to medication adherence.MethodsThe MPRAQ comprises 15 statements describing practical barriers. Responses are scored on a 5‐point Likert scale; higher scores indicate more practical barriers. Initial face validity was evaluated by cognitive testing with patients from a diabetes support group. Following refinement, internal reliability and construct validity were assessed in two samples: patients recruited via Amazon mTurk and the Nivel Dutch Healthcare Consumer Panel (COPA). Respondents completed the Beliefs about Medicines Questionnaire (BMQ‐General and BMQ‐Specific), and the Medication Adherence Report Scale (MARS‐5). The mTurk sample also completed the Perceived Sensitivity to Medicines questionnaire (PSM) and repeated the MPRAQ 2 weeks later to assess test‐retest reliability.ResultsFace validity was evaluated in 15 patients (46% female; mean (SD) age 64 (12) years). A total of 184 mTurk participants completed the questionnaire (in English) and 334 in COPA (in Dutch). Internal reliability was acceptable (mTurk α = 0.89; COPA α = 0.94). Construct validity was confirmed, with significant correlation between the MPRAQ and BMQ‐Specific Concerns (mTurk r = 0.546, P < .0001; COPA r = 0.370, P < .0001), BMQ‐General Harm (mTurk r = 0.504, P < 0.0001; COPA r = 0.219, P < .0001), BMQ‐General Overuse (mTurk r = 0.324, P < .0001; COPA r = 0.109, P = .047) and PSM (mTurk only r = 0.463, P < .0001), and a negative correlation with MARS‐5 (mTurk r = −0.450, P < .0001; COPA r = −0.260, P < .0001). MPRAQ did not correlate with BMQ‐Specific Necessity or BMQ‐General Benefit. Correlation between MPRAQ baseline and 2‐week follow‐up scores confirmed test‐retest reliability (r = 0.745, P < .0001; n = 52).ConclusionMPRAQ is a reliable and valid self‐report measure of practical adherence barriers.
High erythroferrone expression in CD71+ erythroid progenitors predicts superior survival in myelodysplastic syndromes
Authors: Riabov Vladimir , Mossner Maximilian , Stöhr Alexandra , Jann Johann‐Christoph , Streuer Alexander , Schmitt Nanni , Knaflic Antje , Nowak Verena , Weimer Nadine , Obländer Julia , Palme Iris , Schumann Christiane , Baldus Claudia D. , Schulze Torsten J. , Wuchter Patrick , Röhl Henning , Jawhar Ahmed , Weiss Christel , Boch Tobias , Metzgeroth Georgia , Neumann Martin , Hofmann Wolf‐Karsten , Nolte Florian , Nowak Daniel 
Published: January 2021

SummaryIneffective erythropoiesis and iron overload are common in myelodysplastic syndromes (MDS). Erythroferrone (ERFE) and growth/differentiation factor 15 (GDF15) are two regulators of iron homeostasis produced by erythroid progenitors. Elevated systemic levels of ERFE and GDF15 in MDS are associated with dysregulated iron metabolism and iron overload, which is especially pronounced in MDS with SF3B1 gene mutations. However, the role of ERFE and GDF15 in MDS pathogenesis and their influence on disease progression are largely unknown. Here, we analyzed the expression of ERFE and GDF15 in CD71+ erythroid progenitors of n = 111 MDS patients and assessed their effects on patient survival. The expression of ERFE and GDF15 in MDS was highly aberrant. Unexpectedly, ERFE expression in erythroprogenitors was highly relevant for MDS prognosis and independent of International Prognostic Scoring System (IPSS) stratification. Although ERFE expression was increased in patients with SF3B1 mutations, it predicted overall survival (OS) in both the SF3B1wt and SF3B1mut subgroups. Of note, ERFE overexpression predicted superior OS in the IPSS low/Int‐1 subgroup and in patients with normal karyotype. Similar observations were made for GDF15, albeit not reaching statistical significance. In summary, our results revealed a strong association between ERFE expression and MDS outcome, suggesting a possible involvement of ERFE in molecular MDS pathogenesis.
Non‐Hodgkin lymphoma after treatment for classical Hodgkin lymphoma: a report from the German Hodgkin Study Group
Authors: Eichenauer Dennis A. , Müller Horst , Elger Leonard , Goergen Helen , Fuchs Michael , Kreissl Stefanie , Böll Boris , Diehl Volker , von Tresckow Bastian , Borchmann Peter , Engert Andreas 
Published: January 2021

SummaryData on non‐Hodgkin lymphoma (NHL) after classical Hodgkin lymphoma (cHL) are scarce. We therefore performed a retrospective analysis comprising 11·841 cHL patients who had first‐line treatment within the randomized German Hodgkin Study Group (GHSG) HD7–HD15 studies. After a median follow‐up of 106 months, 175 patients (1·5%) had developed NHL. The median time to NHL was 44 months, the median age at NHL diagnosis was 54 years. The five‐year event‐free survival and overall survival estimates from the diagnosis of NHL were 36·9% and 44·2%, respectively. Thus, NHL after cHL is a rare event primarily affecting older individuals and often resulting in the patient´s death.
Therapeutic efficacy of the novel selective RNA polymerase I inhibitor CX‐5461 on pulmonary arterial hypertension and associated vascular remodelling
Authors: Xu Xia , Feng Hua , Dai Chaochao , Lu Weida , Zhang Jun , Guo Xiaosun , Yin Qihui , Wang Jianli , Cui Xiaopei , Jiang Fan 
Published: January 2021

Background and PurposeCX‐5461 is a novel selective RNA polymerase I (Pol I) inhibitor. Previously, we found that CX‐5461 could inhibit pathological arterial remodelling caused by angioplasty and transplantation. In the present study, we explored the pharmacological effects of CX‐5461 on experimental pulmonary arterial hypertension (PAH) and PAH‐associated vascular remodelling.Experimental ApproachPAH was induced in Sprague–Dawley rats by monocrotaline or Sugen/hypoxia.Key ResultsWe demonstrated that CX‐5461 was well tolerated for in vivo treatments. CX‐5461 prevented the development of pulmonary arterial remodelling, perivascular inflammation, pulmonary hypertension, and improved survival. More importantly, CX‐5461 partly reversed established pulmonary hypertension. In vitro, CX‐5461 induced cell cycle arrest in human pulmonary arterial smooth muscle cells. The beneficial effects of CX‐5461 in vivo and in vitro were associated with increased activation (phosphorylation) of p53.Conclusion and ImplicationsOur results suggest that pharmacological inhibition of Pol I may be a novel therapeutic strategy to treat otherwise drug‐resistant PAH.
Targeting the CB2 receptor and other endocannabinoid elements to delay disease progression in amyotrophic lateral sclerosis
Authors: Rodríguez‐Cueto Carmen , García‐Toscano Laura , Santos‐García Irene , Gómez‐Almería Marta , Gonzalo‐Consuegra Claudia , Espejo‐Porras Francisco , Fernández‐Ruiz Javier , de Lago Eva 
Published: January 2021

Cannabinoids form a singular group of plant‐derived compounds, endogenous lipids and synthetic derivatives with multiple therapeutic effects exerted by targeting different elements of the endocannabinoid system. One of their therapeutic applications is the preservation of neuronal integrity exerted by attenuating the multiple neurotoxic events that kill neurons in neurodegenerative disorders. In this review, we will address the potential of cannabinoids as neuroprotective agents in amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disorder characterized by muscle denervation, atrophy and paralysis, and progressive deterioration in upper and/or lower motor neurons. The emphasis will be paid on the cannabinoid type 2 (CB2) receptor, whose activation limits glial reactivity, but the potential of additional endocannabinoid‐related targets will be also addressed. The evidence accumulated so far at the preclinical level supports the need to soon move towards the patients and initiate clinical trials to confirm the potential of cannabinoid‐based medicines as disease modifiers in ALS.LINKED ARTICLESThis article is part of a themed issue on Recent advances in ALS pathogenesis and therapeutics. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.6/issuetoc
Impairment of platelet NO signalling in coronary artery spasm: role of hydrogen sulphide
Authors: Imam Hasan , Nguyen Thanh H. , Stafford Irene , Liu Saifei , Heresztyn Tamila , Chirkov Yuliy Y. , Horowitz John D. 
Published: January 2021

Background and PurposeThe pathophysiology of coronary artery spasm (CAS), with its associated ischaemic crises, is currently poorly understood and treatment is frequently ineffective. In view of increasing evidence that platelet‐based defects may occur in CAS patients, we investigated platelet reactivity in CAS patients and whether symptomatic crises reflect activation of platelet–endothelial interactions.Experimental ApproachCAS patients were evaluated during acute and/or chronic symptomatic phases and compared with healthy control subjects. Inhibition of ADP‐induced platelet aggregation by the NO donor sodium nitroprusside (SNP) and plasma concentrations of syndecan 1 (glycocalyx shedding marker), tryptase (mast cell activation marker) and platelet microparticles were measured.Key ResultsInhibition of platelet aggregation by SNP was diminished in chronic CAS, with further (non‐significant) deterioration during symptomatic crises, whereas plasma concentrations of syndecan 1, tryptase and platelet microparticles increased. Treatment of patients with high‐dose N‐acetylcysteine (NAC) plus glyceryl trinitrate rapidly increased platelet responsiveness to SNP and decreased plasma syndecan 1 concentrations. The effect of NAC on platelet responsiveness to SNP was confirmed in vitro and mimicked by the H2S donor NaHS. Conversely, inhibition of enzymatic production of H2S attenuated NAC effect.Conclusion and ImplicationsCAS is associated with substantial impairment of platelet NO signalling. During acute symptomatic exacerbations, platelet resistance to NO is aggravated, together with mast cell activation and damage to both vasculature and platelets. NAC, via release of H2S, reverses platelet resistance to NO and terminates glycocalyx shedding during symptomatic crises: This suggests that H2S donors may correct the pathophysiological anomalies underlying CAS.
Neurological risks and benefits of cytokine‐based treatments in coronavirus disease 2019: from preclinical to clinical evidence
Authors: Pignataro Giuseppe , Cataldi Mauro , Taglialatela Maurizio 
Published: January 2021

Immunodeficiency and hyperinflammation are responsible for the most frequent and life‐threatening forms of coronavirus disease 2019 (COVID‐19). Therefore, cytokine‐based treatments targeting immuno‐inflammatory mechanisms are currently undergoing clinical scrutiny in COVID‐19‐affected patients. In addition, COVID‐19 patients also exhibit a wide range of neurological manifestations (neuro‐COVID), which may also benefit from cytokine‐based treatments. In fact, such drugs have shown some clinical efficacy also in neuroinflammatory diseases. On the other hand, anti‐cytokine drugs are endowed with significant neurological risks, mainly attributable to their immunodepressant effects. Therefore, the aim of the present manuscript is to briefly describe the role of specific cytokines in neuroinflammation, to summarize the efficacy in preclinical models of neuroinflammatory diseases of drugs targeting these cytokines and to review the clinical data regarding the neurological effects of these drugs currently being investigated against COVID‐19, in order to raise awareness about their potentially beneficial and/or detrimental neurological consequences.LINKED ARTICLESThis article is part of a themed issue on The second wave: are we any closer to efficacious pharmacotherapy for COVID 19? (BJP 75th Anniversary). To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.10/issuetoc
Beneficial effects of a combination of natural product activators of autophagy on endothelial cells and platelets
Authors: Carnevale Roberto , Nocella Cristina , Schiavon Sonia , Cammisotto Vittoria , Cotugno Maria , Forte Maurizio , Valenti Valentina , Marchitti Simona , Vecchio Daniele , Biondi Zoccai Giuseppe , Rubattu Speranza , Martinelli Ombretta , Pignatelli Pasquale , Violi Francesco , Volpe Massimo , Versaci Francesco , Frati Luigi , Frati Giacomo , Sciarretta Sebastiano 
Published: January 2021

Background and PurposeOxidative stress and insufficient autophagy activity are associated with inflammatory processes and are common features of many cardiovascular diseases (CVDs). We investigated if a combination of natural activators of autophagy could modulate oxidative stress, platelet aggregation and endothelial cell survival and function in response to stress.Experimental ApproachEx vivo platelet aggregation and activation, H2O2 production and autophagy were measured in platelets of subjects at high cardiovascular risk, including smokers, patients with metabolic syndrome (MetS) and patients with atrial fibrillation (AF). In vitro, the effects of a mixture of natural pro‐autophagy molecules and antioxidants on platelets and human umbilical vein endothelial cells (HUVECs) were evaluated.Key ResultAutophagy appeared to be inhibited, whereas aggregation was increased in platelets from AF and MetS patients and in smokers, as compared with healthy subjects. Treatment of platelets isolated from these patients with a mixture composed of trehalose, spermidine, catechin and epicatechin (Mix1) or with a mixture composed of trehalose, spermidine and nicotinamide (Mix2), significantly reduced platelet activation and oxidative stress, and increased autophagy, compared with the effect of each compound alone. Similarly, treatment of HUVECs with a combination of these compounds exhibited beneficial effects and increased endothelial cell survival, nitric oxide bioavailability and angiogenesis in response to stress in a potentiated manner.Conclusion and ImplicationsA combination of natural activators of autophagy could inhibit platelet activity and oxidative stress and improve endothelial cell survival and function in a potentiated manner representing a useful strategy to reduce the effect of risk factors on CVD occurrence.LINKED ARTICLESThis article is part of a themed issue on Cellular metabolism and diseases. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.10/issuetoc
Toddlers Prefer Adults as Informants: 2‐ and 3‐Year‐Olds’ Use of and Attention to Pointing Gestures From Peer and Adult Partners
Authors: Kachel Gregor , Moore Richard , Hepach Robert , Tomasello Michael 
Published: January 2021

Two‐ and 3‐year‐old children (N = 96) were tested in an object‐choice task with video presentations of peer and adult partners. An immersive, semi‐interactive procedure enabled both the close matching of adult and peer conditions and the combination of participants’ choice behavior with looking time measures. Children were more likely to use information provided by adults. As the effect was more pronounced in the younger age‐group, the observed bias may fade during toddlerhood. As there were no differences in children’s propensity to follow peer and adult gestures with their gaze, these findings provide some of the earliest evidence to date that young children take an interlocutor’s age into account when judging ostensively communicated testimony.
Allergen skin test reactivity and asthma are inversely associated with ratios of IgG4/IgE and total IgE/allergen‐specific IgE in Ugandan communities
Authors: Nkurunungi Gyaviira , Nassuuna Jacent , Mpairwe Harriet , Kabagenyi Joyce , Nampijja Margaret , Sanya Richard E. , Webb Emily L. , Elliott Alison M. 
Published: January 2021

SummaryBackgroundSerum inhibition of allergen‐specific IgE has been associated with competing IgG4 and non‐specific polyclonal IgE. In allergen immunotherapy, beneficial responses have been associated with high IgG4/IgE ratios. Helminths potentiate antibody class switching to IgG4 and stimulate polyclonal IgE synthesis; therefore, we hypothesized a role for helminth‐associated IgG4 and total IgE in protection against atopic sensitization and clinical allergy (asthma) in tropical low‐income countries.MethodsAmong community residents of Ugandan rural Schistosoma mansoni (Sm)–endemic islands and a mainland urban setting with lower helminth exposure, and among urban asthmatic schoolchildren and non‐asthmatic controls, we measured total, Schistosoma adult worm antigen (SWA)–specific, Schistosoma egg antigen (SEA)–specific and allergen (house dust mite [HDM] and German cockroach)–specific IgE and IgG4 by ImmunoCAP® and/or ELISA. We assessed associations between these antibody profiles and current Sm infection, the rural‐urban environment, HDM and cockroach skin prick test (SPT) reactivity, and asthma.ResultsTotal IgE, total IgG4 and SWA‐, SEA‐ and allergen‐specific IgE and IgG4 levels were significantly higher in the rural, compared to the urban setting. In both community settings, both Sm infection and SPT reactivity were positively associated with allergen‐specific and total IgE responses. SPT reactivity was inversely associated with Schistosoma‐specific IgG4, allergen‐specific IgG4/IgE ratios and total IgE/allergen‐specific IgE ratios. Asthmatic schoolchildren, compared with non‐asthmatic controls, had significantly higher levels of total and allergen‐specific IgE, but lower ratios of allergen‐specific IgG4/IgE and total IgE/allergen‐specific IgE.Conclusions and clinical relevanceOur immuno‐epidemiological data support the hypothesis that the IgG4–IgE balance and the total IgE–allergen‐specific IgE balance are more important than absolute total, helminth‐ or allergen‐specific antibody levels in inhibition of allergies in the tropics.
Effects of stewardship on protected area effectiveness for coastal birds
Authors: Michel Nicole L. , Saunders Sarah P. , Meehan Timothy D. , Wilsey Chad B. 
Published: January 2021

AbstractEvaluation of protected area effectiveness is critical for conservation of biodiversity. Protected areas that prioritize biodiversity conservation are, optimally, located and managed in ways that support relatively large and stable or increasing wildlife populations. Yet evaluating conservation efficacy remains a challenging endeavor. We used an extensive community science data set, eBird, to evaluate the efficacy of protected areas for birds across the Gulf of Mexico and Atlantic coasts of the United States. We modeled trends (2007–2018) for 12 vulnerable waterbirds that use coastal areas during breeding or wintering. We compared two types of protected areas—sites where conservation organizations implemented active stewardship or management or both to reduce human disturbance (hereafter stewardship sites) and local, state, federal, and private protected areas managed to maintain natural land cover (hereafter protected areas)—as well as unprotected areas. We evaluated differences in trends between stewardship, protected, and unprotected areas across the Gulf and Atlantic coasts as a whole. Similar to a background sample, stewardship was known to occur at stewardship sites, but unknown at protected and unprotected areas. Four of 12 target species—Black Skimmer (Rynchops niger), Brown Pelican (Pelecanus occidentalis), Least Tern (Sternula antillarum), and Piping Plover (Charadrius melodus)—had more positive trends (two to 34 times greater) at stewardship sites than protected areas. Furthermore, five target species showed more positive trends at sites with stewardship programs than unprotected sites during at least one season, whereas seven species showed more positive trends at protected than unprotected areas. No species had more negative trends at stewardship sites than unprotected areas, and two species had more negative trends at protected than unprotected areas. Anthropogenic disturbance is a serious threat to coastal birds, and our findings demonstrate that stewardship to reduce its negative impacts helps ensure conservation of vulnerable waterbirds.
A guide to representing variability and uncertainty in biodiversity indicators
Authors: Rowland Jessica A. , Bland Lucie M. , James Simon , Nicholson Emily 
Published: January 2021

AbstractBiodiversity indicators are used to inform decisions and measure progress toward global targets, such as the United Nations Sustainable Development Goals. Indicators aggregate and simplify complex information, so underlying information influencing its reliability and interpretation (e.g., variability in data and uncertainty in indicator values) can be lost. Communicating uncertainty is necessary to ensure robust decisions and limit misinterpretations of trends, yet variability and uncertainty are rarely quantified in biodiversity indicators. We developed a guide to representing uncertainty and variability in biodiversity indicators. We considered the key purposes of biodiversity indicators and commonly used methods for representing uncertainty (standard error, bootstrap resampling, and jackknife resampling) and variability (quantiles, standard deviation, median absolute deviation, and mean absolute deviation) with intervals. Using 3 high‐profile biodiversity indicators (Red List Index, Living Planet Index, and Ocean Health Index), we tested the use, suitability, and interpretation of each interval method based on the formulation and data types underpinning the indicators. The methods revealed vastly different information; indicator formula and data distribution affected the suitability of each interval method. Because the data underpinning each indicator were not normally distributed, methods relying on normality or symmetrical spread were unsuitable. Quantiles, bootstrapping, and jackknifing provided useful information about the underlying variability and uncertainty. We built a decision tree to inform selection of the appropriate interval method to represent uncertainty or variation in biodiversity indicators, depending on data type and objectives. Our guide supports transparent and effective communication of biodiversity indicator trends to facilitate accurate interpretation by decision makers.