bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different routes and formulations of melatonin in critically ill patients. A pharmacokinetic randomized study
Authors: Mistraletti Giovanni , Paroni Rita , Umbrello Michele , Moro Salihovic Bedrana , Coppola Silvia , Froio Sara , Finati Elena , Gasco Paolo , Savoca Adriana , Manca Davide , Chiumello Davide , Reiter Russel J. , Iapichino Gaetano 
Published: April 2019

AbstractBackground and objectivesCritically ill patients present reduced endogenous melatonin blood levels, and they might benefit from its exogenous supplementation. The aim of this research was to evaluate the feasibility of different routes of administration and drug formulations of melatonin. The efficiency of absorption was assessed as well as the adequacy in achieving and maintaining the physiological nocturnal blood peak.MethodsTwenty‐one high‐risk critically ill patients were randomly assigned to receive melatonin either: (a) per os, as a standard tablet (ST‐OS), (b) per os, as a suspension in solid lipid nanoparticles (SLN‐OS) or c) transdermal (TD), by applying a jellified melatonin microemulsion (μE) on the skin (μE‐TD). SLN‐OS and μE‐TD were lipid‐based colloidal systems. The endogenous melatonin blood values were observed for 24 hours; subsequently, melatonin 3 mg was administered and pharmacokinetics was studied for 24 hours further.ResultsIn both groups that received ST‐OS and SLN‐OS, the median time‐to‐peak blood concentration was 0.5 hours; however, the area under the curve (AUC) after administration of SLN‐OS was significantly higher than after ST‐OS (157386 [65732‐193653] vs 44441 [22319‐90705] pg/mL*hours, P = 0.048). μE‐TD presented a delayed time‐to‐peak blood concentration (4 hours), a lower bioavailability (AUC: 3142 [1344‐14573] pg/mL*hours) and reached pharmacological peak concentration (388 [132‐1583] pg/mL).ConclusionsSLN‐melatonin enterally administered offers favourable pharmacokinetics in critically ill patients, with higher bioavailability with respect to the standard formulation; μE‐TD provided effective pharmacological blood levels, with a time‐concentration profile more similar to the physiological melatonin pattern.
Changes of visualised Eustachian tube lengths by age and position: Radiologic study in sitting and supine positions using cone beam and conventional CT
Authors: Ha Seung Cheol , Baik Jin , Park Hyo Jung , Moon Hyun , Kang Byung Chul , Park Jun Woo , Kang Woo Seok , Park Hong Ju 
Published: April 2019

AbstractObjectivesPatulous eustachian tube (ET) has been characterised by the visualisation of full‐length ET on computed tomography (CT) results. We wanted to investigate the changes of visualised ET lengths by age in supine and sitting positions.DesignRetrospective study.SettingTertiary care academic referral centre.ParticipantsOne hundred subjects who underwent cone beam CT (CBCT) in a sitting position and conventional CT in a supine position for non‐otitis‐related or dental complaints.Main outcome measuresVisualised ET lengths from the nasopharyngeal orifice measured by different positions and ages.ResultsSubjects did not show visualisation of full‐length ET throughout the study. The visualised ET lengths (9.0 ± 2.5 mm) of the CBCT group were significantly larger than those (6.8 ± 2.3 mm) of the conventional CT group (P < 0.0001).Women showed longer visualised ET lengths than men in CBCT group (P < 0.001). The visualised ET lengths of the CBCT group were consistent or slightly increasing as a function of age (P = 0.06); however, the visualised ET lengths of the conventional CT group decreased as a function of age (P = 0.001). The slopes of regression lines of the two groups were significantly different.ConclusionsWhen in the supine position, the ET lengths gradually shortened as the subjects got older, most likely due to venous engorgement and the collapse of surrounding tissues; this finding thus suggests that CT in a supine position is an inappropriate method to diagnose patulous ET. The visualised ET lengths by CBCT in a sitting position were consistent throughout the different ages of the subjects and may be used as a diagnostic test for patulous ET.
Correlations between computational fluid dynamics and clinical evaluation of nasal airway obstruction due to septal deviation: An observational study
Authors: Radulesco Thomas , Meister Lionel , Bouchet Gilles , Varoquaux Arthur , Giordano Jérôme , Mancini Julien , Dessi Patrick , Perrier Pierre , Michel Justin 
Published: April 2019

AbstractObjectivesThe primary objective of this study was to determine how computational fluid dynamics (CFD) could be correlated to clinical evaluation of nasal airway obstruction (NAO) in a population of patients with symptomatic septal deviation (SD). The secondary objective was to determine whether CFD could define which side was the more obstructed.DesignThis was an observational study.SettingsFew publications have attempted to correlate CFD with clinical evaluation of NAO. This correlation would permit validation and improved interpretation. This study was performed in a university research laboratory specialised in fluid mechanics.ParticipantsWe included patients referred for septal surgery at our centre. Age range was 19–58 years. Preoperative CT scans were performed. All patients with non‐structural causes of NAO such as rhinitis, sinusitis or tumoral/autoimmune processes (ie, not due to anatomic obstruction) were excluded.Main outcome measurementFor each nasal fossa, we compared CFD data (total pressure, heat flux, wall shear stress, temperatures, velocity and nasal resistances) with both patient perception scores and rhinomanometry using the Spearman correlation test (rs). Perception scores were graded from 0/4 to 4/4 on each side, based on the patient interview. We also compared CFD‐derived nasal resistances with rhinomanometry‐derived nasal resistances.ResultsTwenty‐two patients complaining of NAO with SD were analysed, and 44 analyses were performed comparing each side with its CFD data. Regarding correlations with patient perception scores, the best values we found were heat flux measures (rs = 0.86). Both rhinomanometry and CFD‐calculated nasal resistances had strong correlations with subjective perception scores (rs = 0.75, P < 0.001 and rs = 0.6, P < 0.001, respectively). We found a statistically significant difference between RMM‐NR and CFD‐NR (P = 0.003). Heat flux analysis allowed us to distinguish the more obstructed side (MOS) and the less obstructed side (LOS) in 100% of patients.ConclusionThis study aimed to enhance our ability to interpret CFD‐calculated data in the nasal airway. It highlights and confirms that heat flux measures are very closely correlated to patient perception in cases of SD. It also helps to distinguish the more obstructed side from the less obstructed side and could contribute to further CFD studies.
Circular RNA cMras inhibits lung adenocarcinoma progression via modulating miR‐567/PTPRG regulatory pathway
Authors: Yu Chengtao , Tian Fang , Liu Jun , Su Minhui , Wu Min , Zhu Xuejun , Qian Wang 
Published: April 2019

AbstractObjectivesCircular RNA, a type of RNA formed by a covalently closed loop, possesses sophisticated abilities of gene regulation in tumorigenesis and metastasis. However, the role of circRNAs on lung adenocarcinoma (LUAD) remains largely unknown.Materials and methodsThe role of cMras was examined both in vitro and in vivo. cMras expression in LUAD tissues was determined by quantitative real‐time PCR (qRT‐PCR). Downstream targets of cMras were predicted by bioinformatics tools and confirmed by RNA immunoprecipitation assay and luciferase assay. qRT‐PCR and western blot assay were used to detect the expression of specific targets.ResultsThirty‐six paired LUAD and healthy tissues were collected and cMras resulted significantly downregulated in cancerous tissues. Its expression was negatively associated with tumour stages. cMras overexpression suppressed LUAD growth and metastasis, while endogenous cMras silencing resulted in the opposite effects. Bioinformatics analysis and experimental evidence confirmed that cMras was a sponge of miRNA‐567 and released its direct target, PTPRG. cMras overexpression decreased miR‐567 expression and subsequently increased PTPRG expression, while increased miRNA‐567 expression blocked the effects induced by cMras. Moreover, PTPRG was downregulated in LUAD and patients with low PTPRG expression exhibited significantly poor prognosis. These results suggested that cMras/miR‐567/PTPRG regulatory pathway might be associated to LUAD tumorigenesis and development.ConclusionsA novel circular RNA cMras and its functions were identified, discovering a cMras/miR‐567/PTPRG regulatory pathway in LUAD tumorigenesis and development.
Lymph node fine‐needle cytology in the era of personalised medicine. Is there a role?
Authors: Cozzolino Immacolata , Giudice Valentina , Mignogna Chiara , Selleri Carmine , Caputo Alessandro , Zeppa Pio 
Published: April 2019

AbstractThe 2016 World Health Organisation revised classification of lymphoma has sub‐classified well‐defined entities and added a number of provisional entities on the basis of new knowledge on genetic, epigenetics and phenotypical data; prognostic and predictive features are also part of this classification. New knowledge on well‐defined entities further enlightens the mechanisms of lymphomagenesis, which are more complex and multifactorial than once believed. Therapies are also more complex because traditional clinical trials have been integrated with new drugs and compounds with unique mechanisms of actions against distinct molecular targets. As lymphoma acquires additional genetic and phenotypic features over the time, pathological assessment is also necessary. Histological evaluation and tissue collection by surgical biopsies are necessary for phenotypical and molecular purposes; however, these are demanding procedures for both the patient and the health care system. At the same time, the choice of the best treatment for a specific entity, in different phases and different patients requires information that may not be available when the biopsy is performed. Fine needle aspiration cytology (FNAC) is successfully used in lymph nodes (LNs) in combination with different ancillary techniques and might be used to assess the phenotypic and genetic profile of specific targets and to get key information for therapy, in different phases and stages of the disease, with the option to re‐check the same target over time, without surgical excision. This brief review describes LN‐FNAC diagnostic criteria, current therapies for lymphomas and the potential role of LN‐FNAC in selecting non‐Hodgkin lymphomas patients for specific targeted treatments.
Unravelling Church Land: Transformations in the Relations between Church, State and Community in Uganda
Authors: Alava Henni , Shroff Catrine 
Published: April 2019

ABSTRACTChristian churches control substantial areas of land in Africa. While intensifying struggles over their holdings are partly due to the increased pressure on land in general, they also reflect transformations in the relations through which churches’ claims to land are legitimized, the increased association of churches with business, and churches’ unique positioning as both institutions and communities. This article presents the trajectory of relations between church, state and community in Uganda from the missionary acquisition of land in the colonial era to the unravelling of church landholding under Museveni. Drawing on long‐term ethnographic fieldwork, the authors argue that claims to church land in contemporary Uganda draw on: 1) notions of belonging to the land; 2) views about the nature of churches as communities; 3) discontent regarding whether customary land owners gave churches user rights or ownership; and 4) assessment of the churches’ success in ensuring that the land works for the common good. The article develops a novel approach to analysing the changing meaning of the landholdings of religious institutions, thus extending ongoing discussions about land, politics, development and religion in Africa.
The cost of diabetic foot ulcers and amputations to the National Health Service in England
Authors: Kerr M. , Barron E. , Chadwick P. , Evans T. , Kong W. M. , Rayman G. , Sutton‐Smith M. , Todd G. , Young B. , Jeffcoate W. J. 
Published: April 2019

AbstractAimTo estimate the healthcare costs of diabetic foot disease in England.MethodsPatient‐level data sets at a national and local level, and evidence from clinical studies, were used to estimate the annual cost of health care for foot ulceration and amputation in people with diabetes in England in 2014–2015.ResultsThe cost of health care for ulceration and amputation in diabetes in 2014–2015 is estimated at between £837 million and £962 million; 0.8% to 0.9% of the National Health Service (NHS) budget for England. More than 90% of expenditure was related to ulceration, and 60% was for care in community, outpatient and primary settings. For inpatients, multiple regression analysis suggested that ulceration was associated with a length of stay 8.04 days longer (95% confidence interval 7.65 to 8.42) than that for diabetes admissions without ulceration.ConclusionsDiabetic foot care accounts for a substantial proportion of healthcare expenditure in England, more than the combined cost of breast, prostate and lung cancers. Much of this expenditure arises through prolonged and severe ulceration. If the NHS were to reduce the prevalence of diabetic foot ulcers in England by one‐third, the gross annual saving would be more than £250 million. Diabetic foot ulceration is a large and growing problem globally, and it is likely that there is potential to improve outcomes and reduce expenditure in many countries.
Why is education performance so different across Latvian schools?
Authors: Krasnopjorovs Olegs 
Published: April 2019

AbstractThis paper aims to identify the school characteristics consistently associated with better performance of pupils in state exams in Latvia and understand the reasons behind substantial exam score gap between urban and rural schools. We find that exam scores are positively related to school size and teacher salaries, but negatively related to teacher age. Oaxaca–Ransom decomposition shows that the whole urban–rural exam score gap can be attributed to a few observable characteristics of schools, teachers and pupils.
Effects of defoliation on the resistance and tolerance of rice, Oryza sativa, to root injury by the rice water weevil, Lissorhoptrus oryzophilus
Authors: Kraus Emily C. , Stout Michael J. 
Published: April 2019

AbstractUnderstanding plant‐mediated interactions in agricultural systems may facilitate the development of novel and improved management practices, which is important, as management of these insects is currently heavily reliant on insecticides. The fall armyworm, Spodoptera frugiperda (JE Smith) (Lepidoptera: Noctuidae, Prodeniini), is a sporadic pest of rice fields in the southern USA. In southwestern Louisiana, this defoliating insect typically attacks rice early in the growth season, before fields are flooded. Defoliation by fall armyworm larvae may trigger increased expression of plant defenses, which may result in increased resistance to subsequent herbivores. The rice water weevil (RWW), Lissorhoptrus oryzophilus Kuschel (Coleoptera: Curculionidae, Stenopelmini), enters rice fields as an adult both before and after flooding, but oviposition and larval infestation occur only after fields are flooded. RWW may be affected by changes in plant resistance caused by fall armyworm defoliation before flooding. The objectives of this study were to investigate the plant‐mediated effects of natural and artificial defoliation on population densities of RWW larvae after flooding and on the ability of rice plants to compensate for root injury by RWW larvae. In the 2015 season, fall armyworm defoliation before flooding resulted in reduced RWW densities after flooding. However, in 2016 no significant effects of fall armyworm defoliation on densities of RWW larvae were detected. Similarly, mechanical defoliation of rice before flooding did not affect RWW densities after flooding. Although lowest yields were observed in plots subjected to both root injury and defoliation, there was little evidence of a greater than additive reduction in yields from simultaneous injury. These results suggest a lack of plant‐mediated interactions among these two pests in rice in the southern USA.
The Need for a Theology of Resilience, Coexistence, and Hope
Authors: Jackelén Antje 
Published: April 2019

AbstractIn many countries of the world, people are drinking a dangerous cocktail of poisonous ingredients all starting with the letter P: polarization, populism, protectionism, post‐truth, and patriarchy. As Christians, we cannot do other than work against this. In order to do so, we need to make use of the resources we have in spirituality and theology. This article reflects on these resources in the Lutheran tradition, asking how we, together, are church in this world.
The Challenge and Urgency of Gender Inclusion in Theological Education
Authors: Ortega Ofelia 
Published: April 2019

AbstractTwenty years after the conclusion of the Ecumenical Decade of the Churches in Solidarity with Women, this article considers the development and the need for inclusion of gender in the sphere of theological reflection and education in Latin America and the Caribbean. Rather than a historical account, it proposes an approach that works toward thinking about and developing a new form of relationship between women and men, and between them and today's society and church.
Evidence for adaptive responses to historic drought across a native plant species range
Authors: Dickman Erin E. , Pennington Lillie K. , Franks Steven J. , Sexton Jason P. 
Published: April 2019

AbstractAs climatic conditions change, species will be forced to move or adapt to avoid extinction. Exacerbated by ongoing climate change, California recently experienced a severe and exceptional drought from 2011 to 2017. To investigate whether an adaptive response occurred during this event, we conducted a “resurrection” study of the cutleaf monkeyflower (Mimulus laciniatus), an annual plant, by comparing trait means and variances of ancestral seed collections (“pre‐drought”) with contemporary descendant collections (“drought”). Plants were grown under common conditions to test whether this geographically restricted species has the capacity to respond evolutionarily to climate stress across its range. We examined if traits shifted in response to the recent, severe drought and included populations across an elevation gradient, including populations at the low‐ and high‐elevation edges of the species range. We found that time to seedling emergence in the drought generation was significantly earlier than in the pre‐drought generation, a response consistent with drought adaptation. Additionally, trait variation in days to emergence was reduced in the drought generation, which suggests selection or bottleneck events. Days to first flower increased significantly by elevation, consistent with climate adaptation across the species range. Drought generation plants were larger and had greater reproduction, which was likely a carryover effect of earlier germination. These results demonstrate that rapid shifts in trait means and variances consistent with climate adaptation are occurring within populations, including peripheral populations at warm and cold climate limits, of a plant species with a relatively restricted range that has so far not shifted its elevation distribution during contemporary climate change. Thus, rapid evolution may mitigate, at least temporarily, range shifts under global climate change. This study highlights the need for better understanding rapid adaptation as a means for plant communities to cope with extraordinary climate events.
Phytoplankton growth and stoichiometric responses to warming, nutrient addition and grazing depend on lake productivity and cell size
Authors: Schulhof Marika A. , Shurin Jonathan B. , Declerck Steven A. J. , Van de Waal Dedmer B. 
Published: April 2019

AbstractGlobal change involves shifts in multiple environmental factors that act in concert to shape ecological systems in ways that depend on local biotic and abiotic conditions. Little is known about the effects of combined global change stressors on phytoplankton communities, and particularly how these are mediated by distinct community properties such as productivity, grazing pressure and size distribution. Here, we tested for the effects of warming and eutrophication on phytoplankton net growth rate and C:N:P stoichiometry in two phytoplankton cell size fractions (<30 µm and >30 µm) in the presence and absence of grazing in microcosm experiments. Because effects may also depend on lake productivity, we used phytoplankton communities from three Dutch lakes spanning a trophic gradient. We measured the response of each community to multifactorial combinations of temperature, nutrient, and grazing treatments and found that nutrients elevated net growth rates and reduced carbon:nutrient ratios of all three phytoplankton communities. Warming effects on growth and stoichiometry depended on nutrient supply and lake productivity, with enhanced growth in the most productive community dominated by cyanobacteria, and strongest stoichiometric responses in the most oligotrophic community at ambient nutrient levels. Grazing effects were also most evident in the most oligotrophic community, with reduced net growth rates and phytoplankton C:P stoichiometry that suggests consumer‐driven nutrient recycling. Our experiments indicate that stoichiometric responses to warming and interactions with nutrient addition and grazing are not universal but depend on lake productivity and cell size distribution.
A C‐terminal CXCL8 peptide based on chemokine–glycosaminoglycan interactions reduces neutrophil adhesion and migration during inflammation
Authors: Martínez‐Burgo Beatriz , Cobb Steven L. , Pohl Ehmke , Kashanin Dmitry , Paul Toby , Kirby John A. , Sheerin Neil S. , Ali Simi 
Published: April 2019

SummaryLeucocyte recruitment is critical during many acute and chronic inflammatory diseases. Chemokines are key mediators of leucocyte recruitment during the inflammatory response, by signalling through specific chemokine G‐protein‐coupled receptors (GPCRs). In addition, chemokines interact with cell‐surface glycosaminoglycans (GAGs) to generate a chemotactic gradient. The chemokine interleukin‐8/CXCL8, a prototypical neutrophil chemoattractant, is characterized by a long, highly positively charged GAG‐binding C‐terminal region, absent in most other chemokines. To examine whether the CXCL8 C‐terminal peptide has a modulatory role in GAG binding during neutrophil recruitment, we synthesized the wild‐type CXCL8 C‐terminal [CXCL8 (54–72)] (Peptide 1), a peptide with a substitution of glutamic acid (E) 70 with lysine (K) (Peptide 2) to increase positive charge; and also, a scrambled sequence peptide (Peptide 3). Surface plasmon resonance showed that Peptide 1, corresponding to the core CXCL8 GAG‐binding region, binds to GAG but Peptide 2 binding was detected at lower concentrations. In the absence of cellular GAG, the peptides did not affect CXCL8‐induced calcium signalling or neutrophil chemotaxis along a diffusion gradient, suggesting no effect on GPCR binding. All peptides equally inhibited neutrophil adhesion to endothelial cells under physiological flow conditions. Peptide 2, with its greater positive charge and binding to polyanionic GAG, inhibited CXCL8‐induced neutrophil transendothelial migration. Our studies suggest that the E70K CXCL8 peptide, may serve as a lead molecule for further development of therapeutic inhibitors of neutrophil‐mediated inflammation based on modulation of chemokine–GAG binding.