bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reproductive investments of a small, arid zone tortoise Chersobius signatus: Follicle and egg development
Authors: Hofmeyr Margaretha D. , Henen Brian T. , Loehr Victor J. T. 
Published: July 2018

AbstractWe used ultrasonography and radiography to evaluate whether body size (BS), body condition (BC) and environmental factors influenced reproductive investments by Chersobius signatus in September 2000 and from September 2003 to November 2004. Follicle volume increased with increasing BS, BC and rainfall but decreased with increasing temperature. Egg volume averaged 8.8% of body volume, increased allometrically with BS, but was not affected by BC, rainfall or temperature and did not differ between first and second clutches. Most females produced at least one single‐egg clutch per year, even when BC was low. Many females produced two, possibly more, clutches but some forfeited reproduction in some years. Females often retained large follicles from one season to the next with 18%–71% carrying pre‐ovulatory sized follicles in different times of the year. Increasing temperatures likely influenced timing of first ovulations in August while decreasing water and food availability, linked with high temperatures, possibly terminated ovulations by November. The gravid season was short compared to other winter‐rainfall tortoises in South Africa. We propose that the females' small bodies may constrain investments in eggs, resulting in low fecundity, which is countered by producing large hatchlings with high survivorship in an arid habitat.
Target site pharmacokinetics of doxycycline for rosacea in healthy volunteers is independent of the food effect
Authors: Pal Arindam , Matzneller Peter , Gautam Anirudh , Österreicher Zoe , Wulkersdorfer Beatrix , Reiter Birgit , Stimpfl Thomas , Zeitlinger Markus 
Published: July 2018

AimsDoxycycline (DFD‐09) oral capsules 40 mg are approved for the treatment of inflammatory lesions of rosacea. Unlike the food‐induced lowering of doxycycline's peak plasma concentration (Cmax), its exposure under fed conditions in the skin, the drug's target site for rosacea, is unknown. The present study explored the effect of food on the dermal pharmacokinetics of doxycycline.MethodsThe pharmacokinetics of doxycycline in the dermal interstitial fluid (d‐ISF) and plasma of healthy volunteers were assessed in parallel groups under fed (n = 6) and fasting (n = 6) conditions during a 14‐day once‐daily treatment course with doxycycline oral capsules 40 mg (DFD‐09). Sampling of d‐ISF and plasma was performed on days 1, 10 (fasting group d‐ISF only) and 14.ResultsTwelve subjects were randomized, and 11 analysed. No causally drug‐related adverse events occurred. Dermal doxycycline exposures (Cmax and area under the curve) under the fed state were about 30% lower than under the fasting state at day 1 but were similar at steady state. In analogy to skin, plasma exposure showed no between‐group difference at steady state. Accumulation ratios were higher in the skin than in plasma. Correcting for plasma protein binding (~90%), dermal doxycycline exposure was approximately threefold higher than unbound plasma exposure.ConclusionsAt steady state, doxycycline concentrations in the skin of fed and fasting healthy volunteers were comparable. Doxycycline's efficacy in rosacea is possibly due to considerable dermal accumulation of unbound doxycycline and is independent of the effect of food.
VCE‐004.3, a cannabidiol aminoquinone derivative, prevents bleomycin‐induced skin fibrosis and inflammation through PPARγ‐ and CB2 receptor‐dependent pathways
Authors: del Rio Carmen , Cantarero Irene , Palomares Belén , Gómez‐Cañas María , Fernández‐Ruiz Javier , Pavicic Carolina , García‐Martín Adela , Luz Bellido Maria , Ortega‐Castro Rafaela , Pérez‐Sánchez Carlos , López‐Pedrera Chary , Appendino Giovanni , Calzado Marco A , Muñoz Eduardo 
Published: July 2018

Background and PurposeThe endocannabinoid system and PPARγ are important targets for the development of novel compounds against fibrotic diseases such as systemic sclerosis (SSc), also called scleroderma. The aim of this study was to characterize VCE‐004.3, a novel cannabidiol derivative, and study its anti‐inflammatory and anti‐fibrotic activities.Experimental ApproachThe binding of VCE‐004.3 to CB1 and CB2 receptors and PPARγ and its effect on their functional activities were studied in vitro and in silico. Anti‐fibrotic effects of VCE‐004.3 were investigated in NIH‐3T3 fibroblasts and human dermal fibroblasts. To assess its anti‐inflammatory and anti‐fibrotic efficacy in vivo, we used two complementary models of bleomycin‐induced fibrosis. Its effect on ERK1/2 phosphorylation induced by IgG from SSc patients and PDGF was also investigated.Key ResultsVCE‐004.3 bound to and activated PPARγ and CB2 receptors and antagonized CB1 receptors. VCE‐004.3 bound to an alternative site at the PPARγ ligand binding pocket. VCE‐004.3 inhibited collagen gene transcription and synthesis and prevented TGFβ‐induced fibroblast migration and differentiation to myofibroblasts. It prevented skin fibrosis, myofibroblast differentiation and ERK1/2 phosphorylation in bleomycin‐induced skin fibrosis. Furthermore, it reduced mast cell degranulation, macrophage activation, T‐lymphocyte infiltration, and the expression of inflammatory and profibrotic factors. Topical application of VCE‐004.3 also alleviated skin fibrosis. Finally, VCE‐004.3 inhibited PDGF‐BB‐ and SSc IgG‐induced ERK1/2 activation in fibroblasts.Conclusions and ImplicationsVCE‐004.3 is a novel semisynthetic cannabidiol derivative that behaves as a dual PPARγ/CB2 agonist and CB1 receptor modulator that could be considered for the development of novel therapies against different forms of scleroderma.
Developing a database for Rett syndrome research performed in the European Union: A resource for researchers and stakeholders
Authors: Akinsolu Folahanmi Tomiwa , Balczár Eszter , Kovács Nóra , Gáll Tibor , Harangi Mariann , Varga Orsolya 
Published: July 2018

AbstractBackgroundFor most rare diseases, which are often significantly under‐resourced, sufficient information on funding landscape is missing, which may prevent effective use of research resources and be an obstacle to making effective decisions on research. The objective of this research was to create a database of Rett syndrome research projects carried out in the European Union (EU) and to provide a research landscape analysis.MethodWebsites of organizations funding research projects were identified and systematically checked. Projects were analysed by date, place, funder types, and research topics.ResultsThe analysis revealed that the total expenditure on Rett syndrome research was almost €70 million, allocated among 247 projects mostly performed in Italy and the United Kingdom. The main research sponsor was the European Commission.Highlighting research trends and gaps, this work facilitates changes in rare disease research data management.ConclusionThis work demonstrates the feasibility of creating an EU‐based research database on Rett syndrome projects. It provides a source of information on research development which is useful for individuals, organizations and key players in the private and public sector to make progressive decisions on Rett syndrome research.
Quantifying current and potential contributions of Australian indigenous peoples to threatened species management
Authors: Leiper Ian , Zander Kerstin K. , Robinson Cathy J. , Carwadine Josie , Moggridge Bradley J. , Garnett Stephen T. 
Published: July 2018

AbstractFormal engagement of indigenous peoples in conservation is increasing globally and leads to multiple benefits to communities while contributing to national and international biodiversity goals and obligations. This and ongoing declines in biodiversity have led to calls to increase opportunities for indigenous people to engage in managing their estates. However, there is no overarching understanding of indigenous peoples’ involvement in conservation, which limits the identification of new opportunities. We amalgamated information across governments and large nongovernmental organizations in the megadiverse country of Australia to quantify the involvement of indigenous people in management of threatened species. We identified 153 Australian‐based projects undertaken by different indigenous groups around the nation in 2015 and 2016 that included explicit funds for management of threatened species or threatened ecosystems. Most were in remote parts of western and northern Australia. Almost one‐quarter of all threatened animals and 2% of threatened plants were the subject of some formal conservation action by indigenous people. Occurrence records for 1574 threatened species showed that 823 (89.2%) of 923 species recorded on indigenous peoples’ lands were not listed in management projects. This gap may represent new opportunities for conservation initiatives. Because at least 59.5% of Australia's threatened species occur on indigenous peoples’ lands, efforts to build appropriate and effective indigenous conservation alliances are vital. However, it is also important to recognize that threatened species are part of complex social, ecological, economic and cultural systems, and to achieve successful outcomes requires consideration of indigenous peoples’ priorities, rights, and obligations and relationships with their traditionally owned land and sea.
VA‐ECMO for cardiogenic shock in the contemporary era of heart transplantation: Which patients should be urgently transplanted?
Authors: Habal Marlena V. , Truby Lauren , Ando Masahiko , Ikegami Hirohisa , Garan Arthur R. , Topkara Veli K. , Colombo Paolo , Takeda Koji , Takayama Hiroo , Naka Yoshifumi , Farr Maryjane A. 
Published: July 2018

AbstractWith the impending United Network for Organ Sharing (UNOS) heart allocation policy giving VA‐ECMO supported heart transplant (HT) candidates highest priority status (Tier 1), identifying patients in cardiogenic shock (CS) with severe and irreversible heart failure (HF) appropriate for urgent HT is critically important. In a center where wait times currently preclude this approach, we retrospectively reviewed 119 patients (ages 18‐72) with CS from 1/2014 to 12/2016 who required VA‐ECMO for >24 hours. Underlying aetiologies included postcardiotomy shock (45), acute coronary syndromes (33), and acute‐on‐chronic HF (16). Eighty‐four percent of patients (100) had ≥1 contraindication to HT with 61.3% (73) having preexisting contraindications (eg, multiorgan dysfunction and substance abuse), and 68.1% (81) experienced preclusive complications (eg, renal failure, coagulopathy, and infection). Potential HT candidates were significantly more likely to survive to discharge (potential HT candidates 84.2% vs preexisting contraindications 43.8% vs contraindications developing on VA‐ECMO 33.3%, P = 0.001). Among potential HT candidates, 11 (68.8%) were discharged without advanced therapies and 4 received durable left ventricular assist device (25.0%). Importantly, 1‐year survival was 100% for the 11 patients with follow‐up. Thus, further work is critical to define appropriate candidates for HT from VA‐ECMO while avoiding preemptive transplantation in those with otherwise favorable outcomes.
Methylation of the dopamine transporter gene in blood is associated with striatal dopamine transporter availability in ADHD: A preliminary study
Authors: Wiers Corinde E. , Lohoff Falk W. , Lee Jisoo , Muench Christine , Freeman Clara , Zehra Amna , Marenco Stefano , Lipska Barbara K. , Auluck Pavan K. , Feng Ningping , Sun Hui , Goldman David , Swanson James M. , Wang Gene‐Jack , Volkow Nora D. 
Published: July 2018

AbstractDopamine transporters (DAT) are implicated in the pathogenesis and treatment of attention‐deficit hyperactivity disorder (ADHD) and are upregulated by chronic treatment with methylphenidate, commonly prescribed for ADHD. Methylation of the DAT1 gene in brain and blood has been associated with DAT expression in rodents' brains. Here we tested the association between methylation of the DAT1 promoter derived from blood and DAT availability in the striatum of unmedicated ADHD adult participants and in that of healthy age‐matched controls (HC) using Positron Emission Tomography (PET) and [11C]cocaine. Results showed no between‐group differences in DAT1 promoter methylation or striatal DAT availability. However, the degree of methylation in the promoter region of DAT1 correlated negatively with DAT availability in caudate in ADHD participants only. DAT availability in VS correlated with inattention scores in ADHD participants. We verified in a postmortem cohort with ADHD diagnosis and without, that DAT1 promoter methylation in peripheral blood correlated positively with DAT1 promoter methylation extracted from substantia nigra (SN) in both groups. In the cohort without ADHD diagnosis, DAT1 gene expression in SN further correlated positively with DAT protein expression in caudate; however, the sample size of the cohort with ADHD was insufficient to investigate DAT1 and DAT expression levels. Overall, these findings suggest that peripheral DAT1 promoter methylation may be predictive of striatal DAT availability in adults with ADHD. Due to the small sample size, more work is needed to validate whether DAT1 methylation in blood predicts DAT1 methylation in SN in ADHD and controls.
Patient and caregiver involvement in the formulation of guideline questions: findings from the European Academy of Neurology guideline on palliative care of people with severe multiple sclerosis
Authors: Köpke S. , Giordano A. , Veronese S. , Rahn A. C. , Kleiter I. , Basedow‐Rajwich B. , Fornari A. , Battaglia M. A. , Drulovic J. , Kooij L. , Koops J. , Mens J. , Meza Murillo E. R. , Milanov I. , Milo R. , Patti F. , Pekmezovic T. , Sastre‐Garriga J. , Vosburgh J. , Voltz R. , Bay J. , Oliver D. J. , Solari A. 
Published: July 2018

Background and purposePatient and public involvement in clinical practice guideline development is recommended to increase guideline trustworthiness and relevance. The aim was to engage multiple sclerosis (MS) patients and caregivers in the definition of the key questions to be answered in the European Academy of Neurology guideline on palliative care of people with severe MS.MethodsA mixed methods approach was used: an international online survey launched by the national MS societies of eight countries, after pilot testing/debriefing on 20 MS patients and 18 caregivers, focus group meetings of Italian and German MS patients and caregivers.ResultsOf 1199 participants, 951 (79%) completed the whole online survey and 934 from seven countries were analysed: 751 (80%) were MS patients (74% women, mean age 46.1) and 183 (20%) were caregivers (36% spouses/partners, 72% women, mean age 47.4). Participants agreed/strongly agreed on inclusion of the nine pre‐specified topics (from 89% for ‘advance care planning’ to 98% for ‘multidisciplinary rehabilitation’), and <5% replied ‘I prefer not to answer’ to any topic. There were 569 free comments: 182 (32%) on the pre‐specified topics, 227 (40%) on additional topics (16 guideline‐pertinent) and 160 (28%) on outcomes. Five focus group meetings (three of MS patients, two of caregivers, and overall 35 participants) corroborated the survey findings. In addition, they allowed an explanation of the guideline production process and the exploration of patient‐important outcomes and of taxing issues.ConclusionsMultiple sclerosis patient and caregiver involvement was resource and time intensive, but rewarding. It was the key for the formulation of the 10 guideline questions and for the identification of patient‐important outcomes.
Fast‐track versus long‐term hospitalizations for patients with non‐disabling acute ischaemic stroke
Authors: Fladt J. , Hofmann L. , Coslovsky M. , Imhof A. , Seiffge D. J. , Polymeris A. , Thilemann S. , Traenka C. , Sutter R. , Schaer B. , Kaufmann B. A. , Peters N. , Bonati L. H. , Engelter S. T. , Lyrer P. A. , De Marchis G. M. 
Published: July 2018

Background and purposeThe aim was to assess the feasibility and safety of fast‐track hospitalizations in a selected cohort of patients with stroke.MethodsPatients hospitalized at the Stroke Center of the University Hospital Basel, Switzerland, with an acute ischaemic stroke confirmed on magnetic resonance diffusion‐weighted imaging were included. Neurological deficits of the included patients were non‐disabling, i.e. not interfering with activities of daily living and compatible with a direct discharge home. Patients with premorbid disability were excluded. All patients were admitted to the Stroke Center for ≥24 h. Two study groups were compared – fast‐track hospitalizations (≤72 h) and long‐term hospitalizations (>72 h). The primary end‐point was a composite of any unplanned rehospitalization for any reason within 3 months since hospital discharge and a modified Rankin Scale 3–6 at 3 months. Adjustment for confounders was done using the inverse probability of treatment weights (IPTW).ResultsAmongst the 521 patients who met the inclusion criteria, fast‐track hospitalizations were performed in 79 patients (15%). In the fast‐track group, seven patients (8.9%) met the primary end‐point, compared to 37 (8.4%) in the long‐term group [odds ratio (OR) 1.06, 95% confidence interval (CI) 0.42–2.34, P = 0.88]. After weighting for IPTW, the odds of the primary end‐point remained similar between the two arms (ORIPTW 1.27, 95% CI 0.51–3.16, P = 0.61). The costs of fast‐track hospitalizations were lower, on average, by $4994.ConclusionsFast‐track hospitalizations including a full workup proved to be feasible, showed no increased risk and were less expensive than long‐term hospitalizations.
Ex vivo fluorescence confocal microscopy for intraoperative, real‐time diagnosis of cutaneous inflammatory diseases: A preliminary study
Authors: Bertoni Laura , Azzoni Paola , Reggiani Camilla , Pisciotta Alessandra , Carnevale Gianluca , Chester Johanna , Kaleci Shaniko , Reggiani Bonetti Luca , Cesinaro Anna Maria , Longo Caterina , Pellacani Giovanni 
Published: July 2018

AbstractEx vivo fluorescence confocal microscopy (FCM) is an innovative imaging tool that can be used intraoperatively to obtain real‐time images of untreated excised tissue with almost histologic resolution. As inflammatory diseases often share overlapping clinical features, histopathology evaluation is required for dubious cases, delaying definitive diagnoses, and therefore therapy. This study identifies key‐features at ex vivo FCM for differential diagnoses of cutaneous inflammatory diseases, in particular, psoriasis, eczema, lichen planus and discoid lupus erythematosus. Retrospective ex vivo FCM and histological evaluations with relevant diagnoses were correlated with prospectively reported histopathologic diagnoses, to evaluate agreement and the level of expertise required for correct diagnoses. We demonstrated that ex vivo FCM enabled the distinction of the main inflammatory features in most cases, providing a substantial concordance to histopathologic diagnoses. Moreover, ex vivo FCM and histological evaluations reached a substantial agreement with histopathologic diagnoses both for all raters and for each operator. After a yet to be defined learning curve, these preliminary results suggest that dermatologists may be able to satisfactorily interpret ex vivo FCM images for correct real‐time diagnoses. Despite some limitations mainly related to the equipment of FCM with a single objective lens, our study suggests that ex vivo FCM seems a promising tool in assisting diagnoses of cutaneous inflammatory lesions, with a level of accuracy quite close to that offered by histopathology. This is the first study to investigate ex vivo FCM application in cutaneous inflammatory lesions, and to evaluate the diagnostic capability of this technology.
Characterization of stem‐like cancer cells in basal cell carcinoma and its surgical margins
Authors: Milosevic Maja , Lazarevic Milos , Toljic Bosko , Simonovic Jelena , Trisic Dijana , Nikolic Nađa , Petrovic Milan , Milasin Jelena 
Published: July 2018

AbstractBackgroundUnderstanding the pathogenesis of basal cell carcinoma (BCC) and identifying the cells responsible for propagation and recurrence are crucial for the development of new treatment strategies. The aim of this study was to characterize the cells isolated from BCC and its margin.MethodsPrimary cultures were established from 10 BCCs, their respective close resection margins (3 mm) and 10 control tissues. Stem cell markers analysis was carried out by real‐time PCR and/or flow cytometry. Spheroid formation and MTT assays were also performed.ResultsReal‐time PCR showed a higher expression of embryonic (Oct4, Sox2 and Nanog) and mesenchymal (CD44 and CD73) stem cell markers in tumors compared to margins and controls (P < 0.05). Bmi‐1 and GPR49 were also upregulated in tumors in comparison with margins. Both tumor and margin cells, but not normal, had the capacity to form spheroids. During passages, the number of spheres increased, while the diameter decreased. Tumor cells showed higher chemo‐resistance compared to margin and control cells.ConclusionsBasal cell carcinomas expressed stem cell markers, pointing to the existence of a cancer cell side population with stemness characteristics. Margin also appeared to harbour a small number of cancer‐initiating cells.
Rapid warming is associated with population decline among terrestrial birds and mammals globally
Authors: Spooner Fiona E. B. , Pearson Richard G. , Freeman Robin 
Published: July 2018

AbstractAnimal populations have undergone substantial declines in recent decades. These declines have occurred alongside rapid, human‐driven environmental change, including climate warming. An association between population declines and environmental change is well established, yet there has been relatively little analysis of the importance of the rates of climate warming and its interaction with conversion to anthropogenic land use in causing population declines. Here we present a global assessment of the impact of rapid climate warming and anthropogenic land use conversion on 987 populations of 481 species of terrestrial birds and mammals since 1950. We collated spatially referenced population trends of at least 5 years’ duration from the Living Planet database and used mixed effects models to assess the association of these trends with observed rates of climate warming, rates of conversion to anthropogenic land use, body mass, and protected area coverage. We found that declines in population abundance for both birds and mammals are greater in areas where mean temperature has increased more rapidly, and that this effect is more pronounced for birds. However, we do not find a strong effect of conversion to anthropogenic land use, body mass, or protected area coverage. Our results identify a link between rapid warming and population declines, thus supporting the notion that rapid climate warming is a global threat to biodiversity.