bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mifepristone mediates anti‐proliferative effect on ovarian mesenchymal stem/stromal cells from female BRCA1−/2− carriers
Authors: Ponandai‐Srinivasan Sakthivignesh , Lalitkumar Parameswaran G. , Garcia Laura , Varghese Suby Jo , Carlson Joseph W. , Gemzell‐Danielsson Kristina , Floter Radestad Angelique 
Published: October 2018

AbstractIntroductionWomen with hereditary mutation in breast cancer‐associated genes (BRCA1−/2−) have a higher lifetime risk of developing ovarian cancer. Here, we aimed to investigate the effect of mifepristone, a selective progesterone receptor modulator of ovarian mesenchymal stem/stromal cells (MSC) from BRCA1−/2− carriers.Material and methodsOvarian BRCA1−/2− MSC were positively selected using the markers CD90, CD73 and CD105 from nine healthy women. The effect of dose response and combination treatment with mifepristone and analogs of progesterone‐ or glucocorticoid‐receptors were investigated on BRCA1−/2− MSC in vitro using a panel of markers for proliferation (ki67, BrdU, CDK2, p21CIP), apoptosis (BAX, BCL2, CASPASE3), tumor suppression (TP53, PTEN) and cell survival (PI3KCA, MAPK3, mTOR).ResultsThe dose response with mifepristone treatment suggested an optimal effect with 10 μm mifepristone, exhibiting >90% viability and significantly reducing growth signaling markers (TP53 and MAPK3). Furthermore, combined treatment with progesterone plus mifepristone (PG+MIFE) gave an enhanced anti‐proliferative effect in comparison with hydrocortisone plus mifepristone (HC+MIFE) by significantly reducing markers of proliferation (BrdU+ and Ki67 expression) and tumor suppressors (PTEN, TP53), and increasing the percentage of pro‐apoptotic cells. Consequently, accumulation of p21CIP together with reduced levels of CDK2 confirms growth inhibition by reversibly arresting cell‐cycle progression at the G1‐S phase, not by inducing apoptosis.ConclusionsOur study showed an anti‐proliferative effect on ovarian BRCA1−/2− MSC on in vitro combined treatment with mifepristone and progesterone. These findings suggest that mifepristone or other selective progesterone receptor modulators could be developed as a preventive treatment and postpone early use of prophylactic salpingo‐oophorectomy as well as reduce the risk of ovarian cancer.
Follow‐up study of the early, randomised paracetamol trial to preterm infants, found no adverse reactions at the two‐years corrected age
Authors: Juujärvi S , Kallankari H , Pätsi P , Leskinen M , Saarela T , Hallman M , Aikio O 
Published: October 2018

AbstractAimWe examined the long‐term outcomes and safety of early intravenous paracetamol for ductus arteriosus closure at a corrected age of two years.MethodsThis was a follow‐up of the 2013–2014 randomised, double‐blind Preterm Infant's Paracetamol Study at Oulu University Hospital, Finland, which recruited 48 very preterm infants within 24 hours of birth. They received intravenous paracetamol or a placebo for four days. In 2015–2017, we followed up 44 infants (92%) at two years of corrected age. This included clinical and neurodevelopmental assessments and a parental medical history questionnaire.ResultsThe 44 infants (55% boys) were born at 235–316 weeks of gestation. No differences in the cardiac parameters, including blood pressures and ultrasound scan results, were found. Neurodevelopmental stages, as quantified by the Griffiths test, were similar. No signs of autism were reported. Asthma medication was more common in the control group, but the difference was not significant. Atopy scores, numbers of infections and the use of public health services were similar between the two groups.ConclusionNo long‐term adverse reactions of early intravenous paracetamol were detected two years later. Larger trials are needed on the safety and efficacy of paracetamol prophylaxis for early ductal closure in very preterm infants.
Lack of correlation between the costs of anticancer drugs and clinical benefits in Japan
Authors: Satoh Etsuko , Sasaki Yasutsuna , Ohkuma Ryotaro , Takahashi Takehiro , Kubota Yutaro , Ishida Hiroo , Hamada Kazuyuki , Kiuchi Yuji , Tsunoda Takuya 
Published: October 2018

Both overall survival (OS) and progression‐free survival (PFS) are primary endpoints of phase III studies of new anticancer drugs. Medical care expenditures, especially oncology drug prices, are rapidly increasing; however, the impact of oncology drug prices on OS and PFS is unclear. We analyzed the relationship between oncology drug prices and clinical outcomes in Japan. The costs of a full course or 1 year of treatment were estimated on the basis of the latest National Health Insurance Drug Price Standards, and the relationship between costs and improvements in OS or PFS obtained with each drug were analyzed. Cost‐effectiveness was compared between new‐class drugs and next‐in‐class drugs. We then developed a simple model for estimating the costs required to prolong OS and PFS by 1 day and used this model to compare cost‐effectiveness. Drug costs were not significantly related to treatment outcomes in terms of PFS or OS. There was no significant difference in the median cost between novel drugs and the next‐in‐class drugs (P = 0.39). The oncology drug cost required to prolong PFS by 1 day was more expensive than the drug cost required for prolong OS by 1 day. Prices of oncology drugs should be decided on the basis of actual clinical benefits for cancer patients, and the drug price evaluation process should be disclosed in Japan.
Integrating psychosocial support into routine diabetes care: perspectives from participants at the Self‐Management Alliance meeting 2016
Authors: Joensen L. , Fisher L. , Skinner T. , Doherty Y. , Willaing I. 
Published: October 2018

AbstractAimsTo identify challenges and solutions to integrating psychosocial support into routine diabetes care from the perspective of stakeholders with expertise in diabetes self‐management education and support.MethodsNinety‐four people attended the annual international Diabetes Self‐Management Alliance meeting in 2016, which included plenary sessions and workshops on self‐management education, support and prevention. One workshop focused on how to integrate psychosocial support into routine diabetes care; this was run four times consecutively, allowing all conference participants to attend the workshops in groups of 20–25 people.ResultsChallenges and solutions associated with integrating psychosocial support into routine diabetes care concern the patient–provider relationship, the healthcare system and the community. Challenges identified were: lack of time, skills and resources to deal with psychological well‐being; a culture of patient blame and care expectations; the complexity of person‐centred assessment of psychological issues; and the substantial healthcare system focus on productivity and biomedical indicators. Lack of involvement of local communities and of inclusion of social determinants of health were also highlighted as challenging. Solutions identified were more patient–provider dialogue; more training and better skills among care providers; system incentives for psychosocial outcomes; and targeting social determinants of health and involvement of family and peers.ConclusionsFrom the perspective of international stakeholders with an expertise in diabetes self‐management and support attending the conference in Denmark, substantial new incentives and systematic cultural changes are needed in healthcare systems to integrate psychosocial support into routine diabetes care, as recommended in international guidelines.
The copper‐zinc superoxide dismutase activity in selected diseases
Authors: Lewandowski Łukasz , Kepinska Marta , Milnerowicz Halina 
Published: October 2018

AbstractCopper‐zinc superoxide dismutase (Cu,Zn‐SOD) plays a protective role in various types of tissue protecting them from oxidative damage. Alterations in Cu,Zn‐SOD (SOD1 and SOD3) activity and its expression have been observed in pathological occurrences most prevalent in modern society, including inflammatory bowel disease, obesity and its implications—diabetes and hypertension, and chronic obstructive pulmonary disease. Moreover, several SOD1 and SOD3 gene polymorphisms have been associated with the risk of developing a particular type of disease, or its exacerbation. This article features recent observations in this topic, aiming to show the importance of proper gene sequence and activity of Cu,Zn‐SOD in the aforementioned diseases.
Placebos in the era of open‐label trials: An update for clinicians
Authors: Sagy Iftach , Abres Jonathan , Winnick Ariel , Jotkowitz Alan 
Published: October 2018

AbstractPlacebos have been used extensively by vast numbers of physicians, in a majority of clinical trials. Placebo effects involve behavioural, psychological and genetic factors and have been subject to ethical controversies stemming from the use of deception in treating patients. The patient‐physician encounter, endogenous pharmacological pathways, personality traits and genetic diversity have all been reported to be key players in placebo responses. In the last decade, a new methodological paradigm of placebo research has emerged, using open‐label placebos to investigate their effects which showed promising results for various common medical conditions. In this review, we will summarize the current body of evidence on placebos in clinical practice, with a view to open‐label placebo trials in particular. It is our view that future larger‐scale randomized blinded open placebo trials will benefit physicians and improve patient outcomes.
Pollen limitation as a main driver of fruiting dynamics in oak populations
Authors: Schermer Éliane , Bel‐Venner Marie‐Claude , Fouchet David , Siberchicot Aurélie , Boulanger Vincent , Caignard Thomas , Thibaudon Michel , Oliver Gilles , Nicolas Manuel , Gaillard Jean‐Michel , Delzon Sylvain , Venner Samuel 
Published: October 2018

AbstractIn many perennial wind‐pollinated plants, the dynamics of seed production is commonly known to be highly fluctuating from year to year and synchronised among individuals within populations. The proximate causes of such seeding dynamics, called masting, are still poorly understood in oak species that are widespread in the northern hemisphere, and whose fruiting dynamics dramatically impacts forest regeneration and biodiversity. Combining long‐term surveys of oak airborne pollen amount and acorn production over large‐scale field networks in temperate areas, and a mechanistic modelling approach, we found that the pollen dynamics is the key driver of oak masting. Mechanisms at play involved both internal resource allocation to pollen production synchronised among trees and spring weather conditions affecting the amount of airborne pollen available for reproduction. The sensitivity of airborne pollen to weather conditions might make oak masting and its ecological consequences highly sensitive to climate change.
EQ‐5D‐5L and SF‐6D health utility index scores in patients with myasthenia gravis
Authors: Barnett C. , Bril V. , Bayoumi A. M. 
Published: October 2018

Background and purposeHealth utilities are a preference‐based method of valuing health states that are used in healthcare research, such as economic evaluations. There are limited health utility valuation data for patients with myasthenia gravis (MG). The aim of the study was to describe health utilities for patients with MG and different health states, using the EQ‐5D‐5L and SF‐6D utility instruments, and to explore clinical and demographic determinants of utilities in this population.MethodsPatients completed the EQ‐5D‐5L and SF‐6D. In addition, patients were assessed with the Myasthenia Gravis Foundation of America classification, Myasthenia Gravis Impairment Index and MG‐QOL15 as disease‐specific measures, and the Neuro‐QoL Fatigue scale. We calculated mean utilities for each Myasthenia Gravis Foundation of America severity class. We built regression models for the EQ‐5D‐5L and SF‐6D to determine the clinical and demographic factors that determine patients’ valuation of their health state.ResultsAmong 254 patients, mean EQ‐5D‐5L health utilities were as follows: Remission, 0.94 ± 0.03; Minimal Manifestations, 0.92 ± 0.04; Class I, 0.89 ± 0.06; Class II, 0.78 ± 0.16; Class III, 0.58 ± 0.24 and Class IV, 0.61 ± 0.22. Mean SF‐6D health utilities were as follows: Remission, 0.83 ± 0.07; Minimal Manifestations, 0.86 ± 0.14; Class I, 0.82 ± 0.14; Class II, 0.67 ± 0.12; Class III, 0.56 ± 0.11 and Class IV, 0.50 ± 0.10. The limb/axial scores were more highly correlated to health utilities than ocular or bulbar scores.ConclusionsWe present estimates of health utilities for patients with MG that can be used in cost‐utility and decision analyses. Limb/axial symptoms had a higher impact on health utilities than ocular or bulbar symptoms, which might reflect the impact of mobility on health valuation.
Developmental and neurodegenerative damage in Friedreich's ataxia
Authors: Rezende T. J. R. , Martinez A. R. M. , Faber I. , Girotto Takazaki K. A. , Martins M. P. , de Lima F. D. , Lopes‐Cendes I. , Cendes F. , França M. C. 
Published: October 2018

Background and purposeFriedreich's ataxia (FRDA) is the most common autosomal‐recessive ataxia worldwide. It is characterized by early onset, sensory abnormalities and slowly progressive ataxia. All magnetic resonance imaging (MRI)‐based studies have focused on the evaluation of adult patients. Therefore, we designed a cross‐sectional multimodal MRI‐based study to investigate the anatomical substrates involved in the early stages of FRDA.MethodsWe enrolled 37 patients (12 children) and 38 controls. All subjects underwent MRI in a 3T device to assess gray and white matter. We used measures from FreeSurfer and CERES to evaluate the cerebral and cerebellar cortices. The T1 multiatlas assessed deep gray matter. The diffusion tensor imaging multiatlas was used to investigate microstructural abnormalities in brain white matter and SpineSeg was used to assess the cervical spinal cord. All analyses were corrected for multiple comparisons.ResultsComparison with age‐matched controls showed that pediatric patients have spinal cord, inferior cerebellar peduncle and red nucleus damage. In contrast, adult patients showed more widespread white matter damage than pediatric patients. With regard to gray matter, we found cortical thinning at the left central sulcus and volumetric reduction in the thalami and hippocampi only in adult patients. Finally, values of fractional anisotropy in adult patients and radial diffusivity in pediatric patients from the inferior cerebellar peduncle correlated with disease duration and ataxia severity, respectively.ConclusionsStructural damage in FRDA begins in the spinal cord and inferior cerebellar peduncle as well as the red nucleus, and progresses to cerebral areas in adulthood. These results shed some light on the early stages of FRDA and highlight potential neuroimaging markers for therapeutic trials.
Evaluating fisheries systems: A comprehensive analytical framework and its application to the EU's Common Fisheries Policy
Authors: Belschner Tobias , Ferretti Johanna , Strehlow Harry v. , Kraak Sarah B. M. , Döring Ralf , Kraus Gerd , Kempf Alexander , Zimmermann Christopher 
Published: October 2018

AbstractDespite regular reforms, problems under the EU's Common Fisheries Policy (CFP) persist. In order to identify priorities for future reforms of the policy, we developed an analytical framework consisting of 17 criteria and specifying indicators, derived from scientific, wider fisheries, and common resources literature. We applied the framework to the CFP governance system, its regulations, institutions, and processes at EU as well as member state level. The results show that the CFP does not fully meet any of the 17 criteria for an effective resource policy. Its performance was assessed as “neutral” regarding 10 criteria and “negative” regarding seven criteria. Trend analysis shows that there is a slightly positive trend regarding the CFP's performance, with five criteria trending positively, 11 showing a neutral trend and only one criterion trending negatively (simplicity of rules). The analysis identified five criteria which are performing badly and have not improved over time: simplicity of rules, user‐pays principle, resource efficiency, accountability, and compliance mechanisms. Future reforms of the CFP should first and foremost address these criteria while continuing efforts to improve the CFP's performance regarding other criteria. The evaluation of the CFP demonstrates the applicability of the analytical framework which can also be applied to other multilevel fisheries governance systems. Moreover, the results can inform reforms of Regional Fisheries Management Organisations. Like the CFP, these institutions manage transboundary fisheries and have not effectively addressed the issues of resource rent capture and resource efficiency.
Sustainable Yield of a Hydrothermal Area: From Theoretical Concepts to the Practical Approach
Authors: Piscopo Vincenzo , Di Luca Stefano , Dimasi Michele , Lotti Francesca 
Published: October 2018

AbstractSustainable use of groundwater in the hydrothermal area of Viterbo (Central Italy) was analyzed. In this area, multipurposes utilization of groundwater coexists: several thermal springs and wells supply spas and public pools, cold and fresh water is used for irrigation and drinking‐water. Starting from theoretical concepts, a management plan has been developed to ensure groundwater sustainability in response to the increased demand of withdrawal from thermal wells, by integrating previous hydrogeological studies, new investigations and a new finite‐difference model. The most stringent constraints considered are: to maintain the quality of thermal and fresh waters, to limit the effects on the hydraulic equilibrium existing between overlapping aquifers, to ensure a significant flow to the natural thermal springs and the quality and flow rate of the spring used for drinking purposes. The practical approach included identification of the maximum pumping rate from the wells of the spas, analysis of the response time of the system under development and drafting of a safeguard and monitoring plan. The case examined takes into account the complexity of the task in defining practical measures for groundwater management on the basis of theoretical concepts of its sustainable use. A participative approach among the different water decision‐makers and adaptive management in the use of groundwater resources with different quality represent the key points to overcome conflicts between different users, with the awareness of the ineludible uncertainties of the hydrogeological model.
Expanding the morphological spectrum of ovarian microcystic stromal tumour
Authors: McCluggage W Glenn , Chong Anne‐Sophie , Attygalle Ayoma D , Clarke Blaise A , Chapman William , Rivera Barbara , Foulkes William D 
Published: October 2018

AimsTo expand the morphological spectrum of ovarian microcystic stromal tumour, a rare neoplasm considered to have a relatively constant morphology with microcysts, solid cellular regions and hyalinised fibrous stroma.Methods and resultsWe report four ovarian neoplasms in patients aged 45, 56, 61 and 71 years with the characteristic immunophenotype of microcystic stromal tumour (diffuse nuclear positivity with beta‐catenin, cyclin D1 and WT1; diffuse cytoplasmic positivity with CD10; negative inhibin, calretinin, oestrogen receptor and progesterone receptor). The tumours had variant morphology (diffuse, nested and corded arrangements in three cases, including one with spindle cell elements; nested, corded and tubular in the other). A CTNNB1 point mutation in exon 3 (c.98C>G,p.S33C; c.100G>A,p.G34R; c.97T>G,p.S33A) was present in the three cases with material available for testing.ConclusionsWe feel that the cases we report are related to microcystic stromal tumour but with variant morphology; as such, the morphological spectrum of ovarian microcystic stromal tumour is broader than hitherto reported.
Balanitis xerotica obliterans: a review of diagnosis and management
Authors: Charlton Olivia A. , Smith Saxon D. 
Published: October 2018

AbstractBalanitis xerotica obliterans (BXO), or penile lichen sclerosus, is a progressive sclerosing inflammatory dermatosis of the glans penis and foreskin. It is associated with significant morbidity and may result in impaired urinary and sexual function. It was initially described by Stuhmer in 1928, named after its pathological features, and is considered the male equivalent of vulvar lichen sclerosis (LS).3,40 The etiology of BXO is uncertain; however, autoimmune disease, local trauma, and genetic and infective causes have been proposed. BXO occurs most commonly on the prepuce and glans penis. It is considered to have premalignant potential to transform into squamous neoplasia. This postulation rests on retrospective studies and parallels drawn with vulvar LS and squamous cell carcinoma (SCC) development. Histologically, BXO and vulvar LS are considered the same disease.41 There is a paucity of evidence‐based guidelines to assist with appropriate follow‐up for patients with BXO.
Revisiting acquired aplastic anaemia: current concepts in diagnosis and management
Authors: Clucas Danielle B. , Fox Lucy C. , Wood Erica M. , Hong Frank S. , Gibson John , Bajel Ashish , Szer Jeff , Blombery Piers , McQuilten Zoe K. , Hiwase Devendra , Firkin Frank , Cole‐Sinclair Merrole F. ,   on behalf of the Australian Aplastic Anaemia Registry Steering Committee
Published: October 2018

AbstractAcquired aplastic anaemia is a rare, serious, immunologically mediated bone marrow failure syndrome, characterised by marrow hypoplasia of varying severity and significant pancytopenia. Careful attention and investigation, including molecular testing, is required to confirm the diagnosis and exclude other mimicking conditions, such as inherited bone marrow failure syndromes. In a proportion of patients, the disease evolves to myelodysplasia or acute myeloid leukaemia and in some there is an association with paroxysmal nocturnal haemoglobinuria. The disease has a major impact on patient quality of life. Haemopoietic stem/progenitor cell transplantation for eligible patients with an available donor is the only current curative therapy. Other patients may receive immunosuppression, most commonly with anti‐thymocyte globulin and cyclosporin. An initial response to immunosuppression is often encouraging, but relapse is common. Supportive care, including management of transfusion requirements and infections, is central to management. Promising new diagnostic tools and emerging therapies will likely transform approaches to this important, chronic and life‐threatening condition.