bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unmanipulated haploidentical haematopoietic stem cell transplantation for children with severe aplastic anaemia
Authors: Zhu Hua , Luo Rong Mu , Luan Zuo , Lee Vincent , Zhu Yi Ping , Luo Cheng Juan , Tang Xiang Feng , Si Ying Jian , Chen Jing 
Published: June 2016

SummaryHaploidentical haematopoietic stem cell transplantation (haplo‐HSCT) used to be a third‐line treatment option for childhood severe aplastic anaemia (SAA). We conducted this retrospective study of 36 children (38 transplants) who received haplo‐HSCT from human leucocyte antigen (HLA)‐mismatched related donors between July 2002 and November 2013 at five HSCT centres in China, including 17 cases that were 5/6 HLA matched (Group 1) and 21 that were 4/6 or 3/6 HLA matched (Group 2). Although patients in Group 2 had a higher incidence of grade II‐IV acute graft‐versus‐host disease (57·9% vs. 5·9%, P = 0·001), they had similar rates of graft failure (5·3% vs. 5·9%, P = 0·742) and overall survival (80·8% vs. 93·8%, P = 0·234) as Group 1. Unmanipulated haplo‐HSCT is an effective treatment for SAA children with satisfactory outcome of this cohort, especially in the 5/6 HLA‐matched group. For patients in critical situations, such as unresponsive to immunosuppressive therapy, refractory infection and failing first HSCT, to bring forward the timing of haplo‐HSCT is a feasible salvage strategy with better and faster donor accessibility.
Advances in the pathogenesis of primary and secondary haemophagocytic lymphohistiocytosis: differences and similarities
Authors: Brisse Ellen , Wouters Carine H. , Matthys Patrick 
Published: June 2016

SummaryHaemophagocytic lymphohistiocytosis (HLH) comprises a heterogeneous spectrum of hyperinflammatory conditions that are inherited (primary HLH) or acquired in a context of infections, malignancies or autoimmune/autoinflammatory disorders (secondary HLH). Genetic defects in the cytotoxic machinery of natural killer and CD8+ T cells underlie primary HLH, with residual cytotoxicity determining disease severity. Improved sequencing techniques have expanded the range of causal mutations and have redefined many cases of secondary HLH as primary HLH and vice versa, blurring the distinction between both subtypes. These insights allow HLH to be conceptualized as a threshold disease, in which interplay between various genetic and environmental factors causes progressive inflammation into a critical point, beyond which uncontrolled activation of immune cells and excessive cytokine production give rise to the cardinal symptoms of HLH. Various pathogenic pathways may thus converge to a common end stage of fulminant HLH.
Territorial ‘Fix’? Tenure Insecurity in Titled Indigenous Territories
Authors: FINLEY‐BROOK MARY 
Published: June 2016

Indigenous territorial governments in Nicaragua's North Caribbean Coast Autonomous Region experience ongoing land and resource contests, in many cases building from longstanding disputes or problems, even after titling. I argue that it is naïve to expect that granting titles – a supposed territorial fix – will resolve conflicts created across decades as a result of ineffective policies and economic pressures. As shown with three demarcated Miskitu territories, tenure insecurity arises from challenges with the state, private firms, non‐indigenous colonists, and even from the activities of territorial leaders. These cases suggest the need to move beyond perceptions of Miskitu territories as simple bounded remnants of the past and acknowledge they are complex, porous, trans‐local, and transgressed by processes such as migration, urbanisation, and neoliberal economic integration. Indeed, new territorial governments are encouraged by foreign donors and state laws to mirror government agencies and prioritise market linkages.
The contribution of undiagnosed adrenal insufficiency to euvolaemic hyponatraemia: results of a large prospective single‐centre study
Authors: Cuesta Martín , Garrahy Aoife , Slattery David , Gupta Saket , Hannon Anne Marie , Forde Hannah , McGurren Karen , Sherlock Mark , Tormey William , Thompson Christopher J. 
Published: June 2016

SummaryObjectiveThe syndrome of inappropriate antidiuresis (SIAD) is the commonest cause of hyponatraemia. Data on SIAD are mainly derived from retrospective studies, often with poor ascertainment of the minimum criteria for the correct diagnosis. Reliable data on the incidence of adrenal failure in SIAD are therefore unavailable. The aim of the study was to describe the aetiology of SIAD and in particular to define the prevalence of undiagnosed adrenal insufficiency.DesignProspective, single centre, noninterventional, observational study of patients admitted to Beaumont Hospital with euvolaemic hyponatraemia (plasma sodium ≤ 130 mmol/l) between January 1st and October 1st 2015.PatientsA total of 1323 admissions with hyponatraemia were prospectively evaluated; 576 had euvolaemic hyponatraemia, with 573 (43·4%) initially classified as SIAD.Main outcome measures(i) Aetiology of SIAD, defined by diagnostic criteria; (ii) Incidence of adrenal insufficiency.ResultsCentral nervous system diseases were the commonest cause of SIAD (n = 148, 26%) followed by pulmonary diseases (n = 111, 19%), malignancy (n = 105, 18%) and drugs (n = 47, 8%). A total of 22 patients (3·8%), initially diagnosed as SIAD, were reclassified as secondary adrenal insufficiency on the basis of cortisol measurements and clinical presentation; 9/22 cases had undiagnosed hypopituitarism; 13/22 patients had secondary adrenal insufficiency due to exogenous steroid administration.ConclusionsIn a large, prospective and well‐defined cohort of euvolaemic hyponatraemia, undiagnosed secondary adrenal insufficiency co‐occurred in 3·8% of cases initially diagnosed as SIAD. Undiagnosed pituitary disease was responsible for 1·5% of cases presenting as euvolaemic hyponatraemia.
Risk, resilience and identity construction in the life narratives of young people leaving residential care
Authors: Schofield Gillian , Larsson Birgit , Ward Emma 
Published: June 2016

AbstractThe role of residential care for children has developed very differently internationally, but in all cultural contexts, there are questions about the extent to which it can help young people recover from high risk backgrounds. In the UK, residential care has come to be seen as the placement of last resort, yet new government guidance on permanence has suggested that residential care can provide security and a sense of belonging. Narrative analysis of interviews with 20 care leavers identified their different pathways from birth families through residential care to early adulthood. Some experienced a transformation from a negative sense of self as victims or ‘bad children’ to survivors, while others continued to struggle. Key to successful turning points were four interacting factors, all associated with resilience; connection, agency, activity and coherence. These narratives revealed the importance of nurturing relationships and a sense of ‘family’, and also the role of support after leaving residential care, when transitions workers helped them to move on but stay connected. The study highlighted how residential care leavers from adverse backgrounds attribute very different meanings to their experiences, which affects identity construction, resilience and the need for support.
When to suspect tinea; a histopathologic study of 103 cases of PAS‐positive tinea
Authors: Elbendary Amira , Valdebran Manuel , Gad AbdAllah , Elston Dirk M. 
Published: June 2016

BackgroundThe histopathologic features of tinea vary widely and its diagnosis could be easily missed if the index of suspicion is not high. We aimed in this study to detect histopathologic features that could be a clue for diagnosisMethodsWe retrospectively reviewed 103 cases of tinea, confirmed by Periodic acid–Schiff (PAS) staining. For each case, gender, biopsy site, and pre‐biopsy suspicion were recorded. The presence or absence of 17 microscopic features was noted.ResultsConcordance between pre‐biopsy and histopathologic diagnosis was noted in 57.28% of cases, suggesting that the diagnosis is often not suspected clinically. Among the histopathologic features studied, a compact stratum corneum (either uniform or forming a layer beneath a basket weave stratum corneum), parakeratosis, mild spongiosis and neutrophils in the stratum corneum and within the blood vessels were the most frequent features noted.ConclusionThis study suggests histopathologic clues that should prompt the pathologist to order a PAS stain, especially when diagnosis is not suspected clinically.
Addition of sulphonylurea to metformin does not relevantly change body weight: a prospective observational cohort study (ZODIAC‐39)
Authors: Schrijnders Dennis , Wever Raiza , Kleefstra Nanne , Houweling Sebastiaan T. , van Hateren Kornelis J. J. , de Bock Geertruida H. , Bilo Henk J. G. , Groenier Klaas H. , Landman Gijs W. D. 
Published: June 2016

AimTo investigate changes in body weight trajectories after the addition of individual sulphonylureas (SUs) to metformin in patients with type 2 diabetes.Materials and methodsWe conducted a retrospective observational cohort study, in a primary care setting in the Netherlands. Patients aged ≥18 years with type 2 diabetes who were included in the ZODIAC cohort between 1998 and 2012 and who received metformin monotherapy at inclusion (n = 29 195), and had used metformin as monotherapy for at least 1 year before receiving dual therapy through the addition of an SU for at least 1 year were eligible for inclusion. The primary outcome was within‐drug yearly change in body weight after receiving add‐on therapy with individual SUs during 5 years of follow‐up. The secondary outcome was within‐drug yearly change in glycated haemoglobin (HbA1c). Annual changes in weight and HbA1c were estimated with linear mixed models, adjusted for age, gender and diabetes duration.ResultsA total of 2958 patients were included. No significant weight changes were observed within and between any of the individual SUs after treatment intensification (p = 0.24). In addition, no significant difference in weight between the add‐on therapy combinations was observed (p = 0.26). The average HbA1c the year before intensification was 7.2% (55 mmol/mol) and dropped below 7.0% (53 mmol/mol) the year after.ConclusionsIn patients with type 2 diabetes treated in primary care, strict glycaemic control can be maintained with SUs used as add‐on therapy to metformin, without the offset of relevant weight changes.
Effect of testosterone on insulin sensitivity, oxidative metabolism and body composition in aging men with type 2 diabetes on metformin monotherapy
Authors: Magnussen Line V. , Glintborg Dorte , Hermann Pernille , Hougaard David M. , Højlund Kurt , Andersen Marianne 
Published: June 2016

AimsTo evaluate the effect of testosterone replacement therapy (TRT) on body composition, insulin sensitivity, oxidative metabolism and glycaemic control in aging men with lowered bioavailable testosterone (BioT) levels and type 2 diabetes mellitus (T2D) controlled on metformin monotherapy.Materials and methodsWe conducted a randomized, double‐blind, placebo‐controlled study in 39 men aged 50‐70 years with BioT levels <7.3 nmol/L and T2D treated with metformin monotherapy. Patients were randomized to testosterone gel (TRT, n = 20) or placebo (n = 19) for 24 weeks. Lean body mass (LBM), total and regional fat mass were measured using whole‐body dual‐energy X‐ray absorptiometry scans. Whole‐body peripheral insulin sensitivity, endogenous glucose production (EGP) and substrate oxidation were assessed by euglycaemic‐hyperinsulinaemic clamp with glucose tracer and combined with indirect calorimetry. Coefficients (β) represent the placebo‐controlled mean effect of intervention.Results
LBM (β = 1.9 kg, p = 0.001) increased after TRT, while total fat mass (β = −1.3 kg, p = 0.009), fat mass trunk (β = −0.7 kg, p = 0.043), fat mass legs (β = −0.7 kg, p = 0.025), fat mass arms (β = −0.3 kg, p = 0.001), and HDL cholesterol (β = −0.11 mmol/L, p = 0.009) decreased after TRT compared with placebo. Insulin‐stimulated glucose disposal rates did not change in response to TRT compared with placebo (p = 0.18). Moreover, glycated haemoglobin, and basal and insulin‐stimulated rates of EGP, lipid‐ and glucose‐oxidation were unaltered after TRT.Conclusion
TRT in aging men with lowered BioT levels and T2D controlled on metformin monotherapy improved body composition; however, glycaemic control, peripheral insulin sensitivity, EGP and substrate metabolism were unchanged.
Pericardial effusion due to cholesterol pericarditis in case of rheumatoid arthritis
Authors: Gecmen Cetin , Gecmen Gonca Gul , Kahyaoglu Muzaffer , Ece Dilek , Ozkan Birol , Karaman Ozge , Naser Abdurrahman , Kalayci Arzu , Karabay Can Yucel , Kirma Cevat 
Published: June 2016

Mini‐AbstractA 53‐year‐old male patient with a history of rheumatoid arthritis presented with exertional dyspnea, abdominal distension, and pleuritic chest pain for approximately one month. Transthoracic echocardiography revealed a large, hyperechogenic, and circumferential pericardial effusion. The computer tomography revealed circumferential hyperdense fluid image around the heart. After that findings, we aspirated approximately 900 mL yellow fluid with gold paint by emergency pericardial tapping with transthoracic echocardiographic guidance. Cytopathologic examination of the pericardial effusion showed the presence of multinucleated giant cells. The pathological images revealed rare crystals of cholesterol which were engulfed by multinucleated giant cells. The gold‐paint appearance, high cholesterol content, and cytopathologic characteristics of the pericardial effusion supported the diagnosis of cholesterol pericarditis.
The interconnected rhizosphere: High network complexity dominates rhizosphere assemblages
Authors: Shi Shengjing , Nuccio Erin E. , Shi Zhou J. , He Zhili , Zhou Jizhong , Firestone Mary K. 
Published: June 2016

AbstractWhile interactions between roots and microorganisms have been intensively studied, we know little about interactions among root‐associated microbes. We used random matrix theory‐based network analysis of 16S rRNA genes to identify bacterial networks associated with wild oat (Avena fatua) over two seasons in greenhouse microcosms. Rhizosphere networks were substantially more complex than those in surrounding soils, indicating the rhizosphere has a greater potential for interactions and niche‐sharing. Network complexity increased as plants grew, even as diversity decreased, highlighting that community organisation is not captured by univariate diversity. Covariations were predominantly positive (> 80%), suggesting that extensive mutualistic interactions may occur among rhizosphere bacteria; we identified quorum‐based signalling as one potential strategy. Putative keystone taxa often had low relative abundances, suggesting low‐abundance taxa may significantly contribute to rhizosphere function. Network complexity, a previously undescribed property of the rhizosphere microbiome, appears to be a defining characteristic of this habitat.
Monitoring chromosomal polymorphism in Drosophila subobscura over 40 years
Authors: Orengo Dorcas J. , Puerma Eva , Aguadé Montserrat 
Published: June 2016

AbstractThe inversion chromosomal polymorphism of Drosophila subobscura is considered to be adaptive as a result of its responses at different time scales to temperature changes. This work reports the longest‐term study of chromosomal polymorphism for a single population of D. subobscura with climatic data from the collecting site itself. The chromosomal analysis of D. subobscura samples collected six times over a 40‐year period at the same location and in the same seasonal interval has revealed the continuous presence of 16 common and six moderately rare chromosomal arrangements through the period. This analysis also corroborates the previously detected negative relationship between the frequencies of the standard (cold‐climate) arrangement on each of its five chromosomes and temperature, as well as between a comprehensive measure of cold adaptation (the total autosomal proportion of standard arrangement) and temperature. These and previous results would support that species harboring cold‐ and warm‐adapted polymorphic chromosomal arrangements, like D. subobscura, can rapidly respond to environmental changes.
Drug‐resistant epilepsy in adults: Outcome trajectories after failure of two medications
Authors: Choi Hyunmi , Hayat Matthew J. , Zhang Ruiqi , Hirsch Lawrence J. , Bazil Carl W. , Mendiratta Anil , Kato Kenneth , Javed Asif , Legge Alexander W. , Buchsbaum Richard , Resor Stanley , Heiman Gary A. 
Published: June 2016

SummaryObjectiveTo examine the seizure trajectories of adults with epilepsy developing drug‐resistant epilepsy (DRE) and to identify the predictors of seizure trajectory outcome.MethodsAdult patients failing two antiepileptic drugs (AEDs) due to inefficacy and starting their third AED at a tertiary epilepsy center were followed for seizure trajectory outcome during medical management. Seizure trajectories were categorized into one of four patterns: (1) course with constant seizures; (2) fluctuating course; (3) delayed attainment of seizure freedom (seizure freedom delayed for >12 months after start of the study, but patient stayed in seizure freedom); and (4) early attainment of seizure freedom (within 12 months of starting study). Multiple ordinal logistic regression models were used to estimate the association between trajectory categories and clinical factors.ResultsFour hundred three adult patients met the eligibility criteria. Of these, 212 (53%) never achieved a seizure‐free period of a year or more. The trajectories of 63 patients (16%) had a complex fluctuating trajectory, 62 (15%) had delayed onset of seizure freedom, and 66 (16%) had an early seizure freedom. Independent predictors associated with more favorable outcome trajectories were epilepsy type and length of follow‐up. Specifically, compared to patients with focal epilepsy of temporal lobe, patients with focal epilepsy of occipital lobe (OR 3.80, 95% confidence interval [CI] 1.00–14.51, p = 0.04), generalized genetic (OR 3.23, 95% CI 1.88–5.57, p < 0.0001), unclear epilepsy type (OR 3.82, 95% CI 1.53–9.52, p < 0.005), and both focal and generalized epilepsy(OR 11.73, 95% CI 1.69–81.34, p = 0.01) were significantly more likely to experience a better trajectory pattern.SignificanceExamination of patterns of seizure trajectory of patients with incident DRE showed that 31% were in continuous seizure freedom at the end of the observation period.
Safety, tolerability, and seizure control during long‐term treatment with adjunctive brivaracetam for partial‐onset seizures
Authors: Toledo Manuel , Whitesides John , Schiemann Jimmy , Johnson Martin E. , Eckhardt Klaus , McDonough Belinda , Borghs Simon , Kwan Patrick 
Published: June 2016

SummaryObjectivesTo report pooled safety/tolerability and seizure outcome data from adults with uncontrolled partial‐onset (focal) seizures (POS) receiving adjunctive brivaracetam (BRV) during phase IIb/III and long‐term follow‐up (LTFU) studies.MethodsSeizure outcome data were pooled from phase IIb (NCT00175929 and NCT00175825), III/IIIb (NCT00490035, NCT00464269, NCT00504881, and NCT01261325) and associated LTFU studies (NCT00175916, NCT00150800, and NCT01339559). Safety/tolerability data were pooled from these studies plus NCT01405508, NCT01653262, and NCT01728077 (LTFU). Patients received placebo (during core studies) or BRV 5–200 mg/day. Safety/tolerability and seizure outcomes (BRV modal doses 50–200 mg/day) were assessed until January 17, 2014.ResultsOf 2,186 patients (97.3% with POS and 2.7% with other seizure types) who received BRV 50–200 mg/day, 2,051 (93.8%) completed core studies and continued in LTFU studies. Total BRV exposure: 5,339.4 patient‐years (≥8.0 years in 41 patients); 6‐, 12‐, 24‐, and 60‐month retention: 91.0%, 79.8%, 68.1%, and 54.4%, respectively. Safety/tolerability data pooled from 2,186 patients: ≥1 treatment‐emergent adverse event (TEAE) reported by 1,848 (84.5%) patients; 1,184 (54.2%) reported ≥1 TEAE considered treatment‐related. Most frequent TEAEs (≥10%): headache (20.9%), dizziness (17.5%), somnolence (15.2%), nasopharyngitis (13.2%), fatigue (11.3%), and convulsion (10.6%). Serious TEAEs (SAEs) and treatment‐related SAEs: 401 (18.3%) and 95 (4.3%) patients, respectively. Of 28 (1.3%) deaths, four (14.3%) were considered possibly treatment related by the investigator. Pooled seizure outcome data (1,836 patients): median POS frequency/28 days at baseline was 8.9; on treatment, median percentage reduction from baseline in POS/28 days was 48.8%, and ≥50% responder rate was 48.7%. Complete seizure freedom: 4.9%, 4.2%, 3.0%, and 3.3% for ≥6, 12, 24, and 60 months, respectively. Improvements were seen in health‐related quality of life (HRQoL) from baseline, assessed by Quality of Life in Epilepsy Inventory‐31.SignificanceAdjunctive BRV treatment in adults with POS was effective and generally well tolerated when administered long‐term (≥8.0 years). Retention was high and HRQoL improvements were observed.
Efficacy of the epilepsy nurse: Results of a randomized controlled study
Authors: Pfäfflin Margarete , Schmitz Bettina , May Theodor W. 
Published: June 2016

SummaryObjectiveWe investigated the efficacy of epilepsy nurses on satisfaction with counseling about epilepsy in a randomized, controlled, prospective trial.MethodsPatients with epilepsy treated by neurologists in outpatient clinics were consecutively enrolled and randomly allocated to either the epilepsy nurse (EN) group (n = 92) or the control group (n = 95). Patients in the EN group were advised according to their needs by epilepsy nurses. The control group received routine care without additional counseling. The EN group completed the questionnaires before the first consultation (T1) and 6 months later (T2); the control group completed the questionnaires twice with an interval of 6 months. Primary outcome measure was satisfaction of patients with information and support. Secondary outcome measures were satisfaction with patient–doctor relationship, organization of treatment, epilepsy knowledge, coping, and restrictions in daily life. Anxiety and depression (Hospital Anxiety and Depression Scale) and global Quality of Life (item from QOLIE‐31) were also assessed. Statistical analysis included generalized estimating equation (GEE) and nonparametric tests.ResultsSatisfaction with information and support improved significantly in the EN group compared to the control group (GEE, interaction group × time, p = 0.001). In addition, Epilepsy Knowledge (p = 0.014) and Coping (subscale Information Seeking) (p = 0.023) improved. Increase in satisfaction with counseling was dependent on patients' needs for information and on the amount of received information (Jonckheere‐Terpstra test, p < 0.001). No differences between the groups were observed on other epilepsy‐specific scales.SignificanceA reliable questionnaire for satisfaction with epilepsy care has been developed. Epilepsy nurses improve the satisfaction of patients with counseling and information about epilepsy and concomitant problems.