bluuebunny/crossref_metadata_2025_split huggingface dataset:
Childhood growth of females with Kallmann syndrome and FGFR1 mutations
Authors: Hero Matti , Laitinen Eeva‐Maria , Varimo Tero , Vaaralahti Kirsi , Tommiska Johanna , Raivio Taneli 
Published: May 2014

SummaryObjectiveIn search of phenotypic cues that would allow early detection of Kallmann syndrome (KS), we evaluated the paediatric phenotypes in a series of females with KS.Design, Patients and MeasurementsIn this retrospective cohort study, we investigated childhood growth in six females with KS due to mutations in FGFR1 and evaluated their reproductive phenotypes later in life.ResultsWhile growth during early infancy and childhood was within normal limits, a decreasing trend in height SDS already from mid‐childhood occurred in most patients. The lowest height SDS (mean, −1·2 SDS) occurred between 14 and 15 years of age, before the start of hormone replacement therapy. As adults, these women required assisted reproductive techniques for fertility. One of the probands passed on her G48S mutation to her son, who showed normal reproductive hormone levels during the minipuberty of infancy.ConclusionsEarly diagnosis of female KS remains a challenge as early phenotypic signs, apart from anosmia, are scarce. Females with KS exhibit a slight reduction in growth rate during mid‐childhood, but normal growth rate during the minipuberty of infancy, despite congenital lack of ovarian oestrogen. Women harbouring FGFR1 mutations will have 50% chance of passing on the gene defect to their offspring. We recommend genetic counselling to all females with KS to be carried out as a part of family planning.
Treatment Options to Reduce Disease Activity After Natalizumab: Paradoxical Effects of Corticosteroids
Authors: Rossi Silvia , Motta Caterina , Studer Valeria , Boffa Laura , De Chiara Valentina , Castelli Maura , Barbieri Francesca , Buttari Fabio , Monteleone Fabrizia , Germani Giorgio , Macchiarulo Giulia , Weiss Sagit , Centonze Diego 
Published: May 2014

SummaryAimNatalizumab (NTZ) discontinuation leads to multiple sclerosis (MS) recurrence, but represents the only known strategy to limit the risk of progressive multifocal leukoencephalopathy (PML) in JCV seropositive patients. Here, we compared the clinical and imaging features of three groups of patients who discontinued NTZ treatment.MethodsWe treated 25 patients with subcutaneous INFβ‐1b (INF group), 40 patients with glatiramer acetate (GA group), and 40 patients with GA plus pulse steroid (GA+CS group).ResultsSix of 25 patients (24%) of the INF group were relapse‐free 6 months after NTZ suspension. In GA group, a significant higher proportion of patients (26 of 40 patients, 65%) were relapse‐free (P < 0.05). Far from improving the clinical effects of GA in post‐NTZ setting, combination of GA+CS was associated with lower relapse‐free rate than GA alone (40% vs. 65%, P = 0.04). Also on MRI parameters, combination of GA+CS was associated with worse outcome than GA alone, as 22 of 26 subjects (84.6%) had MRI evidence of disease activity 6 months after NTZ discontinuation.ConclusionCorticosteroids should not be used in combination with GA to prevent post‐NTZ disease recurrence.
Research Participant‐Centered Outcomes at NIH‐Supported Clinical Research Centers
Authors: Kost Rhonda G. , Lee Laura N. , Yessis Jennifer L. , Wesley Robert , Alfano Sandra , Alexander Steven R. , Kassis Sylvia Baedorf , Cola Philip , Dozier Ann , Ford Dan E. , Harris Paul A. , Kim Emmelyn , Lee Simon Craddock , O'Riordan Gerri , Roth Mary‐Tara , Schuff Kathryn , Wasser June , Henderson David K. , Coller Barry S. 
Published: May 2014

AbstractBackgroundAlthough research participation is essential for clinical investigation, few quantitative outcome measures exist to assess participants’ experiences. To address this, we developed and deployed a survey at 15 NIH‐supported clinical research centers to assess participant‐centered outcomes; we report responses from 4,961 participants.MethodsSurvey questions addressed core aspects of the research participants’ experience, including their overall rating, motivation, trust, and informed consent. We describe participant characteristics, responses to individual questions, and correlations among responses.ResultsRespondents broadly represented the research population in sex, race, and ethnicity. Seventy‐three percent awarded top ratings to their overall research experience and 94% reported no pressure to enroll. Top ratings correlated with feeling treated with respect, listened to, and having access to the research team (R2 = 0.80–0.96). White participants trusted researchers more (88%) than did nonwhite participants collectively (80%; p < 0.0001). Many participants felt fully prepared by the informed consent process (67%) and wanted to receive research results (72%).ConclusionsOur survey demonstrates that a majority of participants at NIH‐supported clinical research centers rate their research experience very positively and that participant‐centered outcome measures identify actionable items for improvement of participant's experiences, research protections, and the conduct of clinical investigation.
Optimization of immunocytochemistry in cytology: comparison of two protocols for fixation and preservation on cytospin and smear preparations
Authors: Pinheiro C. , Roque R. , Adriano A. , Mendes P. , Praça M. , Reis I. , Pereira T. , Srebotnik Kirbis I. , André S. 
Published: May 2014

ObjectiveA new protocol for fixation and slide preservation was evaluated in order to improve the quality of immunocytochemical reactions on cytology slides.MethodsThe quality of immunoreactions was evaluated retrospectively on 186 cytology slides (130 direct smears, 56 cytospins) prepared from different cytology samples. Ninety‐three of the slides were air dried, stored at −20 °C and fixed in acetone for 10 minutes (Protocol 1), whereas the other 93 were immediately fixed in methanol at −20 °C for at least 30 minutes, subsequently protected with polyethylene glycol (PEG) and stored at room temperature (Protocol 2). Immunocytochemical staining, with eight primary antibodies, was performed on a Ventana BenchMark Ultra instrument using an UltraView Universal DAB Detection Kit. The following parameters were evaluated for each immunoreaction: morphology preservation, intensity of specific staining, background and counterstain. The slides were blinded and independently scored by four observers with marks from 0 to 20.ResultsThe quality of immunoreactions was better on methanol‐fixed slides protected with PEG than on air‐dried slides stored in the freezer: = 14.44 ± 3.58 versus = 11.02 ± 3.86, respectively (P < 0.001).ConclusionImmediate fixation of cytology slides in cold methanol with subsequent application of PEG is an easy and straightforward procedure that improves the quality of immunocytochemical reactions and allows the storage of the slides at room temperature.
Impact of inconclusive endoscopic ultrasound‐guided fine‐needle aspiration results in the management and outcome of patients with solid pancreatic masses
Authors: Sun Bo , Yang Xiujiang , Ping Bo , He Yiping , Zhang Zhaozhen 
Published: May 2014

Background and AimEndoscopic ultrasound‐guided fine‐needle aspiration (EUS‐FNA) can be inconclusive in diagnosing solid pancreatic masses. The aim of the present study was to evaluate the impact of an inconclusive EUS‐FNA in the management of patients with solid pancreatic masses.MethodsThis is a retrospective analysis of a prospective database of patients with solid pancreatic masses referred for EUS‐FNA between December 2011 and December 2013. Consecutive patients with inconclusive initial EUS‐FNA were included. Demographic, clinical, procedural and outcome data were analyzed.ResultsOver the study period, 387 patients underwent EUS‐FNA of solid pancreatic masses, of which 38 patients had inconclusive cytology. Of the 38 patients, 18 were categorized as atypical, two were categorized as indeterminate or suspicious for malignancy, and 18 were categorized as benign process. Subsequently, 24 (63.2%) patients achieved cytopathological diagnosis by repeat EUS‐FNA (8), transcutaneous FNA (4) and surgery (12). Repeat EUS‐FNA were done a median of 13 days after the index examination and resulted in conclusive diagnosis in 72.7% of cases. Five patients undergoing surgery were confirmed to have benign lesions. In 14 (36.8%) patients not receiving a positive cytopathological diagnosis, 11 were eventually confirmed to be malignant based on clinical outcome and imaging evidence.ConclusionsInconclusive EUS‐FNA could lead to unnecessary surgical procedures in patients with resectable solid pancreatic masses if no cytopathological diagnosis is obtained through either repeat or alternative diagnostic modalities. Repeat EUS‐FNA provided a conclusive diagnosis in a majority of cases, and therefore should be strongly considered ahead of other modalities.
Post‐natal assessment of gestational diabetes: fasting glucose or full glucose tolerance test?
Authors: Myers J. E. , Hasan X. , Maresh M. J. A. 
Published: May 2014

AbstractAimsTo determine the performance of a fasting glucose sample compared with a full oral glucose tolerance test for the detection of glucose abnormalities in a diverse ethnic population after gestational diabetes.MethodsOral glucose tolerance test results for women attending post‐natal testing over a 10‐year (2003–2013) period at St Mary's Hospital, Manchester, UK were reviewed. Demographic data were also extracted from the hospital maternity database.ResultsThe average attendance for a post‐natal oral glucose tolerance test was approximately 45% over the study period. The prevalence of diabetes was 4.8% (30/629), with a higher rate in women of Asian ethnicity compared with other groups (6.6% vs. 3.5%). The sensitivity for a fasting plasma glucose of ≥ 6.1 mmol/l was 90% (95% CI 74.4–96.5%) for the detection of diabetes and 61% (49.1–71.5%) for the detection of diabetes and/or impaired glucose tolerance, with specificities of 91% (88.8–93.3%) and 93% (91.0–95.2%), respectively. The positive and negative likelihood ratios for diabetes and impaired glucose tolerance were 10.4 (7.8–13.8), 0.11 (0.03–0.32) and 9.2 (6.4–13.3), 0.42 (0.31–0.56), respectively. A fasting plasma glucose threshold of 5.6 mmol/l improved the sensitivity for impaired glucose tolerance (from 61% to 77%), but made no difference to the sensitivity for diabetes.ConclusionsThe current study has demonstrated that detection of diabetes after gestational diabetes, in an ethnically diverse population using a fasting plasma glucose only, was approximately 90%. Compliance with post‐natal screening might improve if women attended for a fasting plasma glucose only; this strategy would identify approximately 90% of cases of diabetes and 40% of cases of impaired glucose tolerance.
Subcutaneous injection of hyaluronidase with recombinant human insulin compared with insulin lispro in type 1 diabetes
Authors: Garg S. K. , Buse J. B. , Skyler J. S. , Vaughn D. E. , Muchmore D. B. 
Published: May 2014

AimsPrandial treatment with human regular insulin for diabetes may result in early postprandial hyperglycaemia and late hypoglycaemia due to its slow onset and long duration of action. This study compared injections of recombinant human insulin (rHI) formulated with recombinant human hyaluronidase [rHuPH20] (INSULIN‐PH20) to insulin lispro for prandial treatment in subjects with type 1 diabetes (T1D).MethodsAfter a 1‐month run‐in period using twice‐daily insulin glargine (or usual basal insulin therapy for pump users) with prandial lispro, 46 subjects with T1D (42 ± 13 years; body mass index: 26 ± 4 kg/m2; A1c: 6.8 ± 0.5%) were assigned to INSULIN‐PH20 or lispro in a random sequence for two consecutive, 12‐week periods as the prandial insulin in an intensive treatment regimen.ResultsThe mean glycaemic excursion for INSULIN‐PH20 (0.96 ± 2.00 mmol/l) was comparable (p = 0.322) to lispro (0.80 ± 1.95 mmol/l). The 8‐point self‐monitored blood glucose profiles were also comparable in the two groups. Good glycaemic control (A1c) was maintained for both treatments at 12 weeks (INSULIN‐PH20: 7.0 ± 0.5%; lispro: 6.9 ± 0.6%). Overall rates of hypoglycaemia (≤3.9 mmol/l) were 24 events per patient per 4 weeks for INSULIN‐PH20 and 22 events for lispro. There were no significant differences in adverse events or immunogenicity between treatments and both treatments were well tolerated.ConclusionsUnlike commercially available formulations of regular human insulin, a formulation of rHI with rHuPH20 was comparable to lispro for postprandial glucose excursions in a basal‐bolus treatment regimen for T1D patients. Glycaemic control, safety and tolerability profiles were comparable for both treatments.
Modulation of IL‐33/ST2 system in postinfarction heart failure: correlation with cardiac remodelling markers
Authors: Sánchez‐Más Jesús , Lax Antonio , Asensio‐López María del Carmen , Fernandez‐Del Palacio Maria J. , Caballero Luis , Santarelli Giorgia , Januzzi James L. , Pascual‐Figal Domingo A. 
Published: May 2014

AbstractBackgroundInterleukin (IL)‐33 and sST2 are molecules with an opposite pathophysiologic implications in the myocardial response after acute myocardial infarction (AMI). Both may be a target for therapeutic interventions. The kinetics of IL‐33 and sST2 expression in infarcted myocardium and their correlation with the ongoing processes of fibrosis, inflammation and apoptosis remains poorly defined.Materials and methodsFifty Wistar rats underwent left anterior descending coronary artery surgical ligation and were sacrificed at 1, 2, 4, 12 or 24 weeks post‐AMI. A sham‐operated group was also included. The mRNA cardiac expression levels of IL‐33, sST2, fibrosis markers, inflammatory markers and apoptosis markers were assessed by RT‐PCR. The protein expression of IL‐33 was also measured by Western blotting.ResultsThe mRNA levels of IL‐33 and sST2 were upregulated in the infarcted myocardium during the first week after AMI. However, while IL‐33 levels remained elevated during the first 12 weeks post‐AMI, sST2 levels showed a marked drop at 4 weeks. IL‐33 protein expression showed a similar kinetic than mRNA expression. The expression of sST2 positively correlated with cardiac gene expression of inflammatory and fibrosis markers. However, the IL‐33 level did not correlate with these cardiac remodelling markers. No correlation of sST2 with apoptosis markers was observed.ConclusionAfter AMI, expression of sST2 is rapidly upregulated during the first 4 weeks and, in contrast to IL‐33, its levels correlated with the ongoing processes of fibrosis and inflammation. These findings suggest differential regulation of IL33 and sST2. Therapeutic modulation of early sST2 expression may be of greater importance to prevent adverse remodelling after AMI.
Serum and urinary NGAL but not KIM‐1 raises in human postrenal AKI
Authors: Urbschat Anja , Gauer Stefan , Paulus Patrick , Reissig Manuel , Weipert Christine , Ramos‐Lopez Elizabeth , Hofmann Rainer , Hadji Peyman , Geiger Helmut , Obermüller Nicholas 
Published: May 2014

AbstractBackgroundWe examined the value of the novel acute kidney injury (AKI) markers neutrophil gelatinase‐associated lipocalin (NGAL) and kidney injury molecule‐1 (KIM‐1) in acute postrenal impairment. These biomarkers have been evaluated in prerenal and intrarenal AKI so far, but not in human acute postrenal kidney injury. With regard to multimorbid and critically ill patients the discrimination of different AKI origins often remains a challenge. As the trend goes towards a diagnostic panel of AKI markers, we hereby aim to contribute to evaluate further options of discrimination in an observational case‐control study.Materials and methodsBlood and urine samples were obtained from 53 patients with acute obstructive nephropathy secondary to ureteral calculi and 52 age‐matched healthy controls. Serum NGAL (sNGAL), urinary NGAL (uNGAL) and urinary KIM‐1 (uKIM‐1) levels were determined using a commercially available ELISA kit, creatinine applying the Jaffé's method.ResultsWhile urinary levels of KIM‐1 were not significantly different between patients with obstructive nephropathy and controls, a striking increase in sNGAL (P < 0·001) and uNGAL (P < 0·01) levels was detected in the obstructive nephropathy group. Within the obstructive nephropathy group, sNGAL (P = 0·01) and uNGAL (P = 0·049) but not uKIM‐1 correlated positively with the white blood cell count and uNGAL correlated positively (P = 0·002) with the extent of leucocyturia.ConclusionsHigh levels of sNGAL and uNGAL observed in stone‐induced acute obstructive nephropathy may represent a valuable marker of postrenal AKI. Low uKIM‐1 levels may help to discriminate postrenal AKI events using a panel of markers in this setting.
Enhanced bleaching treatment: opportunities for immune‐assisted melanocyte suicide in vitiligo
Authors: Webb Kirsten C. , Eby Jonathan M. , Hariharan Vidhya , Hernandez Claudia , Luiten Rosalie M. , Le Poole I. Caroline 
Published: May 2014

AbstractDepigmentation in vitiligo occurs by progressive loss of melanocytes from the basal layer of the skin, and can be psychologically devastating to patients. T cell‐mediated autoimmunity explains the progressive nature of this disease. Rather than being confronted with periods of rapid depigmentation and bouts of repigmentation, patients with long‐standing, treatment‐resistant vitiligo can undergo depigmentation treatment. The objective is to remove residual pigmentation to achieve a cosmetically acceptable result – that of skin with a uniform appearance. In the United States, only the use of mono‐benzyl ether of hydroquinone (MBEH) is approved for this purpose. However, satisfactory results can take time to appear, and there is a risk of repigmentation. MBEH induces necrotic melanocyte death followed by a cytotoxic T‐cell response to remaining, distant melanocytes. As cytotoxic T‐cell responses are instrumental to depigmentation, we propose that combining MBEH with immune adjuvant therapies will accelerate immune‐mediated melanocyte destruction to achieve faster, more definitive depigmentation than with MBEH alone. As Toll‐like Receptor (TLR) agonists – imiquimod, CpG, and Heat Shock Protein 70 (HSP 70) – all support powerful Th1 responses, we propose that using MBEH in combination with these agents can achieve superior depigmentation results for vitiligo patients.
Is fisheries production within Large Marine Ecosystems determined by bottom‐up or top‐down forcing?
Authors: Mcowen Chris J , Cheung William W L , Rykaczewski Ryan R , Watson Reg A , Wood Louisa J 
Published: May 2014

AbstractUnderstanding the mechanisms driving fisheries production is essential if we are to accurately predict changes under climate change and exploit fish stocks in a sustainable manner. Traditionally, studies have sought to distinguish between the two most prominent drivers, ‘bottom‐up’ (resource driven) and ‘top‐down’ (consumer driven); however, this dichotomy is increasingly proving to be artificial as the relative importance of each mechanism has been shown to vary through space and time. Nevertheless, the reason why one predominates over another within a region remains largely unknown. To address this gap in understanding, we identified the dominant driver of commercial landings within 47 ecosystems, encompassing a wide range of biogeochemical conditions and fishing practices to elucidate general patterns. We show that bottom‐up and top‐down effects vary consistently with past fishing pressure and oceanographic conditions; bottom‐up control predominates within productive, overfished regions and top‐down in relatively unproductive and under‐exploited areas. We attribute these findings to differences in the species composition and oceanographic properties of regions, together with variation in fishing practices and (indicative) management effectiveness. Collectively, our analyses suggest that despite the complexity of ecological systems, it is possible to elucidate a number of generalities. Such knowledge could be used to increase the parsimony of ecosystem models and to move a step forward in predicting how the global ocean, particularly fisheries productivity, will respond to climate change.
Does wet cupping on the interscapular region improve depression and anxiety?
Authors: Farahmand Seyed Kazem , Gang Li Zhi , Saghebi Seyed Ahmad , Mohammadi Maryam , Mohammadi Shabnam , Mohammadi Ghazaleh , Ferns Gordon A , Ghanbari Majid , Ghayour Razmgah Gholamreza , Ramazani Zahra , Ghayour‐Mobarhan Majid , Esmaily Habibollah , Azizi Hoda 
Published: May 2014

AbstractBackgroundMetabolic syndrome is characterised by at least three of the following clinical features: abdominal obesity, dyslipidaemia, high blood pressure and glucose intolerance; it has also been associated with depression and anxiety. Cupping has been shown to benefit psychological well‐being by alleviating anger, hostility, depression and anxiety.ObjectivesTo investigate the effects of wet cupping on depression and anxiety in patients with metabolic syndrome.MethodsAltogether 136 patients with metabolic syndrome (aged 18–65 years) were included. Ten patients were excluded owing to a history of haemophilia, systemic disorder, infectious disease, stroke, heart attack, type 1 diabetes, secondary dyslipidaemia, renal dysfunction, epilepsy and drug therapy. Patients were randomly divided into an experimental group (n=63), which received dietary advice with wet cupping, and a control group (n=63) receiving dietary advice alone. Treatment was administered for 3 months. Depression and anxiety were assessed using the Beck Depression Inventory at 0, 6 and 12 weeks after treatment. Data were analysed using ANOVA.ResultsThere were no statistically significant correlations between depression and anxiety and weight, BMI and lipid profile (P>0.05). However, there was a statistically significant association between the psychological parameters and blood pressure, age and gender (P<0.05). There was a significant variation in scores between assessment points of P<0.001 for both anxiety and depression, but these did not differ significantly between groups (P=0.78 and P=0.69, respectively).ConclusionWet cupping on the interscapular region does not appear to be useful for the treatment of anxiety and depression in patients with metabolic syndrome.
Morphological and physiological traits for higher biomass production in perennial rhizomatous grasses grown on marginal land
Authors: Jones Michael B. , Finnan John , Hodkinson Trevor R. 
Published: May 2014

AbstractA widespread criticism of growing energy crops is that they displace much needed food crops and cause upward pressure on food prices. One solution is the use of marginal land that is unfavourable for food production and is currently underutilized. However, the yield of crops growing on marginal land is reduced because they are subjected to a range of abiotic stresses such as extremes of temperature and rainfall and edaphic factors such as increased soil salinity. Therefore, to achieve acceptable economic returns on the use of this land it will be necessary to, on the one hand improve management practices and on the other to select for plant genotypes which are able to tolerate and potentially overcome the stressful conditions they are exposed to. Here, we review the morphological and physiological traits of perennial rhizomatous grasses that could be modified to overcome these stresses and to maximize biomass production on marginal land. The traits include aspects of crop phenology, canopy and leaf photosynthesis, biomass partitioning, nutrient and water use efficiency and heat, cold and salt tolerance. It is proposed that newly developed biotechnological methods combined with high‐throughput plant phenotyping offer opportunities to rapidly select new genotypes that could achieve economic yields on large areas of marginal land.