bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identification of deleterious synonymous variants in human genomes
Authors: Buske Orion J. , Manickaraj AshokKumar , Mital Seema , Ray Peter N. , Brudno Michael 
Published: June 2013

Abstract
Motivation: The prioritization and identification of disease-causing mutations is one of the most significant challenges in medical genomics. Currently available methods address this problem for non-synonymous single nucleotide variants (SNVs) and variation in promoters/enhancers; however, recent research has implicated synonymous (silent) exonic mutations in a number of disorders.
Results: We have curated 33 such variants from literature and developed the Silent Variant Analyzer (SilVA), a machine-learning approach to separate these from among a large set of rare polymorphisms. We evaluate SilVA’s performance on in silico ‘infection’ experiments, in which we implant known disease-causing mutations into a human genome, and show that for 15 of 33 disorders, we rank the implanted mutation among the top five most deleterious ones. Furthermore, we apply the SilVA method to two additional datasets: synonymous variants associated with Meckel syndrome, and a collection of silent variants clinically observed and stratified by a molecular diagnostics laboratory, and show that SilVA is able to accurately predict the harmfulness of silent variants in these datasets.
Availability: SilVA is open source and is freely available from the project website: http://compbio.cs.toronto.edu/silva
Contact: silva-snv@cs.toronto.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Circulating microRNA changes in heart failure patients treated with cardiac resynchronization therapy: responders vs. non‐responders
Authors: Marfella Raffaele , Di Filippo Clara , Potenza Nicoletta , Sardu Celestino , Rizzo Maria Rosaria , Siniscalchi Mario , Musacchio Emilio , Barbieri Michelangela , Mauro Ciro , Mosca Nicola , Solimene Francesco , Mottola Maria Teresa , Russo Aniello , Rossi Francesco , Paolisso Giuseppe , D'Amico Michele 
Published: June 2013

AimsMicroRNAs (miRNAs) play an important role in the pathogenesis of structural alterations of the failing heart through their ability to regulate negatively the expression levels of genes that govern the process of adaptive and maladaptive cardiac remodelling. We studied whether LV reverse remodelling after CRT was associated with changes of circulating miRNAs in patients with heart failure (HF) and dyssynchrony.Methods and resultsA prospective, non‐randomized self‐control trial was performed in 81 patients with HF eligible for CRT. At baseline, to select the HF miRNA profile, we evaluated the expression of 84 miRNAs (implicated in the pathogenesis of structural alterations of the failing heart) in three groups of patients: healthy subjects (healthy group, n = 15); patients with HF (HF group, n = 81); and patients without HF matched for age, sex, and concomitant disease with HF patients (control group, n = 60). At 12 months, the selected miRNA profile was evaluated in plasma from responder (n = 55) and non‐responder HF patients (n = 26) to CRT. In the test cohort, the HF patients were characterized by lower expression of 48 miRNAs (all P < 0.04) as compared with healthy subjects. In the validation cohort, the HF patients were characterized by lower expression of 24 miRNAs (all P < 0.03) as compared with control patients. At 12 months, 55 patients (68%) were considered responders and 26 non‐responders to CRT (32%). Responders showed an increase in expression of 19 miRNAs (all P < 0.03) compared with baseline expression, whereas in the non‐responders we observed an increase of six miRNAs (all P < 0.05) compared with baseline expression. At follow‐up, miRNAs were differentially expressed between responders and non‐responders. The responders were characterized by higher expression of five miRNAs (miRNA‐26b‐5p, miRNA‐145‐5p, miRNA‐92a‐3p, miRNA‐30e‐5p, and miRNA‐29a‐3p; P < 0.01 for all) as compared with non‐responders.ConclusionsIn responders, reverse remodelling is associated with favourable changes in miRNAs that regulate cardiac fibrosis, apoptosis, and hypertrophy.
Essay from an early career: to each his/her own “tune”
Authors: Story Joana S.P. 
Published: June 2013

PurposeThe purpose of this essay is to highlight the journey of the author in her early career, along with her main challenges and ways she found to overcome them.Design/methodology/approachThis is an inductive account of the main experiences that the author has encountered or has observed.FindingsThis essay highlights three academic adaptation phases and steps that indicate how these can be worked to your advantage. It also depicts research opportunities and success factors.Originality/valueThis essay informs potential research opportunities for Ibero‐American scholars alongside key success factors for effective research.
Case of phaeohyphomycosis producing sporotrichoid lesions
Authors: Hasei Maki , Takeda Kiminobu , Anzawa Kazushi , Nishibu Akiko , Tanabe Hiroshi , Mochizuki Takashi 
Published: June 2013

AbstractA 90‐year‐old Japanese woman, taking prednisolone (5–10 mg/day) for polyarthritis, presented to our hospital with multiple subcutaneous lesions on her left arm in 2009. Her history included excision of a phaeomycotic cyst on the left middle finger in 2007. There were three subcutaneous nodules approximately 15 mm in diameter around her left wrist and a large soft cystic lesion measuring 80 mm × 60 mm on her left elbow. A granuloma with neutrophilic infiltration was detected in the deep dermis of a biopsy specimen. Chains composed of round brown cells and short pseudomycelia were found in the granuloma. Fungal cultures from the samples confirmed Exophiala sp. to be the causative agent. Treatment with terbinafine and local hyperthermia seemed effective as all the lesions tended to subside. However, the patient died due to pneumonia approximately 1 month after commencement of therapy.
Seed dispersal by wind: towards a conceptual framework of seed abscission and its contribution to long‐distance dispersal
Authors: Pazos Gustavo E. , Greene David F. , Katul Gabriel , Bertiller Mónica B. , Soons Merel B. 
Published: June 2013

Summary

Diaspore abscission determines many aspects of seed dispersal by wind. While there is yet no complete mechanistic framework for understanding abscission by wind, empirical studies to date have suggested that abscission generally (i) occurs above some threshold wind speed and (ii) depends on the drag force generated by the wind.

We revisit these findings and formulate two alternative hypotheses for abscission mechanisms based on a simple model of a forced harmonic oscillator: large diaspore displacement [through a maximum deflection threshold, (MDT)] and material fatigue [through a maximum cumulative stress threshold (MCST)]. We use simulations of abscission events based on these hypotheses and experiments on diaspore abscission of three Patagonian grasses and a cosmopolitan herb to test the performance of two abscission functions differing in whether they have a threshold wind speed for abscission. We also quantify the effects of non‐random diaspore abscission on dispersal distances using a well‐tested model for seed dispersal by wind.

Both the MDT and MCST hypotheses appear realistic and indicate that while the instantaneous wind speed determines abscission, the history of wind speeds experienced prior to the detachment from the plant also plays a role.

An evaluation of abscission functions against simulated and experimental abscission data shows that while the presence of a threshold wind speed in theory appears unrealistic, in practice a threshold may appear to exist in high‐wind‐speed environments where all diaspores are blown off the plant before the abscission layer can develop sufficiently to break during lower wind speeds.

Under non‐random diaspore abscission, high‐wind‐speed events during otherwise calm periods increase long‐distance dispersal (LDD), thereby decreasing differences in dispersal distances between low‐ and high‐wind‐speed environments.

Synthesis. We formulated two realistic mechanisms of diaspore abscission by applying concepts from materials science: large diaspore displacement and material fatigue. These reveal that the ambient wind speed ‘history’ experienced by a diaspore plays an important role in the timing of abscission and in the distance travelled, without any thresholds, and that the effect of the diaspore–wind interaction on LDD varies between environments with different wind speed regimes.
Complementary contribution of parents and therapists in the assessment process of children
Authors: Rosenberg Limor , Bart Orit , Ratzon Navah Z. , Jarus Tal 
Published: June 2013

Background/aimTraditional developmental models assume that the underlying capacities of children contribute to their participation. In this framework, preschoolers who are referred for occupational therapy services usually undergo an assessment intended to identify capacities in certain domains. Contrary to this, newer ecological models assume that child participation is a consequence of a multidimensional interaction between personal and environmental factors. As a result clinicians are increasingly focusing their assessment on performance and participation. This study aimed to assess the correlation between children's performance skills, their capacities and participation; and to explore whether parents' observations, alongside therapist observations and standardised assessments, contribute to an enhanced understanding of child participation.MethodParticipants included 188 parents and their children, aged 4–6 years, with and without mild developmental difficulties. Data were collected using standardised assessments for child capacities, and questionnaires completed by parents and occupational therapists regarding child participation and performance skills.ResultsSignificant correlations were found between parent assessments of child performance skills and child participation, but not with child capacities. The opposite was found to be true for occupational therapist assessments of child performance skills which were found to correlate with child capacities, but not with participation. Additionally, an interaction effect was found for both groups. Occupational therapists reported higher performance skills as compared to parents, but the difference was only significant for children without mild difficulties.ConclusionAs suggested by ecological models of child participation, the findings highlight the importance of parent‐therapist collaboration in the assessment process of children.
Delivery of enteral nutrition for critically ill children
Authors: Abdul Manaf Zahara , Kassim Norasimah , Hamzaid Nur Hana , Razali Nurul Huda 
Published: June 2013

AbstractAimOptimal nutrition support is important in the care of critically ill children as they are at higher risk of malnutrition and have a higher incidence of complications and mortality. The aim of this study was to review the delivery of enteral feeding to critically ill paediatric patients in the Paediatric Intensive Care Unit in a tertiary hospital in Malaysia.MethodsThis cross‐sectional study was conducted in 53 subjects (30 males and 23 females) who were recruited on the day of admission and remained in the study until they were discharged, deceased or for a maximum of 14 days of Paediatric Intensive Care Unit stay. The median age of subjects was 10.2 (interquartile range 5.1–50.5) months old.ResultsEnteral nutrition was initiated within 21.0 (interquartile range 5.3–33.8) hours after admission and was interrupted in 66% of patients during the study, with a median duration of 11.5 (interquartile range 6.1–28.3) hours for each patient. The overall duration of enteral feeding interruptions was 20% of the total feeding time. The main reasons for interruptions were medical procedures (55%) and non‐gastrointestinal complications (27%). Twenty‐two (43.2%) of the patients were malnourished when admitted to the Paediatric Intensive Care Unit. The feeding initiation time, referral to the dietitian, and the frequency and duration of feeding interruptions were all positively associated with cumulative energy and protein deficits.ConclusionsMalnutrition among critically ill children in the Paediatric Intensive Care Unit was prevalent; energy and protein deficits were substantial. Strategies to improve the delivery of nutritional support to this group of patients should be planned and implemented by multidisciplinary clinical teams.
Mammographic and ultrasound features of invasive lobular carcinoma of the breast
Authors: Porter Alan J , Evans Elizabeth B , Foxcroft Loani M , Simpson Peter T , Lakhani Sunil R 
Published: June 2013

AbstractIntroductionInvasive lobular cancer (ILC) is an important contributor to false negative mammography. This study aims to assess the value of digital mammography and to identify imaging features that could assist the radiologist to suggest the diagnosis of ILC prior to biopsy.MethodsThree hundred sixty‐one cases of pure ILC diagnosed at the Wesley Breast Clinic during the period 1995–2010 were reviewed by one of the authors (AP). Radiological features were categorized, and clinical features and needle sampling results were recorded.ResultsMammography was negative in 29.9% of ILCs. The commonest positive finding was a localized spiculated mass (41.8%). Thirty‐four point nine per cent of lesions were visible in only one view, usually cranio‐caudal. Calcification was not a feature of ILC. The use of digital mammography in 30% of cases did not decrease the false negative rate for ILC. Breast ultrasound (BUS) showed an abnormality in 97.8%, most commonly a localized irregular hypoechoic mass with shadowing.ConclusionsDigital mammography does not reduce false negative mammography in ILC. The poor visibility of ILCs may be partly related to their low density (mass/unit volume). ILCs may sometimes be poor attenuators of X‐rays but excellent attenuators of ultrasound, causing marked acoustic shadowing. Bilateral whole BUS has a very low false negative rate in experienced hands and is mandatory in symptomatic women. The combination of poor visibility on mammography with high visibility on ultrasound, as well as certain characteristic ultrasound appearances of ILC, may enable the radiologist to suggest ILC as a diagnostic possibility, prior to biopsy.
Comparison of behavioral treatment conditions in buprenorphine maintenance
Authors: Ling Walter , Hillhouse Maureen , Ang Alfonso , Jenkins Jessica , Fahey Jacqueline 
Published: June 2013

AbstractBackground and aimsThe Controlled Substances Act requires physicians in the United States to provide or refer to behavioral treatment when treating opioid‐dependent individuals with buprenorphine; however, no research has examined the combination of buprenorphine with different types of behavioral treatments. This randomized controlled trial compared the effectiveness of four behavioral treatment conditions provided with buprenorphine and medical management (MM) for the treatment of opioid dependence.DesignAfter a 2‐week buprenorphine induction/stabilization phase, participants were randomized to one of four behavioral treatment conditions provided for 16 weeks: cognitive behavioral therapy (CBT = 53); contingency management (CM = 49); both CBT and CM (CBT + CM = 49); and no additional behavioral treatment (NT = 51).SettingStudy activities occurred at an out‐patient clinical research center in Los Angeles, California, USA.ParticipantsIncluded were 202 male and female opioid‐dependent participants.MeasurementsPrimary outcome was opioid use, measured as a proportion of opioid‐negative urine results over the number of tests possible. Secondary outcomes include retention, withdrawal symptoms, craving, other drug use and adverse events.FindingsNo group differences in opioid use were found for the behavioral treatment phase (χ2 = 1.25, P = 0.75), for a second medication‐only treatment phase, or at weeks 40 and 52 follow‐ups. Analyses revealed no differences across groups for any secondary outcome.ConclusionThere remains no clear evidence that cognitive behavioural therapy and contingency management reduce opiate use when added to buprenorphine and medical management in opiate users seeking treatment.
Efficacy and safety of lidocaine for treatment of neonatal seizures
Authors: Lundqvist M , Ågren J , Hellström‐Westas L , Flink R , Wickström R 
Published: June 2013

AbstractAimTreatment of neonatal seizures still relies primarily on phenobarbital, despite an estimated efficacy of less than 50% and concern over neurodegenerative side effects. The objective of this study was to evaluate the efficacy and safety of lidocaine as second‐line treatment of neonatal seizures in infants following benzodiazepine treatment but without previous treatment with phenobarbital.MethodsIn a 10‐year cohort, a retrospective chart review was conducted for all infants (gestational age ≥ 37 w, age ≤ 28 days) who had received lidocaine as second‐line treatment of neonatal seizures prior to treatment with phenobarbital between January 2000 and June 2010. Infants were included if they had electroencephalographic seizures.ResultsCessation of seizure activity was seen in 16 of 30 infants based on clinical and electroencephalographic features, and a probable response was seen in an additional 3 of 30 patients. Suspected adverse effects were seen in only one patient, who developed a transient bradycardia.ConclusionLidocaine has a moderate efficacy as second‐line therapy following benzodiazepines for treating neonatal seizures and is not frequently associated with cardiovascular adverse effects. Lidocaine should therefore be considered in the treatment of seizures in the neonatal period to a higher extent than is the case today.
Health‐related quality of life among Norwegian children and adolescents with type 1 diabetes on intensive insulin treatment: a population‐based study
Authors: Frøisland Dag Helge , Graue Marit , Markestad Trond , Skrivarhaug Torild , Wentzel‐Larsen Tore , Dahl‐Jørgensen Knut 
Published: June 2013

AbstractAimTo examine health‐related quality of life (HRQOL) in children and adolescents with type 1 diabetes on intensive insulin treatment.MethodsAll children and adolescents with type 1 diabetes above 8 years of age scheduled for follow‐up at 21 paediatric departments in Norway, and one of their parents was invited to describe HRQOL by completing DISABKIDS questionnaires. HRQOL was related to sociodemographic factors (i.e. parental economy, education, marital status and to level of physical activity and disease characteristics, obtained from the Norwegian Childhood Diabetes Registry).ResultsNine hundred and thirty seven (48%) and one of their parents responded. Mean duration of diabetes was 4.9 years (SD 3.3), 51% were girls, 56% used insulin pumps, and 44% used multiple insulin injections, predominantly of long‐acting and rapid insulin analogues. Mean HbA1c was 8.5% (SD 1.3). Lower HRQOL scores were significantly associated with higher HbA1c, being a girl and experience of diabetes ketoacidosis. Mothers scored lower than fathers on total score and most subscales. No significant differences in scores were found between users of an insulin pump and multi‐injection treatment.ConclusionsHealth‐related quality of life was related to metabolic control and gender, but not to mode of intensified insulin treatment.
OnabotulinumtoxinA significantly attenuates bladder afferent nerve firing and inhibits ATP release from the urothelium
Authors: Collins Valerie M. , Daly Donna M. , Liaskos Marina , McKay Neil G. , Sellers Donna , Chapple Christopher , Grundy David 
Published: June 2013

Objective
To investigate the direct effect of onabotulinumtoxinA (OnaBotA) on bladder afferent nerve activity and release of ATP and acetylcholine (ACh) from the urothelium.
Materials and Methods
Bladder afferent nerve activity was recorded using an in vitro mouse preparation enabling simultaneous recordings of afferent nerve firing and intravesical pressure during bladder distension.
Intraluminal and extraluminal ATP, ACh, and nitric oxide (NO) release were measured using the luciferin–luciferase and Amplex® Red assays (Molecular Probes, Carlsbad, CA, USA), and fluorometric assay kit, respectively.
OnaBotA (2U), was applied intraluminally, during bladder distension, and its effect was monitored for 2 h after application.
Whole‐nerve activity was analysed to classify the single afferent units responding to physiological (low‐threshold [LT] afferent <15 mmHg) and supra‐physiological (high‐threshold [HT] afferent >15 mmHg) distension pressures.
Results
Bladder distension evoked reproducible pressure‐dependent increases in afferent nerve firing.
After exposure to OnaBotA, both LT and HT afferent units were significantly attenuated.
OnaBotA also significantly inhibited ATP release from the urothelium and increased NO release.
Conclusion
These data indicate that OnaBotA attenuates the bladder afferent nerves involved in micturition and bladder sensation, suggesting that OnaBotA may exert its clinical effects on urinary urgency and the other symptoms of overactive bladder syndrome through its marked effect on afferent nerves.
Social support provided to caregivers of children with cerebral palsy
Authors: Pfeifer L. I. , Silva D. B. R. , Lopes P. B. , Matsukura T. S. , Santos J. L. F. , Pinto M. P. P. 
Published: June 2013

AbstractObjectiveTo describe the perception of caregivers of children with cerebral palsy (CP) concerning social support received and to verify how the characteristics of the children (i.e. type of CP and severity of motor impairment) and those of their caregivers (i.e. age, level of education, occupation, income and number of children) are significantly related to this perception.MethodA total of 50 children with CP aged between 3 and 12 years and their respective caregivers participated in this study. Children were grouped in terms of type of CP and according to the severity of motor impairment through the Gross Motor Function Classification System (GMFCS). The Social Support Questionnaire (SSQ) was used to evaluate the perception of caregivers concerning the social support they receive (number of people offering support – SSQ‐N index, and level of satisfaction concerning such support – SSQ‐S index).ResultsThe caregivers reported receiving support from a mean of 1.67 people. Core and extended family members (i.e. husband, mother, siblings) and friends are the most common providers of support. In regard to level of satisfaction, caregivers considered the support they received to be positive, obtaining a mean of 5.52 out of a total of six points. Children's and caregivers' characteristics were not significantly related to the SSQ‐N and SSQ‐S indexes.ConclusionFamily members are the caregivers' primary source of social support and caregivers reported being satisfied with the support they received.