bluuebunny/crossref_metadata_2025_split huggingface dataset:
Homozygous/Compound Heterozygous Triadin Mutations Associated With Autosomal-Recessive Long-QT Syndrome and Pediatric Sudden Cardiac Arrest
Authors: Altmann Helene M. , Tester David J. , Will Melissa L. , Middha Sumit , Evans Jared M. , Eckloff Bruce W. , Ackerman Michael J. 
Published: April 2015

Background—
Long-QT syndrome (LQTS) may result in syncope, seizures, or sudden cardiac arrest. Although 16 LQTS-susceptibility genes have been discovered, 20% to 25% of LQTS remains genetically elusive.

Methods and Results—

We performed whole-exome sequencing child–parent trio analysis followed by recessive and sporadic inheritance modeling and disease-network candidate analysis gene ranking to identify a novel underlying genetic mechanism for LQTS. Subsequent mutational analysis of the candidate gene was performed with polymerase chain reaction, denaturing high-performance liquid chromatography, and DNA sequencing on a cohort of 33 additional unrelated patients with genetically elusive LQTS. After whole-exome sequencing and variant filtration, a homozygous p.D18fs*13
TRDN
-encoded triadin frameshift mutation was discovered in a 10-year-old female patient with LQTS with a QTc of 500 milliseconds who experienced recurrent exertion-induced syncope/cardiac arrest beginning at 1 year of age. Subsequent mutational analysis of
TRDN
revealed either homozygous or compound heterozygous frameshift mutations in 4 of 33 unrelated cases of LQTS (12%). All 5 TRDN-null patients displayed extensive T-wave inversions in precordial leads V
1
through V
4
, with either persistent or transient QT prolongation and severe disease expression of exercise-induced cardiac arrest in early childhood (≤3 years of age) and required aggressive therapy. The overall yield of TRDN mutations was significantly greater in patients ≤10 years of age (5 of 10, 50%) compared with older patients (0 of 24, 0%;
P
=0.0009).

Conclusions—

We identified
TRDN
as a novel underlying genetic basis for recessively inherited LQTS. All TRDN-null patients had strikingly similar phenotypes. Given the recurrent nature of potential lethal arrhythmias, patients fitting this phenotypic profile should undergo cardiac
TRDN
genetic testing.
Identification of Different Moisture Sources through Isotopic Monitoring during a Storm Event
Authors: Li Jie , Tao Tao , Pang Zhonghe , Tan Ming , Kong Yanlong , Duan Wuhui , Zhang Yuwei 
Published: April 2015

AbstractRain samples were collected for isotopic analyses during the entirety of an extreme rainfall event in Beijing, China, on 21 July 2012, the city’s heaviest rainfall event in the past six decades. Four stages of the storm event have been identified with corresponding isotopic characteristics: 1) isotopes deplete as rain increases, 2) isotopes enrich as rain decreases, 3) isotopes quickly deplete as rain increases, and 4) isotopes remain constant as rain reduces to a small amount. The rainout effect dominates the depletion of isotopic composition in stages 1 and 3. The incursion of a new air mass with enriched heavy isotopes was the main cause for the enriched isotopic composition during stage 2. A Rayleigh distillation model was used to describe the isotopic trends during stages 1 and 3. The Rayleigh distillation model and a binary mixing model were used to estimate the initial isotopic composition of different air masses, which were found to be similar to δ18O of precipitation at nearby Global Network of Isotopes in Precipitation stations representing southwest and southeast trajectories. The results are in agreement with meteorological arrays analysis. This model also indicates that 29% of the initial vapor from the southwest trajectory was precipitated in stage 1, followed by a mixing process between southeast and southwest moisture. In stage 3, up to 56% of mixed moisture was precipitated, among which ~65%–100% was from southeast moisture.
The Deep Equatorial Ocean Circulation in Wind-Forced Numerical Solutions
Authors: Ascani François , Firing Eric , McCreary Julian P. , Brandt Peter , Greatbatch Richard J. 
Published: April 2015

AbstractWe perform eddy-resolving and high vertical resolution numerical simulations of the circulation in an idealized equatorial Atlantic Ocean in order to explore the formation of the deep equatorial circulation (DEC) in this basin. Unlike in previous studies, the deep equatorial intraseasonal variability (DEIV) that is believed to be the source of the DEC is generated internally by instabilities of the upper-ocean currents. Two main simulations are discussed: solution 1, configured with a rectangular basin and with wind forcing that is zonally and temporally uniform, and solution 2, with realistic coastlines and an annual cycle of wind forcing varying zonally. Somewhat surprisingly, solution 1 produces the more realistic DEC; the large, vertical-scale currents [equatorial intermediate currents (EICs)] are found over a large zonal portion of the basin, and the small, vertical-scale equatorial currents [equatorial deep jets (EDJs)] form low-frequency, quasi-resonant, baroclinic equatorial basin modes with phase propagating mostly downward, consistent with observations. This study demonstrates that both types of currents arise from the rectification of DEIV, consistent with previous theories. The authors also find that the EDJs contribute to maintaining the EICs, suggesting that the nonlinear energy transfer is more complex than previously thought. In solution 2, the DEC is unrealistically weak and less spatially coherent than in the first simulation probably because of its weaker DEIV. Using intermediate solutions, this study finds that the main reason for this weaker DEIV is the use of realistic coastlines in solution 2. It remains to be determined what needs to be modified or included to obtain a realistic DEC in the more realistic configuration.
Incorporating the Effects of Moisture into a Dynamical Parameter: Moist Vorticity and Moist Divergence
Authors: Qian Weihong , Du Jun , Shan Xiaolong , Jiang Ning 
Published: April 2015

Abstract
Properly including moisture effects into a dynamical parameter can significantly increase the parameter’s ability to diagnose heavy rain locations. The relative humidity–based weighting approach used to extend the moist potential vorticity (MPV) to the generalized moist potential vorticity (GMPV) is analyzed and demonstrates such an improvement. Following the same approach, two new diagnostic parameters, moist vorticity (MV) and moist divergence (MD), have been proposed in this study by incorporating moisture effects into the traditional vorticity and divergence. A regional heavy rain event that occurred along the Yangtze River on 1 July 1991 is used as a case study, and 41 daily regional heavy rain events during the notorious flooding year of 1998 in eastern China are used for a systematic evaluation. Results show that after the moisture effects were properly incorporated, the improved ability of all three parameters to capture a heavy rain area is significant (statistically at the 99% confidence level): the GMPV is improved over the MPV by 194%, the MD over the divergence by 60%, and the MV over the vorticity by 34% in terms of the threat score (TS). The average TS is 0.270 for the MD, 0.262 for the MV, and 0.188 for the GMPV. Application of the MV and MD to assess heavy rain potential is not intended to replace a complete, multiscale forecasting methodology; however, the results from this study suggest that the MV and MD could be used to postprocess a model forecast to potentially improve heavy rain location predictions.
The defeat-entrapment theory versus Beck’s hopelessness theory of depression and suicidality: A cross-national analysis in Iran and the United States
Authors: Tarsafi Mahdieh , Kalantarkousheh Seyed Mohammad , Lester David 
Published: April 2015

Background: The defeat-entrapment theory has been proposed to explain both depression and suicidal behavior. Methods: Measures of defeat, entrapment, hopelessness and depression were administered to Iranian and American students. Results: Scores on measures of hopelessness, defeat, entrapment and depression were strongly associated. In both nations, scores for defeat and entrapment were stronger predictors of past suicidal ideation and attempted suicide. Overall, the Iranian respondents had higher scores on the measures of defeat, entrapment, hopelessness and depression, but less often reported prior suicidal ideation. Conclusion: The defeat-entrapment theory of depression and suicidal behavior appears to have validity in both Iran and America.
European rating of drug harms
Authors: van Amsterdam Jan , Nutt David , Phillips Lawrence , van den Brink Wim 
Published: April 2015

Background: The present paper describes the results of a rating study performed by a group of European Union (EU) drug experts using the multi-criteria decision analysis model for evaluating drug harms. Methods: Forty drug experts from throughout the EU scored 20 drugs on 16 harm criteria. The expert group also assessed criteria weights that would apply, on average, across the EU. Weighted averages of the scores provided a single, overall weighted harm score (range: 0–100) for each drug. Results: Alcohol, heroin and crack emerged as the most harmful drugs (overall weighted harm score 72, 55 and 50, respectively). The remaining drugs had an overall weighted harm score of 38 or less, making them much less harmful than alcohol. The overall weighted harm scores of the EU experts correlated well with those previously given by the UK panel. Conclusion: The outcome of this study shows that the previous national rankings based on the relative harms of different drugs are endorsed throughout the EU. The results indicates that EU and national drug policy measures should focus on drugs with the highest overall harm, including alcohol and tobacco, whereas drugs such as cannabis and ecstasy should be given lower priority including a lower legal classification.
The Impact of Implementation of an ICU Consult Service on Hospital-Wide Outcomes and ICU-Specific Outcomes
Authors: Al-Rajhi Amjad , Mardini Louay , Jayaraman Dev 
Published: April 2015

Background: Rapid response teams (RRTs) were developed to promote assessment of and early intervention for clinically deteriorating hospitalized patients. Although the ideal composition of RRTs is not known, their implementation does require significant resources. Objective: To test the effectiveness of a dedicated daytime/weekday intensive care unit (ICU) consult service without formal training of ward teams. Methods: Pre- and postintervention study with weekends/nights during implementation period acting as a concurrent control. Setting: An adult tertiary care university center in Montreal without an RRT. Intervention: A daytime/weekday ICU consult service with a dedicated intensivist. Results: Total hospital mortality rate did not differ between the control and the implementation period (6.65% vs 6.60%; P = .84). The hospital code blue rates also did not differ (1.21/1000 vs 1.14/1000 patient days; P = .58). In contrast, 30-day mortality of patients admitted to the ICU following an ICU consult decreased (39% vs 24% P = .01). Multivariate analysis confirmed this effect on 30-day mortality (odds ratio for implementation period: 0.53 [95% confidence interval: 0.33-0.85] P = .009). The 14-day ICU readmission rate was reduced with the intervention (5.1% vs 4.1%; P < .001). The effect on 30-day mortality and ICU readmissions were only present during daytime/weekdays. Conclusion: Implementation of an ICU consult service without any formal afferent limb training was associated with decreased mortality and 14-day readmission rates of patients admitted to the ICU. In contrast, hospital-wide mortality and code blue rates were unaffected.
Survey of current practice in clinical transvaginal ultrasound scanning in the UK
Authors: Martin Eleanor , Shaw Adam , Lees Christoph 
Published: April 2015

During transvaginal ultrasound scanning, the fetus and other sensitive tissues are placed close to the transducer. Heating of these tissues occurs by direct conduction from the transducer and by absorption of ultrasound in the tissue. The extent of any heating will depend on the equipment and settings used, the duration of the scan, imaging modes and other aspects of scanning practice. To ensure that scans are performed with minimum risk, staff should have an appropriate knowledge of safety and follow guidelines issued by professional bodies. An online survey aiming to document current practice in transvaginal ultrasound in the UK was created and distributed to individuals performing this type of scanning. The survey posed questions about the respondents, the departments where scans were performed, the equipment used, knowledge of ultrasound safety, scanning practice and the frequency, duration and mode of transvaginal ultrasound scans for gynaecology, obstetrics and fertility applications. In all, 294 responses were obtained, mostly from sonographers (94%). From the analysis of the responses, it was clear that there was a good understanding of the general meaning of thermal and mechanical index and high awareness of guidelines issued by professional bodies. However, 40% of respondents stated that they rarely or never monitor Thermal or Mechanical indices during scanning. Scanning practice was consistent in terms of the duration of scans, scan protocols followed and use of imaging modes. The results highlight the importance of continued ultrasound safety training and promotion of safety guidelines to users.
Machine learning methods for the classification of gliomas: Initial results using features extracted from MR spectroscopy
Authors: Ranjith G , Parvathy R , Vikas V , Chandrasekharan Kesavadas , Nair Suresh 
Published: April 2015

Context With the advent of new imaging modalities, radiologists are faced with handling increasing volumes of data for diagnosis and treatment planning. The use of automated and intelligent systems is becoming essential in such a scenario. Machine learning, a branch of artificial intelligence, is increasingly being used in medical image analysis applications such as image segmentation, registration and computer-aided diagnosis and detection. Histopathological analysis is currently the gold standard for classification of brain tumors. The use of machine learning algorithms along with extraction of relevant features from magnetic resonance imaging (MRI) holds promise of replacing conventional invasive methods of tumor classification. Aims The aim of the study is to classify gliomas into benign and malignant types using MRI data. Settings and design Retrospective data from 28 patients who were diagnosed with glioma were used for the analysis. WHO Grade II (low-grade astrocytoma) was classified as benign while Grade III (anaplastic astrocytoma) and Grade IV (glioblastoma multiforme) were classified as malignant. Methods and materials Features were extracted from MR spectroscopy. The classification was done using four machine learning algorithms: multilayer perceptrons, support vector machine, random forest and locally weighted learning. Results Three of the four machine learning algorithms gave an area under ROC curve in excess of 0.80. Random forest gave the best performance in terms of AUC (0.911) while sensitivity was best for locally weighted learning (86.1%). Conclusions The performance of different machine learning algorithms in the classification of gliomas is promising. An even better performance may be expected by integrating features extracted from other MR sequences.
A Misdiagnosed Recurrent Pleural Effusion
Authors: Rappaport Maximilien , Meyer Armin 
Published: April 2015

Introduction: Dyspnea due to pleural effusions is a common clinical scenario and has many underlying etiologies. Our case of a recurrent pleural effusion was misdiagnosed in part due to the complicated nature of the patient’s medical history. Nonetheless after a bedside thoracic ultrasound examination (TUE), the diagnosis became obvious. Case Description: A 63-year-old black female with congestive heart failure, end-stage renal disease, atrial fibrillation as well as a previously treated rare odontogenic carcinoma presented with shortness of breath. She reported having had “fluid drained” from her lungs a few months prior. During our encounter with this patient, a TUE was performed at beside and a large diaphragmatic mass was visualized. A malignant pleural effusion was suspected and an efficient and focused workup was tailored to our patient. Discussion: Apart from guiding the thoracentesis, the TUE is not part of the current recognized guidelines when evaluating a pleural effusion. The TUE may be undervalued and play an important impact on diagnosis and management of this condition. Our case demonstrates the utility of a thorough TUE in conjunction with the full clinical picture. A few studies have shown good sensitivities and specificities in the use of the TUE to determine the type and etiology of pleural effusions. This case is a further example of the utility in performing this relatively inexpensive diagnostic test in the evaluation of the patient with a pleural effusion.
STAT1 is phosphorylated and downregulated by the oncogenic tyrosine kinase NPM-ALK in ALK-positive anaplastic large-cell lymphoma
Authors: Wu Chengsheng , Molavi Ommoleila , Zhang Haifeng , Gupta Nidhi , Alshareef Abdulraheem , Bone Kathleen M. , Gopal Keshav , Wu Fang , Lewis Jamie T. , Douglas Donna N. , Kneteman Norman M. , Lai Raymond 
Published: April 2015

Key PointsOncogenic tyrosine kinase NPM-ALK binds to and phosphorylates STAT1, thereby promoting its proteasome-/STAT3-dependent degradation. STAT1 tumor suppressor effects in ALK+ ALCL include creating a STAT1/interferon-γ loop and interfering with STAT3 transcriptional activities.
Look beyond Catechol-O-Methyltransferase genotype for cathecolamines derangement in migraine: the BioBIM rs4818 and rs4680 polymorphisms study
Authors: De Marchis Maria Laura , Barbanti Piero , Palmirotta Raffaele , Egeo Gabriella , Aurilia Cinzia , Fofi Luisa , Piroso Serena , Ialongo Cristiano , Della-Morte David , D’Andrea Giovanni , Ferroni Patrizia , Guadagni Fiorella 
Published: April 2015

Abstract

Background
The study of COMT gene polymorphisms in migraine could be of particular interest since impaired catecholaminergic neurotransmission, namely chronic dopaminergic and noradrenergic hypofunction, is a peculiar migraine trait. In this study, for the first time, we focused on the role of COMT rs4818 genetic variant, the polymorphism most strongly affecting COMT activity, in migraine. This study was conducted in a cohort of carefully clinical characterized Caucasian migraineurs recruited in a specifically dedicated migraine biobank, providing also a replication study on rs4680 polymorphism.

Findings
Genotyping of rs4680 and rs4818 Catechol-O-Methyltransferase gene polymorphisms was performed on 380 unrelated migraine patients, and 132 healthy subjects matched for age, gender and race-ethnicity, with no clinical evidence or family history of migraine or other neurological diseases. The rs4680 and rs4818 genotypic frequencies did not deviate from those expected for a population in Hardy-Weinberg equilibrium and did not correlate with demographics or clinical migraine features, even when considering migraine subtypes such as dopaminergic migraine, menstrual migraine, and menstrually related migraine.

Conclusions
COMT genotype does not influence migraine susceptibility or phenotype, even considering rs4818 polymorphism and peculiar clinical subtypes. This finding prompts to go over COMT to explain catecholamine derangement in migraine, exploring enzymes involved in catecholamines synthesis and catabolism, such as monoamine-oxidase, dopamine beta-hydroxylase, tyrosine-hydroxylase or tyrosine-decarboxylase, among others.
Domain atrophy creates rare cases of functional partial protein domains
Authors: Prakash Ananth , Bateman Alex 
Published: April 2015

Abstract
Background
Protein domains display a range of structural diversity, with numerous additions and deletions of secondary structural elements between related domains. We have observed a small number of cases of surprising large-scale deletions of core elements of structural domains. We propose a new concept called domain atrophy, where protein domains lose a significant number of core structural elements.

Results
Here, we implement a new pipeline to systematically identify new cases of domain atrophy across all known protein sequences. The output of this pipeline was carefully checked by hand, which filtered out partial domain instances that were unlikely to represent true domain atrophy due to misannotations or un-annotated sequence fragments. We identify 75 cases of domain atrophy, of which eight cases are found in a three-dimensional protein structure and 67 cases have been inferred based on mapping to a known homologous structure. Domains with structural variations include ancient folds such as the TIM-barrel and Rossmann folds. Most of these domains are observed to show structural loss that does not affect their functional sites.

Conclusion
Our analysis has significantly increased the known cases of domain atrophy. We discuss specific instances of domain atrophy and see that there has often been a compensatory mechanism that helps to maintain the stability of the partial domain. Our study indicates that although domain atrophy is an extremely rare phenomenon, protein domains under certain circumstances can tolerate extreme mutations giving rise to partial, but functional, domains.
Bone geometry of the hip is associated with obesity and early structural damage – a 3.0 T magnetic resonance imaging study of community-based adults
Authors: Teichtahl Andrew J , Wang Yuanyuan , Smith Sam , Wluka Anita E , Zhu Michael , Urquhart Donna , Giles Graham G , O’Sullivan Richard , Cicuttini Flavia M 
Published: April 2015

Abstract
Introduction
The mechanism by which obesity increases the risk of hip osteoarthritis is unclear. One possibility may be by mediating abnormalities in bony geometry, which may in turn be associated with early structural abnormalities, such as cartilage defects and bone marrow lesions.

Methods
One hundred and forty one older adults with no diagnosed hip osteoarthritis had weight and body mass index measured between 1990 and 1994 and again in 2009 to 2010. Acetabular depth and lateral centre edge angle, both measures of acetabular over-coverage, as well as femoral head cartilage volume, cartilage defects and bone marrow lesions were assessed with 3.0 T magnetic resonance imaging performed in 2009 to 2010.

Results
Current body mass index, weight and weight gain were associated with increased acetabular depth and lateral centre edge angle (all P ≤ 0.01). For every 1 mm increase in acetabular depth, femoral head cartilage volume reduced by 59 mm3 (95% confidence interval (CI) 20 mm3 to 98 mm3, P < 0.01). Greater acetabular depth was associated with an increased risk of cartilage defects (odds ratio (OR) 1.22, 95% CI 1.03 to 1.44, P = 0.02) and bone marrow lesions (OR 1.29, 95% CI 1.01 to 1.64, P = 0.04) in the central region of the femoral head. Lateral centre edge angle was not associated with hip structure.

Conclusions
Obesity is associated with acetabular over-coverage. Increased acetabular depth, but not the lateral centre edge angle, is associated with reduced femoral head cartilage volume and an increased risk of cartilage defects and bone marrow lesions. Minimising any deepening of the acetabulum (for example, through weight management) might help to reduce the incidence of hip osteoarthritis.