bluuebunny/crossref_metadata_2025_split huggingface dataset:
Improving validation methods for molecular diagnostics: application of Bland-Altman, Deming and simple linear regression analyses in assay comparison and evaluation for next-generation sequencing
Authors: Misyura Maksym , Sukhai Mahadeo A , Kulasignam Vathany , Zhang Tong , Kamel-Reid Suzanne , Stockley Tracy L 
Published: July 2017

AimsA standard approach in test evaluation is to compare results of the assay in validation to results from previously validated methods. For quantitative molecular diagnostic assays, comparison of test values is often performed using simple linear regression and the coefficient of determination (R2), using R2as the primary metric of assay agreement. However, the use of R2alone does not adequately quantify constant or proportional errors required for optimal test evaluation. More extensive statistical approaches, such as Bland-Altman and expanded interpretation of linear regression methods, can be used to more thoroughly compare data from quantitative molecular assays.MethodsWe present the application of Bland-Altman and linear regression statistical methods to evaluate quantitative outputs from next-generation sequencing assays (NGS). NGS-derived data sets from assay validation experiments were used to demonstrate the utility of the statistical methods.ResultsBoth Bland-Altman and linear regression were able to detect the presence and magnitude of constant and proportional error in quantitative values of NGS data. Deming linear regression was used in the context of assay comparison studies, while simple linear regression was used to analyse serial dilution data. Bland-Altman statistical approach was also adapted to quantify assay accuracy, including constant and proportional errors, and precision where theoretical and empirical values were known.ConclusionsThe complementary application of the statistical methods described in this manuscript enables more extensive evaluation of performance characteristics of quantitative molecular assays, prior to implementation in the clinical molecular laboratory.
Unbounded evidence accumulation characterizes subjective visual vertical forced-choice perceptual choice and confidence
Authors: Lim Koeun , Wang Wei , Merfeld Daniel M. 
Published: July 2017

Humans can subjectively yet quantitatively assess choice confidence based on perceptual precision even when a perceptual decision is made without an immediate reward or feedback. However, surprisingly little is known about choice confidence. Here we investigate the dynamics of choice confidence by merging two parallel conceptual frameworks of decision making, signal detection theory and sequential analyses (i.e., drift-diffusion modeling). Specifically, to capture end-point statistics of binary choice and confidence, we built on a previous study that defined choice confidence in terms of psychophysics derived from signal detection theory. At the same time, we augmented this mathematical model to include accumulator dynamics of a drift-diffusion model to characterize the time dependence of the choice behaviors in a standard forced-choice paradigm in which stimulus duration is controlled by the operator. Human subjects performed a subjective visual vertical task, simultaneously reporting binary orientation choice and probabilistic confidence. Both binary choice and confidence experimental data displayed statistics and dynamics consistent with both signal detection theory and evidence accumulation, respectively. Specifically, the computational simulations showed that the unbounded evidence accumulator model fits the confidence data better than the classical bounded model, while bounded and unbounded models were indistinguishable for binary choice data. These results suggest that the brain can utilize mechanisms consistent with signal detection theory—especially when judging confidence without time pressure.NEW & NOTEWORTHY We found that choice confidence data show dynamics consistent with evidence accumulation for a forced-choice subjective visual vertical task. We also found that the evidence accumulation appeared unbounded when judging confidence, which suggests that the brain utilizes mechanisms consistent with signal detection theory to determine choice confidence.
Carbon Monoxide Preserves Circadian Rhythm to Reduce the Severity of Subarachnoid Hemorrhage in Mice
Authors: Schallner Nils , Lieberum Judith-Lisa , Gallo David , LeBlanc Robert H. , Fuller Patrick M. , Hanafy Khalid A. , Otterbein Leo E. 
Published: July 2017

Background and Purpose—

Subarachnoid hemorrhage (SAH) is associated with a temporal pattern of stroke incidence. We hypothesized that natural oscillations in gene expression controlling circadian rhythm affect the severity of neuronal injury. We moreover predict that heme oxygenase-1 (HO-1/
Hmox1
) and its product carbon monoxide (CO) contribute to the restoration of rhythm and neuroprotection.

Methods—
Murine SAH model was used where blood was injected at various time points of the circadian cycle. Readouts included circadian clock gene expression, locomotor activity, vasospasm, neuroinflammatory markers, and apoptosis. In addition, cerebrospinal fluid and peripheral blood leukocytes from SAH patients and controls were analyzed for clock gene expression.

Results—

Significant elevations in the clock genes
Per-1
,
Per-2
, and
NPAS-2
were observed in the hippocampus, cortex, and suprachiasmatic nucleus in mice subjected to SAH at zeitgeber time (ZT) 12 when compared with ZT2. Clock gene expression amplitude correlated with basal expression of HO-1, which was also significantly greater at ZT12. SAH animals showed a significant reduction in cerebral vasospasm, neuronal apoptosis, and microglial activation at ZT12 compared with ZT2. In animals with myeloid-specific HO-1 deletion (
Lyz-Cre-Hmox1

fl/fl

),
Per-1, Per-2
, and
NPAS-2
expression was reduced in the suprachiasmatic nucleus, which correlated with increased injury. Treatment with low-dose CO rescued
Lyz-Cre-Hmox1

fl/fl

mice, restored
Per-1, Per-2
,
and NPAS-2
expression, and reduced neuronal apoptosis.

Conclusions—
Clock gene expression regulates, in part, the severity of SAH and requires myeloid HO-1 activity to clear the erythrocyte burden and inhibit neuronal apoptosis. Exposure to CO rescues the loss of HO-1 and thus merits further investigation in patients with SAH.
A new population and subspecies of the critically endangered Anatolian meadow viper Vipera anatolica Eiselt and Baran, 1970 in eastern Antalya province
Authors: Göçmen Bayram , Mebert Konrad , Karış Mert , Oğuz Mehmet Anıl , Ursenbacher Sylvain 
Published: July 2017

We report on a new population ofVipera anatolicafrom the Geyik Mountain Range in eastern Antalya Province, Turkey. It represents only the second known location, and is situated in a valley about 200 km east from the terra typica at Kohu Dağ in western Antalya Province. We compare both populations and, based on marked differences in morphology, habitat, genetics, and its geographically isolated location, we describe the recently discovered population as a new subspecies. Aspects of ecology, threats, and conservation needs are discussed.
Hepatitis-Associated (Australia) Antigen and Down's Syndrome
Authors: Shiono Hiroshi , Kadowaki Junichi , Fujiwara Takeki , Nakao Tooru 
Published: July 2017

Hepatitis-Associated (Australia) Antigen (HAA) was detected in 13 (5.8%) of 223 patients with Down's syndrome and in 14 (3.7%) of 378 patients with other forms of mental retardation. The frequency of HAA was 2.4 per cent in 127 noninstitutionalized patients with Down's syndrome, and 10.4 per cent in 96 institutionalized patients. The frequency of HAA with Down's syndrome was lower on the average in Japan than in the United States or Germany.HAA was detected in one (1.3%) of 78 mothers of infants with Down's syndrome. Our study suggests that maternal exposure to HAA, as reflected by the presence of either HAA or anti-HAA, was not associated with the subsequent birth of an infant with Down's syndrome.
Aggregation of state variables in an RC model
Authors: Długosz Marek 
Published: July 2017

The paper presents a method for reducing the order of the thermal dynamics model of a building or room, obtained by application of a lumped parameter method. The reduced model has the same dynamic characteristics as the primary model, while additionally it is an observable one. The described model order reduction method involves the identification and aggregation of non-distinguishable state variables. The paper presents a sample calculation confirming the validity of the deliberations. The proposed reduction method of state variables can be used with other dynamic systems provided that the assumptions concerning the structures of the system matrices are fulfilled. Practical application: The use of simplified but accurate mathematical models of the dynamics of heat in buildings enables the efficient design of high-performance control systems, e.g. the stabilisation of air temperature in the building. Simplified mathematical models also require less computing power and can be implemented in embedded control systems. This gives the ability to design, for example, distributed systems of predictive control, which requires mathematical models of controlled processes.
Association between US features of primary tumor and axillary lymph node metastasis in patients with clinical T1–T2N0 breast cancer
Authors: Bae Min Sun , Shin Sung Ui , Song Sung Eun , Ryu Han Suk , Han Wonshik , Moon Woo Kyung 
Published: July 2017

Background Most patients with early-stage breast cancer have clinically negative lymph nodes (LNs). However, 15–20% of patients have axillary nodal metastasis based on the sentinel LN biopsy. Purpose To assess whether ultrasound (US) features of a primary tumor are associated with axillary LN metastasis in patients with clinical T1–T2N0 breast cancer. Material and Methods This retrospective study included 138 consecutive patients (median age = 51 years; age range = 27–78 years) who underwent breast surgery with axillary LN evaluation for clinically node-negative T1–T2 breast cancer. Three radiologists blinded to the axillary surgery results independently reviewed the US images. Tumor distance from the skin and distance from the nipple were determined based on the US report. Association between US features of a breast tumor and axillary LN metastasis was assessed using a multivariate logistic regression model after controlling for clinicopathologic variables. Results Of the 138 patients, 28 (20.3%) had nodal metastasis. At univariate analysis, tumor distance from the skin ( P = 0.019), tumor size on US ( P = 0.023), calcifications ( P = 0.036), architectural distortion ( P = 0.001), and lymphovascular invasion ( P = 0.049) were associated with axillary LN metastasis. At multivariate analysis, shorter skin-to-tumor distance (odds ratio [OR] = 4.15; 95% confidence interval [CI] = 1.01–16.19; P = 0.040) and masses with associated architectural distortion (OR = 3.80; 95% CI = 1.57–9.19; P = 0.003) were independent predictors of axillary LN metastasis. Conclusion US features of breast cancer can be promising factors associated with axillary LN metastasis in patients with clinically node-negative early-stage breast cancer.
Differentiation between papillary renal cell carcinoma and fat-poor angiomyolipoma: a preliminary study assessing detection of intratumoral hemorrhage with chemical shift MRI and T2*-weighted gradient echo
Authors: Woo Sungmin , Kim Sang Youn , Cho Jeong Yeon , Kim Seung Hyup 
Published: July 2017

Background Recent literature suggests that intratumoral hemorrhage detection may be helpful in differentiating papillary renal cell carcinoma (pRCC) from fat-poor angiomyolipoma (fpAML). Purpose To determine whether intratumoral hemorrhage detected using chemical shift magnetic resonance imaging (MRI) and T2*-weighted (T2*W) gradient echo (GRE) can be used to differentiate pRCC from fpAML. Material and Methods This retrospective study included 42 patients with pRCC (n = 28) and fpAML (n = 14) who underwent MRI followed by surgery. Two blinded radiologists independently assessed the presence of intratumoral hemorrhage using chemical shift MRI (decrease in signal intensity from opposed- to in-phase) and T2*W GRE (“blooming”). Consensus reading was determined for discrepant cases. MRI findings were compared using Chi-square test. Inter-observer agreement was assessed using kappa statistics. Results Inter-observer agreement was substantial for both sequences ( k = 0.622 and 0.793, P < 0.001). For chemical shift MRI, the prevalence of intratumoral hemorrhage was significantly greater in pRCC than in fpAML (71.4% versus 28.6%, P = 0.019 for reader 1; 64.3% versus 14.3%, P = 0.003 for reader 2; and 75% versus 21.4%, P = 0.002 for the consensus). T2*W GRE showed a similar tendency (46.4% versus 14.3%, P = 0.049 for both readers; and 50% versus 14.3%, P = 0.042 for the consensus). Using the consensus reading, sensitivity and specificity of determining pRCC were 75% and 78.6% for chemical shift MRI and 50% and 85.7% for T2*W GRE. Conclusion The prevalence of intratumoral hemorrhage identified from chemical shift MRI or T2*W GRE was significantly different between pRCC and fpAML. These hemorrhage-sensitive MRI sequences may be used as an adjunctive tool for discriminating between the two entities.
Current concepts on the neurobiology of Attention-Deficit/Hyperactivity Disorder
Authors: Biederman J. , Faraone S. V. 
Published: July 2017

Attention-Deficit/Hyperactivity Disorder (ADHD) is an early onset, clinically heterogeneous disorder of inattention, hyperactivity, and impulsivity. In contrast to the widespread acceptance of ADHD as a childhood diagnosis, its prevalence in adults and its implications for clinical practice remain a source of controversy. Throughout the lifecycle, a key clinical feature observed in ADHD patients is comorbidity with Conduct, Depressive, Bipolar, and Anxiety disorders. Family studies consistently support the assertion that ADHD runs in families. Heritabillty data from twin studies of ADHD attribute about 80 percent of the etiology of ADHD to genetic factors. Adoption studies of ADHD also implicate genes in its etiology. Molecular genetic data are bolstered by considerations suggesting that DRD4 and DAT genes may be relevant for ADHD. Independently of genes, prenatal exposure to nicotine and psychosocial adversity have also been identified as risk factors for ADHD. Structural and functional Imaging studies consistently implicate catecholamine-rich fronto-subcortical systems in the pathophysiology of ADHD. The effectiveness of stimulants, along with animal models of hyperactivity, point to catecholamine disruption as at least one source of ADHD brain dysfunction. Although not entirely sufficient, changes in dopaminergic and noradrenergic function appear necessary for the clinical efficacy of pharmacological treatments for ADHD, providing support for the hypothesis that alteration of monoaminergic transmission in critical brain regions may be the basis for therapeutic action in ADHD.
Mechanism of action of methylphenidate: Insights from PET imaging studies
Authors: Volkow N. D. , Fowler J. S. , Wang G. , Ding Y. , Gatley S. J. 
Published: July 2017

Methylphenidate (MPH) is the most commonly prescribed drug for the treatment of Attention-Deficit/Hyperactivity Disorder (ADHD). We have used Positron Emission Tomography (PET) to investigate the mechanism of action of MPH in the human brain. We have shown (a) that oral MPH reaches peak concentration in the brain 60–90 minutes after its administration, (b) that therapeutic doses of MPH block more than 50% of the dopamine transporters (DAT), and (c) that of the two enantiomers that compose MPH, it is d-threo-methylphenidate (d-MPH) and not l-threo-methylphenidate (l-MPH) that binds to the DAT. We have also shown that therapeutic doses of MPH significantly enhance extracellular dopamine (DA) in the basal ganglia, which is an effect that appears to be modulated by the rate of DA release and that is affected by age (older subjects show less effect). Thus, we postulate (a) that MPH's therapeutic effects are in part due to amplification of DA signals, (b) that variability in responses is in part due to differences in DA tone between subjects, and (c) that MPH's effects are context dependent. Because DA enhances task specific neuronal signaling and decreases noise, we also postulate that MPH-induced increases In DA could improve attention and decrease distractibility; and that since DA modulates motivation, the increases in DA would also enhance the saliency of the task facilitating the “interest it elicits” and thus improving performance.
Use of mental-health services by Australian medical students: a cross-sectional survey
Authors: Ryan Geoffrey , Marley Ian , Still Melanie , Lyons Zaza , Hood Sean 
Published: July 2017

Objective: Medical students have higher rates of mental illness compared to the general population. Little is known about services accessed by medical students for mental-health problems. This study aimed to assess the use of mental-health services by Australian medical students and to identify barriers that may prevent students from using mental-health services. Method: A cross-sectional online survey was designed and administered to medical students at the University of Western Australia. Questions focused on self-reported psychological well-being, use of mental-health services, the perceived usefulness of services and barriers to the use of services. Results: The response rate was 41% ( n=286). Sixty-two per cent self-reported experiencing mental-health problems, and of these, 75% had used at least one service. General practitioners and psychiatrists were rated as the most effective service type. The main barriers to seeking help were not enough time, affordability and concerns regarding stigma, including disclosure and peer judgement. Conclusion: A high proportion of students with self-reported mental-health problems had accessed services. However, barriers were also identified. Access to mental-health services needs to be improved, and strategies aimed at reducing stigma and raising awareness of mental-health issues should be encouraged by medical faculties.
A perspective on the contribution of animal models to the pharmacological treatment of posttraumatic stress disorder
Authors: Bertaina-Anglade Valerie , O’Connor Susan M , Andriambeloson Emile 
Published: July 2017

Objectives: Posttraumatic stress disorder (PTSD) is a prevalent, chronic, disabling disorder that may develop following exposure to a traumatic event. This review summarizes currently used animal models of PTSD and their potential role in the development of better therapeutics. Heterogeneity is one of the main characteristics of PTSD with the consequence that many pharmacological approaches are used to relieve symptoms of PTSD. To address the translational properties of the animal models, we discuss the types of stressors used, the rodent correlates of human PTSD (DSM-5) symptoms, and the efficacy of approved, recommended and off-label drugs used to treat PTSD in ‘PTSD-animals’. Conclusions: Currently available animal models reproduce most PTSD symptoms and are validated by existing therapeutics. However, novel therapeutics are needed for this disorder as not one drug alleviates all symptoms and many have side effects that lead to non-compliance among PTSD patients. The true translational power of animal models of PTSD will only be demonstrated when new therapeutics acting through novel mechanisms become available for clinical practice.
Stroke profile and outcome between urban and rural regions of Northwest India: Data from Ludhiana population-based stroke registry
Authors: Kaur Paramdeep , Verma Shweta J , Singh Gagandeep , Bansal Rajinder , Paul Birinder S , Singla Monika , Singh Shavinder , Samuel Clarence J , Sharma Meenakshi , Pandian Jeyaraj D 
Published: July 2017

Introduction The objective of this study is to compare the clinical profile, risk factors, type and outcome of stroke patients in urban and rural areas of Punjab, India. Methods The primary data source was from the Ludhiana urban population-based stroke registry. The data of first-ever stroke patients with age ≥18 years were collected using WHO stepwise approach from all hospitals, general practitioners, physiotherapy and scan centres between 26 March 2011 and 25 March 2013. Results A total of 4989 patients were included and out of 4989 patients, 3469 (69%) were from urban areas. Haemorrhagic stroke was seen more in rural as compared to urban regions (urban 1104 (32%) versus rural 552 (36%); p = 0.01). There were significant differences seen in stroke risk factors; hypertension (urban 1923 (84%) versus rural 926 (89%); p = 0.001) and hyperlipidaemia (urban 397 (18%) versus rural 234 (23%); p = 0.001) between two groups. In the multivariable analysis the rural patients were more likely to be younger (age < 40 years) (OR: 1.82; 95% CI: 1.24–2.68; p = 0.002), Sikhs (OR: 2.57; 95% CI: 1.26–5.22; p = 0.009), farmers (OR: 9.41; 95% CI: 5.36–16.50; p < 0.001), housewives (OR: 2.71; 95% CI: 1.45–5.06; p = 0.002), and consumed alcohol (OR: 1.57; 95% CI: 1.19–2.06; p = 0.001) as compared to urban patients. In addition, use of imaging was higher in rural patients (OR: 1.99; 95% CI: 1.06–3.74; p = 0.03) as compared to urban patients. Discussion and Conclusion In this large cohort of patients, rural and urban differences were seen in risk factors and type of stroke. Stroke prevention strategies need to take into consideration these factors including regional sociocultural practices.
How I treat myeloma with new agents
Authors: Moreau Philippe 
Published: July 2017

Abstract
At present, multiple classes of agents with distinct mechanisms of action are available for the treatment of patients with multiple myeloma (MM), including alkylators, steroids, immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), histone deacetylase inhibitors (DACIs), and monoclonal antibodies (mAbs). Over the last 5 years, several new agents, such as the third-generation IMiD pomalidomide, the second-generation PIs carfilzomib and ixazomib, the DACI panobinostat, and 2 mAbs, elotuzumab and daratumumab, have been approved, incorporated into clinical guidelines, and have transformed our approach to the treatment of patients. These agents may be part of doublet or triplet combinations, or incorporated into intensive strategies with autologous stem cell transplantation. In this review, I discuss the different treatment options available today for the treatment of MM in frontline and relapse settings.
Handpad: a virtual mouse for controlling laptops in a smart home
Authors: Taing Clerc-Manne , Rau Pei-Luen Patrick , Huang Hanjing 
Published: July 2017

AbstractThis study investigates the possibilities of equipping fixed furniture with touch screens to control laptops or other smart home devices, to create a holistic smart home control system. Although multi-touch screens have recently been integrated into desktop use, most users prefer a classical mouse for desktop input. This study introduces Handpad, which is a new indirect touch input device designed to control laptops in a smart home. Handpad combines the mobility of a touch screen with the precision of a mouse by tracking whole-hand movement on the touch screen and moving the screen pointer accordingly. In a user test, participants showed a high level of acceptance and positive attitudes toward Handpad.