Miracle-dz/UniFAR-FTUs huggingface dataset:
Assessing incremental value of biomarkers with multi‐phase nested case‐control studies

Accurate risk prediction models are needed to identify different risk groups for individualized prevention and treatment strategies. In the Nurses’ Health Study, to examine the effects of several biomarkers and genetic markers on the risk of rheumatoid arthritis (RA), a three‐phase nested case‐control (NCC) design was conducted, in which two sequential NCC subcohorts were formed with one nested within the other, and one set of new markers measured on each of the subcohorts. One objective of the study is to evaluate clinical values of novel biomarkers in improving upon existing risk models because of potential cost associated with assaying biomarkers. In this paper, we develop robust statistical procedures for constructing risk prediction models for RA and estimating the incremental value (IncV) of new markers based on three‐phase NCC studies. Our method also takes into account possible time‐varying effects of biomarkers in risk modeling, which allows us to more robustly assess the biomarker utility and address the question of whether a marker is better suited for short‐term or long‐term risk prediction. The proposed procedures are shown to perform well in finite samples via simulation studies.
Electromyographic Findings After Different Selective Neck Dissections

Objectives: The objective was to compare electrophysiologic investigations of the upper trapezius muscle (UT) after different selective neck dissections (SND) and analyze the differences between types of SND and the preservation and excision of the cervical nerves (the C2–4 rami of the cervical plexus).
A comparison of effective connectivity methods using different performance metrics

Different analysis methods have been developed to determine brain connectivity patterns. To select suitable methods depending on application contexts, it is essential to evaluate different methods using suitable performance metrics. We propose three application-oriented metrics which enable to measure multivariate causality qualitatively. Using the proposed metrics, the most used analysis methods (Directed Transfer Function, Partial Directed Coherence, Granger-Geweke Causality) are compared on synthetic electroencephalographic data with a predefined causality structure. Furthermore, the performances obtained by using all metrics are evaluated. Such analysis allows us to select the most stable analysis method. Also, the optimal metric can be found by comparing the performances obtained by using different metrics with the graph-based performance in the graphically displayed predicted network.
Electroencephalography monitoring in critically ill children: Current practice and implications for future study design

Survey data indicate that continuous electroencephalography (EEG) (CEEG) monitoring is used with increasing frequency to identify electrographic seizures in critically ill children, but studies of current CEEG practice have not been conducted. We aimed to describe the clinical utilization of CEEG in critically ill children at tertiary care hospitals with a particular focus on variables essential for designing feasible prospective multicenter studies evaluating the impact of electrographic seizures on outcome.
Abductor Pollicis Longus “Hammock” Ligamentoplasty for Treatment of First Carpometacarpal Arthritis

The association of trapeziectomy with ligamentoplasty is a simple treatment for osteoarthritis at the base of the thumb. Here we present the long-term results of a technique that creates a “hammock” under the first metacarpal bone using the Abductor Pollicis Longus tendon. This paper reports the results of treatment by this operation of 60 thumbs in 50 patients, including 13 men and 37 women of average age 60 (46–75) years. Thirty thumbs presented with severe pain and 30 with moderate pain. At final follow-up, 47 thumbs (78%) had experienced dramatic relief of pain following the procedure, 12 (20%) thumbs still had mild pain and one (2%) thumb had severe pain. No patients needed revision.
A distinct carbonic anhydrase in the mucus of the colon of humans and other mammals

SUMMARY We have collected gastrointestinal, mainly colonic, mucus from humans, guinea pigs, rats, and normal and carbonic anhydrase II (CAII)-deficient mice. In the mucus of all species, substantial CA activity was present. Using antibodies against human CA isoforms we found that the human mucus CA differs from cytosolic CAI and CAII, membrane-bound CAIV, and the secreted CAVI of saliva. The high sensitivity of mucus CA to acetazolamide rules out its identity with cytosolic CAIII. Partial sequences obtained from the purified human mucus CA show similarity, but not identity, with human CAI, and clear differences from the other known CAs. Additional evidence concerning the CA isoform present in mucus was obtained for the mucus CA of other species and was derived from: (1) the mucus of CAII-deficient mice, whose high CA activity confirms that it is not CAII that is responsible; (2) the inhibitory effect of iodide, which shows that mucus CA from mice, guinea pig and humans does not have the high anion sensitivity of CAI; (3) the inactivating effect of 0.2% SDS on guinea pig, mouse and human mucus CA, ruling out the SDS-resistant CAIV; and (4) the partitioning of guinea-pig mucus CA into the water phase in Triton X114 phase separation experiments, which also argues against its identity with membrane-bound CAs, such as CAIV. A comparison of colonic mucus CA activity in normal and germ-free rats indicates that the mucus CA is not of bacterial origin but is produced by the gastrointestinal tissues. We conclude (from its immunoreactivity, from iodide inhibition and from partial amino acid sequences) that mucus CA of human origin probably represents an isozyme, which is specific for mucus and is not identical with the known CA isozymes. The results obtained for mucus CA of other species collectively point in the same direction.
Clinical outcomes of surgically resected combined small cell lung cancer: a two-institutional experience.

BACKGROUND The combined small cell lung cancer (c-SCLC) was rare and its clinicopathological characteristics had not been thoroughly described. The aim of this study was to determine prognostic factors and survival in c-SCLC patients. METHODS Clinical records of patients with c-SCLC who underwent surgery between January 2009 and December 2013 in two institutions were retrospectively reviewed. RESULTS Ninety-seven patients were identified. The most common pathology was combined SCLC and large cell neuroendocrine carcinoma (LCNEC, N=46), followed by combined SCLC and squamous cell carcinoma (SCC) (N=32), combined SCLC and adenocarcinoma (AC) (N=12), and combined SCLC and adenosquamous carcinoma (ASC) (N=7). The overall survival (OS) rates of the entire cohort were 42.4% and 35.2% at 3 and 5 years, respectively. Multivariate analysis identified sex [female vs. male, hazards ratio (HR) =0.38; 95% confidence interval (CI): 0.19-0.79; P=0.010], age (<53 vs. >53 years, HR =0.28; 95% CI: 0.09-0.81; P=0.019), performance status (<2 vs. >2, HR =0.08; 95% CI: 0.02-0.32; P<0.001), combined non-small cell lung cancer (NSCLC) components (LCNEC vs. non-LCNEC, HR =3.00; 95% CI: 1.03-8.76; P=0.045), adjuvant therapy (yes vs. no, HR =0.33; 95% CI: 0.17-0.67; P=0.002) as significantly prognostic factors of OS in patients with complete resection and lymphadenectomy. CONCLUSIONS The mixed NSCLC components within c-SCLCs had a significant influence on the survival. Compared with surgery alone, adjuvant therapy was associated with significantly improved survival in patients with complete resection and lymphadenectomy.
Decision-Making in Frontotemporal Dementia: Clinical, Theoretical and Legal Implications

Background: The behavioral variant of frontotemporal dementia (bvFTD) is characterized by progressive changes in personality and social interaction, loss of empathy, disinhibition and impulsivity, most of which generally precede the onset of cognitive deficits. In this study, we investigated decision-making cognition in a group of patients with an early bvFTD diagnosis whose standard neuropsychological performance was within normal range for all variables. Methods: The Iowa Gambling Task was administered to this group of early bvFTD patients, to a group of early bvFTD patients who had shown impaired performance on the classical neuropsychological battery and to healthy controls. Results: Decision-making was impaired in both bvFTD patient groups, whether they had shown impaired or normal performance in the classical neuropsychological evaluation. Conclusions: Patients with early bvFTD may perform normally on standard cognitive tests, and yet develop severe deficits in judgment and decision-making. In many current legal systems, early bvFTD patients showing preserved cognitive functioning who commit unlawful acts run the risk of not being able to plead insane or not guilty on the grounds of diminished responsibility beyond reasonable doubt. This represents a unique legal and ethical dilemma. Our findings have important implications for medicolegal decisions relating to capacity and culpability, and regarding the philosophical concept of ‘free will’.
A study of cardio-metabolic risk profile in patients with psoriasis.

INTRODUCTION/BACKGROUND Psoriasis is a chronic immune mediated inflammatory disorder of the skin and joints. Recent studies have shown increased prevalence of traditional cardiovascular risk factors such as diabetes mellitus, hypertension and metabolic syndrome. Since atherosclerosis and psoriasis share a common link of inflammation, different workers have shown psoriasis to be a risk factor for atherosclerosis. The aim of our study was assessment of cardiovascular risk factors and evidence of subclinical atherosclerosis in patients of psoriasis. METHODS In a hospital based, cross-sectional study, 96 patients with psoriasis and 100 age, sex and weight matched controls were enrolled. Prevalence of diabetes, hypertension, metabolic syndrome was studied. They were also assessed for endothelial dysfunction by brachial artery flow mediated dilatation(FMD) and carotid intima media thickness (CIMT). RESULTS There was higher prevalence of hypertension, hypertriglyceridaemia, diabetes mellitus and metabolic syndrome in patients with psoriasis than in controls. FMD was lower in patients with psoriasis than in controls (5.6 +/- 2 vs7.5 +/- 2.8, P = 0.02). The mean CIMT was significantly increased (0.78 +/- 0.12 vs 0.62 +/- 0.08, P = 0.001) in patients with psoriasis compared with controls. In psoriasis patients, CIMT was associated with hypertension, hypertriglyceridaemia, diabetes, insulin resistance, increased severity and duration of psoriasis while in multivariate analysis insulin resistance (OR 2.8, 95% CI 1.92-6.34 P = 0.02) and increased duration of disease (OR 3.12, 95% CI 2.34-7.56) a were the independent risk factors associated with higher CIMT. CONCLUSION Patients of psoriasis have higher prevalence of metabolic syndrome, cardiovascular risk factors and subclinical atherosclerosis than general population. As a routine, individuals with moderate to severe psoriasis of long duration should be recognised as being at increased cardio vascular risk and thus encouraged for therapeutic interventions to reduce the modifiable risk factors.
Differentially Expressed in Chondrocytes 2 (DEC2) Increases the Expression of IL-1β and Is Abundantly Present in Synovial Membrane in Rheumatoid Arthritis

Objective Patients with rheumatoid arthritis (RA) have altered circadian rhythm of circulating serum cortisol, melatonin and IL-6, as well as disturbance in the expression of clock genes ARNTL2 and NPAS2. In humans, TNFα increases the expression ARNTL2 and NPAS2 but paradoxically suppresses clock output genes DPB and PER3. Our objective was to investigate the expression of direct clock suppressors DEC1 and DEC2 (BHLHE 40 and 41 proteins) in response to TNFα and investigate their role during inflammation. Methods Cultured primary fibroblasts were stimulated with TNFα. Effects on DEC2 were studied using RT-qPCR and immunofluorescence staining. The role of NF-κB in DEC2 increase was analyzed using IKK-2 specific inhibitor IMD-0354. Cloned DEC2 was transfected into HEK293 cells to study its effects on gene expression. Transfections into primary human fibroblasts were used to confirm the results. The presence of DEC2 was analyzed in (RA) and osteoarthritis (OA) synovial membranes by immunohistochemistry. Results TNFα increased DEC2 mRNA and DEC2 was mainly detected at nuclei after the stimulus. The effects of TNFα on DEC2 expression were mediated via NF-κB. Overexpression, siRNA and promoter activity studies disclosed that DEC2 directly regulates IL-1β, in both HEK293 cells and primary human fibroblasts. DEC2 was increased in synovial membrane in RA compared to OA. Conclusion Not only ARNTL2 and NPAS2 but also DEC2 is regulated by TNFα in human fibroblasts. NF-κB mediates the effect on DEC2, which upregulates IL-1β. Circadian clock has a direct effect on inflammation in human fibroblasts.
Combining interest points and edges for content-based image retrieval

This paper presents a novel approach using combined features to retrieve images containing specific objects, scenes or buildings. The content of an image is characterized by two kinds of features: Harris-Laplace interest points described by the SIFT descriptor and edges described by the edge color histogram. Edges and corners contain the maximal amount of information necessary for image retrieval. The feature detection in this work is an integrated process: edges are detected directly based on the Harris function; Harris interest points are detected at several scales and Harris-Laplace interest points are found using the Laplace function. The combination of edges and interest points brings efficient feature detection and high recognition ratio to the image retrieval system. Experimental results show this system has good performance.
Differential Changes in Responses of Hypothalamic and Brainstem Neuronal Populations to Prolactin During Lactation in the Mouse1

During lactation, there are numerous functional adaptations in the maternal brain. There is evidence that the high levels of circulating prolactin present during lactation might contribute to these adaptive changes. The present study aimed to investigate levels of functional prolactin-mediated signal transduction in the brain of lactating mice, using prolactin-induced phosphorylation of signal transducer and activator of transcription 5 (pSTAT5) as a marker, and compare these to the effect of exogenous prolactin during diestrus. On Day 7 of lactation, widespread induction of pSTAT5 was observed in numerous regions of the mouse forebrain and brainstem. In the medial preoptic nucleus, bed nuclei stria terminalis, paraventricular nucleus, and medial amygdala of the forebrain, and in the rostral periaqueductal gray, parabrachial nucleus, dorsal raphe, and the raphe obscurus nucleus of the brainstem, pSTAT5 expression was markedly increased during lactation compared with the response to exogenous prolactin during diestrus. In the anteroventral periventricular nucleus, arcuate nucleus, ventromedial nucleus, and dorsomedial nucleus, responses in lactation were comparable to diestrus. Conversely, in the area postrema of the brainstem, there was a reduction in response to prolactin, with a loss of pSTAT5 expression, during lactation. These differential responses following either acute or chronic elevations in prolactin were not accompanied by any changes in levels of prolactin receptor mRNA, when measured by in situ hybridization. These data are consistent with the hypothesis that prolactin might mediate widespread adaptive responses in the maternal brain.
Statistica Sinica Preprint No : SS-2016-0011 R 1 Title Almost the Best of Three Worlds : Risk , Consistency and Optional Stopping for the Switch Criterion in Nested Model Selection

We study the switch distribution, introduced by Van Erven et al. (2012), applied to model selection and subsequent estimation. While switching was known to be strongly consistent, here we show that it achieves minimax optimal parametric risk rates up to a log log n factor when comparing two nested exponential families, partially confirming a conjecture by Lauritzen [2012] and Cavanaugh [2012] that switching behaves asymptotically like the Hannan-Quinn criterion. Moreover, like Bayes factor model selection but unlike standard significance testing, when one of the models represents a simple hypothesis, the switch criterion defines a robust null hypothesis test, meaning that its Type-I error probability can be bounded irrespective of the stopping rule. Hence, switching is consistent, insensitive to optional stopping and almost minimax risk optimal, showing that, Yang’s (2005) impossibility result notwithstanding, it is possible to ‘almost’ combine the strengths of AIC and Bayes factor model selection.
Physiologically grounded metrics of model skill: a case study estimating heat stress in intertidal populations

Models of biological responses to climate change often use environmental variables measured at large scales, which are only indirect drivers of organism physiology and survival. We used skill scores based on physiology to assess the performance of several biophysical models. While all models had similar levels of overall accuracy using more traditional model skill metrics, their ability to predict stress levels differed.
Effect of Seated Trunk Posture on Eye Blink Startle and Subjective Experience: Comparing Flexion, Neutral Upright Posture, and Extension of Spine

Postures are known to be able to affect emotion and motivation. Much less is known about whether (affective) modulation of eye blink startle occurs following specific postures. The objective of the current study was to explore this. Participants in the present study were requested to assume three different sitting postures: with the spine flexed (slouched), neutral upright, and extended. Each posture was assumed for four minutes, and was followed by the administration of brief self-report questionnaires before proceeding to the next posture. The same series of postures and measures were repeated prior to ending the experiment. Results indicate that, relative to the other postures, the extended sitting posture was associated with an increased startle, was more unpleasant, arousing, had smaller levels of dominance, induced more discomfort, and was perceived as more difficult. The upright and flexed sitting postures differed in the level of self-reported positive affect, but not in eye blink startle amplitudes.
Serotonin and Nociception

A key r6le of serotonin (5-hydroxytryptamine, 5-HT) in regulating the transmission of nociceptive information at various levels of the peripheral and central nervous systems is undisputed. In fact a recent review of research in this area quoted more than 400 papers on this subject, most of which have appeared in the last 5 years. ’ Moreover neuronal systems containing serotonin seem not only to be involved in regulation of segmental nociceptive input a t a spinal and supraspinal level, but also in mediating the nociceptive action of morphine and that resulting from electrical stimulation of certain brain stem Despite a general acceptance of the above statements, much of the pharmacology of nociception is nevertheless contraindicatory and this almost certainly relates to differences in the species studied, the type of anesthesia employed, the mode of drug application and the responses measured. In addition, there is a general lack of appreciation that the purportedly selective drug tools which have been used in the past, in fact have actions at more than one of the seven 5-HT receptor subtypes which are now known to exist.4 However, with the advent of truly selective compounds it is finally becoming possible to dissect these responses pharmacologically and thereby identify the particular subtype of 5-HT receptor involved in eliciting them. ’ The main purpose of the current review is to define the particular subtypes of 5-HT receptor involved in regulating the forward transmission of nociceptive input a t various hierachial levels of the peripheral and central nervous systems and thereby indicate approaches to the development of novel analgesic compounds.
The Pain of Helping: Psychological Injury of Helping Professionals

Foreword Preface Acknowledgements Introduction Chapter 1:Traumatology: An Overview Chapter 2:Stress Chapter 3:Acute Stress Disorder Chapter 4:Posttraumatic Stress Disorder Chapter 5: Compassion Fatigue/ Secondary Traumatic Stress Disorder Chapter 6: Critical Incident Stress Chapter 7: Vicarious Traumatization Chapter 8: Burnout
Stabilizing markets via a novel auction based pricing mechanism for short-term contracts for network services

This paper studies pricing mechanisms for short-term contracts for network services in a recurring auction with sealed bids. We propose and evaluate a novel winner selection policy in such an auction. The new approach was motivated by an observation that in a recurring auction enough customers must be willing to participate in future auction rounds to prevent collapse of prices. Using simulations, we compare the proposed mechanism with traditional ones. The results demonstrate that the new method (i) increases revenues of the network service provider, (ii) minimizes loss of fairness, and (iii) enlarges the active customer base of a recurring auction.
How Does Regression Test Prioritization Perform in Real-World Software Evolution?

In recent years, researchers have intensively investigated various topics in test prioritization, which aims to re-order tests to increase the rate of fault detection during regression testing. While the main research focus in test prioritization is on proposing novel prioritization techniques and evaluating on more and larger subject systems, little effort has been put on investigating the threats to validity in existing work on test prioritization. One main threat to validity is that existing work mainly evaluates prioritization techniques based on simple artificial changes on the source code and tests. For example, the changes in the source code usually include only seeded program faults, whereas the test suite is usually not augmented at all. On the contrary, in real-world software development, software systems usually undergo various changes on the source code and test suite augmentation. Therefore, it is not clear whether the conclusions drawn by existing work in test prioritization from the artificial changes are still valid for real-world software evolution. In this paper, we present the first empirical study to investigate this important threat to validity in test prioritization. We reimplemented 24 variant techniques of both the traditional and time-aware test prioritization, and investigated the impacts of software evolution on those techniques based on the version history of 8 real-world Java programs from GitHub. The results show that for both traditional and time-aware test prioritization, test suite augmentation significantly hampers their effectiveness, whereas source code changes alone do not influence their effectiveness much.