Miracle-dz/UniFAR-FTUs huggingface dataset:
Extreme Value Theory for Novelty Detection in Vital Sign Monitoring

Studies indicate that a large number of in-hospital cardiac events could be prevented, provided that the preceding physiological abnormalities are identified and acted upon. Continuous patient monitoring is not a task that can reasonably be assigned to the nursing staff, but one that could benefit from the use of an automated system. With this in mind, an early warning system based on a data-driven novelty detection scheme has been designed by Tarassenko et al. [2005]. Vital sign data collected from clinical trials are fused to create a multi-patient ‘model of normality’ in the form of a multivariate probability density function. A novelty threshold is set in the probability space and used to discriminate between normal and abnormal test data. Performances of this methodology on clinically reviewed data are reported in Hann [2008]. In this investigation, we attempt to extend the research in two directions. First, we introduce a principled method for assigning novelty scores and setting novelty thresholds based on an extension of Extreme Value Theory, theory which focuses on describing the tails of univariate distributions. For the purpose of this work, we redefine ‘extrema’ to include all regions of low probability and propose a methodology for the study of multivariate distributions. We show that our novel scoring system is more stable and easier to interpret than the original one, and requires very little postprocessing. Second, we use the first 24 hours of a patient’s vital sign data to build a patient-specific model. Using our scoring system, we compare its results with those from the multi-patient model. On both our test and control group, we show that if patient’s vital signs are indeed normal over the training period, the patient-specific score is in turn less volatile and responsible for fewer false alarms.
Feature context for image classification and object detection

In this paper, we presents a new method to encode the spatial information of local image features, which is a natural extension of Shape Context (SC), so we call it Feature Context (FC). Given a position in a image, SC computes histogram of other points belonging to the target binary shape based on their distances and angles to the position. The value of each histogram bin of SC is the number of the shape points in the region assigned to the bin. Thus, SC requires knowing the location of the points of the target shape. In other words, an image point can have only two labels, it belongs to the shape or not. In contrast, FC can be applied to the whole image without knowing the location of the target shape in the image. Each image point can have multiple labels depending on its local features. The value of each histogram bin of FC is a histogram of various features assigned to points in the bin region. We also introduce an efficient coding method to encode the local image features, call Radial Basis Coding (RBC). Combining RBC and FC together, and using a linear SVM classifier, our method is suitable for both image classification and object detection.
About pyramid structure in convolutional neural networks

Deep convolutional neural networks (CNN) brought revolution without any doubt to various challenging tasks, mainly in computer vision. However, their model designing still requires attention to reduce number of learnable parameters, with no meaningful reduction in performance. In this paper we investigate to what extend CNN may take advantage of pyramid structure typical of biological neurons. A generalized statement over convolutional layers from input till fully connected layer is introduced that helps further in understanding and designing a successful deep network. It reduces ambiguity, number of parameters, and their size on disk without degrading overall accuracy. Performance are shown on state-of-the-art models for MNIST, Cifar-10, Cifar-100, and ImageNet-12 datasets. Despite more than 80% reduction in parameters for Caffe LENET, challenging results are obtained. Further, despite 10 - 20% reduction in training data along with 10 - 40% reduction in parameters for Alexnet model and its variations, competitive results are achieved when compared to similar well-engineered deeper architectures.
Long-Term Impact of a Cell Phone–Enhanced Parenting Intervention

Home visiting programs support positive parenting in populations at-risk of child maltreatment, but their impact is often limited by poor retention and engagement. The current study assessed whether a cellular phone–supported version (PCI-C) of the Parent-Child Interactions (PCI) intervention improved long-term parenting practices, maternal depression, and children’s aggression. Low-income mothers (n = 371) of preschool-aged children were assigned to one of the three groups: PCI-C, PCI, and a wait-list control (WLC) group. Parenting improved in both intervention groups between baseline and 12-month follow-up compared to the WLC. Children in the PCI-C group were rated to be more cooperative and less aggressive than children in the WLC. The results offer evidence of the long-term effectiveness of PCI and the additional benefits of cellular phone supports for promoting intervention retention and improving children’s behavior.
Downregulation of exosomal miR-204-5p and miR-632 as a biomarker for FTD: a GENFI study

Objective To determine whether exosomal microRNAs (miRNAs) in cerebrospinal fluid (CSF) of patients with frontotemporal dementia (FTD) can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic Frontotemporal Dementia Initiative (GENFI) cohort and in sporadic FTD. Methods GENFI participants were either carriers of a pathogenic mutation in progranulin, chromosome 9 open reading frame 72 or microtubule-associated protein tau or were at risk of carrying a mutation because a first-degree relative was a known symptomatic mutation carrier. Exosomes were isolated from CSF of 23 presymptomatic and 15 symptomatic mutation carriers and 11 healthy non-mutation carriers. Expression of 752 miRNAs was measured using quantitative PCR (qPCR) arrays and validated by qPCR using individual primers. MiRNAs found differentially expressed in symptomatic compared with presymptomatic mutation carriers were further evaluated in a cohort of 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer’s disease (AD) and 10 healthy controls (HCs) of similar age. Results In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared with presymptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 (90% CI 0.79 to 0.98) and 0.81 (90% CI 0.68 to 0.93), respectively, and when combined an area of 0.93 (90% CI 0.87 to 0.99). In sporadic FTD, only miR-632 was significantly decreased compared with AD and HCs. Decrease of miR-632 revealed an area of 0.90 (90% CI 0.81 to 0.98). Conclusions Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.
SPECIAL ISSUE TWO FURTHER INVESTIGATIONS OF AUTOBIOGRAPHICAL MEMORY IN SEMANTIC DEMENTIA

A number of investigations in semantic dementia have documented better retrieval of recent personal events compared to those in the more distant past (Graham and Hodges, 1997). Westmacott et al. (2001) challenged this result, however, finding relative preservation of remote memories in a single case of semantic dementia when he was tested using family photographs. In Experiment 1, we tested two possible explanations for the discrepancy between the published papers: (a) that there is a significant effect of modality in autobiographical retrieval in semantic dementia (e.g., patients will show better, or even preserved, remote memory when tested on nonverbal, compared to verbal, tasks); and (b) that the distinct pattern seen between patients is attributable to the different methods adopted for scoring the episodic quality of the memories. A patient with semantic dementia, AM, produced autobiographical memories to both words and family photographs. These personal events were scored by two raters using the scoring method described by Westmacott et al. (2001) and that reported by Graham and Hodges (1997). It was found that AM showed similar levels of remote memory impairment regardless of whether the cue was verbal or nonverbal. In addition, significant effects of time were revealed in AM’s performance on the verbal memory test, regardless of which method was used to score the memories. In Experiment 2, we investigated a related question: whether the relatively better retrieval of memories in semantic dementia could be due to over rehearsal of highly salient recent experiences? Four patients were tested on their ability to remember a recent event (either a trip to London or events from a Formula One Grand Prix race) using specially designed autobiographical questionnaires. It was found that all four were able to perform this task, although one patient showed evidence of some forgetting over three months, and another exhibited difficulty discriminating between two similar events. Together, the two experiments further confirm that patients with semantic dementia show a modality independent autobiographical memory deficit, with better retrieval of recent events.
Efficacy and Safety of Vedolizumab for Induction of Remission in Inflammatory Bowel Disease—the Israeli Real-World Experience

Background: Vedolizumab (VDZ) is an anti-integrin monoclonal antibody effective in ulcerative colitis (UC) and Crohn's disease (CD). The aim of this study was to examine the “real world” efficacy and safety of VDZ in a large national patient cohort. Methods: Patients with inflammatory bowel disease treated with VDZ were prospectively followed for 14 weeks. Patients who completed the induction protocol (week 0/2/6/14) or discontinued the treatment before week 14 for adverse events (AEs) or primary nonresponse were included. The primary outcome was induction of clinical remission at week 14; secondary outcomes included clinical response and corticosteroid-free clinical remission. Results: A total of 204 patients (CD-130, UC-69, inflammatory bowel disease–unclassified-5) from 8 centers in Israel were included. Fifteen (7.4%) of the patients were anti–tumor necrosis factor naive and 46 (35.4%) had a previous surgery. For patients with CD, 69/130 (53.1%) responded to treatment; 45 (34.6%) achieved clinical remission; and 38 (29.2%) achieved corticosteroid-free remission at week 14. Fourteen (10.7%) patients discontinued VDZ before week 14 due to primary nonresponse or AEs. For UC, 32/74 (43.2%) responded to treatment; 20 (28.4%) achieved clinical remission, and 18 (24.3%) achieved corticosteroid-free remission at week 14. Fifteen (20.3%) patients with UC did not complete the induction due to primary nonresponse or AEs. AEs were reported by 29 (14.2%) patients (CD and UC combined), most common being nasopharyngitis and skin eruptions. Conclusions: In a large real-world Israeli cohort of anti–tumor necrosis factor–experienced patients with inflammatory bowel disease, VDZ was effective and safe in induction of clinical remission and steroid-free clinical remission.
Posterior α EEG Dynamics Dissociate Current from Future Goals in Working Memory-Guided Visual Search

Current models of visual search assume that search is guided by an active visual working memory representation of what we are currently looking for. This attentional template for currently relevant stimuli can be dissociated from accessory memory representations that are only needed prospectively, for a future task, and that should be prevented from guiding current attention. However, it remains unclear what electrophysiological mechanisms dissociate currently relevant (serving upcoming selection) from prospectively relevant memories (serving future selection). We measured EEG of 20 human subjects while they performed two consecutive visual search tasks. Before the search tasks, a cue instructed observers which item to look for first (current template) and which second (prospective template). During the delay leading up to the first search display, we found clear suppression of α band (8–14 Hz) activity in regions contralateral to remembered items, comprising both local power and interregional phase synchronization within a posterior parietal network. Importantly, these lateralization effects were stronger when the memory item was currently relevant (i.e., for the first search) compared with when it was prospectively relevant (i.e., for the second search), consistent with current templates being prioritized over future templates. In contrast, event-related potential analysis revealed that the contralateral delay activity was similar for all conditions, suggesting no difference in storage. Together, these findings support the idea that posterior α oscillations represent a state of increased processing or excitability in task-relevant cortical regions, and reflect enhanced cortical prioritization of memory representations that serve as a current selection filter. SIGNIFICANCE STATEMENT Our days are filled with looking for relevant objects while ignoring irrelevant visual information. Such visual search activity is thought to be driven by current goals activated in working memory. However, working memory not only serves current goals, but also future goals, with differential impact upon visual selection. Little is known about how the brain differentiates between current and future goals. Here we show, for the first time, that modulations of brain oscillations in the EEG α frequency band in posterior cortex can dissociate current from future search goals in working memory. Moreover, the dynamics of these oscillations uncover how we flexibly switch focus between memory representations. Together, we reveal how the brain assigns priority for selection.
Conjugated linoleic acid inhibits proliferation but stimulates lipid filling of murine 3T3-L1 preadipocytes.

This study documented the effects of conjugated linoleic acid (CLA) on the proliferation and differentiation of 3T3-L1 preadipocytes. During proliferation, preadipocytes were cultured in Dulbecco's modified Eagle's medium (DMEM), 100 g/L fetal bovine serum (FBS), 0. 584 g/L L-glutamine and 0 (control), 0.5, 1.0, 5.0 or 10.0 mg/L CLA. Proliferation of 3T3-L1 preadipocytes was measured directly by cell counting and indirectly by radiolabeled thymidine incorporation into DNA at 96 h postinoculation. Conjugated linoleic acid was not cytotoxic during proliferation or differentiation. The 0.5, 1.0, 5.0 or 10.0 mg/L CLA treatments inhibited proliferation by 8, 12, 31 and 36%, respectively (all P < 0.05). Treatment with 10 mg/L CLA or 10 mg/L linoleic acid (cis-9,12) reduced the incorporation of 3H-thymidine into DNA by 56 and 35%, respectively, suggesting that some portion of the effect of CLA on preadipocyte proliferation was nonspecific. After the initiation of differentiation, preadipocytes were cultured in DMEM, 100 g/L FBS, 0.584 g/L L-glutamine, 1.7 micromol/L insulin and 0 (control), 0.5, 1.0, 5.0 or 10.0 mg/L CLA. Radiolabeled glucose incorporation into cellular lipids was increased from 7.4 to 11.1, 11.1, 17.4 and 22.5 nmol/(h.10(6 )cells) (all P < 0.05) by 0.5, 1.0, 5.0 and 10.0 mg/L CLA, respectively. A media concentration of 10 mg/L CLA increased total cellular CLA (from 0 to 0.16 +/- 0.01 micromol/10(6 )cells), palmitic acid (from 0.47 to 1.10 +/- 0.03 micromol/10(6 )cells) and palmitoleic acid (from 0.24 to 0.81 +/- 0.03 micromol/10(6 )cells) (means +/- pooled SEM; all P < 0.05). Conjugated linoleic acid had no effect on arachidonic acid content, but decreased its proportion (g arachidonic acid/100 g total fatty acids) by >50% (P < 0.05). These data indicate that CLA inhibited proliferation and promoted de novo lipogenesis and lipid filling in 3T3-L1 preadipocytes, suggesting that CLA may reduce overall fat accumulation in growing animals by inhibiting stromal vascular preadipocyte hyperplasia.
ERβ inhibits cyclin dependent kinases 1 and 7 in triple negative breast cancer

Triple negative breast cancer (TNBC), which comprises approximately 15% of all primary breast cancer diagnoses, lacks estrogen receptor alpha, progesterone receptor and human epidermal growth factor receptor 2 expression. However, we, and others, have demonstrated that approximately 30% of TNBCs express estrogen receptor beta (ERβ), a nuclear hormone receptor and potential drug target. Treatment of ERβ expressing MDA-MB-231 cells with estrogen or the ERβ selective agonist, LY500307, was shown to result in suppression of cell proliferation. This inhibitory effect was due to blockade of cell cycle progression. In vivo, estrogen treatment significantly repressed the growth of ERβ expressing MDA-MB-231 cell line xenografts. Gene expression studies and ingenuity pathway analysis identified a network of ERβ down-regulated genes involved in cell cycle progression including CDK1, cyclin B and cyclin H. siRNA mediated knockdown or drug inhibition of CDK1 and CDK7 in TNBC cells resulted in substantial decreases in proliferation regardless of ERβ expression. These data suggest that the tumor suppressive effects of ERβ in TNBC result from inhibition of cell cycle progression, effects that are in part mediated by suppression of CDK1/7. Furthermore, these data indicate that blockade of CDK1/7 activity in TNBC may be of therapeutic benefit, an area of study that has yet to be explored.
Fibrinogen synthesis is elevated in fasting cancer patients with an acute phase response.

The unusual amino acid composition of acute phase proteins may be relevant to our understanding of the mechanism of tissue wasting in chronic inflammatory disease. During periods in which demand for amino acids outstrips dietary supply, skeletal muscle protein may be mobilized to meet this demand. An imbalance in the amino acid composition of these proteins may thus be detrimental to the body's nitrogen economy. To address this problem, we have measured the synthetic rate of fibrinogen (perhaps the major acute phase protein) and plasma amino acid profiles in a group of patients with adenocarcinoma of the pancreas and an ongoing inflammatory response (serum C-reactive protein >10 mg/L in the absence of any other obvious infective or inflammatory cause). These were also measured in a control group with no evidence of inflammation. Fibrinogen synthesis was measured after an overnight fast, using a flooding dose of 2H5-phenylalanine. The fractional rate of fibrinogen synthesis was significantly elevated in the cancer group compared with healthy controls [39.3 (20.0-49.9) and 21.9 (13.2-37.7) %/d, respectively; median (range), P < 0.05]. The absolute rate of fibrinogen synthesis was also elevated [84 (33-143) and 26 (15-43) mg/(kg.d), respectively; median (range), P < 0.01]. We calculated that, in cancer patients with anorexia-cachexia (i.e., documented ongoing weight loss in the absence of an obvious cause such as obstruction or malabsorption), aromatic amino acid supply (predominantly tryptophan) most limits fibrinogen synthesis from skeletal muscle reserves. Demand for the nonessential amino acids serine and glycine was elevated. Assuming that tryptophan is limiting, up to 2.6 g muscle protein ( approximately 12 g skeletal muscle tissue) may be wasted to synthesize 1 g fibrinogen. Interpretation of the observation that circulating free tryptophan concentrations were significantly reduced in the cancer patients will have to await flux measurements. The metabolic changes accompanying the inflammatory response suggest that down-regulation of this process may be beneficial.
Effect of acute dietary standardization on the urinary, plasma, and salivary metabolomic profiles of healthy humans.

BACKGROUND Metabolomics in human nutrition research is faced with the challenge that changes in metabolic profiles resulting from diet may be difficult to differentiate from normal physiologic variation. OBJECTIVE We assessed the extent of intra- and interindividual variation in normal human metabolic profiles and investigated the effect of standardizing diet on reducing variation. DESIGN Urine, plasma, and saliva were collected from 30 healthy volunteers (23 females, 7 males) on 4 separate mornings. For visits 1 and 2, free food choice was permitted on the day before biofluid collection. Food choice on the day before visit 3 was intended to mimic that for visit 2, and all foods were standardized on the day before visit 4. Samples were analyzed by using 1H nuclear magnetic resonance spectroscopy followed by multivariate data analysis. RESULTS Intra- and interindividual variations were considerable for each biofluid. Visual inspection of the principal components analysis scores plots indicated a reduction in interindividual variation in urine, but not in plasma or saliva, after the standard diet. Partial least-squares discriminant analysis indicated time-dependent changes in urinary and salivary samples, mainly resulting from creatinine in urine and acetate in saliva. The predictive power of each model to classify the samples as either night or morning was 85% for urine and 75% for saliva. CONCLUSIONS Urine represented a sensitive metabolic profile that reflected acute dietary intake, whereas plasma and saliva did not. Future metabolomics studies should consider recent dietary intake and time of sample collection as a means of reducing normal physiologic variation.
Optimization of Quantitative PCR Methods for Enteropathogen Detection

Detection and quantification of enteropathogens in stool specimens is useful for diagnosing the cause of diarrhea but is technically challenging. Here we evaluate several important determinants of quantification: specimen collection, nucleic acid extraction, and extraction and amplification efficiency. First, we evaluate the molecular detection and quantification of pathogens in rectal swabs versus stool, using paired flocked rectal swabs and whole stool collected from 129 children hospitalized with diarrhea in Tanzania. Swabs generally yielded a higher quantification cycle (Cq) (average 29.7, standard deviation 3.5 vs. 25.3 ± 2.9 from stool, P<0.001) but were still able to detect 80% of pathogens with a Cq < 30 in stool. Second, a simplified total nucleic acid (TNA) extraction procedure was compared to separate DNA and RNA extractions and showed 92% (318/344) sensitivity and 98% (951/968) specificity, with no difference in Cq value for the positive results (ΔCq(DNA+RNA-TNA) = -0.01 ± 1.17, P = 0.972, N = 318). Third, we devised a quantification scheme that adjusts pathogen quantity to the specimen’s extraction and amplification efficiency, and show that this better estimates the quantity of spiked specimens than the raw target Cq. In sum, these methods for enteropathogen quantification, stool sample collection, and nucleic acid extraction will be useful for laboratories studying enteric disease.