Miracle-dz/UniFAR-FTUs huggingface dataset:
Duration of Untreated Psychosis and Duration of Untreated Illness: New Vistas

ABSTRACT The duration of untreated illness (DUI), defined as the interval between the onset of a psychiatric disorder and the administration of the first pharmacological treatment, has been increasingly investigated in the last decade as a predictor of outcome across different psychiatric conditions including schizophrenia and psychotic disorders (duration of untreated psychosis), and mood and anxiety disorders. Converging evidence indicates that a prolonged DUI may be viewed as a negative prognostic factor in schizophrenia and increasing data point toward a similar conclusion in mood and anxiety disorders. Through a Medline search, the present article highlights the role of the DUI in this group of psychiatric disorders, focusing on social and psychopathological determinants of the DUI, as well as the clinical consequences related to a longer DUI in terms of outcome. Hypotheses on neurobiological mechanisms underpinning outcome differences in relation to a prolonged DUI are provided and methodological limitations related to the assessment of the DUI in published studies and clinical practice discussed. Finally, given that DUI is supposed to be a potentially modifiable prognostic factor, intervention programs aimed to reduce this variable are briefly considered and discussed.
Public Insurance Eligibility and Enrollment for Special Health Care Needs Children

We estimated the proportion of children with special health care needs (CSHCN) eligible for Medicaid and the State Children's Health Insurance Program (SCHIP) using data from the 2000 and 2001 National Health Interview Survey (NHIS) and an algorithm to determine likely eligibility We find that CSHCN were more likely to be eligible compared with other children (50 versus 43 percent), and that they were eligible through different program mechanisms. Relatively few faced waiting periods and premiums to participate in public programs. Participation rates were higher for CSHCN eligible through Medicaid Program rules prior to the SCHIP expansions, compared with those newly eligible after 1997. CSHCN had higher rates of participation than children without special needs (CWOSN), across all eligibility categories.
Comprehension of self‐report evidence‐based measures of anxiety

Background: Given their applicability in diverse settings and for a wide range of purposes, the generalizability of self‐report symptom measures is particularly important. An understudied factor in the development and validation of self‐report measures is the degree to which they are difficult to comprehend. This study evaluated the difficulty of self‐report measures of anxiety with respect to several domains, including formatting, length, and linguistic problems. Methods: Ninety‐two evidence based measures of anxiety were evaluated for comprehension level. Results: The majority of anxiety measures included challenging elements of formatting, linguistic ability, and readability. Measures of obsessive–compulsive disorder were associated with the highest level of comprehension (i.e., greatest difficulty). Conclusions: The validity of self‐report measures relies on the ability of respondents to understand the instructions and measure items. Factors related to the comprehension of self‐report measures should be included among the basic psychometric properties in measure development and validation. Future research on the development of self‐report measures that can be more broadly applicable across levels of education and literacy are of particular importance to research, clinical, and public health agendas. Depression and Anxiety, 2011. © 2011 Wiley‐Liss, Inc.
Genetics of melanocytic nevi

Melanocytic nevi are a benign clonal proliferation of cells expressing the melanocytic phenotype, with heterogeneous clinical and molecular characteristics. In this review, we discuss the genetics of nevi by salient nevi subtypes: congenital melanocytic nevi, acquired melanocytic nevi, blue nevi, and Spitz nevi. While the molecular etiology of nevi has been less thoroughly studied than melanoma, it is clear that nevi and melanoma share common driver mutations. Acquired melanocytic nevi harbor oncogenic mutations in BRAF, which is the predominant oncogene associated with melanoma. Congenital melanocytic nevi and blue nevi frequently harbor NRAS mutations and GNAQ mutations, respectively, while Spitz and atypical Spitz tumors often exhibit HRAS and kinase rearrangements. These initial ‘driver’ mutations are thought to trigger the establishment of benign nevi. After this initial phase of the cell proliferation, a senescence program is executed, causing termination of nevi growth. Only upon the emergence of additional tumorigenic alterations, which may provide an escape from oncogene‐induced senescence, can malignant progression occur. Here, we review the current literature on the pathobiology and genetics of nevi in the hope that additional studies of nevi promise to inform our understanding of the transition from benign neoplasm to malignancy.
Prospective evaluation of metabolic syndrome and its components among long‐term liver recipients

Survival after liver transplantation (LTx) has increased. Metabolic syndrome (MS) is widely reported in patients in the early years after LTx; few studies have researched this condition in relatively long‐term liver recipients. To describe, prospectively, the prevalence of MS, its components and its associated factors in relatively long‐term liver recipients.
Performance of Birmingham Vasculitis Activity Score and disease extent index in childhood vasculitides.

OBJECTIVES To evaluate the performance of the Birmingham Vasculitis Activity Score (BVAS) v3 and the Disease Extent Index (DEI) for the assessment of disease activity in 4 primary childhood (c-) systemic vasculitides. METHODS Patients fulfilling the EULAR/PRINTO/PRES (Ankara) c-vasculitis classification criteria for Henoch-Schönlein purpura (HSP), childhood (c) polyarteritis nodosa (c-PAN), c-Wegener's granulomatosis (c-WG) and c-Takayasu arteritis (c-TA) with disease duration at the time of diagnosis ≤3 months were extracted from the PRINTO database. The performance of the BVAS and DEI were examined by assessing convergent validity, the pattern of disease involvement, and responsiveness. We also evaluated alternative unweighted scoring methods for both tools. RESULTS The analysis set included 796 patients with 669 HSP, 80 c-PAN, 25 c-WG and 22 c-TA. The median age at diagnosis was 6.9 years (6.6-12) and median delay in making the diagnosis from the onset of signs/symptoms was 0.01 (0.003-0.027) years. A strong correlation was found between the BVAS and DEI (rs=0.78) while correlation with the physician global assessment was moderate (rs=0.48) with BVAS and poor with DEI (rs=0.25). Both the BVAS and DEI sub-scores and total scores were able to descrive the disease involvement in the 4 childhood vasculitides. Responsiveness was large (>1.5) for both tools. The performance characteristics of the BVAS and DEI with the unweighted methods were comparable. CONCLUSIONS This study demonstrates that both the BVAS and DEI are valid tools for the assessment of the level of disease activity in a large cohort of childhood acute and chronic vasculitides.
Molecular docking based virtual screening of natural compounds as potential BACE1 inhibitors: 3D QSAR pharmacophore mapping and molecular dynamics analysis

Beta-site APP cleaving enzyme1 (BACE1) catalyzes the rate determining step in the generation of Aβ peptide and is widely considered as a potential therapeutic drug target for Alzheimer’s disease (AD). Active site of BACE1 contains catalytic aspartic (Asp) dyad and flap. Asp dyad cleaves the substrate amyloid precursor protein with the help of flap. Currently, there are no marketed drugs available against BACE1 and existing inhibitors are mostly pseudopeptide or synthetic derivatives. There is a need to search for a potent inhibitor with natural scaffold interacting with flap and Asp dyad. This study screens the natural database InterBioScreen, followed by three-dimensional (3D) QSAR pharmacophore modeling, mapping, in silico ADME/T predictions to find the potential BACE1 inhibitors. Further, molecular dynamics of selected inhibitors were performed to observe the dynamic structure of protein after ligand binding. All conformations and the residues of binding region were stable but the flap adopted a closed conformation after binding with the ligand. Bond oligosaccharide interacted with the flap as well as catalytic dyad via hydrogen bond throughout the simulation. This led to stabilize the flap in closed conformation and restricted the entry of substrate. Carbohydrates have been earlier used in the treatment of AD because of their low toxicity, high efficiency, good biocompatibility, and easy permeability through the blood–brain barrier. Our finding will be helpful in identify the potential leads to design novel BACE1 inhibitors for AD therapy.
Statistical Latent Space Approach for Mixed Data Modelling and Applications

The analysis of mixed data has been raising challenges in statistics and machine learning. One of two most prominent challenges is to develop new statistical techniques and methodologies to effectively handle mixed data by making the data less heterogeneous with minimum loss of information. The other challenge is that such methods must be able to apply in large-scale tasks when dealing with huge amount of mixed data. To tackle these challenges, we introduce parameter sharing and balancing extensions to our recent model, the mixed-variate restricted Boltzmann machine (MV.RBM) which can transform heterogeneous data into homogeneous representation. We also integrate structured sparsity and distance metric learning into RBM-based models. Our proposed methods are applied in various applications including latent patient profile modelling in medical data analysis and representation learning for image retrieval. The experimental results demonstrate the models perform better than baseline methods in medical data and outperform state-of-the-art rivals in image dataset.
A 950 MHz rectifier circuit for sensor networks with 10 m-distance

A high-sensitivity rectifier is fabricated in a 0.3 /spl mu/m CMOS technology. The circuit can rectify an RF signal less than the NMOS threshold voltage by using a bias voltage between the gate and the drain terminals of a transistor. The IC achieves a 950 MHz signal rectification over -14 dBm corresponding to 10 m-distance communication and recharges a 1.2 V secondary battery.
Proteomic interrogation of HSP90 and insights for medical research

ABSTRACT Introduction: Heat shock protein 90 (HSP90) regulates protein homeostasis in eukaryotes. As a ‘professional interactor’, HSP90 binds to and chaperones many proteins and has both housekeeping and disease-related functions but its regulation remains in part elusive. HSP90 complexes are a target for therapy, notably against cancer, and several inhibitors are currently in clinical trials. Proteomic studies have revealed the vast interaction network of HSP90 and, in doing so, the extent of cellular processes the chaperone takes part in, especially in yeast and human cells. Furthermore, small-molecule inhibitors were used to probe the global impact of its inhibition on the proteome. Areas covered: We review here recent HSP90-related interactomics and total proteome studies and their relevance for research on cancer, neurodegenerative and pathogen diseases. Expert commentary: Proteomics experiments are our best chance to identify the context-dependent global proteome of HSP90 and thus uncover and understand its disease-specific biology. However, understanding the complexity of HSP90 will require multiple complementary, quantitative approaches and novel bioinformatics to translate interactions into ordered functional networks and pathways. Developing therapies will necessitate more knowledge on HSP90 complexes and networks with disease relevance and on total proteome changes induced by their perturbation. Most work has been done in cancer, thus a lot remains to be done in the context of other diseases.
Transcallosal transfer of information and functional asymmetry of the human brain

The corpus callosum is the largest commissure in the brain and acts as a “bridge” of nerve fibres connecting the two cerebral hemispheres. It plays a crucial role in interhemispheric integration and is responsible for normal communication and cooperation between the two hemispheres. Evolutionary pressures guiding brain size are accompanied by reduced interhemispheric and enhanced intrahemispheric connectivity. Some lines of evidence suggest that the speed of transcallosal conduction is limited in large brains (e.g., in humans), thus favouring intrahemispheric processing and brain lateralisation. Patterns of directional symmetry/asymmetry of transcallosal transfer time may be related to the degree of brain lateralisation. Neural network modelling and electrophysiological studies on interhemispheric transmission provide data supporting this supposition.
Transition Times for Manipulation Tasks in Hybrid Interfaces

Previous work has shown that uninstrumented in-air interaction is slower and not as precise for pointing tasks compared to the mouse. Yet, there are interaction scenarios where it is preferable or advantageous to use in-air input. Therefore, we examine a three-device hybrid setup involving the mouse, keyboard, and a Leap Motion. We performed a user study to quantify the costs associated with transitioning between these interaction devices and also for performing simple 2D manipulation tasks using the mouse and Leap Motion. We discovered that transitioning to and from the Leap Motion takes on average 0.87 seconds longer than transitions between the mouse and keyboard.
Molecular characteristics and predictors of survival in patients with malignant neuroendocrine tumors

To better understand the molecular pathogenesis of neuroendocrine tumors (NET), we investigated the molecular and clinical characteristics of malignant poorly differentiated colorectal NET and compared these findings with sporadic CRC and well‐differentiated benign and malignant fore‐/midgut NET. Tumors were analyzed and correlated for microsatellite instability (MSI) and the CpG island methylator phenotype (CIMP). NET were scored for proliferation using Ki‐67. A total of 34 malignant poorly differentiated colorectal NET, 38 well‐differentiated benign and malignant fore‐/midgut‐NET and 150 sporadic colorectal cancers (CRC) with known MSI status were investigated. Among the sporadic CRC, CIMP was significantly correlated with MSI‐high (MSI‐H) (p < 0.001). Of the 34 colorectal NET, 0/1 of the MSI‐H, 3/5 (60%) of the MSI‐L and 13/19 (68%) of the MSS tumors were CIMP+ (p = 0.17). Of the fore‐/midgut‐NET, none was MSI‐H. 20/34 (59%) colorectal NET vs. 11/38 (29%) fore‐/midgut‐NET were CIMP+ (p = 0.01). The Ki‐67 index was significantly higher in poorly differentiated colorectal NET compared to the less malignant fore‐/midgut‐NET (p < 0.0001). Besides the location in the colon, Ki‐67 predicted poor outcome in NET (p < 0.0001). CIMP status did not affect survival. In NET, p16 methylation predicted a poor outcome (p = 0.0004). We conclude that molecular pathogenesis in sporadic CRC and poorly differentiated colorectal NET is different despite some similarities. Main differences between malignant well‐differentiated and poorly differentiated NET are the Ki‐67 proliferation rate and differential methylation in tumor‐associated genes. Predictors of a poor outcome in patients with NET are poor differentiation, a high Ki‐67 index and p16 methylation. © 2008 Wiley‐Liss, Inc.
BRCA, the Oviduct, and the Space and Time Continuum of Pelvic Serous Carcinogenesis

Abstract In recent years, the distal oviduct has emerged as a critical organ in the pathogenesis of pelvic (“ovarian”) serous cancer. Studies have uncovered early serous tubal intraepithelial carcinomas in approximately 8% of asymptomatic women with germline BRCA1 or BRCA2 mutations, linked serous tubal intraepithelial carcinomas to one half of serous cancers irrespective of genetic risk, and described a precursor lesion in the distal tube with early alterations in p53 function (the p53 signature). This work has established a linear serous carcinogenic sequence in a single focus within the fimbria. In addition, a more broadly distributed array of gene alterations has been discovered in the oviduct, manifested as secretory (or stem) cell outgrowths that are increased in frequency as a function of older age and serous cancer status. These “surrogate precursors” expand the existing model beyond the fimbria, implying that the molecular events leading to serous cancer are distributed over space and time. The potential promise of these discoveries is “targeted prevention” by discovering of multiple pathways integral to carcinogenesis and successfully preventing malignancy by interrupting one or a few of these pathways.
Exposure system to study hypotheses of ELF and RF electromagnetic field interactions of mobile phones with the central nervous system

A novel exposure system for double‐blind human electromagnetic provocation studies has been developed that satisfies the precision, control of fields and potential artifacts, and provides the flexibility to investigate the response of hypotheses‐driven electromagnetic field exposure schemes on brain function, ranging from extremely low frequency (ELF) to radio frequency (RF) fields. The system can provide the same exposure of the lateral cerebral cortex at two different RF frequencies (900 and 2140 MHz) but with different exposure levels at subcortical structures, and also allows uniform ELF magnetic field exposure of the brain. The RF modulation and ELF signal are obtained by a freely programmable arbitrary signal generator allowing a wide range of worst‐case exposure scenarios to be simulated, including those caused by wireless devices. The maximum achievable RF exposure is larger than 60 W/kg peak spatial specific absorption rate averaged over 10 g of tissue. The maximum ELF magnetic field exposure of the brain is 800 A/m at 50 Hz with a deviation from uniformity of 8% (SD). Bioelectromagnetics 33:527–533, 2012. © 2012 Wiley Periodicals, Inc.
Elements required for transcription initiation of the human U2 snRNA gene coincide with elements required for snRNA 3′ end formation.

Formation of the human U1 and U2 snRNA 3′ ends requires both a conserved sequence, the 3′ box, located downstream of the snRNA termini and sequences within the snRNA promoter regions. Indeed, replacement of the U1 snRNA promoter by mRNA promoters inhibits U1 3′ end formation. We have now mutated the 5′ flanking region of the human U2 gene and assayed the effects on initiation of transcription and 3′ end formation. The 5′ flanking region of the U2 gene contains two major promoter elements, a previously characterized distal element that enhances the efficiency of transcription and a proximal element, which our analysis localizes between positions −59 and −43 in a segment conserved in vertebrate snRNA genes. The 5′ flanking region does not contain an element required solely for 3′ end formation. However, when enhancer elements from an mRNA‐encoding gene are introduced into a U2 promoter lacking its distal element, 3′ end formation is inhibited. Together, these results suggest that the U2 promoter elements themselves are involved in 3′ end formation, presumably by directing the formation of a unique transcription complex which is compatible with 3′ end formation at the 3′ box. Alteration of the composition of this transcription complex results in increased read‐through at the 3′ box.
Advances in imaging of cardiopulmonary involvement in sarcoidosis

Purpose of review To highlight recent advances of imaging modalities with focus on interstitial lung disease, pulmonary vascular disease and cardiac involvement of sarcoidosis. The contribution of key imaging features to the assessment of disease activity and their impact in the prognostic evaluation and management of sarcoidosis are also described. Recent findings Imaging plays a central role in the management of patients with sarcoidosis, particularly in the diagnosis and monitoring of disease activity. The correlation of the severity and extent of organ involvement with inflammatory activity helps guide the clinician in determining the optimal treatment strategy for the patient and may also provide prognostic information. The emergence of cardiac MRI and fluoro-deoxyglucose positron emission tomography has enabled an improved understanding of the pathophysiology of sarcoidosis, particularly in relation to cardiac involvement and pulmonary vascular manifestations. Summary In many patients with pulmonary sarcoidosis, a confident diagnosis can be made based on clinical and imaging features, without the need for histological sampling. In cardiac sarcoidosis, advanced imaging modalities have an increasing role in the identification of active disease, risk stratification and optimal management.
Preventing behavior problems among elementary schoolchildren: impact of a universal school-based program in China.

BACKGROUND To evaluate the effect on problem behaviors of a universal school-based prevention curriculum of third grade students. METHODS Six regular classes in 1 elementary school were randomly assigned to an intervention (n = 208) or control (n = 209) group. A 13-session program was offered to students in the intervention group. The Achenbach Child Behavior Checklist (CBCL), parent report, was used to assess problem behaviors at baseline, at the conclusion of the curriculum, and again at 6-month follow up. RESULTS The unadjusted mean estimates of behavioral problems were significantly lower in the intervention group posttest (at the conclusion of the curriculum), -3.53 (95% confidence interval [CI] = -6.59 to -0.48; p = .023) and at the 6-month follow up, -5.22 (95% CI: -8.27 to -2.16; p = .001). After adjusting for potential confounders, gender (female), father's educational status (high school), family relationships (good and average), and child's age in months, intervention groups (intervention posttest and intervention after 6-month follow up) showed significantly lower total behavioral scores. CONCLUSIONS A universal school-based prevention program for Chinese elementary school-age children resulted in a significant positive change in behavioral problems. This is an important finding in the context of the Chinese 1-child policy that places great value on the achievement of the child.
Predicting amino acid adequacy of diets fed to Holstein steers.

The Cornell Net Carbohydrate and Protein System (CNCPS) and NRC (1985) models were evaluated for accuracy in predicting metabolizable protein (MP) and essential amino acid (EAA) allowable ADG, using chemical body and feed composition data from feeding trials with Holstein steers. Nine Holstein steers (113 to 200 kg) were slaughtered and determined to have the following whole-body essential amino acid composition of (grams/100 grams of protein): arginine, 5.94; histidine, 2.07; isoleucine, 2.28; leucine, 5.72; lysine, 5.81; methionine, 1.99; phenylalanine, 3.04; threonine, 3.52; tryptophan, . 57; and valine, 3.32. The NRC and CNCPS were then tested against data from 25 feeding periods, each representing the 56-d growth of 10 Holstein steers (mean BW of 162 kg), to determine their ability to predict the gain allowed by the supply of MP and the first-limiting EAA. The NRC (1985) system accounted for 46% of the variation in MP allowable gain, with an average bias of -30%. The CNCPS accounted for 87 and 73% of the variation in MP and EAA allowable gain, with a bias of 8 and 5%, respectively. The bias was reduced to 3% (R2 of .82) when ADG was predicted by the factor (ME, MP, or EAA) first-limiting ADG.