Miracle-dz/UniFAR-FTUs huggingface dataset:
Pathway-Specific Polygenic Scores Improve Cross-Ancestry Prediction of Psychosis and Clinical Outcomes

Psychotic disorders are debilitating conditions with disproportionately high public health burden. Genetic studies indicate high heritability, but current polygenic scores (PGS) account for only a fraction of variance in psychosis risk. PGS often show poor portability across ancestries, performing significantly worse in non-European populations. Pathway-specific PGS (pPGS), which restrict PGS to genomic locations within distinct biological units, could lead to increased mechanistic understanding of pathways that lead to risk and improve cross-ancestry prediction by reducing noise in genetic predictors. This study examined the predictive power of genome-wide PGS and nine pathway-specific pPGS in a unique Chinese-ancestry sample of deeply-phenotyped psychosis patients and non-psychiatric controls. We found strong evidence for the involvement of schizophrenia-associated risk variants within "nervous system development" (p=2.5e-4) and "regulation of neuron differentiation" pathways (p=3.0e-4) in predicting risk for psychosis. We also found the "ion channel complex" pPGS, with weights derived from GWAS of bipolar disorder, to be strongly associated with the number of inpatient psychiatry admissions a patient experiences (p=1.5e-3) and account for a majority of the signal in the overall bipolar PGS. Importantly, although the schizophrenia genome-wide PGS alone explained only 3.7% of the variance in liability to psychosis in this Chinese ancestry sample, the addition of the schizophrenia-weighted pPGS for "nervous system development" and "regulation of neuron differentiation" increased the variance explained to 6.9%, which is on-par with the predictive power of PGS in European ancestry samples. Thus, not only can pPGS provide greater insight into mechanisms underlying genetic risk for disease and clinical outcomes, but may also improve cross-ancestry risk prediction accuracy.
Single-cell evidence for plasmid addiction mediated by toxin–antitoxin systems

Toxin-antitoxin (TA) systems are small selfish genetic modules that increase vertical stability of their replicons. They have long been thought to stabilize plasmids by killing cells that fail to inherit a plasmid copy through a phenomenon called post-segregational killing (PSK) or addiction. While this model has been widely accepted, no direct observation of PSK was reported in the literature. Here, we devised a system that enables visualization of plasmid loss and PSK at the single-cell level using meganuclease-driven plasmid curing. Using the ccd system, we show that cells deprived of a ccd-encoding plasmid show hallmarks of DNA damage, i.e. filamentation and induction of the SOS response. Activation of ccd-triggered cell death in most plasmid-free segregants, although some intoxicated cells were able to resume growth, showing that PSK-induced damage can be repaired in a SOS-dependent manner. Damage induced by ccd activates resident lambdoid prophages, which potentiate the killing effect of ccd. The loss of a model plasmid containing TA systems encoding toxins presenting various molecular mechanisms induced different morphological changes, growth arrest and loss of viability. Our experimental setup enables further studies of TA-induced phenotypes and suggests that PSK is a general mechanism for plasmid stabilization by TA systems.
Mini-dose methotrexate combined with methylprednisolone as a first-line treatment for acute graft-versus-host disease: A phase 2 trial

Abstract Background and Objectives Acute graft-versus-host disease (aGvHD) remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). Methylprednisolone (MP; 1–2 mg/kg/day) remains the standard first-line therapy for aGvHD, although no response is detected in nearly one-half of the patients with aGvHD. This study aimed to investigate the feasibility of mini-dose methotrexate (MTX) combined with standard-dose MP as a front-line therapy for aGvHD. Materials and Methods A prospective Phase 2 clinical trial was performed to evaluate the safety and efficacy of 5 mg/m2 MTX combined with 1 mg/kg/day MP as the initial therapy in 31 patients with aGvHD. Moreover, the effects of MTX combined with MP were explored in a humanized xenogeneic murine model of aGvHD. Results The overall response and complete response rate at 7 days after the initial treatment were 100% and 83%, respectively. The overall response rate on day 28 was 87%. The complete response rates for aGvHD grades I, II, and III were 100% (6/6), 82% (18/22), and 66% (2/3), respectively. Grade 3 toxicities occurred in only three patients presenting with cytopenia. Importantly, MTX and MP demonstrated synergistic effects on ameliorating aGvHD in humanized xenogeneic murine model. Conclusion The current study suggests that mini-dose MTX combined with standard-dose MP could potentially become a novel first-line therapy for patients with aGvHD.
Endoscopic diagnosis and treatment of superficial non-ampullary duodenal epithelial tumors: A review

Abstract The surface of the small bowel mucosa is covered more than any other section of the digestive canal; however, the overall prevalence of small bowel tumors of the whole gastrointestinal tract is evidently low. Owing to the improvement in endoscopic techniques, the prevalence of small bowel tumors has increased across multiple countries, which is mainly due to an increase in duodenal tumors. Superficial non-ampullary duodenal epithelial tumors (SNADETs) are defined as tumors originating from the non-ampullary region in the duodenum that share similarities and discrepancies with their gastric and colorectal counterparts in the pathogenesis and clinicopathologic characteristics. To date, white light endoscopy (WLE) remains the cornerstone of endoscopic diagnosis for SNADETs. Besides, narrow-band imaging (NBI) techniques and magnifying endoscopy (ME) have been widely used in the clinic and endorsed by multiple guidelines and consensuses for SNADETs’ evaluation. Confocal laser endomicroscopy (CLE), endocytoscopy (ECS), and artificial intelligence (AI) are also up-and-coming methods, showing an exceptional value in the diagnosis of SNADETs. Similar to the endoscopic treatment for colorectal polyps, the choices for SNADETs mainly include cold snare polypectomy (CSP), endoscopic mucosal resection (EMR), endoscopic submucosal dissection (ESD), and laparoscopic endoscopic cooperative surgery (LECS). However, owing to the narrow lumen, rich vascularity, weak muscle layer, abundant Brunner’s gland, and the hardship of endoscope control, the duodenum ranks as one of the most dangerous operating areas in the digestive tract. Therefore, endoscopists must anticipate the difficulties in endoscopic maneuverability, remain aware of the increased risk of complications, and then select the appropriate treatment according to the advantages and disadvantages of each method.
Secondary Contact, Introgressive Hybridization, and Genome Stabilization in Sticklebacks

Advances in genomic studies have revealed that hybridization in nature is pervasive and raised questions about the dynamics of different genetic and evolutionary factors following the initial hybridization event. While recent research has proposed that the genomic outcomes of hybridization might be predictable to some extent, many uncertainties remain. With comprehensive whole-genome sequence data, we investigated the genetic introgression between two divergent lineages of nine-spined sticklebacks (Pungitius pungitius) in the Baltic Sea. We found that the intensity and direction of selection on the introgressed variation varied across different genomic elements: while functionally important regions had experienced reduced rates of introgression, promoter regions showed enrichment. Despite the general trend of negative selection, we identified specific genomic regions that were enriched for introgressed variants and within these regions, we detected footprints of selection, indicating adaptive introgression. We found the selection against the functional changes to be strongest in the vicinity of the secondary contact zone and weaken as a function of distance from the initial contact. Altogether, the results suggest that the stabilization of introgressed variation in the genomes is a complex, multi-stage process involving both negative and positive selection. In spite of the predominance of negative selection against introgressed variants, we also found evidence for adaptive introgression variants likely associated with adaptation to Baltic Sea environmental conditions.
More Is Better: Large Scale Partially-supervised Sentiment Classication

We describe a bootstrapping algorithm to learn from partially labeled data, and the results of an empirical study for using it to improve performance of sentiment classication using up to 15 million unlabeled Amazon product reviews. Our experiments cover semi-supervised learning, domain adaptation and weakly supervised learning. In some cases our methods were able to reduce test error by more than half using such large amount of data.
Dimensiones de la Calidad de los Servicios. Estudio de Caso: Sector Turismo de Ciudad Guayana, Venezuela

In the present study were identified by statistical methods multivariants the dimensions that determine the Service Quality of the Tourism Sector in Guayana City, Venezuela. To gather information designed a survey of 24 items according to the SERVQUAL Model. The survey was applied to 120 users of Tourism Sector in Guayana City, through a casual sampling where only determines the size of the sample, but the members are selected without any established criterion. After demonstration of the adequacy of the data, index KMO = 0.819, were identified dimensions of the Service Quality of tourist in the Guayana Region: (1) tourist service and ability to do it right the first time, (2) infrastructure and speed of process of a tour operator, (3) responsiveness of the tour operator (4) feel at home, (5) security during the time of lodging. These five dimensions explained 71% of the total variance. Moreover, the reliability analysis performed (Cronbach's alpha> 0.775 for all dimensions) shows the internal consistency of the scale used and statistical tests performed (significant at 5%) allowed determining the content validity of concept and approach of the survey.
Divided Industries in the Fight for Two US Free Trade Agreements

Variation in ﬁrm export performance suggests that industries may be internally divided over trade liberalization. This paper empirically examines the circumstances under which industries will feature both supporters and opponents of bilateral trade liberalization. Three conditions are emphasized: both countries must reduce tariﬀs or trade barriers; neither country can be overwhelmingly competitive; and, the product must be diﬀerentiated. Under these conditions, both trade partners will feature support for trade liberalization even in the same industry, and commercial rivals’ interests may align across borders. This theory is then tested on a new dataset of industry attitudes towards the US-Korea FTA and the Australia-US FTA. Patterns of intra-industry disagreement and bilateral support in the same industry are closely linked to the possibility of intra-industry trade, but not consistently explained by the extent of FDI or foreign sourcing of inputs. This paper therefore systematizes the circumstances under which the new, new trade theory’s predictions of divided industries should apply, and explores several testable implications of this approach to the politics of trade.
Physiological responses of marine organisms to environmental stresses

This document contains a synthesis of research carried out over the last five years under the auspices of the Marine Physiological Ecology Program (MPEP). It covers contributions of MPEP to basic scientific knowledge, to predictive capabilities for potential environmental problems and their impact, and to economically and environmentally sound solutions to environmental problems. A general overview of major findings is presented in Part I. The overview is followed by the project summaries and representative reprints submitted by the individual investigators. This document is intended for both general educational reading and for reference use by the scientist. Individual papers are processed separately for the data base.
POLA MUTASI EPIDERMAL GROWTH FACTOR RECEPTOR (EGFR) PADA PENDERITA ADENOKARSINOMA PARU DI RSUP SANGLAH DENPASAR TAHUN 2013-2018

Karsinoma paru merupakan jenis keganasan penyebab kematian pertama terkait kanker di dunia. Diperlukan suatu sarana diagnostik yang memiliki sensitifitas dan spesifisitas tinggi untuk mendeteksi awal lesi kanker paru guna mencegah berkembangnya lesi menjadi kanker stadium lanjut. Tujuan daripada penilitian ini untuk mengetahui data pola mutasi EGFR pada penderita adenokarsinoma paru di RSUP Sanglah Denpasar 2013-2018. Penelitian ini bersifat deskriptif retrospe`ktif dengan pendekatan cross-sectional menggunakan data sekunder pasien adenokarsinoma paru dengan pola mutasi EGFR yang didapat dari laporan pemeriksaan sitologi di Laboratorium Patologi Anatomi RSUP Sanglah Denpasar tahun 2013-2018 yang kemudian dianalisis secara deskriptif.Selama penelitian ini terkumpul sebanyak 71 kasus yang memenuhi kriteria inklusi dan eksklusi sehingga didapatkan hasil gambaran diagnosis sitologi yang paling banyak adalah adenokarsinoma paru (90,1%) dengan pola mutasi exon 19 (52,1%). Adenokarsinoma paru secara umum paling banyak terjadi pada kelompok usia 61-71 tahun (26,8%), jenis kelamin perempuan (53,5%). Kata kunci: Adenokarsinoma paru, EGFR, Mutasi
About the Cost of Central Privacy in Density Estimation

We study non-parametric density estimation for densities in Lipschitz and Sobolev spaces, and under central privacy. In particular, we investigate regimes where the privacy budget is not supposed to be constant. We consider the classical definition of central differential privacy, but also the more recent notion of central concentrated differential privacy. We recover the result of Barber \&Duchi (2014) stating that histogram estimators are optimal against Lipschitz distributions for the L2 risk, and under regular differential privacy, and we extend it to other norms and notions of privacy. Then, we investigate higher degrees of smoothness, drawing two conclusions: First, and contrary to what happens with constant privacy budget (Wasserman \&Zhou, 2010), there are regimes where imposing privacy degrades the regular minimax risk of estimation on Sobolev densities. Second, so-called projection estimators are near-optimal against the same classes of densities in this new setup with pure differential privacy, but contrary to the constant privacy budget case, it comes at the cost of relaxation. With zero concentrated differential privacy, there is no need for relaxation, and we prove that the estimation is optimal.
Developing a Concept of Operations for Joint All-Domain Command and Control with an Embedded Role for Artificial Intelligence Applications

efore one can leverage artificial intelligence (AI) and machine learning (ML) for multi-domain operations (MDOs) as part of Joint All-Domain Command and Control (JADC2), one must do the grunt work of laying an “information foundation. ” Laying this foundation—in which data are tagged, securely stored and transported
Nrc Publications Archive (nparc) Archives Des Publications Du Cnrc (nparc) Virtual Reality High Dimensional Objective Spaces for Multi- Objective Optimization: an Improved Representation Virtual Reality High Dimensional Objective Spaces for Multi-objective Optimization: an Improved Representation * 

L'accès à ce site Web et l'utilisation de son contenu sont assujettis aux conditions présentées dans le site Access and use of this website and the material on it are subject to the Terms and Conditions set forth at Permission is granted to quote short excerpts and to reproduce figures and tables from this report, provided that the source of such material is fully acknowledged. Abstract— This paper presents an approach for constructing improved visual representations of high dimensional objective spaces using virtual reality. These spaces arise from the solution of multi-objective optimization problems with more than 3 objective functions which lead to high dimensional Pareto fronts. The 3-D representations of m-dimensional Pareto fronts, or their approximations, are constructed via similarity structure mappings between the original objective spaces and the 3-D space. Alpha shapes are introduced for the representation and compared with previous approaches based on convex hulls. In addition, the mappings minimizing a measure of the amount of dissimilarity loss are obtained via genetic programming. This approach is preliminarily investigated using both theoretically derived high dimensional Pareto fronts for a test problem (DTLZ2) and practically obtained objective spaces for the 4 dimensional knapsack problem via multi-objective evolutionary algorithms like HLGA, NSGA, and VEGA. The improved representation captures more accurately the real nature of the m-dimensional objective spaces and the quality of the mappings obtained with genetic programming is equivalent to those computed with classical optimization algorithms.
Imageodesy: A Tool for Mapping Subpixel Terrain Displacements in Satellite Imagery

Visual comparison of images acquired by SPOT satellites before and after the Landers earthquake clearly depict spatial differences related to fault displacements. These can be seen as motion when presented in a rapidly alternating display (EOS, v. 73, no. 43, p. 364) or as relief when presented as a stereo pair, despite the 6 meter maximum size of the displacements and the 10 meter pixel size of the SPOT imagery. Quantification of the displacements is made through subpixel image matching by correlation analysis, applied at each point on a fine grid. Resolution of the displacement measurements is limited to about 1/20 pixel by systematic factors (e.g. one-byte quantization), but further by the characteristics of the terrain (e.g. radiometric variability related to the distinctiveness of terrain patterns, such as topographic shading), A consequence of the later limitation is that imageodesy works best in areas of rugged, eroded bedrock. The method is thus complementary with radar interferometry, which is more precise, but generally works best in low-rel ief terrains wi th smal l d isplacement gradients. Advantageously, imageodesy measures both geographic dimensions, rather than interferometry ’s one-dimensional differences in slant range.
Quality or Control: Why Not Both? Rethinking 3DMM-Conditional Face Generation

We present a novel conditional model derived from a mathematical framework for 3DMM-conditioned face generation. Our model shows strong performance in both quality and controllability, effectively eliminating the trade-off between these two factors and thereby making control “tax free”. Furthermore, our mathematical framework can be applied to future explorations in conditional generation, allowing future investigators to analyze other parametric models in a rigorous manner
FINANCIAL INCENTIVES AND STUDENT ACHIEVEMENT: EVIDENCE FROM RANDOMIZED TRIALS

This article describes a series of school-based field experiments in over 200 urban schools across three cities designed to better understand the impact of financial incentives on student achievement. In Dallas, students were paid to read books. In New York, students were rewarded for performance on interim assessments. InChicago, students werepaidforclassroomgrades. I estimatethat the impact of financial incentives on student achievement is statistically 0, in each city. Due to a lack of power, however, I cannot rule out the possibility of effect sizes that wouldhave positive returns on investment. The only statistically significant effect is on English-speaking students in Dallas. The article concludes with a speculative discussion of what might account for intercity differences in estimatedtreatment effects. JEL Codes: I20, I21, I24, J15.
Biodiversity of Coastal Areas of Valsad, South Gujarat

: The present study documents the diversity and quantitative assessment of fringing mangroves in these nine different estuarine regions of Valsad district of South Gujarat. The most outstanding feature of our study is that we observed four species of mangrove and sixspecies of mangrove associate namely Avicennia marina, Sonneratia apetala, Salvadora persica, Acanthus illicifolius, Ipomoea pes caprae, Sesuviarum portulacastrum, Clerodendrum inerme, Derris heterophylla, Cressa cretica,and Aeluropus lagopoides.The dominant mangroves in these areas are Avicennia species and Acanthus illicifolius.Earlier works included Rhizophora mucronata which was not found during this study in any of the nine spots of mangrove forests.We have used the Jaccardian similarity index to analysis the floral diversity of our mangrove sites. Our studyhighlighted the relation between water quality parameters, environmental and anthropogenic stress and speciescomposition and structures of mangrove.
THROMBOPHILIA:ITS CAUSES AND A ROUGH ESTIMATE OF ITS PREVALENCE

Idiopathic venous thrombosis and embolism have gained widespread interest since the discovery that, deficiencies of antithrombin III, protein C, and protein S are associated with familial venous thrombophilia. The purpose of our study was to obtain an estimate of the prevalence of this syndrome and to establish the etiology in as many cases as possible. We collaborated with specialists from 37 Dutch hospitals, covering about 10% of the Dutch population. A history as well as blood samples were obtained from 113 unrelated cases with familial thrombophilia and from 90 isolated cases. Assuming that each proband in a family with thrombophilia has an average of four affected relatives, a rough estimate of the prevalence of familial thrombophilia in The Netherlands is 40 cases per 100.000. The prevalence of non-familial thrombophilia is probably lower. In 35 out of the 113 familial cases we established a diagnosis of hereditary antithrombin III deficiency (n=5), protein C deficiency (type I: n=9; type II: n=4), protein S deficiency (n=15) and dysfibrinogenemia (n=2). In 36 cases we found no abnormality at all and in the remaining 42 cases abnormalities were found in one or more of the following: heparin cofactor II, factor V, factor VII, factor VIII, von Willebrand factor, plasminogen, tissue plasminogen activator, plasminogen activator inhibitor, alpha 2 antiplasmin and histidine rich glycoprotein. In most of these cases, however, the hereditary nature of the abnormalities could not be demonstrated and the causal relationships remain to be established. In the 90 isolated cases, we diagnosed hereditary deficiencies of anti thrombin III, protein C and protein S each in one case and a lupus anticoagulant in two cases. In 54 cases no abnormality was found and in the remaining 31 cases various abnormalities were found in one or more of the proteins mentioned above. We conclude that the syndrome of thrombophilia is not rare but its true prevalence needs to be established by more rigorous means. An etiological diagnosis can be made with confidence in only one third of the familial cases and in less than 10 percent of the isolated cases.