Miracle-dz/UniFAR-FTUs huggingface dataset:
Anti-CD105 Antibody Eliminates Tumor Microenvironment Cells and Enhances Anti-GD2 Antibody Immunotherapy of Neuroblastoma with Activated Natural Killer Cells

Purpose: We determined whether elimination of CD105+ cells in the tumor microenvironment (TME) with anti-CD105 antibodies enhanced anti-disialoganglioside (GD2) antibody dinutuximab therapy of neuroblastoma when combined with activated natural killer (aNK) cells. Experimental Design: The effect of MSCs and monocytes on antibody-dependent cellular cytotoxicity (ADCC) mediated by dinutuximab with aNK cells against neuroblastoma cells was determined in vitro. ADCC with anti-CD105 mAb TRC105 and aNK cells against MSCs, monocytes, and endothelial cells, which express CD105, was evaluated. Anti-neuroblastoma activity in immunodeficient NSG mice of dinutuximab with aNK cells without or with anti-CD105 mAbs was determined using neuroblastoma cell lines and a patient-derived xenograft. Results: ADCC mediated by dinutuximab with aNK cells against neuroblastoma cells in vitro was suppressed by addition of MSCs and monocytes, and dinutuximab with aNK cells was less effective against neuroblastomas formed with coinjected MSCs and monocytes in NSG mice than against those formed by tumor cells alone. Anti-CD105 antibody TRC105 with aNK cells mediated ADCC against MSCs, monocytes, and endothelial cells. Neuroblastomas formed in NSG mice by two neuroblastoma cell lines or a patient-derived xenograft coinjected with MSCs and monocytes were most effectively treated with dinutuximab and aNK cells when anti-human (TRC105) and anti-mouse (M1043) CD105 antibodies were added, which depleted human MSCs and murine endothelial cells and macrophages from the TME. Conclusions: Immunotherapy of neuroblastoma with anti-GD2 antibody dinutuximab and aNK cells is suppressed by CD105+ cells in the TME, but suppression is overcome by adding anti-CD105 antibodies to eliminate CD105+ cells.
ResPRE: high-accuracy protein contact prediction by coupling precision matrix with deep residual neural networks

MOTIVATION Contact-map of a protein sequence dictates the global topology of structural fold. Accurate prediction of the contact-map is thus essential to protein 3D structure prediction, which is particularly useful for the protein sequences that do not have close homology templates in the PDB. RESULTS We developed a new method, ResPRE, to predict residue-level protein contacts using inverse covariance matrix (or precision matrix) of multiple sequence alignments (MSAs) through deep residual convolutional neural network training. The approach was tested on a set of 158 non-homologous proteins collected from the CASP experiments and achieved an average accuracy of 50.6% in the top-L long-range contact prediction with L being the sequence length, which is 11.7% higher than the best of other state-of-the-art approaches ranging from coevolution coupling analysis to deep neural network training. Detailed data analyses show that the major advantage of ResPRE lies at the utilization of precision matrix that helps rule out transitional noises of contact-maps compared to the previously used covariance matrix. Meanwhile, the residual network with parallel shortcut layer connections increases the learning ability of deep neural network training. It was also found that appropriate collection of MSAs can further improve the accuracy of final contact-map predictions. The standalone package and online server of ResPRE are made freely available, which should bring important impact on protein structure and function modeling studies in particular for the distant- and non-homology protein targets. AVAILABILITY https://zhanglab.ccmb. med.umich. edu/ResPRE and https://github.com/leeyang/ResPRE. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.
Methodological Quality and Reporting of Generalized Linear Mixed Models in Clinical Medicine (2000–2012): A Systematic Review

Background Modeling count and binary data collected in hierarchical designs have increased the use of Generalized Linear Mixed Models (GLMMs) in medicine. This article presents a systematic review of the application and quality of results and information reported from GLMMs in the field of clinical medicine. Methods A search using the Web of Science database was performed for published original articles in medical journals from 2000 to 2012. The search strategy included the topic “generalized linear mixed models”,“hierarchical generalized linear models”, “multilevel generalized linear model” and as a research domain we refined by science technology. Papers reporting methodological considerations without application, and those that were not involved in clinical medicine or written in English were excluded. Results A total of 443 articles were detected, with an increase over time in the number of articles. In total, 108 articles fit the inclusion criteria. Of these, 54.6% were declared to be longitudinal studies, whereas 58.3% and 26.9% were defined as repeated measurements and multilevel design, respectively. Twenty-two articles belonged to environmental and occupational public health, 10 articles to clinical neurology, 8 to oncology, and 7 to infectious diseases and pediatrics. The distribution of the response variable was reported in 88% of the articles, predominantly Binomial (n = 64) or Poisson (n = 22). Most of the useful information about GLMMs was not reported in most cases. Variance estimates of random effects were described in only 8 articles (9.2%). The model validation, the method of covariate selection and the method of goodness of fit were only reported in 8.0%, 36.8% and 14.9% of the articles, respectively. Conclusions During recent years, the use of GLMMs in medical literature has increased to take into account the correlation of data when modeling qualitative data or counts. According to the current recommendations, the quality of reporting has room for improvement regarding the characteristics of the analysis, estimation method, validation, and selection of the model.
Phylogenetic Analysis of Polyomavirus Simian Virus 40 from Monkeys and Humans Reveals Genetic Variation

ABSTRACT A phylogenetic analysis of 14 complete simian virus 40 (SV40) genomes was conducted in order to determine strain relatedness and the extent of genetic variation. This analysis included infectious isolates recovered between 1960 and 1999 from primary cultures of monkey kidney cells, from contaminated poliovaccines and an adenovirus seed stock, from human malignancies, and from transformed human cells. Maximum-parsimony and distance methods revealed distinct SV40 clades. However, no clear patterns of association between genotype and viral source were apparent. One clade (clade A) is derived from strain 776, the reference strain of SV40. Clade B contains isolates from poliovaccines (strains 777 and Baylor), from monkeys (strains N128, Rh911, and K661), and from human tumors (strains SVCPC and SVMEN). Thus, adaptation is not essential for SV40 survival in humans. The C terminus of the T-antigen (T-ag-C) gene contains the highest proportion of variable sites in the SV40 genome. An analysis based on just the T-ag-C region was highly congruent with the whole-genome analysis; hence, sequencing of just this one region is useful in strain identification. Analysis of an additional 16 strains for which only the T-ag-C gene was sequenced indicated that further SV40 genetic diversity is likely, resulting in a provisional clade (clade C) that currently contains strains associated with human tumors and human strain PML-1. Four other polymorphic regions in the genome were also identified. If these regions were analyzed in conjunction with the T-ag-C region, most of the phylogenetic signal could be captured without complete genome sequencing. This report represents the first whole-genome approach to establishing phylogenetic relatedness among different strains of SV40. It will be important in the future to develop a more complete catalog of SV40 variation in its natural monkey host, to determine if SV40 strains from different clades vary in biological or pathogenic properties, and to identify which SV40 strains are transmissible among humans.
Prevalence and correlates of autism spectrum disorder in Qatar: a national study

Background Few epidemiological data on autism spectrum disorders (ASD) exist for Arabic countries. We conducted the first survey of ASD in Qatar, a population with high consanguinity level. Methods This cross‐sectional survey was conducted from 2015 to 2018 in Qatar school‐age children (N = 176,960) from national and immigrant families. Children diagnosed with ASD were identified through medical centers and special needs schools. Records were abstracted and supplemented by parental interviews. Additionally, children attending 93 schools were screened; ASD case status was confirmed in random samples of screen‐positive and screen‐negative children. Prevalence was estimated after taking into account different sampling fractions and participation rates at each survey phase. Results One thousand three hundred and ninety‐three children already diagnosed with ASD were identified. Among 9,074 school survey participants, 760 screen‐negative children and 163 screen‐positive children were evaluated; 17 were confirmed to have ASD including five children newly diagnosed. Prevalence was 1.14% (95% CI: 0.89–1.46) among 6‐ to 11‐year‐olds. ASD was reported in full siblings/extended relatives in 5.9% (95% CI: 0.042–0.080)/11.8% (95% CI: 0.095–0.146) families. First‐degree consanguinity in Qatari cases (45%) was comparable to known population levels. Among 844 ASD cases (mean age: 7.2 years; 81% male), most children experienced language delay (words: 75.1%; phrase speech: 91.4%), and 19.4% reported developmental regression. At the time of the survey, persisting deficits in expressive language (19.4%) and peer interactions (14.0%) were reported in conjunction with behavioral problems (ADHD: 30.2%; anxiety: 11.0%). In multivariate logistic regression, ASD severity was associated with parental consanguinity, gestational diabetes, delay in walking, and developmental regression. Conclusions ASD prevalence in Qatar is consistent with recent international studies. The methods employed in this study should help designing comparable surveys in the region. We estimated that 187,000 youths under age 20 have ASD in Gulf countries. This figure should assist in planning health and educational services for a young, fast‐growing population.
Ethical Criteria for Health-Promoting Nudges: A Case-by-Case Analysis

Health-promoting nudges have been put into practice by different agents, in different contexts and with different aims. This article formulates a set of criteria that enables a thorough ethical evaluation of such nudges. As such, it bridges the gap between the abstract, theoretical debates among academics and the actual behavioral interventions being implemented in practice. The criteria are derived from arguments against nudges, which allegedly disrespect nudgees, as these would impose values on nudgees and/or violate their rationality and autonomy. Instead of interpreting these objections as knock-down arguments, I take them as expressing legitimate worries that can often be addressed. I analyze six prototypical nudge cases, such as Google’s rearrangement of fridges and the use of defaults in organ donation registration. I show how the ethical criteria listed are satisfied by most—but not all—nudges in most—but not all—circumstances.
Deregulation of Hepatic Mek1/2–Erk1/2 Signaling Module in Iron Overload Conditions

The liver, through the production of iron hormone hepcidin, controls body iron levels. High liver iron levels and deregulated hepcidin expression are commonly observed in many liver diseases including highly prevalent genetic iron overload disorders. In spite of a number of breakthrough investigations into the signals that control hepcidin expression, little progress has been made towards investigations into intracellular signaling in the liver under excess of iron. This study examined hepatic signaling pathways underlying acquired and genetic iron overload conditions. Our data demonstrate that hepatic iron overload associates with a decline in the activation of mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (Erk) kinase (Mek1/2) pathway by selectively affecting the phosphorylation of Erk1/2. We propose that Mek1/2-Erk1/2 signaling is uncoupled from iron-Bmp-Smad-mediated hepcidin induction and that it may contribute to a number of liver pathologies in addition to toxic effects of iron. We believe that our findings will advance the understanding of cellular signaling events in the liver during iron overload of different etiologies.
Overlooked biodiversity loss in tropical smallholder agriculture

Smallholder agriculture is the main driver of deforestation in the western Amazon, where terrestrial biodiversity reaches its global maximum. Understanding the biodiversity value of the resulting mosaics of cultivated and secondary forest is therefore crucial for conservation planning. However, Amazonian communities are organized across multiple forest types that support distinct species assemblages, and little is known about smallholder impacts across the range of forest types that are essential for sustaining biodiversity. We addressed this issue with a large‐scale field inventory of birds (point counts) and trees (transects) in primary forest and smallholder agriculture in northern Peru across 3 forest types that are key for Amazonian biodiversity. For birds smallholder agriculture supported species richness comparable to primary forest within each forest type, but biotic homogenization across forest types resulted in substantial losses of biodiversity overall. These overall losses are invisible to studies that focus solely on upland (terra firma) forest. For trees biodiversity losses in upland forests dominated the signal across all habitats combined and homogenization across habitats did not exacerbate biodiversity loss. Proximity to forest strongly predicted the persistence of forest‐associated bird and tree species in the smallholder mosaic, and because intact forest is ubiquitous in our study area, our results probably represent a best‐case scenario for biodiversity in Amazonian agriculture. Land‐use planning inside and outside protected areas should recognize that tropical smallholder agriculture has pervasive biodiversity impacts that are not apparent in typical studies that cover a single forest type. The full range of forest types must be surveyed to accurately assess biodiversity losses, and primary forests must be protected to prevent landscape‐scale biodiversity loss.
Review of the phenotypic spectrum associated with haploinsufficiency of MYRF

The myelin regulatory factor gene (MYRF) encodes a transcription factor that is widely expressed. There is increasing evidence that heterozygous loss‐of‐function variants in MYRF can lead to abnormal development of the heart, genitourinary tract, diaphragm, and lungs. Here, we searched a clinical database containing the results of 12,000 exome sequencing studies. We identified three previously unreported males with putatively deleterious variants in MYRF: one with a point mutation predicted to affect splicing and two with frameshift variants. In all cases where parental DNA was available, these variants were found to have arisen de novo. The phenotypes identified in these subjects included a variety of congenital heart defects (CHD) (hypoplastic left heart syndrome, scimitar syndrome, septal defects, and valvular anomalies), genitourinary anomalies (ambiguous genitalia, hypospadias, and cryptorchidism), congenital diaphragmatic hernia, and pulmonary hypoplasia. The phenotypes seen in our subjects overlap those described in individuals diagnosed with PAGOD syndrome [MIM# 202660], a clinically defined syndrome characterized by pulmonary artery and lung hypoplasia, agonadism, omphalocele, and diaphragmatic defects that can also be associated with hypoplastic left heart and scimitar syndrome. These cases provide additional evidence that haploinsufficiency of MYRF causes a genetic syndrome whose cardinal features include CHD, urogenital anomalies, congenital diaphragmatic hernia, and pulmonary hypoplasia. We also conclude that consideration should be given to screening individuals with PAGOD for pathogenic variants in MYRF, and that individuals with MYRF deficiency who survive the neonatal period should be monitored closely for developmental delay and intellectual disability.
Knowledge of physical activity guidelines and mental health benefits among Emirati university students

Aims: The purpose of this study was to assess Emirati university students’ knowledge of physical activity guidelines and perceptions of the benefits of physical activity for mental health. Methods: A random sample (n = 628) completed an online questionnaire assessing the recommended amount of physical activity for good health (min/week) and to what extent exercise can help improve wellbeing, and manage depression and anxiety/stress (5-point Likert-type scale). Results: Only 3% of respondents identified 150 min/week and less than half (39%) of the respondents reported an amount within the range of 150–300 min/week. Most respondents believed that physical activity could improve wellbeing (69%), and manage depression (71%) and anxiety/stress (74%). Females were more likely than males to view physical activity as a way to manage depression (p = .003), and anxiety/stress (p = .002). Conclusions: More work may be required to promote awareness of physical activity guidelines in this population, and males’ awareness of mental health benefits of physical activity.
High levels of isocyanic acid in smoke generated during hot iron cauterization

Abstract Pyrolysis of nitrogen containing biofuels generates isocyanic acid (ICA) and we here studied if ICA also is present in cauterization smoke. Air sampling was performed when animal technicians that had developed airway symptoms worked with dehorning. Tissue heated in a laboratory model was used to mimic cauterization. ICA in air at the workplace exceeded 10 times the national exposure limit. In the laboratory, the ICA generated per mg tissue from heated hair, horn and nail was 13.9 ± 7.8, 24.0 ± 4.1 and 32.0 ± 2.9 µg, respectively. Three workers were medically examined and two were diagnosed with asthma and a third had severe airway problem that resembled asthma. The study shows that high levels of ICA are generated during cauterization of nitrogen-containing tissue. If this could trigger airway symptoms deserves to be investigated further.
Extensive hybridization in a contact zone between MacGillivray ’ s and mourning warblers ( Oporornis tolmiei and O . philadelphia ) detected using molecular and morphological analyses

This is a pre-acceptance preprint of: Irwin DE, Brelsford A, Toews DPL, MacDonald C, Phinney M. Extensive hybridization in a contact zone between MacGillivray’s and mourning warblers (Oporornis tolmiei and O. philadelphia) detected using molecular and morphological analyses. Journal of Avain Biology, in press (accepted 12 January 2009). For the definitive version, please see the Journal of Avian Biology.
Character based identification system for Elasmobranchs for conservation and forensic applications

Abstract The term Elasmobranchs or Chondrichthyans refer to the group of marine organisms include sharks, skates, rays and chimeras. Due to high demand most of the Elasmobranch species depleted drastically in recent years. Being the apex predators in the marine environment most of the Chondrichthyan species are vulnerable with some risk of extinction. Accurate identification of species is prerequisite for conservation and management of these declining resources. In this context, character-based identification methods are of immense use which classify specimen to species using classification rules that compactly characterized species in terms of key diagnostic nucleotides in the selected gene sequences. In the present study, a total of 82 species of elasmobranches distributed in Indian waters is taken as the target group. A total of 20–30 mitochondrial CO1 sequences of each species were downloaded and modified. Using the BLOG2.0 software, species specific diagnostic nucleotides were identified for the selected group of species. Based on identified diagnostic nucleotide sites, species-specific probes with a length range of 23–30 bp were designed. These probes could be useful in detecting species of interest in customized microarrays (DNA chip). The technique is a powerful tool to obtain a significant amount of accurate information quickly and conveniently and could be used for forensic applications and conservation of elasmobranches in Indian waters.
COMBINING SPEEDED-UP ROBUST FEATURES WITH PRINCIPAL COMPONENT ANALYSIS IN FACE RECOGNITION SYSTEM

Recently, the techniques of face recognition have been widely used in security application such as security monitoring, and access control. However, there are still some problems in face recognition system in which the light changes, expression changes, head movements and accessory occlusion are the main issues. In this article, a robust face recognition scheme is proposed. Speeded-Up Robust Features algorithm is used for extracting the feature vectors with scale invariance and pose invariance from face images. Then PCA is introduced for projecting the SURF feature vectors to the new feature space as PCA-SURF local descriptors. Finally, the K-means algorithm is applied to clustering feature points, and the local similarity and global similarity are then combined to classify the face images. Experimental results show that the performance of the proposed scheme is better than other methods, and PCA-SURF feature is more robust than original SURF and SIFT local descriptors against the accessory, expression, and pose variations.
Global existence and uniqueness of solutions for multidimensional weakly parabolic systems arising in chemistry and biology

In this paper we establish general well-posedeness results for a wide class of weakly parabolic $2\times 2$ systems in a bounded domain of $\mathbb R^N$. Our results cover examples arising in sulphation of marbles and chemotaxis, when the density of one chemical component is not diffusing. We show that, under quite general assumptions, uniform $L^\infty$ estimates are sufficient to establish the global existence and stability of solutions, even if in general the nonlinear terms in the equations depend also on the gradient of the solutions. Applications are presented and discussed.
Monetary-Labor Interactions, International Monetary Regimes, and Central Bank Conservatism

A two-country general equilibrium model with large wage setters and conservative monetary authorities is employed to investigate the welfare implications of three international monetary regimes: i) non-cooperative, ii) cooperative, and iii) monetary union. The analysis shows that the unions’ wage claims depend on three strategic effects which are substantially different between the international policy arrangements. In contrast with recent studies, a switch from non-cooperation to monetary union is welfare improving with a sufficiently conservative central bank because unions perceive wage hikes as delivering lower terms-of-trade gains; while a switch from non-cooperation to cooperation is always beneficial because wage hikes do not yield any terms-of-trade gain. Finally, the paper qualifies Lippi’s (2003) findings about the real effects of central bank conservatism and centralized wage bargaining.