Miracle-dz/UniFAR-FTUs huggingface dataset:
Matching Cancer Genomes to Established Cell Lines for Personalized Oncology

The diagnosis and treatment of cancers, which rank among the leading causes of mortality in developed nations, presents substantial clinical challenges. The genetic and epigenetic heterogeneity of tumors can lead to differential response to therapy and gross disparities in patient outcomes, even for tumors originating from similar tissues. High-throughput DNA sequencing technologies hold promise to improve the diagnosis and treatment of cancers through efficient and economical profiling of complete tumor genomes, paving the way for approaches to personalized oncology that consider the unique genetic composition of the patient's tumor. Here we present a novel method to leverage the information provided by cancer genome sequencing to match an individual tumor genome with commercial cell lines, which might be leveraged as clinical surrogates to inform prognosis or therapeutic strategy. We evaluate the method using a published lung cancer genome and genetic profiles of commercial cancer cell lines. The results support the general plausibility of this matching approach, thereby offering a first step in translational bioinformatics approaches to personalized oncology using established cancer cell lines.
Sweet taste preferences are partly genetically determined: identification of a trait locus on chromosome 16.

BACKGROUND Humans have an innate preference for sweet taste, but the degree of liking for sweet foods varies individually. OBJECTIVE The proportion of inherited sweet taste preference was studied. A genome-wide linkage analysis was performed to locate the underlying genetic elements in the genome. DESIGN A total of 146 subjects (32% men, 68% women) aged 18-78 y from 26 Finnish families evaluated the intensity and pleasantness of 3 suprathreshold solutions of sucrose (3.0%, 7.5%, and 18.75%) and plain water and the intensity of filter paper impregnated with 6-n-propylthiouracil (PROP). The subjects also reported the pleasantness and the use frequency of 5 sweet foods (chocolate, candy, ice cream, sweet desserts, and sweet pastry) and completed a food-behavior questionnaire that measured their craving for sweet foods. RESULTS Of the chemosensory functions, the pleasantness rating of the strongest (18.75%) sucrose solution and the intensity rating of PROP yielded the highest heritability estimates (41% and 66%, respectively). The pleasantness and the use frequency of sweet foods (both variables calculated as a mean of ratings for 5 food items) and the craving for sweet foods showed significant heritability (40%, 50%, and 31%, respectively). A logarithm of odds score of 3.5 (P=0.00003) was detected for use frequency of sweet foods on chromosome 16p11.2 (marker D16S753). CONCLUSIONS Sweet taste preferences are partly inherited. Chromosome 16p11.2 may harbor genetic variations that affect the consumption of sweet foods.
Comparing Versions of the Good Behavior Game

Disruptions can prevent the classroom from being an effective learning environment. The Good Behavior Game (GBG) is a group contingency that has been proven to effectively prevent disruptions and increase engagement. However, the traditional methods of the GBG include teacher scanning for negative student behaviors, and may not align with Positive Behavioral Interventions and Supports (PBIS), which is becoming widely adopted in many schools. Extending the findings of Wright and McCurdy, the current study compared the effects of the GBG and a positive version of the GBG, called the Caught Being Good Game (CBGG), on student behavior, including engagement and off-task behaviors, as well as teachers’ use of positive and negative statements. Results showed both the GBG and the CBGG improved student behavior, with data not clearly indicating one was superior. Neither intervention led to an increase in positive teacher statements. Implications for teachers and suggestions for further research are discussed.
Integrated Karyotyping of Woodland Strawberry (Fragaria vesca) with Oligopaint FISH Probes

Chromosome identification is critical for many aspects of cytogenetic research. However, for Fragaria vesca, definite identification of individual chromosomes is almost impossible because of their small size and high similarity. Here, we demonstrate that bulked oligonucleotide (oligo) probes can be used as chromosome-specific DNA markers for chromosome identification in F. vesca. Oligos specific to entire pseudochromosomes in the draft genome of F. vesca were identified and synthesized as libraries. In all, we synthesized 6 oligo libraries corresponding to 6 pseudochromosomes of F. vesca. These libraries were amplified and labeled as probes for fluorescence in situ hybridization (FISH). Two rounds of multicolor FISH analysis were sequentially conducted on the same metaphase cells with each round including 3 probe libraries, which permitted simultaneous identification of all chromosomes of F. vesca. Moreover, 45S and 5S rDNA were mapped to chromosomes 1, 2, and 7, respectively. A karyotype of metaphase chromosomes was constructed, representing the first FISH-based molecular cytogenetic karyotype of F. vesca. Our study can serve as a basis for future comparative cytogenetic research through cross-species chromosome painting using bulked oligo probes and will facilitate the application of breeding technologies that rely on the identification of chromosomes in the genus Fragaria.
Use of Continuous Subcutaneous Insulin Infusion Pump in Patients With Type 2 Diabetes Mellitus

Purpose In patients with type 2 diabetes, the control of hyperglycemia is often difficult despite full doses of oral hypoglycemic agents and extremely large doses of insulin. These patients pose a major management problem. The authors therefore investigated whether insulin given as a subcutaneous continuous infusion of insulin (CSII) would result in an improvement in glucose homeostasis. Methods Four patients with badly controlled type 2 diabetes, on treatment with extremely high doses of insulin and oral hypoglycemic agents, were started on CSII. Results All four patients had a marked improvement in plasma glucose concentrations with a corresponding fall in HbA1c levels. This improvement was associated with a marked fall in the insulin doses necessary to maintain adequate glucose homeostasis. Conclusions Since HbA1c levels fell from levels that would be associated with diabetic complications to those at which complications are markedly reduced, we recommend that patients with type 2 diabetes uncontrolled on extremely high doses of insulin be given a trial of treatment with CSII.
Possible Contribution of Taurine to Distorted Glucagon Secretion in Intra-Islet Insulin Deficiency: A Metabolome Analysis Using a Novel α-Cell Model of Insulin-Deficient Diabetes

Glycemic instability is a serious problem in patients with insulin-deficient diabetes, and it may be due in part to abnormal endogenous glucagon secretion. However, the intracellular metabolic mechanism(s) involved in the aberrant glucagon response under the condition of insulin deficiency has not yet been elucidated. To investigate the metabolic traits that underlie the distortion of glucagon secretion under insulin deficient conditions, we generated an αTC1-6 cell line with stable knockdown of the insulin receptor (IRKD), i.e., an in vitro α-cell model for insulin-deficient diabetes, which exhibits an abnormal glucagon response to glucose. A comprehensive metabolomic analysis of the IRKD αTC1-6 cells (IRKD cells) revealed some candidate metabolites whose levels differed markedly compared to those in control αTC1-6 cells, but also which could affect the glucagon release in IRKD cells. Of these candidates, taurine was remarkably increased in the IRKD cells and was identified as a stimulator of glucagon in αTC1-6 cells. Taurine also paradoxically exaggerated the glucagon secretion at a high glucose concentration in IRKD cells and islets with IRKD. These results indicate that the metabolic alterations induced by IRKD in α-cells, especially the increase of taurine, may lead to the distorted glucagon response in IRKD cells, suggesting the importance of taurine in the paradoxical glucagon response and the resultant glucose instability in insulin-deficient diabetes.
Micro-architectured materials: past, present and future

Micro-architectured materials offer the opportunity of obtaining unique combinations of material properties. First, a historical perspective is given to the expansion of material property space by the introduction of new alloys and new microstructures. Principles of design of micro-architecture are then given and the role of nodal connectivity is emphasized for monoscale and multi-scale microstructures. The stiffness, strength and damage tolerance of lattice materials are reviewed and compared with those of fully dense solids. It is demonstrated that micro-architectured materials are able to occupy regions of material property space (such as high stiffness, strength and fracture toughness at low density) that were hitherto empty. Some challenges for the development of future materials are highlighted.
Effect of image variation on computer-aided detection systems

As the importance of Computer Aided Detection (CAD) systems application is rising in medical imaging field due to the advantages they generate; it is essential to know their weaknesses and try to find a proper solution for them. A common possible practical problem that affects CAD systems performance is: dissimilar training and testing datasets declines the efficiency of CAD systems. In this paper normalizing images is proposed, three different normalization methods are applied on chest radiographs namely (1) Simple normalization (2) Local Normalization (3) Multi Band Local Normalization. The supervised lung segmentation CAD system performance is evaluated on normalized chest radiographs with these three different normalization methods in terms of Jaccard index. As a conclusion the normalization enhances the performance of CAD system and among these three normalization methods Local Normalization and Multi band Local normalization improve performance of CAD system more significantly than the simple normalization.
Bootstrapping Relational Affordances of Object Pairs Using Transfer

Robots acting in everyday environments need a good knowledge of how a manipulation action can affect pairs of objects in a relationship, such as “inside” or “behind” or “on top. ” These relationships afford certain means-end actions such as pulling a container to retrieve the contents, or pulling a tool to retrieve a desired object. We investigate how these relational affordances could be learned by a robot from its own action experience. A major challenge in this approach is to reduce the number of training samples needed to achieve accuracy, and hence we investigate an approach which can leverage past knowledge to accelerate current learning (which we call bootstrapping). We learn random forest-based affordance predictors from visual inputs and demonstrate two approaches to knowledge transfer for bootstrapping. In the first approach [direct bootstrapping (DB)], the state-space for a new affordance predictor is augmented with the output of previously learned affordances. In the second approach [category-based bootstrapping (CB)], we form categories that capture underlying commonalities of a pair of existing affordances and augment the state-space with this category classifier’s output. In addition, we introduce a novel heuristic, which suggests how a large set of potential affordance categories can be pruned to leave only those categories which are most promising for bootstrapping future affordances. Our results show that both bootstrapping approaches outperform learning without bootstrapping. We also show that there is no significant difference in performance between DB and CB.
Novel Tools for Conservation Genomics: Comparing Two High-Throughput Approaches for SNP Discovery in the Transcriptome of the European Hake

The growing accessibility to genomic resources using next-generation sequencing (NGS) technologies has revolutionized the application of molecular genetic tools to ecology and evolutionary studies in non-model organisms. Here we present the case study of the European hake (Merluccius merluccius), one of the most important demersal resources of European fisheries. Two sequencing platforms, the Roche 454 FLX (454) and the Illumina Genome Analyzer (GAII), were used for Single Nucleotide Polymorphisms (SNPs) discovery in the hake muscle transcriptome. De novo transcriptome assembly into unique contigs, annotation, and in silico SNP detection were carried out in parallel for 454 and GAII sequence data. High-throughput genotyping using the Illumina GoldenGate assay was performed for validating 1,536 putative SNPs. Validation results were analysed to compare the performances of 454 and GAII methods and to evaluate the role of several variables (e.g. sequencing depth, intron-exon structure, sequence quality and annotation). Despite well-known differences in sequence length and throughput, the two approaches showed similar assay conversion rates (approximately 43%) and percentages of polymorphic loci (67.5% and 63.3% for GAII and 454, respectively). Both NGS platforms therefore demonstrated to be suitable for large scale identification of SNPs in transcribed regions of non-model species, although the lack of a reference genome profoundly affects the genotyping success rate. The overall efficiency, however, can be improved using strict quality and filtering criteria for SNP selection (sequence quality, intron-exon structure, target region score).
minepath.org: a free interactive pathway analysis web server

Abstract Minepath (www.minepath.org) is a web-based platform that elaborates on, and radically extends the identification of differentially expressed sub-paths in molecular pathways. Besides the network topology, the underlying MinePath algorithmic processes exploit exact gene-gene molecular relationships (e.g. activation, inhibition) and are able to identify differentially expressed pathway parts. Each pathway is decomposed into all its constituent sub-paths, which in turn are matched with corresponding gene expression profiles. The highly ranked, and phenotype inclined sub-paths are kept. Apart from the pathway analysis algorithm, the fundamental innovation of the MinePath web-server concerns its advanced visualization and interactive capabilities. To our knowledge, this is the first pathway analysis server that introduces and offers visualization of the underlying and active pathway regulatory mechanisms instead of genes. Other features include live interaction, immediate visualization of functional sub-paths per phenotype and dynamic linked annotations for the engaged genes and molecular relations. The user can download not only the results but also the corresponding web viewer framework of the performed analysis. This feature provides the flexibility to immediately publish results without publishing source/expression data, and get all the functionality of a web based pathway analysis viewer.
Convergence Insufficiency Identifies Athletes at Risk of Prolonged Recovery From Sport-Related Concussion

Background: Sensitive and specific screening methods are needed to identify athletes at risk of prolonged recovery after sport-related concussion (SRC). Convergence insufficiency (CI) is a common finding in concussed athletes. Purpose: To assess the relationship between CI and recovery after SRC at the initial office visit. Study Design: Case-control study; Level of evidence, 3. Methods: In this retrospective cohort study, 270 athletes (147 male, 123 female), mean ± SD age 14.7 ± 2.0 years (range, 10-21 years), with the diagnosis of SRC who presented for initial office visit between January 2014 and January 2016 were evaluated for near point of convergence (NPC). The athletes were categorized into 2 groups: normal near point of convergence (NPC ≤6 cm), and convergence insufficiency (NPC >6 cm). These athletes were then followed to determine recovery time. Results: Athletes presented for initial office visit at a mean of 5.2 ± 4.2 days (range, 1-21 days) after SRC. Half of the athletes had CI after SRC (50.4%; n = 136). Athletes with CI (NPC 12.3 ± 4.7 cm) took significantly longer to recover after SRC, requiring 51.6 ± 53.9 days, compared with athletes with normal NPC (4.1 ± 1.3 cm), who required 19.2 ± 14.7 days (P < .001). After controlling for potential confounding variables, CI significantly increased the odds of prolonged recovery (≥28 days from injury) by 12.3-fold (P < .001; 95% confidence interval, 6.6-23.0). CI screening correctly classified 75.2% of our sample with 84.2% sensitivity and 70.0% specificity. The positive predictive value for CI and prolonged recovery was 62.5%, and the negative predictive value was 88.1%. Conclusion: CI at the initial office visit identified athletes at increased risk of prolonged recovery after SCR. Clinicians should consider measuring NPC in concussed athletes as a quick and inexpensive prognostic screening method.
Rapid sexual and genomic isolation in sympatric Drosophila without reproductive character displacement

Abstract The rapid evolution of sexual isolation in sympatry has long been associated with reinforcement (i.e., selection to avoid maladaptive hybridization). However, there are many species pairs in sympatry that have evolved rapid sexual isolation without known costs to hybridization. A major unresolved question is what evolutionary processes are involved in driving rapid speciation in such cases. Here, we focus on one such system; the Drosophila athabasca species complex, which is composed of three partially sympatric and interfertile semispecies: WN, EA, and EB. To study speciation in this species complex, we assayed sexual and genomic isolation within and between these semispecies in both sympatric and allopatric populations. First, we found no evidence of reproductive character displacement (RCD) in sympatric zones compared to distant allopatry. Instead, semispecies were virtually completely sexually isolated from each other across their entire ranges. Moreover, using spatial approaches and coalescent demographic simulations, we detected either zero or only weak heterospecific gene flow in sympatry. In contrast, within each semispecies we found only random mating and little population genetic structure, except between highly geographically distant populations. Finally, we determined that speciation in this system is at least an order of magnitude older than previously assumed, with WN diverging first, around 200K years ago, and EA and EB diverging 100K years ago. In total, these results suggest that these semispecies should be given full species status and we adopt new nomenclature: WN—D. athabasca, EA—D. mahican, and EB—D. lenape. While the lack of RCD in sympatry and interfertility do not support reinforcement, we discuss what additional evidence is needed to further decipher the mechanisms that caused rapid speciation in this species complex.
The Short-Term Training and Detraining Effects of Supervised Versus Unsupervised Resistance Exercise in Aging Adults.

This study compared the effects of a 4-week supervised (SUP) and unsupervised (UNSUP) resistance training programme followed by 12 weeks of detraining (DET). Thirty-six healthy aging adults (age: 53.6 ± 3.6 years; body mass index: 28.3 ± 5.1 kg/m) were randomly allocated to a SUP group (n = 17) or an UNSUP group (n = 19). Participants completed three training sessions per week using resistance bands and body weight movements. Measures of physical performance were administered at baseline, at the end of the training programme, and after the DET period. Function was assessed with the six minute walk test (6MWT), timed up-and-go (TUG), 30 s chair sit-to-stand (STS), stair-climb test (SCT), 40 m fast-paced walk test (FPWT) and sit-and-reach test (SRT), whereas the isometric mid-thigh pull (IMTP) and hand grip test were used to measure muscle strength. Following training, improvements in performance were found in the 6MWT, TUG, 30 s chair STS, SCT, FPWT, SRT, and IMTP (p < 0.05), with no significant differences between groups (p > 0.05). In addition, the majority of training-induced improvements remained significantly above baseline values after the DET period (p < 0.05). No significant between-group differences were observed following training or DET (p > 0.05). Four weeks of either SUP or UNSUP resistance training is sufficient to substantially improve muscle strength and function in aging adults, and these gains are largely preserved following prescribed exercise cessation. Home-based resistance training appears to be a practical and effective alternative to traditional SUP programmes that may help circumvent many barriers to physical activity in aging adults.
A Melodic Contour Repeatedly Experienced by Human Near-Term Fetuses Elicits a Profound Cardiac Reaction One Month after Birth

Background Human hearing develops progressively during the last trimester of gestation. Near-term fetuses can discriminate acoustic features, such as frequencies and spectra, and process complex auditory streams. Fetal and neonatal studies show that they can remember frequently recurring sounds. However, existing data can only show retention intervals up to several days after birth. Methodology/Principal Findings Here we show that auditory memories can last at least six weeks. Experimental fetuses were given precisely controlled exposure to a descending piano melody twice daily during the 35th, 36th, and 37th weeks of gestation. Six weeks later we assessed the cardiac responses of 25 exposed infants and 25 naive control infants, while in quiet sleep, to the descending melody and to an ascending control piano melody. The melodies had precisely inverse contours, but similar spectra, identical duration, tempo and rhythm, thus, almost identical amplitude envelopes. All infants displayed a significant heart rate change. In exposed infants, the descending melody evoked a cardiac deceleration that was twice larger than the decelerations elicited by the ascending melody and by both melodies in control infants. Conclusions/Significance Thus, 3-weeks of prenatal exposure to a specific melodic contour affects infants ‘auditory processing’ or perception, i.e., impacts the autonomic nervous system at least six weeks later, when infants are 1-month old. Our results extend the retention interval over which a prenatally acquired memory of a specific sound stream can be observed from 3–4 days to six weeks. The long-term memory for the descending melody is interpreted in terms of enduring neurophysiological tuning and its significance for the developmental psychobiology of attention and perception, including early speech perception, is discussed.