Miracle-dz/UniFAR-FTUs huggingface dataset:
Prediction of Smoking Behavior From Single Nucleotide Polymorphisms With Machine Learning Approaches

Smoking is a complex behavior with a heritability as high as 50%. Given such a large genetic contribution, it provides an opportunity to prevent those individuals who are susceptible to smoking dependence from ever starting to smoke by predicting their inherited predisposition with their genomic profiles. Although previous studies have identified many susceptibility variants for smoking, they have limited power to predict smoking behavior. We applied the support vector machine (SVM) and random forest (RF) methods to build prediction models for smoking behavior. We first used 1,431 smokers and 1,503 non-smokers of African origin for model building with a 10-fold cross-validation and then tested the prediction models on an independent dataset consisting of 213 smokers and 224 non-smokers. The SVM model with 500 top single nucleotide polymorphisms (SNPs) selected using logistic regression (p<0.01) as the feature selection method achieved an area under the curve (AUC) of 0.691, 0.721, and 0.720 for the training, test, and independent test samples, respectively. The RF model with 500 top SNPs selected using logistic regression (p<0.01) achieved AUCs of 0.671, 0.665, and 0.667 for the training, test, and independent test samples, respectively. Finally, we used the combined logistic (p<0.01) and LASSO (λ=10−3) regression to select features and the SVM algorithm for model building. The SVM model with 500 top SNPs achieved AUCs of 0.756, 0.776, and 0.897 for the training, test, and independent test samples, respectively. We conclude that machine learning methods are promising means to build predictive models for smoking.
Optimality Principles in Human Point-to-Manifold Reaching Accounting for Muscle Dynamics

Human arm movements are highly stereotypical under a large variety of experimental conditions. This is striking due to the high redundancy of the human musculoskeletal system, which in principle allows many possible trajectories toward a goal. Many researchers hypothesize that through evolution, learning, and adaption, the human system has developed optimal control strategies to select between these possibilities. Various optimality principles were proposed in the literature that reproduce human-like trajectories in certain conditions. However, these studies often focus on a single cost function and use simple torque-driven models of motion generation, which are not consistent with human muscle-actuated motion. The underlying structure of our human system, with the use of muscle dynamics in interaction with the control principles, might have a significant influence on what optimality principles best model human motion. To investigate this hypothesis, we consider a point-to-manifold reaching task that leaves the target underdetermined. Given hypothesized motion objectives, the control input is generated using Bayesian optimization, which is a machine learning based method that trades-off exploitation and exploration. Using numerical simulations with Hill-type muscles, we show that a combination of optimality principles best predicts human point-to-manifold reaching when accounting for the muscle dynamics.
The Role of Metabolic Changes in Shaping the Fate of Cancer-Associated Adipose Stem Cells

Adipose tissue in physiological and in metabolically altered conditions (obesity, diabetes, metabolic syndrome) strictly interacts with the developing tumors both systemically and locally. In addition to the cancer-associated fibroblasts, adipose cells have also recently been described among the pivotal actors of the tumor microenvironment responsible for sustaining tumor development and progression. In particular, emerging evidence suggests that not only the mature adipocytes but also the adipose stem cells (ASCs) are able to establish a strict crosstalk with the tumour cells, thus resulting in a reciprocal reprogramming of both the tumor and adipose components. This review will focus on the metabolic changes induced by this interaction as a driver of fate determination occurring in cancer-associated ASCs (CA-ASCs) to support the tumor metabolic requirements. We will showcase the major role played by the metabolic changes occurring in the adipose tumor microenvironment that regulates ASC fate and consequently cancer progression. Our new results will also highlight the CA-ASC response in vitro by using a coculture system of primary ASCs grown with cancer cells originating from two different types of adrenal cancers [adrenocortical carcinoma (ACC) and pheochromocytoma]. In conclusion, the different factors involved in this crosstalk process will be analyzed and their effects on the adipocyte differentiation potential and functions of CA-ASCs will be discussed.
Predicting spatial aspects of human–elephant conflict

1. Human-elephant conflict (HEC) in Africa occurs wherever these two species coincide, and poses serious challenges to wildlife managers, local communities and elephants alike. Mitigation requires a detailed understanding of underlying patterns and processes. Although temporal patterns of HEC are relatively predictable, spatial variation has shown few universal trends, making it difficult to predict where conflict will take place. While this may be due to unpredictability in male elephant foraging behaviour (the male behaviour hypothesis) it may also be due to variations in the data resolution of earlier studies. 2. This study tested the male behaviour and data resolution hypotheses using HEC data from a 1000-km(2) unprotected elephant range adjacent to the Masai Mara National Reserve in Kenya. HEC incidents were divided into crop raiding and human deaths or injuries. Crop raiding was further subdivided into incidents involving only male elephants or family groups. A relatively fine-resolution, systematic, grid-based method was used to assign the locations of conflict incidents, and spatial relations with underlying variables were explored using correlation analysis and logistic regression. 3. Crop raiding was clustered into distinct conflict zones. Both occurrence and intensity could be predicted on the basis of the area under cultivation and, for male elephant groups, proximity to major settlements. Conversely, incidents of elephant-induced human injury and death were less predictable but were correlated with proximity to roads. 4. A grid-based geographical information system (GIS) with a 25-km(2) resolution utilizing cost-effective data sources, combined with simple statistical tools, was capable of identifying spatial predictors of HEC. At finer resolutions spatial autocorrelation compromised the analyses. 5. Synthesis and applications . These results suggest that spatial correlates of HEC can be identified, regardless of the sex of the elephants involved. Moreover, the method described here is fully transferable to other sites for comparative analysis of HEC. Using these results to map vulnerability will enable the development and deployment of appropriate conflict mitigation strategies, such as guarding, early warning systems, barriers and deterrents. The utility of such methods and their strategic deployment should be assessed alongside alternative land-use and livelihood strategies that limit cultivation within the elephant range.
Team Health and Project Quality Are Improved When Peer Evaluation Scores Affect Grades on Team Projects

The use of team projects is common in higher education. Teamwork offers an avenue to help students learn to collaborate and develop the interpersonal skills needed for career success. However, student teams are not always effective, which may undermine learning, growth, and development. In the current research, we integrate accountability, valence, motivation, and social loafing theories to advance an understanding of the role of peer evaluations conducted at the end of a team project. We use a state-of-the-art peer feedback system that allows students to assess and evaluate each other on five competencies critical to teamwork. We also used the system for the assessment of overall team functioning. Finally, grades on team projects were collected as a measure of team performance. Over three cohorts and using a total sample size of 162 teams and 873 students, we found that the use of peer evaluations for grading purposes, compared to a control group, promoted effective team member behavior, overall team health, and higher grades on team projects (i.e., team performance). Future research is needed to further investigate the optimal use of peer evaluations in a variety of contexts using a variety of methods.
Transitional Locomotor Tasks in People With Mild to Moderate Parkinson's Disease

Background: People with Parkinson's disease (PD) exhibit deficits in maintaining balance both during quiet standing and during walking, turning, standing up from sitting, and step initiation. Objective: The purpose of this study was to examine balance disorders during a transitional task under different conditions in participants with PD. Methods: The research was conducted on 15 PD-II (mild) and 15 PD-III (moderate) individuals (H&Y II-III stage) and 30 healthy elderly. The transitional task was measured on two force platforms (A and B). The procedure consisted of three phases: (1) quiet standing on platform A, (2) crossing to platform B, and (3) quiet standing on platform B, each until measurements were completed. There were four conditions: crossing without an obstacle, crossing with an obstacle, and walking up and down the step. Results: There were no significant differences between mild PD individuals and healthy elderly during quiet standing before the transitional task and after completing the task. The temporal aspects describing the different transitional tasks were comparable between mild PD and healthy subjects. Moderate PD participants presented a significantly higher COP velocity after the transitional task compared to the healthy older adults (p < 0.05). Additionally, the moderate PD group showed significantly higher values for transit time relative to healthy subjects during the transitional task in all conditions (p < 0.05). Conclusions: Disease severity affects the temporal aspects of different transitional tasks in people with PD. The procedure of completing a transitional task under different conditions allowed differences between moderate and mild PD stages and healthy subjects to be observed.
The special senses in grazing animals. I. Sight and dietary habits in sheep

The diets and productivity of sheep unable to see what they ate (blinkered) and control (unblinkered) sheep were compared in a number of experiments. Diet composition differed for control and blinkered sheep under some pasture conditions. These differences are attributed to the use of sight by sheep to orientate themselves whilst grazing; habit of grazing was altered in blinkered sheep. Preference ranking of species was unaltered by blinkering sheep.
GC-AG Introns Features in Long Non-coding and Protein-Coding Genes Suggest Their Role in Gene Expression Regulation

Long non-coding RNAs (lncRNAs) are recognized as an important class of regulatory molecules involved in a variety of biological functions. However, the regulatory mechanisms of long non-coding genes expression are still poorly understood. The characterization of the genomic features of lncRNAs is crucial to get insight into their function. In this study, we exploited recent annotations by GENCODE to characterize the genomic and splicing features of long non-coding genes in comparison with protein-coding ones, both in human and mouse. Our analysis highlighted differences between the two classes of genes in terms of their gene architecture. Significant differences in the splice sites usage were observed between long non-coding and protein-coding genes (PCG). While the frequency of non-canonical GC-AG splice junctions represents about 0.8% of total splice sites in PCGs, we identified a significant enrichment of the GC-AG splice sites in long non-coding genes, both in human (3.0%) and mouse (1.9%). In addition, we found a positional bias of GC-AG splice sites being enriched in the first intron in both classes of genes. Moreover, a significant shorter length and weaker donor and acceptor sites were found comparing GC-AG introns to GT-AG introns. Genes containing at least one GC-AG intron were found conserved in many species, more prone to alternative splicing and a functional analysis pointed toward their enrichment in specific biological processes such as DNA repair. Our study shows for the first time that GC-AG introns are mainly associated with lncRNAs and are preferentially located in the first intron. Additionally, we discovered their regulatory potential indicating the existence of a new mechanism of non-coding and PCGs expression regulation.
Robust and accurate decoding of hand kinematics from entire spiking activity using deep learning

Objective. Brain–machine interfaces (BMIs) seek to restore lost motor functions in individuals with neurological disorders by enabling them to control external devices directly with their thoughts. This work aims to improve robustness and decoding accuracy that currently become major challenges in the clinical translation of intracortical BMIs. Approach. We propose entire spiking activity (ESA)—an envelope of spiking activity that can be extracted by a simple, threshold-less, and automated technique—as the input signal. We couple ESA with deep learning-based decoding algorithm that uses quasi-recurrent neural network (QRNN) architecture. We evaluate comprehensively the performance of ESA-driven QRNN decoder for decoding hand kinematics from neural signals chronically recorded from the primary motor cortex area of three non-human primates performing different tasks. Main results. Our proposed method yields consistently higher decoding performance than any other combinations of the input signal and decoding algorithm previously reported across long-term recording sessions. It can sustain high decoding performance even when removing spikes from the raw signals, when using the different number of channels, and when using a smaller amount of training data. Significance. Overall results demonstrate exceptionally high decoding accuracy and chronic robustness, which is highly desirable given it is an unresolved challenge in BMIs.
Mapping glycan-mediated galectin-3 interactions by live cell proximity labeling

Significance Because of the weak interactions between individual glycan-binding proteins (GBPs), such as galectin-3, and glycans, strategies that enable the direct interrogation of these interactions in living cells remain limited. Thus, the glycan and glycoprotein ligands that are physiologically relevant for galectin-3 binding are insufficiently described. Here we used a proximity labeling approach that catalytically tags interactors for galectin-3 and identified its pertinent glycan and glycoprotein counter-receptors in live cells. This study demonstrates that proximity labeling is a powerful tool for mapping GBP complexes in living cells, and when coupled with chemical inhibitors, it can discriminate between protein–protein and protein–glycan interactions. Galectin-3 is a glycan-binding protein (GBP) that binds β-galactoside glycan structures to orchestrate a variety of important biological events, including the activation of hepatic stellate cells and regulation of immune responses. While the requisite glycan epitopes needed to bind galectin-3 have long been elucidated, the cellular glycoproteins that bear these glycan signatures remain unknown. Given the importance of the three-dimensional (3D) arrangement of glycans in dictating GBP interactions, strategies that allow the identification of GBP receptors in live cells, where the native glycan presentation and glycoprotein expression are preserved, have significant advantages over static and artificial systems. Here we describe the integration of a proximity labeling method and quantitative mass spectrometry to map the glycan and glycoprotein interactors for galectin-3 in live human hepatic stellate cells and peripheral blood mononuclear cells. Understanding the identity of the glycoproteins and defining the structures of the glycans will empower efforts to design and develop selective therapeutics to mitigate galectin-3–mediated biological events.
Emerging Threat of Antimicrobial Resistance in β-Hemolytic Streptococci

Highly variable resistance rates to erythromycin and clindamycin have been reported in the β-hemolytic streptococcal species Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus dysgalactiae, depending on geographic and temporal context. In the present study we aimed to examine the longitudinal trends of antimicrobial resistance in these three species in a northern European setting. Furthermore, we used whole genome sequencing to identify resistance determinants and the mobile genetic elements involved in their dissemination, as well as elucidate phylogenetic relationships. All cases of invasive β-hemolytic streptococcal diseases in Health Region Bergen, western Norway, in the period 2004 to 2018 were retrospectively identified, comprising 271, 358, and 280 cases of S. pyogenes, S. agalactiae, and S. dysgalactiae, respectively. Antimicrobial susceptibility testing revealed a gradual but significant increase in erythromycin and clindamycin resistance for S. agalactiae and S. dysgalactiae during the study period. Whole genome sequencing of the erythromycin and clindamycin resistant bacterial population revealed a substantial phylogenetic diversity in S. agalactiae and S. dysgalactiae. However, the mobile genetic elements harboring the resistance determinants showed remarkable intra- and interspecies similarities, suggesting a dissemination of antimicrobial resistance predominantly through conjugative transfer rather than clonal expansion of resistant strains in these two species. Conversely, antimicrobial resistance in S. pyogenes remained low, apart from a transient outbreak of a clindamycin and erythromycin resistant emm11/ST403-clone in 2010–2012. Increased epidemiological attentiveness is warranted to monitor the emerging threat of antimicrobial resistance in β-hemolytic streptococci, particularly in S. agalactiae and S. dysgalactiae.
No evidence for a difference in 2D:4D ratio between youth with elevated prenatal androgen exposure due to congenital adrenal hyperplasia and controls

The second-to-fourth digit ratio (2D:4D) has been associated with sexual dimorphism, with a lower 2D:4D in males. A large body of research has relied on the 2D:4D as a proxy for prenatal androgen exposure, and includes reports of relationships between 2D:4D and a wide range of human traits. Here, we examine the validity of the 2D:4D proxy by studying the association between 2D:4D and classical Congenital Adrenal Hyperplasia (CAH) due to 21-hydroxylase deficiency, a condition characterized by excessive prenatal exposure to androgens during most of the gestational period. To this end, we retrospectively examine serial radiographs of the left hand obtained clinically in 90 youth with classical CAH (45 female) and 70 control youth (31 female). Replicating previous reports, we observe associations of the 2D:4D with sex (lower 2D:4D in males) and age (increase of 2D:4D through development). However, we find no evidence for differences in 2D:4D between CAH and controls (full sample: beta = −0.001 (−0.008, 0.006)]; females: beta = −0.004 [−0.015, 0.007]; males: beta = 0.001, [−0.008, 0.011]). Although our findings do not rule out a small association between the 2D:4D and CAH, they cast doubt on the usefulness of the 2D:4D as a biomarker for prenatal androgen exposure in behavioral research.
Quantitative faecal immunochemical test for patients with high risk bowel symptoms: a prospective cohort study

Objectives: To evaluate whether quantitative measurement of faecal haemoglobin (f-Hb) using faecal immunochemical testing (FIT) can be used to rule out colorectal cancer (CRC) for patients who present to primary care with high risk symptoms defined by national guidelines for urgent referral for suspected cancer (NICE NG12). Design: Prospective cohort study carried out between April 2017 and March 2019. Setting: 59 GP practices in London and 24 hospitals in England. Participants: Symptomatic patients in England referred to the urgent CRC pathway who provided a faecal sample for FIT in addition to standard investigations for cancer. Main outcome measures: CRC was confirmed by established clinical and histopathology procedures. f-Hb (microgr per gram of stool) was measured in a central laboratory blinded to cancer outcome. We calculated sensitivity (percentage of patients with CRC who have f-Hb exceeding specified cut-offs); false-positive rate [FPR] (percentage of patients without CRC whose f-Hb exceeds the same cut-offs); and positive predictive value [PPV] (percentage of all patients with f-Hb above the cut-offs who have CRC). Results: 4676 patients were recruited of whom 3596 patients were included (had a valid FIT test and a known definitive diagnosis). Among the 3596, median age was 67 years, 53% were female and 78% had colonoscopy. 90 patients were diagnosed with CRC, 7 with other cancers, and 3499 with no cancer found. f-Hb did not correlate with age, sex or ethnicity. Using f-Hb greater than or equal to 4 microgr/g (lowest limit of detection), sensitivity, FPR and PPV were 87.8%, 27.0% and 7.7% respectively. Using f-Hb greater than or equal to 10 microgr/g, the corresponding measures were 83.3%, 19.9% and 9.7%. 15 patients with CRC had f-Hb below 10 microgr/g. If FIT had been used at thresholds of 10 microg/gr or 4 microgr/g, 1 in 6 or 1 in 8 patients with cancer respectively would have been missed. If the absence of anaemia or abdominal pain is used alongside f-Hb 10 microgr/g, only 1 in 18 cancers would be missed but 56% of people without CRC could potentially avoid further investigations including colonoscopies. Conclusions: In our study, if FIT alone had been used to determine urgent referral for patients with high risk symptoms for definitive cancer investigation, some patients with bowel cancer would not have been diagnosed. If used in conjunction with clinical features, particularly in the absence of anaemia, the efficacy of FIT is significantly improved. With appropriate safety netting, FIT could be used to focus secondary care diagnostic capacity on patients most at risk of CRC.
Evolutionary transition to a semelparous life history in the socially parasitic ant Acromyrmex insinuator

The recently discovered social parasite Acromyrmex insinuator ( Schultz, Bekkevold & Boomsma 1998 ) exploits colonies of the leafcutter ant A. echinatior. We document that A. insinuator represents a rare early stage in the evolution of social parasitism, because a worker caste is still partially present and mating phenology has remained at least partially similar to that of the host. A. insinuator is tolerant of host queens, and sexual offspring produced in parasitized colonies can be either exclusively A. insinuator or a mix of A. insinuator and A. echinatior. The remarkably high abundance of A. insinuator in nests of the investigated Panamanian host population and the fact that A. insinuator colonies readily reproduce under laboratory conditions allowed us to test evolutionary predictions on reproductive life history evolution that are not possible in most other socially parasitic ants. We show that (1) A. insinuator has a semelparous ‘big bang’ reproductive life history which exploits host colonies without leaving reserves for survival; (2) social parasite sexuals are significantly smaller than A. echinatior host sexuals, but still large compared to host workers, confirming an evolutionary scenario of gradual size reduction and loss of the worker caste after transition towards a socially parasitic life history; (3) major changes in the life history of ants can evolve relatively quickly compared to adaptations in morphology, caste differentiation and mating phenology.