Miracle-dz/UniFAR-FTUs huggingface dataset:
Multivariate morphometrics, quantitative genetics, and neutral theory: Developing a “modern synthesis” for primate evolutionary morphology

Anthropologists are increasingly turning to explicit model‐bound evolutionary approaches for understanding the morphological diversification of humans and other primate lineages. Such evolutionary morphological analyses rely on three interconnected conceptual frameworks; multivariate morphometrics for quantifying similarity and differences among taxa, quantitative genetics for modeling the inheritance and evolution of morphology, and neutral theory for assessing the likelihood that taxon diversification is due to stochastic processes such as genetic drift. Importantly, neutral theory provides a framework for testing more parsimonious explanations for observed morphological differences before considering more complex adaptive scenarios. However, the consistency with which these concepts are applied varies considerably, which mirrors some of the theoretical obstacles faced during the “modern synthesis” of classical population genetics in the early 20th century. Here, each framework is reviewed and some potential stumbling blocks to the full conceptual integration of multivariate morphometrics, quantitative genetics, and neutral theory are considered.
The side population enriches for leukemia-propagating cell activity and Wnt pathway expression in zebrafish acute lymphoblastic leukemia

Cancer stem cells have been strongly linked to resistance and relapse in many malignancies. However, purifying them from within the bulk tumor has been challenging, so their precise genetic and functional characteristics are not well defined. The side population assay exploits the ability of some cells to efflux Hoechst dye via ATP-binding cassette transporters. Stem cells have increased expression of these transporters and this assay has been shown to enrich for stem cells in various tissues and cancers. This study identifies the side population within a zebrafish model of acute lymphoblastic leukemia and correlates the frequency of side population cells with the frequency of leukemia stem cells (more precisely referred to as leukemia-propagating cells within our transplantation model). In addition, the side population within the leukemia evolves with serial transplantation, increasing in tandem with leukemia-propagating cell frequency over subsequent generations. Sorted side population cells from these tumors are enriched for leukemia-propagating cells and have enhanced engraftment compared to sorted non-side population cells when transplanted into syngeneic recipients. RNA-sequencing analysis of sorted side population cells compared to non-side population cells identified a shared expression profile within the side population and pathway analysis yielded Wnt-signaling as the most overrepresented. Gene set enrichment analysis showed that stem cell differentiation and canonical Wnt-signaling were significantly upregulated in the side population. Overall, these results demonstrate that the side population in zebrafish acute lymphoblastic leukemia significantly enriches for leukemia-propagating cells and identifies the Wnt pathway as a likely genetic driver of leukemia stem cell fate.
Identification, Characterization, and Optimization of Integrin αvβ6-Targeting Peptides from a One-Bead One-Compound (OBOC) Library: Towards the Development of Positron Emission Tomography (PET) Imaging Agents

The current translation of peptides identified through the one-bead one-compound (OBOC) technology into positron emission tomography (PET) imaging agents is a slow process, with a major delay between ligand identification and subsequent lead optimization. This work aims to streamline the development process of 18F-peptide based PET imaging agents to target the integrin αvβ6. By directly identify αvβ6–targeting peptides from a 9-mer 4-fluorobenzoyl peptide library using the on-bead two-color (OBTC) cell-screening assay, a total of 185 peptide beads were identified and 5 beads sequenced for further evaluation. The lead peptide 1 (VGDLTYLKK(FB), IC50 = 0.45 ± 0.06 μM, 25% stable in serum at 1 h) was further modified at the N-, C-, and bi-termini. C-terminal PEGylation increased the metabolic stability (>95% stable), but decreased binding affinity (IC50 = 3.7 ± 1 μM) was noted. C-terminal extension (1i, VGDLTYLKK(FB)KVART) significantly increased binding affinity for integrin αvβ6 (IC50 = 0.021 ± 0.002 μM), binding selectivity for αvβ6-expressing cells (3.1 ± 0.8:1), and the serum stability (>99% stable). Our results demonstrate the challenges in optimizing OBOC-derived peptides, indicate both termini of 1 are sensitive to modifications, and show that further modification of 1 is necessary to demonstrate utility as an 18F-peptide imaging agent.
Modifiable factors for disability: Is there potential for reducing racial disparities in disability in older age?

Cognitive function represents a risk factor in the disablement process, and empirical findings indicate that some of the White-Black disparities in disability result from older Blacks lower cognitive status. Considering the vast evidence of the beneficial effects of lifestyle behaviors such as physical activity participation, moderate alcohol consumption, and not smoking on both cognitive performance and disability, this study examines whether cognition mediates the effects of these behaviors on disability, and whether these mediation effects vary between White and Black older adults. Data from White and Black participants from the Asset and Health Dynamics among the Oldest Old study (AHEAD) (N=4,472) who were followed up biannually from 1995 to 2002 are used to test these multilevel mediation models. Disability is measured by difficulty with basic activities of daily living (ADL) and difficulty with three cognitive instrumental activities of daily living (IADL).
c-Src Recruitment is Involved in c-MET-Mediated Malignant Behaviour of NT2D1 Non-Seminoma Cells

c-MET pathway over-activation is the signature of malignancy acquisition or chemotherapy resistance of many cancers. We recently demonstrated that type II Testicular Germ Cell Tumours (TGCTs) express c-MET receptor. In particular, we elucidated that the non-seminoma lesions express c-MET protein at higher level, compared with the seminoma ones. In line with this observation, NTERA-2 clone D1 (NT2D1) non-seminoma cells increase their proliferation, migration and invasion in response to Hepatocyte Growth Factor (HGF). One of the well-known adaptor-proteins belonging to c-MET signaling cascade is c-Src. Activation of c-Src is related to the increase of aggressiveness of many cancers. For this reason, we focused on the role of c-Src in c-MET-triggered and HGF-dependent NT2D1 cell activities. In the present paper, we have elucidated that this adaptor-protein is involved in HGF-dependent NT2D1 cell proliferation, migration and invasion, since Src inhibitor-1 administration abrogates these responses. Despite these biological evidences western blot analyses have not revealed the increase of c-Src activation because of HGF administration. However, notably, immunofluorescence analyses revealed that cytoplasmic and membrane-associated localization of c-Src shifted to the nuclear compartment after HGF stimulation. These results shed new light in the modality of HGF-dependent c-Src recruitment, and put the basis for novel investigations on the relationship between c-Src, and TGCT aggressiveness.
Genomic Signals of Adaptation towards Mutualism and Sociality in Two Ambrosia Beetle Complexes

Mutualistic symbiosis and eusociality have developed through gradual evolutionary processes at different times in specific lineages. Like some species of termites and ants, ambrosia beetles have independently evolved a mutualistic nutritional symbiosis with fungi, which has been associated with the evolution of complex social behaviors in some members of this group. We sequenced the transcriptomes of two ambrosia complexes (Euwallacea sp. near fornicatus⁻Fusarium euwallaceae and Xyleborus glabratus⁻Raffaelea lauricola) to find evolutionary signatures associated with mutualism and behavior evolution. We identified signatures of positive selection in genes related to nutrient homeostasis; regulation of gene expression; development and function of the nervous system, which may be involved in diet specialization; behavioral changes; and social evolution in this lineage. Finally, we found convergent changes in evolutionary rates of proteins across lineages with phylogenetically independent origins of sociality and mutualism, suggesting a constrained evolution of conserved genes in social species, and an evolutionary rate acceleration related to changes in selective pressures in mutualistic lineages.
Thrombophilia screening and thromboprophylaxis may benefit specific ethnic subgroups with paediatric acute lymphoblastic leukaemia

This study investigated the prevalence of inherited thrombophilia, risk of venous thromboembolism (VTE) and benefit of low molecular weight heparin prophylaxis in 476 Israeli children with acute lymphoblastic leukaemia (ALL) treated between 2004 and 2016. Thrombophilia was found in 15·5%. Arab children had a higher prevalence of F5 R506Q (factor V Leiden) than Jewish children (19·4% vs. 2·9%, P < 0·01). Patients with thrombophilia had higher VTE rates VTE (26·5% vs. 5·6%, P < 0·001). None of the thrombophilic children given prophylaxis had severe VTE. Routine evaluation for inherited thrombophilia followed by thromboprophylaxis when findings are positive may benefit at‐risk patients with ALL.
Affective variability in depression: Revisiting the inertia–instability paradox

How can depression be associated with both instability and inertia of affect? Koval et al. (2013, Emotion, 13, 1132) showed that this paradox can be solved by accounting for the statistical overlap between measures of affect dynamics. Nevertheless, these measures are still often studied in isolation. The present study is a replication of the Koval et al. study. We used experience sampling data (three times a day, 1 month) of 462 participants from the general population and a subsample thereof (N = 100) selected to reflect a uniform range of depressive symptoms. Dynamics measures were calculated for momentary negative affect scores. When adjusting for the overlap among affect dynamics measures, depression was associated with ‘dispersion’ (SD) but not ‘instability’ (RMSSD) or ‘inertia’ (AR) of negative affect. The association between dispersion and depression became non‐significant when mean levels of negative affect were adjusted for. These findings substantiate the evidence that the presumed association between depression and instability is largely accounted for by the SD, while the association between dispersion and depression may largely reflect mean levels of affect. Depression may thus not be related to higher instability per se, which would be in line with theories on the adaptive function of moment‐to‐moment fluctuations in affect.
Predicting social withdrawal, anxiety and depression symptoms in pediatric brain tumor survivors

Abstract Objective: Pediatric brain tumor survivors (PBTSs) are at risk for impairments in social adjustment and psychological distress. This study investigated longitudinal associations between symptoms of social withdrawal and anxiety/depression in PBTS, as well as medical, demographic, and personal characteristics that may also influence reports of social withdrawal and anxiety/depression. Method: About 91 PBTS (51% male, mean age 11.21 years, off-treatment) participated. At baseline and 8 months follow-up, primary caregivers of PBTS completed measures of social withdrawal, anxiety, and depression symptoms. Medical information (e.g. tumor type and location, cranial irradiation therapy) and child personal characteristics (e.g. child’s age and gender, executive function, social skills) were obtained at baseline. Results: Baseline reports of depression symptoms and social skills predicted social withdrawal 8 months later. Social withdrawal at baseline predicted greater combined anxiety and depression symptoms 8 months later. Depression alone predicted greater anxiety symptoms at follow-up. Anxiety symptoms and poor global executive functioning predicted greater depression symptoms at follow-up. Conclusions: The social adjustment and psychological distress of PBTSs are interrelated and can influence each other across time. These findings support the importance of multifaceted interventions targeting both psychological distress and social adjustment, in order to support the optimal psychosocial adjustment of PBTSs.
Prognostic significance of elevated preoperative neutrophil-to-lymphocyte ratio for patients with colorectal cancer undergoing curative surgery

Background: Preoperative neutrophil-to-lymphocyte ratio (NLR) has been suggested as a useful predictive factor for prognosis in patients with various cancers. However, the prognostic value of NLR in patients with colorectal cancer (CRC) remains controversial. Therefore, the goal of this study was to perform a meta-analysis to evaluate the prognostic value of NLR in patients with CRC undergoing curative surgery. Methods: PubMed, EMBASE and Cochrane Library databases were searched to screen the relevant studies. Pooled hazard ratio (HR) with 95% confidence interval (CI) was used to assess the associations of preoperative NLR and overall survival (OS), disease-free survival (DFS), recurrence free survival (RFS) and disease specific survival (DSS) by STATA 13.0 software. Results: Sixteen studies involving 5897 patients were included in our meta-analysis. Our pooled results demonstrated that high NLR was associated with poor OS (HR: 1.66, 95%CI: 1.36–2.02, P < .001), DFS (HR = 1.54, 95%CI: 1.18–2.02, P = .002), RFS (HR = 2.31, 95%CI: 1.68–3.17, P < .001) and DSS (HR = 2.27; 95% CI: 1.75–2.96, P < .001). When the patients were stratified according to country, sample size, NLR cut-off, follow up and postoperative chemotherapy, high NLR was still significantly correlated with OS. The limitation was that the majority of enrolled studies were retrospective. Conclusion: Preoperative NLR may be an effective predictive biomarker for prognosis in patients with CRC. Detection of NLR may be beneficial to identify the high-risk patients who need other antitumor therapies in addition to surgery.
Milk biosynthesis requires the Golgi cation exchanger TMEM165

Milk is a hallmark of mammals that is critical for normal growth and development of offspring. During biosynthesis of lactose in the Golgi complex, H+ is produced as a by-product, and there is no known mechanism for maintaining luminal pH within the physiological range. Here, using conditional, tissue-specific knockout mice, immunostaining, and biochemical assays, we test whether the putative H+/Ca2+/Mn2+ exchanger known as TMEM165 (transmembrane protein 165) participates in normal milk production. We find TMEM165 is crucial in the lactating mammary gland for normal biosynthesis of lactose and for normal growth rates of nursing pups. The milk of TMEM165-deficient mice contained elevated concentrations of fat, protein, iron, and zinc, which are likely caused by decreased osmosis-mediated dilution of the milk caused by the decreased biosynthesis of lactose. When normalized to total protein levels, only calcium and manganese levels were significantly lower in the milk from TMEM165-deficient dams than control dams. These findings suggest that TMEM165 supplies Ca2+ and Mn2+ to the Golgi complex in exchange for H+ to sustain the functions of lactose synthase and potentially other glycosyl-transferases. Our findings highlight the importance of cation and pH homeostasis in the Golgi complex of professional secretory cells and the critical role of TMEM165 in this process.
Should minimally invasive lung adenocarcinoma be transferred from stage IA1 to stage 0 in future updates of the TNM staging system?

Background The 8th International Association Study of Lung Cancer (IASLC) TNM classification staging project for lung cancer has classified patients with adenocarcinoma in situ (AIS) into stage 0, while patients with a minimally invasive adenocarcinoma (MIA) were classified into stage IA1. However, MIA patients, similar to AIS patients, have an approximately a 100% 5-year survival. This study aimed to investigate if MIA could be transferred from stage IA to stage 0 in the next TNM staging system. Methods We retrospectively reviewed 1,524 consecutive patients with a pathologically confirmed AIS, MIA and an invasive adenocarcinoma (IADC) in stage IA1. Disease-free survival (DFS) and overall survival (OS) were analyzed to evaluate survival difference between these three groups. Results There were 412 AIS, 675 MIA and 437 IADC patients in stage IA1. No statistically significant differences for DFS and OS (P=0.109) were seen between the AIS and MIA groups. Patients of the IADC group had significantly worse DFS (P=0.003) but the OS rate (P=0.941) was insignificant when compared with the MIA patients. Similar survival results were seen when comparisons were made between the IADC and AIS/MIA groups. The IADC group had a worse DFS (P=0.001) rate but no OS (P=0.380) difference with the AIS/MIA groups. Conclusions Patients with AIS and MIA had similar post-surgical survival rates. We propose that MIA may potentially be transferred from IA1 to stage 0 in the future.
Epidemiological, clinical and molecular characterization of Lynch‐like syndrome: A population‐based study

Colorectal carcinomas that are mismatch repair (MMR)‐deficient in the absence of MLH1 promoter methylation or germline mutations represent Lynch‐like syndrome (LLS). Double somatic events inactivating MMR genes are involved in the etiology of LLS tumors. Our purpose was to define the clinical and broader molecular hallmarks of LLS tumors and the population incidence of LLS, which remain poorly characterized. We investigated 762 consecutive colorectal carcinomas operated in Central Finland in 2000–2010. LLS cases were identified by a stepwise protocol based on MMR protein expression, MLH1 methylation and MMR gene mutation status. LLS tumors were profiled for CpG Island Methylator Phenotype (CIMP) and somatic mutations in 578 cancer‐relevant genes. Among 107 MMR‐deficient tumors, 81 (76%) were attributable to MLH1 promoter methylation and 9 (8%) to germline mutations (Lynch syndrome, LS), leaving 14 LLS cases (13%) (3 remained unclassified). LLS carcinomas were diagnosed at a mean age of 65 years (vs. 44 years in LS, p < 0.001), had a proximal to distal ratio of 1:1, and all were BRAF V600E‐negative. Two somatic events in MMR genes were identifiable in 11 tumors (79%). As novel findings, the tumors contained an average of 31 nonsynonymous somatic mutations/Mb and 13/14 were CIMP‐positive. In conclusion, we establish the epidemiological, clinical and molecular characteristics of LLS in a population‐based study design. Significantly more frequent CIMP‐positivity and lower rates of somatic mutations make a distinction to LS. The absence of BRAF V600E mutation separates LLS colorectal carcinomas from MLH1‐methylated colorectal carcinomas with CIMP‐positive phenotype.
Diagnosis and Management of Parastomal Hernias

CASE SUMMARY: A 63-year-old woman with history of stage II rectal adenocarcinoma status postneoadjuvant chemoradiation and subsequent abdominoperineal resection presented with worsening bulge and inability to pouch stoma. CT scan revealed a 4-cm parastomal hernia. After discussion with the patient regarding management options, she elected to undergo repair of hernia defect. A robot-assisted laparoscopic parastomal hernia repair with synthetic mesh via the Sugarbaker technique was performed. After a short stay in the hospital, the patient recovered well and reported no recurrent symptoms.
Caffeine Supplementation Has No Effect on Dribbling Speed in Elite Basketball Players.

PURPOSE: To examine the effect of caffeine supplementation on dribbling speed in elite female and male basketball players. METHODS: A double-blind, counterbalanced, randomized, crossover design was utilized. Elite basketball players (n = 21; female, n = 10; male, n = 11; age = 18.3 ± 3.3 yr) completed placebo (3 mg·kg-1 of body mass of dextrose) and caffeine (3 mg·kg-1 of body mass) trials 1 week apart during the in-season phase. During each trial, players completed 20-m linear sprints with and without dribbling a basketball. Performance times were recorded at 5-m, 10-m, and 20-m splits. Dribbling speed was measured using traditional (total performance time) and novel (Dribble Deficit) methods. Dribble Deficit isolates the added time taken to complete a task when dribbling compared to a non-dribbling version of the same task. Comparisons between placebo and caffeine conditions were conducted at group and individual levels. RESULTS: Non-significant (P > 0.05), trivial-small (effect size = 0.04-0.42) differences in dribbling speed were observed between conditions. The majority (20 out of 21) of players were classified as non-responders to caffeine, with 1 player identified as a negative responder using Dribble Deficit measures. CONCLUSIONS: Results indicate caffeine offers no ergogenic benefit to dribbling speed in elite basketball players. The negative response to caffeine in one player indicates caffeine supplementation may be detrimental to dribbling speed in specific cases and emphasizes the need for individualized analyses in nutrition-based sport science research.
Methylation Status of the Adeno-Associated Virus Type 2 (AAV2)

To analyze the methylation status of wild-type adeno-associated virus type 2 (AAV2), bisulfite PCR sequencing (BPS) of the packaged viral genome and its integrated form was performed and 262 of the total 266 CG dinucleotides (CpG) were mapped. In virion-packaged DNA, the ratio of the methylated cytosines ranged between 0–1.7%. In contrast, the chromosomally integrated AAV2 genome was hypermethylated with an average of 76% methylation per CpG site. The methylation level showed local minimums around the four known AAV2 promoters. To study the effect of methylation on viral rescue and replication, the replication initiation capability of CpG methylated and non-CpG methylated AAV DNA was compared. The in vitro hypermethylation of the viral genome does not inhibit its rescue and replication from a plasmid transfected into cells. This insensitivity of the viral replicative machinery to methylation may permit the rescue of the integrated heavily methylated AAV genome from the host’s chromosomes.
Estimation de la pose d'une caméra à partir d'un flux vidéo en s'approchant du temps réel

Trouver une methode permettant de calculer la pose d'une image avec robustesse et rapidite est essentiel en realite augmentee. Nous allons presenter ici l'approche que nous avons suivi pour nous rapprocher du temps reel en utilisant les points caracteristiques SIFT [4]. Nous proposons de filtrer a la fois les points SIFT mais aussi les images a utiliser, afin de concentrer nos calculs sur les donnees pertinentes.