Miracle-dz/UniFAR-FTUs huggingface dataset:
The anticancer peptide RT53 induces immunogenic cell death

In recent years, immunogenic cell death (ICD) has emerged as a revolutionary concept in the development of novel anticancer therapies. This particular form of cell death is able, through the spatiotemporally defined emission of danger signals by the dying cell, to induce an effective antitumor immune response, allowing the immune system to recognize and eradicate malignant cells. To date, only a restricted number of chemotherapeutics can trigger ICD of cancer cells. We previously reported that a peptide, called RT53, spanning the heptad leucine repeat region of the survival protein AAC-11 fused to a penetrating sequence, selectively induces cancer cell death in vitro and in vivo. Interestingly, B16F10 melanoma cells treated by RT53 were able to mediate anticancer effects in a tumor vaccination model. Stimulated by this observation, we investigated whether RT53 might mediate ICD of cancer cells. Here, we report that RT53 treatment induces all the hallmarks of immunogenic cell death, as defined by the plasma membrane exposure of calreticulin, release of ATP and the exodus of high-mobility group box 1 protein (HMGB1) from dying cancer cells, through a non-regulated, membranolytic mode of action. In a prophylactic mouse model, vaccination with RT53-treated fibrosarcomas prevented tumor growth at the challenge site. Finally, local intratumoral injection of RT53 into established cancers led to tumor regression together with T-cell infiltration and the mounting of an inflammatory response in the treated animals. Collectively, our results strongly suggest that RT53 can induce bona fide ICD of cancer cells and illustrate its potential use as a novel antitumor and immunotherapeutic strategy.
Dietary L-Tryptophan Modulates the Structural and Functional Composition of the Intestinal Microbiome in Weaned Piglets

Background: Intestinal microbiota plays an important role in regulating metabolism, physiology, and immune response of the host. L-Tryptophan (Trp) are metabolized by several genera of bacteria. It remains largely unknown whether Trp can regulate the composition and diversity of the intestinal microbiota and contribute to intestinal homeostasis. Methods: A total of 126 weaning piglets were fed a corn- and soybean meal-based diet supplemented with 0, 0.2, or 0.4% Trp for 4 weeks. The intestinal microbiota was measured by using bacterial 16S rRNA gene-based high-throughput sequencing methods. Metabolites of Trp and short-chain fatty acids (SCFAs) in the hindgut were determined by high-performance liquid chromatography and gas chromatography, respectively. The mRNA levels for aromatic hydrocarbon receptor (AhR), tumor necrotic factor-α (TNF-α), interleukin-8 (IL-8), and protein abundances of tight junction proteins were determined. Results: Compared with the control group, Trp supplementation enhanced piglet growth performance and markedly altered the intestinal microbial composition as evidenced by enhanced alpha and beta diversity in the microbiome (P < 0.05). The abundances of Prevotella, Roseburia, and Succinivibrio genera were enriched, but those of Clostridium sensu stricto and Clostridium XI, opportunistic pathogens, were decreased with dietary Trp supplementation. Analysis of metabolic pathways indicated enhanced indole alkaloid biosynthesis and Trp metabolism, which was validated by elevated concentrations of 3-indoleacetic acid and indole in the intestinal contents of Trp-supplemented piglets (P < 0.05). These changes in Trp metabolites were correlated with activation of AhR and cytochrome p4501 A1 (CYP1A1) in cecum and colonic tissues, and with a decrease in the intestinal mucosal IL-8 mRNA level. Moreover, the protein abundances for zonula occluden (ZO)-1 and occludin were upregulated by Trp supplementation in colonic tissues. Conclusion: Dietary Trp supplementation altered intestinal microbial composition and diversity, improved intestinal mucosal barrier function, activated AhR signaling, and downregulated expression of inflammatory cytokines in the large intestine of weaned piglets. These results indicate a crosstalk between dietary Trp and intestine in nutrition, microbial metabolism, and mucosal immunity.
Low testosterone is associated with frailty, muscle wasting and physical dysfunction among men receiving hemodialysis: a longitudinal analysis.

BACKGROUND Despite the high prevalence of frailty among patients receiving hemodialysis, few preventable or treatable contributing causes have been identified. Hypogonadism is also common in this population and low serum testosterone concentrations share several clinical phenotypes with frailty. We hypothesized that low serum testosterone concentrations would be associated with frailty and several of its individual components. METHODS We used data from 440 men from A Cohort Study To Investigate the Value of Exercise in ESRD/Analysis Designed to Investigate the Paradox of Obesity and Survival in ESRD, a longitudinal study that recruited participants from 14 dialysis centers in Atlanta, GA and the San Francisco, CA Bay Area from 2009 to 2011. We assessed frailty using the Fried Frailty Phenotype. We examined the association between free testosterone (as a continuous and dichotomous variable) and frailty, individual frailty components, sarcopenia, lower extremity function and muscle mass estimation by creatinine and body impedance spectroscopy over 12 months using generalized estimating equations. RESULTS The mean age was 56.1 ± 14.2 years and 27% were white. A 50% lower concentration of free testosterone was associated with 1.40-fold higher odds of being frail [95% confidence interval (CI) 1.05-1.53] and 1.40-fold higher odds of becoming frail over 12 months (95% CI 1.07-1.73). This association was mainly due to an association with two components of frailty: grip strength and gait speed. In addition, 50% lower free testosterone concentration was associated with a 1.55-fold higher odds of having sarcopenia (95% CI 1.09-2.02) and 1.72-fold higher odds for developing sarcopenia (95% CI 1.13-2.33) as well as with lower muscle mass and a decrease in muscle mass over 12 months as estimated by serum creatinine and by bioelectrical impedance spectroscopy. CONCLUSION Serum free testosterone concentration was associated with frailty, physical function, sarcopenia and muscle mass as well as with changes in these outcomes over 12 months. Testosterone replacement may be a feasible therapeutic target toward prevention of frailty, although clinical trials are needed to test this possibility.
G1 and S phase arrest in Candida albicans induces filamentous growth via distinct mechanisms

Candida albicans is an opportunistic fungal pathogen. In immunocompromised individuals, it can cause bloodstream infections with high mortality rates. The ability to switch between yeast and hyphal morphologies is a critical virulence factor of C. albicans. In response to diverse environmental cues, several signaling pathways are activated resulting in filamentous growth. Interestingly, cell cycle arrest can also trigger filamentous growth although the pathways involved are not well‐understood. Here, we demonstrate that the cAMP‐PKA pathway is involved in the filamentous growth caused by G1 arrest due to the depletion of the G1 cyclin Cln3 and S phase arrest due to hydroxyurea treatment. The downstream mechanisms involved in filamentation are different between the two cell cycle arrest phenomena. Cln3‐depleted cells require HGC1 and UME6 for filamentous growth, but hydroxyurea‐induced filamentation does not. Also, the hyphal repressor Nrg1 is not involved in the suppression of Cln3‐depletion and hydroxyurea‐induced filamentous growth. The findings highlight the complexity of the signaling networks that control filamentous growth in which different mechanisms downstream of the cAMP‐PKA pathway are activated based on the nature of the inducing signals.
Decreased incidence of venous thromboembolism found in trauma patients with positive blood alcohol concentration on admission

ABSTRACT Background: The reported incidence of venous thromboembolism (VTE) disease in trauma is 1–58% and is considered a preventable cause of mortality. Positive blood alcohol concentration (BAC) is found in 8–45% of trauma admissions; however, its association with VTE is controversial. Objectives: We hypothesized that a positive BAC on admission would be associated with a lower rate of VTE in a large national database of trauma patients. Methods: We queried the largest United States trauma registry, National Trauma Data Bank (2007–2015), for any patient with positive BAC on admission. The primary outcome was VTE and the secondary outcome was mortality. A multivariable logistic regression model was used for analysis. Results: From 2,725,032 patients (70.1% male, 29.9% female), 1,800,216 (66.1%) had a negative BAC while 924,816 (33.9%) had a positive BAC. A positive BAC was associated with lower rates of VTE (OR = 0.88, CI = 0.86–0.90, p < 0.001) and mortality (OR = 0.91, CI = 0.90–0.93, p < 0.001). Conclusion: In a large national database, trauma patients with a positive BAC were associated with a lower rate of VTE compared to those with negative BAC. Additionally, trauma patients with positive BAC had a lower association with mortality. These findings remained after adjustment of well-known risk factors for VTE and mortality, respectively.
Betaine improves the growth performance and muscle growth of partridge shank broiler chickens via altering myogenic gene expression and insulin‐like growth factor‐1 signaling pathway

Abstract This study was conducted to investigate the effect of betaine on growth performance, carcass characteristics, myogenic gene expression, and insulin‐like growth factor‐1 (IGF‐1) signaling pathway in partridge shank broiler chickens. A total of 192 one‐day‐old partridge shank broiler chickens were randomly divided into 4 groups with 6 replicates of 8 chickens for a 52‐d feeding trial. Broilers were fed a basal diet supplemented with 0 (control), 250 (B250), 500 (B500), or 1,000 (B1000) mg/kg betaine. Compared with the control group, the B500 and B1000 groups had higher (P < 0.05) body weight gain (BWG), and the B500 group had a lower (P < 0.05) feed/gain ratio (F:G) during the whole trial period. Moreover, the B1000 group increased (P < 0.05) the breast muscle yield and decreased (P < 0.05) relative abdominal fat weight. The mRNA expression of myocyte enhancer factor 2B (MEF2B) and mechanistic target of rapamycin (mTOR) and mTOR phosporylation were higher (P < 0.05) in both breast and thigh muscles in the B500 and B1000 groups than those in the control group. The higher (P < 0.05) concentration and mRNA expression of IGF‐1 were also observed in breast muscle in the B500 and B1000 groups. Additionally, the B1000 group up‐regulated (P < 0.05) the mRNA level of myogenic differentiation factor 1 (MyoD1) in breast muscle and myogenin (MyoG) in thigh muscle. In conclusion, diets supplemented with 500 or 1,000 mg/kg betaine improved the growth performance of partridge shank broiler chickens during the whole trial period, and the B1000 group significantly improved the breast muscle growth. These improvements might result from increased mRNA expression of MyoD1 and MEF2B in breast muscle and MyoG and MEF2B in thigh muscle, and through alterations in IGF‐1/mTOR signaling pathway.
The Power of Complementary Regularizers: Image Recovery via Transform Learning and Low-Rank Modeling

Recent works on adaptive sparse and on low-rank signal modeling have demonstrated their usefulness in various image / video processing applications. Patch-based methods exploit local patch sparsity, whereas other works apply low-rankness of grouped patches to exploit image non-local structures. However, using either approach alone usually limits performance in image reconstruction or recovery applications. In this work, we propose a simultaneous sparsity and low-rank model, dubbed STROLLR, to better represent natural images. In order to fully utilize both the local and non-local image properties, we develop an image restoration framework using a transform learning scheme with joint low-rank regularization. The approach owes some of its computational efficiency and good performance to the use of transform learning for adaptive sparse representation rather than the popular synthesis dictionary learning algorithms, which involve approximation of NP-hard sparse coding and expensive learning steps. We demonstrate the proposed framework in various applications to image denoising, inpainting, and compressed sensing based magnetic resonance imaging. Results show promising performance compared to state-of-the-art competing methods.
Anomalous morphology in left hemisphere motor and premotor cortex of children who stutter

Stuttering is a neurodevelopmental disorder that affects the smooth flow of speech production. Stuttering onset occurs during a dynamic period of development when children first start learning to formulate sentences. Although most children grow out of stuttering naturally, ∼1% of all children develop persistent stuttering that can lead to significant psychosocial consequences throughout one's life. To date, few studies have examined neural bases of stuttering in children who stutter, and even fewer have examined the basis for natural recovery versus persistence of stuttering. Here we report the first study to conduct surface-based analysis of the brain morphometric measures in children who stutter. We used FreeSurfer to extract cortical size and shape measures from structural MRI scans collected from the initial year of a longitudinal study involving 70 children (36 stuttering, 34 controls) in the 3-10-year range. The stuttering group was further divided into two groups: persistent and recovered, based on their later longitudinal visits that allowed determination of their eventual clinical outcome. A region of interest analysis that focused on the left hemisphere speech network and a whole-brain exploratory analysis were conducted to examine group differences and group × age interaction effects. We found that the persistent group could be differentiated from the control and recovered groups by reduced cortical thickness in left motor and lateral premotor cortical regions. The recovered group showed an age-related decrease in local gyrification in the left medial premotor cortex (supplementary motor area and and pre-supplementary motor area). These results provide strong evidence of a primary deficit in the left hemisphere speech network, specifically involving lateral premotor cortex and primary motor cortex, in persistent developmental stuttering. Results further point to a possible compensatory mechanism involving left medial premotor cortex in those who recover from childhood stuttering.
Localization of cells expressing SGLT1 mRNA in the yolk sac and small intestine of broilers

ABSTRACT The uptake of glucose is mediated mainly by the sodium‐glucose cotransporter, SGLT1. Previous studies using quantitative PCR showed that SGLT1 mRNA was induced in the yolk sac and in the small intestine prior to hatch. However, PCR analysis did not allow for the localization of cells expressing SGLT1 mRNA. The objective of this study was to use in situ hybridization to identify cells in the yolk sac and small intestine that expressed SGLT1 mRNA during the transition from late embryogenesis to early post‐hatch. Expression of SGLT1 mRNA in yolk sac epithelial cells was low from embryonic d 11 to 17, peaked at embryonic d 19, and declined at day of hatch. In the small intestine, cells expressing SGLT1 mRNA were present not only along the intestinal villi but also in the crypts. There was greater expression of SGLT1 mRNA in the intestinal epithelial cells that line the villus than in the olfactomedin 4‐expressing stem cells located in the crypts. The latter result suggests that stem cells have the ability to import glucose. Expression of SGLT1 mRNA in the intestine increased from embryonic d 19 to day of hatch and then maintained a high level of expression from d 1 to d 7 post‐hatch. For both the yolk sac and small intestine, the temporal pattern of SGLT1 mRNA expression detected by in situ hybridization was consistent with the pattern revealed by PCR.
Differential Innervation of Secretory Coils and Ducts in Human Eccrine Sweat Glands

Background: Previous studies demonstrate that eccrine sweat glands are innervated by both cholinergic and adrenergic nerves. However, it is still unknown whether the secretory coils and ducts of eccrine sweat glands are equally innervated by the sympathetic nerve fibers. To well understand the mechanisms on sweat secretion and reabsorption, the differential innervation of secretory coils and ducts in human eccrine sweat glands was investigated in the study. Methods: From June 2016 to June 2017, six human skins were fixed, paraffin-embedded, and cut into 5 &mgr;m-thick sections, followed by costaining for nerve fiber markers protein gene product 9.5 (PGP 9.5), tyrosine hydroxylase (TH) and vasoactive intestinal peptide (VIP), and eccrine sweat gland markers K7, S100P, and K14 by combining standard immunofluorescence with tyramide signal amplification (IF-TSA). Stained sections were observed under the microscope, photographed, and analyzed. Results: The fluorescent signals of PGP 9.5, TH, and VIP were easily visualized, by IF-TSA, as circular patterns surrounding eccrine sweat glands, but only PGP 9.5 could be observed by standard IF. The IF-TSA method is more sensitivity than standard IF in detecting antigens expressed at low levels. PGP 9.5, TH, and VIP appeared primarily surrounding the secretory coils and sparsely surrounding the sweat ducts. Conclusion: Sweat secretion is mainly controlled by autonomic nerves whereas sweat reabsorption is less affected by nerve activity.
Exploration of the Regulatory Mechanism of Secondary Metabolism by Comparative Transcriptomics in Aspergillus flavus

Mycotoxins cause a huge threaten to agriculture, food safety, and human and animal life. Among them, aflatoxins (AFs) have always been considered the most potent carcinogens, and filamentous fungi from Aspergillus genus are their major producers, especially A. flavus. Although the biosynthesis path of these chemicals had been well-identified, the regulatory mechanisms controlling expression of AF gene cluster were poorly understood. In this report, genome-wide transcriptome profiles of A. flavus from AF conducing [yeast sucrose media (YES)] and non-conducing [yeast peptone media (YEP)] conditions were compared by using deep RNA sequencing (RNA-seq), and the results revealed that AF biosynthesis pathway and biosynthesis of amino acids were significantly upregulated in YES vs. YEP. Further, a novel LaeA-like methyltransferase AFLA_121330 (Lael1) was identified for the first time, to play a specific role in the regulation of AF biosynthesis. Contrary to LaeA, which gene deletion reduced the level, lael1 deletion resulted in a significant increase in AF production. Further, co-expression network analysis revealed that mitochondrial pyruvate transport and signal peptide processing were potentially involved in AF synthesis for the first time, as well as biological processes of ribosome, branched-chain amino acid biosynthetic process and translation were co-regulated by AfRafA and AfStuA. To sum up, our analyses could provide novel insights into the molecular mechanism for controlling the AF and other secondary metabolite synthesis, adding novel targets for plant breeding and making fungicides.
No association of serum PSA with vitamin D or total oxidant-antioxidant capacity in healthy men

Abstract Background and aim: Vitamin D deficiency and oxidative stress were suggested to be related to prostate cancer risk. We aimed to investigate the association of serum PSA concentration with vitamin D and total oxidant/antioxidant levels. Materials and methods: A total of 95 healthy men were enrolled for the cross sectional study. Serum PSA, 25(OH)D, serum total oxidant status, and total antioxidant status were measured. Results: Serum PSA was significantly negatively correlated with serum total oxidant status (r= −0.309, p = .003) but there was no significant correlation between PSA and 25(OH)D (p = .383) or total antioxidant levels (p = .233). After adjustment for age BMI and smoking status with multiple regression analysis, there was no significant association between serum PSA and total oxidant status. Conclusion: We find no evidence for an association between PSA and vitamin D levels or serum total oxidant/antioxidant levels.
NumaMMA: NUMA MeMory Analyzer

Non Uniform Memory Access (NUMA) architectures are nowadays common for running High-Performance Computing (HPC) applications. In such architectures, several distinct physical memories are assembled to create a single shared memory. Nevertheless, because there are several physical memories, access times to these memories are not uniform depending on the location of the core performing the memory request and on the location of the target memory. Hence, threads and data placement are crucial to efficiently exploit such architectures. To help in taking decision about this placement, profiling tools are needed. In this work, we propose NUMA MeMory Analyzer (NumaMMA), a new profiling tool for understanding the memory access patterns of HPC applications. NumaMMA combines efficient collection of memory traces using hardware mechanisms with original visualization means allowing to see how memory access patterns evolve over time. The information reported by NumaMMA allows to understand the nature of these access patterns inside each object allocated by the application. We show how NumaMMA can help understanding the memory patterns of several HPC applications in order to optimize them and get speedups up to 28% over the standard non optimized version.
Potential Marker Pathways in the Endometrium That May Cause Recurrent Implantation Failure

The aim of this prospective cohort study was to identify altered biologic processes in the endometrium that may be potential markers of receptive endometrium in patients with repeated implantation failure (RIF) as compared with fertile controls. The study was conducted in a university-affiliated in vitro fertilization (IVF) gynecology clinic and molecular biology and genetics laboratory. Healthy fertile controls (n = 24) and patients with RIF (n = 24) were recruited. Window of implantation gene profiling associated with RIF was performed. Six hundred forty-one differentially expressed genes were identified, and 44 pathways were found enriched. Upon clustering of the enriched pathways, 9 representative pathways were established. The important pathways that were identified included circadian rhythm, pathways in cancer, proteasome, complement and coagulation cascades, citrate cycle, adherens junction, immune system and inflammation, cell cycle, and renin–angiotensin system. The involvement of the circadian rhythm pathway and other related pathways may alter the endometrium’s functioning to ultimately cause RIF. Furthermore, we found that the pathogenesis of RIF was multifaceted and that numerous processes were involved. We believe that a better understanding of the underlying mechanisms of RIF will ultimately give rise to better treatment opportunities and to better outcomes in IVF.
A Short Note about Kinetics-600

We describe an extension of the DeepMind Kinetics human action dataset from 400 classes, each with at least 400 video clips, to 600 classes, each with at least 600 video clips. In order to scale up the dataset we changed the data collection process so it uses multiple queries per class, with some of them in a language other than english -- portuguese. This paper details the changes between the two versions of the dataset and includes a comprehensive set of statistics of the new version as well as baseline results using the I3D neural network architecture. The paper is a companion to the release of the ground truth labels for the public test set.