Miracle-dz/UniFAR-FTUs huggingface dataset:
An increase in the Akkermansia spp. population induced by metformin treatment improves glucose homeostasis in diet-induced obese mice

Background Recent evidence indicates that the composition of the gut microbiota contributes to the development of metabolic disorders by affecting the physiology and metabolism of the host. Metformin is one of the most widely prescribed type 2 diabetes (T2D) therapeutic agents. Objective To determine whether the antidiabetic effect of metformin is related to alterations of intestinal microbial composition. Design C57BL/6 mice, fed either a normal-chow diet or a high-fat diet (HFD), were treated with metformin for 6 weeks. The effect of metformin on the composition of the gut microbiota was assessed by analysing 16S rRNA gene sequences with 454 pyrosequencing. Adipose tissue inflammation was examined by flow cytometric analysis of the immune cells present in visceral adipose tissue (VAT). Results Metformin treatment significantly improved the glycaemic profile of HFD-fed mice. HFD-fed mice treated with metformin showed a higher abundance of the mucin-degrading bacterium Akkermansia than HFD-fed control mice. In addition, the number of mucin-producing goblet cells was significantly increased by metformin treatment (p<0.0001). Oral administration of Akkermansia muciniphila to HFD-fed mice without metformin significantly enhanced glucose tolerance and attenuated adipose tissue inflammation by inducing Foxp3 regulatory T cells (Tregs) in the VAT. Conclusions Modulation of the gut microbiota (by an increase in the Akkermansia spp. population) may contribute to the antidiabetic effects of metformin, thereby providing a new mechanism for the therapeutic effect of metformin in patients with T2D. This suggests that pharmacological manipulation of the gut microbiota in favour of Akkermansia may be a potential treatment for T2D.
Distinct plasma proteomic changes in male and female African American stroke patients.

BACKGROUND Stroke occurs more often and results in more severe brain injury in African Americans than in Caucasians. The former also exhibit different responses to thrombolytic therapy than the latter do. There is an imminent need for stroke biomarkers for African Americans, who have been underrepresented in biomarker research for stroke diagnosis and prognosis. Proteomics offers sources for protein biomarkers that are not available by other Omics approaches. In this pilot study, plasma proteomes of African American stroke patients were analyzed and compared to that of hypertensive, non-stroke controls. METHODS Plasma samples were prepared from whole blood specimens that were collected from stroke patients admitted to Grady Memorial Hospital in Atlanta, and their age- and sex-matched, hypertensive controls from the outpatient clinic. Samples were pooled according to patient groups and sex. Plasma proteins were analyzed with quantitative mass spectrometry. The identified and quantified proteins were compared between stroke and control patients of each sex. Proteins that showed changes in abundances in stroke patients were further analyzed with the assistance of bioinformatics tools for their known biological functions or potential implications in stroke. RESULTS A total of 128 annotated proteins were identified. Results of bioinformatic analysis of plasma proteins whose levels were increased in stroke patients showed, as expected, their association with blood coagulation and inflammation processes. Interestingly, a number of proteins showed different or even opposing changes in male and female stroke patients, notably those involved in IL-4 and IL-6 signaling, complement activation, and blood coagulation disorders. For a few proteins that were increased in female but unchanged or decreased in male stroke patients, an association with fibromuscular dysplasia was recognized. CONCLUSION Plasma proteins that differ in quantities between stroke patients and controls were readily detected using a simple proteomic approach. Sex-dependent changes and changes that have not been reported for African American stroke patients offer potentially novel biomarkers for stroke in this underserved population.
Best practices on immunomodulators and biologic agents for ulcerative colitis and Crohn’s disease in Asia

The Asia-Pacific Working Group on inflammatory bowel disease (IBD) was established in Cebu, Philippines, under the auspices of the Asian Pacific Association of Gastroenterology with the goal of improving IBD care in Asia. This consensus is carried out in collaboration with Asian Organization for Crohn’s and Colitis. With biologic agents and biosimilars becoming more established, it is necessary to conduct a review on existing literature and establish a consensus on when and how to introduce biologic agents and biosimilars in the conjunction with conventional treatments for ulcerative colitis (UC) and Crohn’s disease (CD) in Asia. These statements also address how pharmacogenetics influence the treatments of UC and CD and provide guidance on response monitoring and strategies to restore loss of response. Finally, the review includes statements on how to manage treatment alongside possible hepatitis B and tuberculosis infections, both common in Asia. These statements have been prepared and voted upon by members of IBD workgroup employing the modified Delphi process. These statements do not intend to be all-encompassing and future revisions are likely as new data continue to emerge.
Stereological and gene expression examinations on the combined effects of photobiomodulation and curcumin on wound healing in type one diabetic rats

We examined the effects of photobiomodulation (PBM) independently and combined with curcumin on stereological parameters and basic fibroblast growth factor (bFGF), hypoxia‐inducible factor‐1α (HIF‐1α), and stromal cell‐derived factor‐1α (SDF‐1α) gene expressions in an excisional wound model of rats with type one diabetes mellitus (T1DM). T1DM was induced by an injection of streptozotocin (STZ) in each of the 90 male Wistar rats. One round excision was generated in the skin on the back of each of the 108 rats. The rats were divided into six groups (n = 18 per group): control (diabetic), untreated group; vehicle (diabetic) group, which received sesame oil; PBM (diabetic) group; curcumin (diabetic) group; PBM + curcumin (diabetic) group; and a healthy control group. On days 4, 7, and 15, we conducted both stereological and quantitative real‐time PCR (qRT‐PCR) analyses. The PBM and PBM + curcumin groups had significantly better inflammatory response modulation in terms of macrophages (P < .01), neutrophils (P < .001), and increased fibroblast values compared with the other groups at day 4 (P < .001), day 7 (P < .01), and day 15 (P < .001). PBM treatment resulted in increased bFGF gene expression on days 4 (P < .001) and 7 (P < .001), and SDF‐1α gene expression on day 4 (P < .001). The curcumin group had increased bFGF (P < .001) expression on day 4. Both the PBM and PBM + curcumin groups significantly increased wound healing by modulation of the inflammatory response, and increased fibroblast values and angiogenesis. The PBM group increased bFGF and SDF‐1α according to stereological and gene expression analyses compared with the other groups. The PBM and PBM + curcumin groups significantly increased the skin injury repair process to more rapidly reach the proliferation phase of the wound healing in T1DM rats.
Shifting from the Perceptual Brain to the Logical Brain: The Neural Impact of Cognitive Inhibition Training

Abstract What happens in the human brain when the mind has to inhibit a perceptual process in order to activate a logical reasoning process? Here, we use functional imaging to show the networks of brain areas involved in a deductive logic task performed twice by the same subjects, first with a perceptual bias and then with a logical response following bias-inhibition training. The main finding is a striking shift in the cortical anatomy of reasoning from the posterior part of the brain (the ventral and dorsal pathways) to a left-prefrontal network including the middle-frontal gyrus, Broca's area, the anterior insula, and the pre-SMA. This result indicates that such brain shifting is an essential element for human access to logical thinking.
Normal 0-1 Polytopes

We study the question of when 0-1 polytopes are normal or, equivalently, having the integer decomposition property. In particular, we shall associate to each 0-1 polytope a labeled hypergraph, and examine the equality between its Ehrhart and polytopal rings via the combinatorial structures of the labeled hypergraph.
The scourge of head injury among commercial motorcycle riders in Kampala; a preventable clinical and public health menace.

BACKGROUND Trauma is an increasingly important cause of disease globally. Half of this trauma is from road traffic injuries with motorcycles contributing 21-58%. Low protective gear use, lack of regulation and weak traffic law enforcement contribute to unsafe nature of commercial motorcycles also known as "boda boda" in Uganda. OBJECTIVES To determine the prevalence of protective gear use, the occurrence of head injury and the relationship between the two among commercial motorcycle riders in Kampala. METHODS Following ethical approval we recruited consecutive consenting participants to this analytical cross-sectional study. Data was collected using pretested interviewer administered questionnaires, double entered in Epidata and analyzed with STATA. Proportions and means were used to summarize data. Odds ratios were calculated for association between wearing helmets and occurrence and severity of head injury. RESULTS All 328 participants recruited were male. Of these, 18.6% used Protective gear and 71.1 % sustained head injury. Helmets protected users from head injury (OR 0.43, 95% CI, 0.23-0.8) and significantly reduced its severity when it occurred. CONCLUSION Protective gear use was low, with high occurrence of head injury among commercial motorcycle riders in Uganda. More effective strategies are needed to promote protective gear use among Uganda's commercial motorcycle riders.
Analysis of force vector field during centrifugation for optimizing cell sheet adhesion

A three‐dimensional tissue was fabricated by layering cell sheets with centrifugation. In this system, an optimal centrifugal force promoted the adhesion between (a) a cell sheet and a culture dish, and (b) layered cell sheets, resulting in a significant decrease in the fabrication time of the tissue. However, negative effects like sliding/significant deformation of cell sheets were observed upon high rotational speed use. These negative effects inhibit the further shortening of the fabrication time. The sliding/deformation suggests that the centrifugal forces were applied on the cell sheets in unwanted directions. Studies on the force vector field applied to the object placed on the plate during centrifugation are not available, and thus, the reason for the occurrence of such negative effects is unclear. Here, we theoretically derived the spatial distribution of acceleration applied on a plate during centrifugation. Using this theory, we found that the negative effects were triggered by the centrifugal force in the direction parallel to the plate surface, which appeared due to an inclination of the plate surface against a horizontal plane. Therefore, by adding weights on the plate edge to maintain the plate surface in a horizontal position, we succeeded in eliminating the negative effects and in increasing the rotational speed, with the minimum risk of sliding/deformation of cell sheets. We succeeded in reducing the time to establish tight adhesion between a mouse myoblast sheet and a culture dish, and layered cell sheets by increasing the centrifugal force from 5 min to 1 min without significant cytotoxicity.
HIV mediated immune aging in young adults infected perinatally or during childhood.

BACKGROUND HIV-infected patients progressing towards disease present a premature immune aging profile, characterized by the exhaustion of lymphopoiesis. The development of these anomalies may be prevented in young HIV-infected patients owing to their robust immune resources and lymphocyte regeneration capacities. METHODS An immunomonitoring substudy was designed for young adults aged between 18 and 25 years, living with HIV since childhood included in the national ANRS Co19 COVERTE Cohort. We compared markers associated with immune aging, including the frequency of circulating hematopoietic progenitors and the phenotype of lymphocyte populations, with those of patients infected with HIV in adulthood. RESULTS HIV-infected young adults displayed decreasing numbers of CD34 hematopoietic progenitors and mature lymphocytes, indicative of general lymphopenia and reminiscent of the alterations found in patients infected in adulthood or uninfected elderly people. This highlights the strong impact of HIV on the immune system despite patient young age at infection. Immune aging related alterations were particularly obvious in young patients who presented high viral loads. CONCLUSIONS HIV-infected young adults can present increased markers of immune activation and senescence, related to uncontrolled viral replication. This highlights the issue of non-compliance to antiretroviral therapy in patients at a young age, resulting in loss of viral control, premature immunosenescence, and potentially irreversible damage of their lymphopoietic system.
Recombinant Strains of Human Parechovirus in Rural Areas in the North of Brazil

We characterized the 24 nearly full-length genomes of human parechoviruses (PeV) from children in the north of Brazil. The initial phylogenetic analysis indicated that 17 strains belonged to genotype 1, 5 to genotype 4, and 1 to genotype 17. A more detailed analysis revealed a high frequency of recombinant strains (58%): A total of 14 of our PeV-As were chimeric, with four distinct recombination patterns identified. Five strains were composed of genotypes 1 and 5 (Rec1/5); five strains shared a complex mosaic pattern formed by genotypes 4, 5, and 17 (Rec4/17/5); two strains were composed of genotypes 1 and 17 (Rec1/17); and two strains were composed of genotype 1 and an undetermined strain (Rec1/und). Coalescent analysis based on the Vp1 gene, which is free of recombination, indicated that the recombinant strains most likely arose in this region approximately 30 years ago. They are present in high frequencies and are circulating in different small and isolated cities in the state of Tocantins. Further studies will be needed to establish whether the detected recombinant strains have been replacing parental strains or if they are co-circulating in distinct frequencies in Tocantins.
Effect of Polyphenol-Rich Dark Chocolate on Salivary Cortisol and Mood in Adults

The aim of the present study was to investigate whether ingestion of polyphenol-rich dark chocolate improved salivary cortisol levels and subjective mood states in adults recruited from a health and social care setting. Twenty-six participants ingested 25 g/day of a high polyphenol dark chocolate (containing 500 mg of total flavonoids) or a similar amount of a control dark chocolate containing negligible flavonoids for four weeks. Twenty-four-hour salivary glucocorticoid levels (cortisol and cortisone) were measured by an enzyme-linked immunosorbent assay, and subjective mood was assessed using a validated Positive Affect and Negative Affect Schedule. Total daily cortisol, morning cortisol, and the cortisol/cortisone ratio were significantly reduced (p < 0.001) after ingestion of only the high polyphenol dark chocolate. There were no significant differences between groups for overall scores for positive affect and negative affect. No changes were observed after the control dark chocolate, or any other parameter measured. In conclusion, the findings from this small-scale study indicate lowering of salivary cortisol levels following polyphenol-rich dark chocolate in adults recruited from a health and social care setting. Such changes may be attributable to their ability to inhibit 11β-hydroxysteroid dehydrogenase type 1 activity and warrant further investigation.
Subcortical amyloid load is associated with shape and volume in cognitively normal individuals

Amyloid‐beta (Aβ) deposition is one of the main hallmarks of Alzheimer's disease. The study assessed the associations between cortical and subcortical 11C‐Pittsburgh Compound B (PiB) retention, namely, in the hippocampus, amygdala, putamen, caudate, pallidum, and thalamus, and subcortical morphology in cognitively normal individuals. We recruited 104 cognitive normal individuals who underwent extensive neuropsychological assessment, PiB–positron emission tomography (PET) scan, and 3‐T magnetic resonance imaging (MRI) acquisition of T1‐weighted images. Global, cortical, and subcortical regional PiB retention values were derived from each scan and subcortical morphology analyses were performed to investigate vertex‐wise local surface and global volumes, including the hippocampal subfields volumes. We found that subcortical regional Aβ was associated with the surface of the hippocampus, thalamus, and pallidum, with changes being due to volume and shape. Hippocampal Aβ was marginally associated with volume of the whole hippocampus as well as with the CA1 subfield, subiculum, and molecular layer. Participants showing higher subcortical Aβ also showed worse cognitive performance and smaller hippocampal volumes. In contrast, global and cortical PiB uptake did not associate with any subcortical metrics. This study shows that subcortical Aβ is associated with subcortical surface morphology in cognitively normal individuals. This study highlights the importance of quantifying subcortical regional PiB retention values in these individuals.
JNK2 in myeloid cells impairs insulin's vasodilator effects in muscle during early obesity development through perivascular adipose tissue dysfunction.

Reduced vasodilator properties of insulin in obesity are caused by changes in perivascular adipose tissue and contribute to microvascular dysfunction in skeletal muscle, the causes of this dysfunction are unknown. The effects of a short Western diet on c-jun N-terminal kinase 2 (JNK2) expressing cells in PVAT on insulin induced vasodilation and perfusion of skeletal muscle were assessed. In vivo, two weeks of Western diet (WD) reduced whole-body insulin sensitivity, and insulin-stimulated muscle perfusion, determined using contrast ultrasonography during the hyperinsulinemic clamp. Ex vivo, WD triggered accumulation of PVAT in skeletal muscle and blunted its ability to facilitate insulin-induced vasodilation. Labeling of myeloid cells with green fluorescent protein identified bone marrow as a source of PVAT in muscle. To study whether JNK2 expressing inflammatory cells from bone marrow were involved, we transplanted JNK2-/- bone marrow to WT mice. Deletion of JNK2 in bone marrow rescued the vasodilator phenotype of PVAT during WD exposure. JNK2 deletion in myeloid cells prevented the WD-induced increase in F4/80 expression. Even though WD and JNK2 deletion resulted in specific changes in gene expression of PVAT, epididymal-, and subcutaneous adipose tissue, expression of tumor necrosis factor-α, interleukin1β, interleukin-6, or protein inhibitor of STAT1 was not affected. In conclusion, short term Western diet triggers infiltration of JNK2 positive myeloid cells into PVAT, resulting in PVAT dysfunction, non-classical inflammation and loss of insulin-induced vasodilatation in vivo, and ex vivo.
Towards an understanding of apoptosis detection by SYTO dyes

SYTO probes are gaining momentum as reliable and easy to use markers of apoptotic cell death, but the phenomenon underlying reduced SYTO fluorescence in apoptotic cells as compared with normal cells is still not fully elucidated. Herein, we attempt to provide further insights into mechanisms of reduced SYTO16 fluorescence during apoptosis.
Concise Review: Cellular and Molecular Mechanisms of Postnatal Injury‐Induced Enteric Neurogenesis

Although still controversial, there is increasing agreement that postnatal neurogenesis occurs in the enteric nervous system (ENS) in response to injury. Following acute colitis, there is significant cell death of enteric neurons and evidence suggests that subsequent neural regeneration follows. An enteric neural stem/progenitor cell population with neurogenic potential has been identified in culture; in vivo, compensatory neurogenesis is driven by enteric glia and may also include de‐differentiated Schwann cells. Recent evidence suggests that changes in the enteric microenvironment due to injury‐associated increases in glial cell‐derived neurotrophic factor (GDNF), serotonin (5‐hydroxytryptamine [HT]), products from the gut microbiome, and possibly endocannabinoids may lead to the transdifferentiation of mature enteric glia and may reprogram recruited Schwann cells. Targeting neurogenic pathways presents a promising avenue toward the development of new and innovative treatments for acquired damage to the ENS. In this review, we discuss potential sources of newly generated adult enteric neurons, the involvement of GDNF, 5‐HT, endocannabinoids, and lipopolysaccharide, as well as therapeutic applications of this evolving work. Stem Cells 2019;37:1136–1143
Expression of PD-1 and PD-L1 in Extramammary Paget Disease: Implications for Immune-Targeted Therapy

Extramammary Paget disease (EMPD) is a locally aggressive cutaneous malignancy that usually arises in anogenital or axillary skin. Immune checkpoint inhibitors targeting programmed cell death receptor (PD-1) and/or its ligand (PD-L1) are approved for the treatment of several types of cancer, and response to these generally correlates with increased PD-L1 expression by tumor cells. The expression of PD-L1 and composition and density of the tumor-associated immune infiltrate in EMPD have been little studied. To determine whether EMPD might be amenable to immune checkpoint blockade, we analyzed the expression of PD-1 and PD-L1 and the composition and density of the tumor-associated immune infiltrate in EMPD and evaluated associations between biomarker expression and clinicopathologic parameters. Twenty-one EMPD tumors were evaluated for tumor cell PD-L1 expression and for relative expression and distribution of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate by using a combination of visual and image analysis (Aperio ImageScope). In addition, PD-L1 expression was assessed in 10 cases of mammary Paget disease (MPD). In EMPD cases, PD-L1 was expressed by tumor cells (3/21; 14%) and the tumor-associated immune infiltrate (15/21; 71%), and PD-1 was expressed by the tumor-associated immune infiltrate in all cases analyzed (18/18). However, PD-L1 expression by EMPD tumor cells did not correlate with the density of CD3-, CD8-, or PD-1-positive cells in the tumor-associated immune infiltrate or other clinicopathologic parameters. Furthermore, the density of CD3, CD8, PD-1, and PD-L1 in the tumor-associated immune infiltrate did not correlate with any clinicopathologic parameters evaluated with the exception that CD3 positive values were significantly higher in patients who were still alive (median, 1310 cells/mm2; range, 543–2115;) than in those who died (median, 611 cells/mm2; range, 481–908; p = 0.049). In all MPD cases, PD-L1 was absent in tumor cells but present in the tumor-associated immune infiltrate, and PD-L1 expression in lymphocytes was lower in patients with HER2/neu-positive than in those with HER2/neu-negative disease (p = 0.07). Our findings raise the possibility of therapeutic targeting of the PD-1/PD-L1 axis in EMPD.