Miracle-dz/UniFAR-FTUs huggingface dataset:
Targeted-Release Organic Acids and Essential Oils Improve Performance and Digestive Function in Broilers under a Necrotic Enteritis Challenge

Simple Summary Controlling digestive diseases in the poultry industry is crucial to maximize profitability. Necrotic enteritis (NE) is a real threat for poultry that leads to high financial losses. Microencapsulated blends of organic acids and essential oils have gained increasing interest as feed additives that could alleviate the effects of these diseases by controlling the intestinal microbiota and enhancing the gut function of broiler chickens. Organic acids actually used as feed additives, including short-chain fatty acids (C1-C6), medium-chain fatty acids (C7-C12), and other organic acids, may show a range of variable physiological effects in the animals when combined with different phytogenic compounds. This study was designed to understand the mechanisms of action of these feed additives, their effect on intestinal morphology and growth performance, as well as their interaction with the gut microbiome. Our results provide evidence on the importance of designing proper combinations and doses of these additives to enhance growth performance, the microbiota profile, and histomorphology. Dietary supplementation of 0.5 g/kg of BUTYTEC-PLUS and 2 g/kg of ACITEC-MC as microencapsulated blends are recommended to improve broiler chickens performance under NE challenge due to their positive effect on gut microbiome and the absorptive capacity of the intestine. Abstract An experiment was performed to evaluate the effect of four different microencapsulated blends of organic acids (OA) and nature-identical aromatic compounds (AC) on growth performance and gut health of broilers challenged with a recycled NE litter. A total of 600 one-day-old male Ross 308 broilers were randomly assigned to five treatments consisting of a basal diet (as negative control) supplemented with each of the tested microencapsulated blends: OA1 (malic and fumaric acid) + AC; 2.5 g/kg; OA2 (calcium butyrate+fumaric acid) + AC; 1.7 g/kg; MCFA (capric-caprylic; caproic and lauric acid) + AC; 2 g/kg; and MCFA + OA3 (calcium butyrate+fumaric and citric acid) + AC; 1.5 g/kg. The AC used was the same for all treatments; including cinnamaldehyde, carvacrol, and thymol (8:1:1), as major compounds. Three tested blends enhanced growth performance by improving intestinal histomorphology (p < 0.001). The tested blends enhanced the abundance of some beneficial families such as Ruminococcaceae and Lachnospiraceae; while reducing that of harmful ones such as Enterobacteriaceae and Helicobacteraceae. A further dose-response experiment showed that 0.5 g/kg of the blend 2 and 2 g/kg of the blend 4 improved growth performance and intestinal histomorphology of chickens on d 42 and decreased fecal Enterobacteriaceae and C. perfringens counts. Similar effects to the previous experiment were observed for cecum microbiota.
Expression of the muscle-associated gene MYF6 in hairy cell leukemia

Hairy cell leukemia (HCL) is a purine analog-responsive B-cell malignancy containing the BRAF V600E mutation, expressing CD22, CD11c, CD103, tartrate resistant acid phosphatase (TRAP) CD25, CD123, and annexin 1A. BRAF V600E and the latter 4 markers are usually absent in the more aggressive and chemoresistant variant HCLv. To evaluate differences between HCL and HCLv, expression microarrays comparing HCL with HCLv were performed for 24694 genes using 47323 probes. Microarray data from 35 HCL and 27 HCLv purified samples showed the greatest HCL-HCLv difference in the muscle-associated gene MYF6, expressed by its 2 probes 18.5- and 10.8-fold higher in HCL than HCLv (p<0.0001). By real-time quantitative PCR (RQ-PCR), 100% of 152 classic HCL samples were MYF6-positive, vs 5 (6%) of 90 blood donors. MYF6-expression was also detected in 18 (35%) of 51 with HCLv, 11 (92%) of 12 with HCL expressing unmutated IGHV4-34, 35 (73%) of 48 with chronic lymphocytic leukemia (CLL), and 1 (8%) of 12 with mantle cell lymphoma. Hypomethylation status of MYF6 supported expression in HCL more than HCLv. Posttreatment blood samples becoming negative by flow cytometry remained MYF6+ by RQ-PCR in 42 (48%) of 87 HCL patients, and MYF6 RQ-PCR could detect 1 HCL in 105 normal cells. MYF6, universally expressed in HCL and in most CLL samples, may be a useful biomarker for these leukemias. Further studies are underway to determine the role of MYF6 in HCL.
Plant extracts rich in polyphenols: antibacterial agents and natural preservatives for meat and meat products

Abstract Plant extracts contain large amounts of bioactive compounds, mainly polyphenols. Polyphenols inhibit the growth of microorganisms, especially bacteria. Their mechanism of action is still not fully understood but may be related to their chemical structure. They can cause morphological changes in microorganisms, damage bacterial cell walls and influence biofilm formation. Polyphenols also influence protein biosynthesis, change metabolic processes in bacteria cells and inhibit ATP and DNA synthesis (suppressing DNA gyrase). Due to the antioxidant and antibacterial activity of phenolic compounds, plant extracts offer an alternative to chemical preservatives used in the meat industry, especially nitrates (III). They can inhibit the growth of spoilage and pathogenic microflora, suppress oxidation of meat ingredients (lipids and proteins) and prevent discoloration. In this paper, we describe the factors that influence the content of polyphenols in plants and plant extracts. We present the antimicrobial activities of plant extracts and their mechanisms of action, and discuss the effects of plant extracts on the shelf-life of meat and meat products.
Is there enough evidence to justify the use of laser and other thermal therapies in female lower urinary tract dysfunction? Report from the ICI‐RS 2019

There is increasing evidence to suggest that thermomodulation may have a role in the management of women with lower urinary tract dysfunction (LUTD) and there has been widespread adoption of laser and radiofrequency (RF) therapies within clinical practice. However, in many areas of LUTD, the data are still limited and there remains a need for further evaluation of the safety and efficacy of thermal therapy. The aim of this study proposal is to report the findings of the International Consultation on Incontinence Research Society to clarify our current knowledge regarding the evidence for thermal therapy in LUTD and to set research priorities for the future.
Physical Activity in Older Adults: An Investigation in a Metropolitan Area of Southern Italy

Physical activity (PA) and exercise are fundamental to maintaining health in older adults. World Health Organization guidelines state that older adults should practice at least 150 min/week of moderate/vigorous intensity PA to obtain health benefits. We assessed PA levels among older adults in southern Italy and evaluated possible associated determinants. The study was carried out between September and November 2019 in the metropolitan area of Bari. We collected information from participants over 65 years using a self-administered questionnaire. We investigated associations between sociodemographic characteristics, health conditions, and inactivity/PA levels. A total of 383 individuals completed the questionnaire. Mean body mass index indicated that 45.4% of participants were overweight. Mean time spent in PA was 476.2 ± 297.8 min/week, with women reporting lower levels than men (370.8 ± 210 vs. 555.2 ± 334.3 min/week, p = 0.08). Weekly sitting time was positively related to age. Attending religious or recreational activities was related to moderate PA. Educational level was positively associated with PA while dog ownership represented an obstacle to achieving recommended PA levels in our population. Participants generally met the recommended levels of PA, especially men; the educational level was the main determinant. Interventions aimed at promoting PA among older adults with lower education levels and women are needed in this setting.
Pre- and Neonatal Exposure to Lead (Pb) Induces Neuroinflammation in the Forebrain Cortex, Hippocampus and Cerebellum of Rat Pups

Lead (Pb) is a heavy metal with a proven neurotoxic effect. Exposure is particularly dangerous to the developing brain in the pre- and neonatal periods. One postulated mechanism of its neurotoxicity is induction of inflammation. This study analyzed the effect of exposure of rat pups to Pb during periods of brain development on the concentrations of selected cytokines and prostanoids in the forebrain cortex, hippocampus and cerebellum. Methods: Administration of 0.1% lead acetate (PbAc) in drinking water ad libitum, from the first day of gestation to postnatal day 21, resulted in blood Pb in rat pups reaching levels below the threshold considered safe for humans by the Centers for Disease Control and Prevention (10 µg/dL). Enzyme-linked immunosorbent assay (ELISA) method was used to determine the levels of interleukins IL-1β, IL-6, transforming growth factor-β (TGF-β), prostaglandin E2 (PGE2) and thromboxane B2 (TXB2). Western blot and quantitative real-time PCR were used to determine the expression levels of cyclooxygenases COX-1 and COX-2. Finally, Western blot was used to determine the level of nuclear factor kappa B (NF-κB). Results: In all studied brain structures (forebrain cortex, hippocampus and cerebellum), the administration of Pb caused a significant increase in all studied cytokines and prostanoids (IL-1β, IL-6, TGF-β, PGE2 and TXB2). The protein and mRNA expression of COX-1 and COX-2 increased in all studied brain structures, as did NF-κB expression. Conclusions: Chronic pre- and neonatal exposure to Pb induces neuroinflammation in the forebrain cortex, hippocampus and cerebellum of rat pups.
Operative Times Have Remained Stable for Total Hip Arthroplasty for >15 Years

Background: Understanding trends in operative times has become increasingly important in light of total hip arthroplasty (THA) being added to the Centers for Medicare & Medicaid Services (CMS) 2019 Potentially Misvalued Codes List. The purpose of this review was to explore the mean THA operative times reported in the literature in order (1) to determine if they have increased, decreased, or remained the same for patients reported on between 2000 and 2019 and (2) to determine what factors might have contributed to the difference (or lack thereof) in THA operative time over a contemporary study period. Methods: The PubMed and EBSCOhost databases were queried to identify all articles, published between 2000 and 2019, that reported on THA operative times. The keywords used were “operative,” “time,” and “total hip arthroplasty. ” An article was included if the full text was available, it was written in English, and it reported operative times of THAs. An article was excluded if it did not discuss operative time; it reported only comparative, rather than absolute, operative times; or the cohort consisted of total knee arthroplasties (TKAs) and THAs, exclusively of revision THAs, or exclusively of robotic THAs. Data on manual or primary THAs were extracted from studies including robotic or revision THAs. Thirty-five articles reporting on 630,675 hips that underwent THA between 1996 and 2016 met our criteria. Results: The overall weighted average operative time was 93.20 minutes (range, 55.65 to 149.00 minutes). When the study cohorts were stratified according to average operative time, the highest number fell into the 90 to 99-minute range. Operative time was stable throughout the years reported. Factors that led to increased operative times included increased body mass index (BMI), less surgical experience, and the presence of a trainee. Conclusions: The average operative time across the included articles was approximately 95 minutes and has been relatively stable over the past 2 decades. On the basis of our findings, we cannot support CMS lowering the procedural valuation of THA given the stability of its operative times and the relationship between operative time and cost.
NANOG expression in human development and cancerogenesis

NANOG is an important stem cell transcription factor involved in human development and cancerogenesis. Its expression is complex and regulated on different levels. Moreover, NANOG protein might regulate hundreds of target genes at the same time. NANOG is crucial for preimplantation development phase and progressively decreases during embryonic stem cells differentiation, thus regulating embryonic and fetal development. Postnatally, NANOG is undetectable or expressed in very low amounts in the majority of human tissues. NANOG re-expression can be detected during cancerogenesis, already in precancerous lesions, with increasing levels of NANOG in high grade dysplasia. NANOG is believed to enable cancer cells to obtain stem-cell like properties, which are believed to be the source of expanding growth, tumor maintenance, metastasis formation, and tumor relapse. High NANOG expression in cancer is frequently associated with advanced stage, poor differentiation, worse overall survival, and resistance to treatment, and is therefore a promising prognostic and predictive marker. We summarize the current knowledge on the role of NANOG in cancerogenesis and development, including our own experience. We provide a critical overview of NANOG as a prognostic and diagnostic factor, including problems regarding its regulation and detection. Impact statement NANOG has emerged as a key stem cell transcription factor in normal development and cancerogenesis. It is generally regarded as a good prognostic and predictive factor in various human cancers. It is less known that it is expressed already at precancerous stages in various organs, suggesting that finally an ideal candidate diagnostic marker has been discovered, enabling to distinguish between true dysplasia and reactive atypia. NANOG regulation is complex, and new insights into our understanding of its regulation might provide important information for future development in a broad field of two entirely different processes, i.e. normal development and cancerogenesis, showing how a physiologic mechanism can be used and abused, transforming itself into a key mechanism of disease development and progression.
Clinical Relevance of Immune Checkpoints on Circulating Tumor Cells in Breast Cancer

The role of CD47 and PD-L1 expression on circulating tumor cells (CTCs) remains unclear, and it is currently unknown whether their distribution varies between the blood and tumor tissue in breast cancer (BC). In this study, CD47 and PD-L1 expression was investigated a) on peripheral blood mononuclear cell (PBMC) cytospins from early (n = 100) and metastatic (n = 98) BC patients, by triple immunofluorescence for CD47/PD-L1/Cytokeratins, and b) on matched primary and/or metastatic tumor tissue from CTC-positive patients using immunohistochemistry. CD47+and/orPD-L1+ CTCs were detected in 11%, 16.9%, and 29.6% of early, recurrent, and de novo metastatic patients (p = 0.016). In metastatic disease, CD47highand/orPD-L1high CTCs were associated with disease progression (p = 0.005) and shorter progression-free survival (PFS) (p = 0.010), and independently predicted for an increased risk of relapse (HR: 2.719; p = 0.008) and death (HR: 2.398; p = 0.034). PD-L1 expression rates differed between CTCs and tissue tumor cells and between peripheral blood mononuclear cells (PBMCs) and tumor-infiltrating lymphocytes (TILs) (positive concordance of 3.8% and 4%, respectively). CD47 expression also differed between CTCs and tumor cells (positive concordance of 11.5%). In conclusion, CTCs expressing CD47 and PD-L1 have independent poor prognostic implications in metastatic BC, indicating a potential role of innate and adaptive immune evasion mechanisms in their metastatic potential. The clinical value of the parallel assessment of the peripheral and local immune response merits further evaluation in BC.
Exercise training improves radiotherapy efficiency in a murine model of prostate cancer

Engaging in exercise while undergoing radiotherapy (RT) has been reported to be safe and achievable. The impact of exercise training (ET) on RT efficiency is however largely unknown. Our study aims to investigate the interactions between ET and RT on prostate cancer growth. Athymic mice received a subcutaneous injection of PPC‐1 cells and were randomly assigned to either cancer control, cancer ET, cancer RT, or cancer RT combined with ET (CaRT‐ET). Mice were sacrificed 24 days post‐injection. All three intervention groups had reduced tumor size, the most important decrease being observed in CaRT‐ET mice. Apoptotic marker cleaved caspase‐3 was not modified by ET, but enhanced with RT. Importantly, this increase was the highest when the two strategies were combined. Furthermore, NK1.1 staining and gene expression of natural killer (NK) cell receptors Klrk1 and Il2rβ were not affected by ET alone but were increased with RT, this effect being potentiated when combined with ET. Overall, our study shows that (a) ET enhances RT efficiency by potentiating NK cell infiltration, and (b) while ET alone and ET combined with RT both reduce tumor growth, the mechanisms mediating these effects are different.
Diagnostic performance of reticulocyte hemoglobin equivalent in assessing the iron status

Measurement of reticulocyte hemoglobin equivalent (RET‐He) is rapid, convenient, and cost‐effective. Yet, researches on its performance in diagnosing iron deficiency with concurrent inflammation are limited. Hence, this study investigated RET‐He value in various states, including inflammation, and evaluated its diagnostic performance in iron status assessment.
Atraumatic Restorative Treatments reduce the need for Dental General Anaesthesia: a Non-inferiority randomised controlled trial.

BACKGROUND A dental general anaesthesia (DGA) is commonly undertaken for the management of dental caries in young children. A randomised controlled trial was undertaken to test the feasibility of using the Atraumatic Restorative Treatment and Hall Technique approaches (ART/HT) to manage the dental treatment of children recommended for a DGA. METHODS Consenting children, recommended a DGA for caries management, at the Oral Health Centre of Western Australia were randomised. Test group children were treated using the ART/HT approach and the control group under a DGA. Children were examined after 12 months by two blinded, calibrated examiners. Analysis was on an intention to treat basis; between and within group comparisons were undertaken using appropriate paired and unpaired tests. Logistic regression was used to test restorative success, controlling for clustering of teeth. RESULTS Sixty-five children participated, (Test=32; Control=33). At study termination, 28 children (88%) in the ART/HT group and 20 children (61%) in the DGA group had been provided with care, p<0.01. Crown restorations were protective of restorative failure in a multivariate logistic model (OR 0.05, p<0.01). CONCLUSION Use of the ART/HT approach enabled timely dental treatment of young children recommended for a DGA, and should be among the treatment options considered.
Comprehensive Profiling of Zika Virus Risk with Natural and Artificial Mitigating Strategies, United States

Zika virus is transitioning to become a long-term public health challenge, and countries should remain informed of the risk for emergence. We developed a stochastic epidemiologic model to profile risk for Zika virus emergence, including trimester-specific fetal risk across time, in all 3,208 counties in the United States, including Puerto Rico. Validation against known transmission in North America demonstrated accuracy to predict epidemic dynamics and absolute case counts across scales (R2 = 0.98). We found that, although sporadic single transmission events could occur in most US counties, outbreaks will likely be restricted to the Gulf Coast region and to late spring through autumn. Seasonal fluctuations in birth rates will confer natural population-level protection against early-trimester infections. Overall, outbreak control will be more effective and efficient than prevention, and vaccination will be most effective at >70% coverage. Our county-level risk profiles should serve as a critical resource for resource allocation.
Mapping the extent of heterogeneity of human CCR5+ CD4 T-cells in peripheral blood and lymph nodes.

BACKGROUND CD4 T-cells that express the chemokine receptor, CCR5, are the most important target of HIV-1 infection, but their functions, phenotypes and anatomical locations are poorly understood. We aimed to use multiparameter flow cytometry to better define the full breadth of these cells. METHODS High-parameter fluorescence flow and mass cytometry were optimized to analyse subsets of CCR5+ memory CD4 T-cells, including CD25CD127 Tregs, CXCR3+CCR6- Th1, CCR6+CD161+CXCR3- Th17, integrins α4+ß7+ gut-homing, CCR4+ skin-homing, CD62L+ lymph node-homing, CD38+HLA-DR+ activated cells, and CD27-CD28- cytotoxic T lymphocytes (CTL), in a total of 22 samples of peripheral blood, ultrasound-guided fine needle biopsies of lymph nodes and excised tonsils. CCR5+ antigen-specific CD4 T-cells were studied using the OX40 flow-based assay. RESULTS 10-20% of CCR5+ memory CD4 T-cells were Tregs, 10-30% were gut-homing, 10-30% were skin-homing, 20-40% were lymph node-homing, 20-50% were Th1 and 20-40% were Th17 cells. Up to 30% were CTL in CMV-seropositive donors, including cells that were either CCR5Granzyme K+ or CCR5Granzyme B+. When all possible phenotypes were exhaustively analysed, > 150 different functional and trafficking subsets of CCR5+ CD4 T-cells were seen. Also, a small population of resident CD69+Granzyme K+CCR5+ CD4 T-cells was found in lymphoid tissues. CMV- and M tuberculosis-specific CD4 T-cells were predominantly CCR5+. CONCLUSIONS These results reveal for the first time the prodigious heterogeneity of function and trafficking of CCR5+ CD4 T-cells in blood and in lymphoid tissue, with significant implications for rational approaches to prophylaxis for HIV-1 infection and for purging of the HIV-1 reservoir in those subjects already infected.
Tear and aqueous humour cytokine profile in primary open-angle glaucoma.

PURPOSE To evaluate the concentrations of pro-inflammatory cytokines in tear and aqueous humour of patients with primary open-angle glaucoma (POAG), relative to healthy controls. METHOD Tear and aqueous humour samples were collected from 29 healthy controls and 27 POAG patients. Twenty-seven inflammatory cytokines were analysed: interleukin (IL)-1β, IL-1ra, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL9, IL-10, IL-12, IL-13, IL-15, IL-17, eotaxin, fibroblast growth factor (FGF) basic, granulocyte colony-stimulating factor, granulocyte-monocyte colony-stimulating factor, interferon (IFN)-γ, interferon gamma-induced protein, monocyte chemo-attractant protein-1, macrophage inflammatory protein (MIP)-1α, MIP-1β, platelet-derived growth factor, regulated on activation normal T cell expressed and secreted, tumour necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF). RESULTS In tear samples of glaucoma patients, an increase in IL-4, IL-12, IL-15, FGF-basic and VEGF was observed, as well as a decrease in MIP-1a relative to the control group (p < 0.05). IL-5, IL-12, IL-15, IFN-γ and MIP-1a were significantly higher in aqueous humour of glaucoma eyes (p < 0.05). A poor correlation between cytokine levels in tear and aqueous humour was observed. CONCLUSION The different profiles of inflammatory marker expression of patients with POAG and healthy controls confirm the inflammatory activity of the pathology, indicating that some of them could be used as potential biomarkers of this disease.