Miracle-dz/UniFAR-FTUs huggingface dataset:
Plasma miR-200c-3p, miR-100-5p, and miR-1826 serve as potential diagnostic biomarkers for knee osteoarthritis

Abstract Objective: To study the potential diagnostic value of plasma miR-200c-3p, miR-100-5p, and miR-1826 levels in knee osteoarthritis (KOA). Methods: Real-time quantitative PCR (RT-PCR) was used to measure the expression levels of serum miR-200c-3p, miR-100-5p, and miR-1826 in 150 KOA patients and 150 control controls. In addition, the levels of DNMT3A, ZEB1, MMP13, and CTNNB1 mRNAs in the synovial fluid were also measured by RT-PCR. Results: The expression levels of miR-100-5p, miR-200c-3p, and miR-1826 in the synovial fluid of 150 KOA patients were significantly lower than those in 54 controls (P < .001). In the synovial fluid, the miR-100-5p and DNMT3A mRNA levels, miR-100-5p and ZEB1 mRNA levels, miR-200c-3p and MMP13 mRNA levels, and miR-1826 and CTNNB1 mRNA levels were all negatively correlated (r = −0.83, −0.81, −0.83, −0.58, respectively). The AUCs of the diagnosis for KOA using the plasma levels of miR-200c-3p, miR-100-5p, and miR-1826 were 0.755, 0.845, and 0.749, respectively. Conclusion: The plasma levels of miR-200c-3p, miR-100-5p, and miR-1826 are of potentially high value in the diagnosis of KOA.
Impact Of Rabbit Anti-Thymocyte Globulin-Containing Reduced-Intensity Conditioning Regimens On Outcomes Of Adults Undergoing Unrelated Cord Blood Transplantation For Hematological Malignancies

To assess the impact of antithymocyte globulins (ATG), on patients' outcome after unrelated cord blood transplantation (UCBT) following a reduced-intensity regimen (RIC), we conducted a retrospective registry-based analysis on 661 adults with hematological malignancies who underwent unrelated single (s) or double (d) UCBT following RIC with the TBI/cyclophosphamide/fludarabine regimen (TCF) between 2004 and 2011 in EBMT centers. Participating centers were asked to provide additional information on type, timing and total dose of ATG used. Diagnosis was AML/ALL in 51%, MDS/CML in 19% and lymphoid malignancies in 30%; 28% of patients were transplanted in early disease status, 28% in intermediate and 44% in advanced disease. Thirty percent of patients had a previous autologous transplantation. Single UCBT was used in 226 (34%) patients, while 435 (66%) were transplanted with dUCBT. HLA matching was defined as low resolution for HLA-A and HLA-B, and high resolution for HLA-DRB1, and for dUCBT, the highest degree of HLA incompatibility was considered. Therefore, most of the HLA incompatibilities were 4/6 (n=435, 72%). Median number of collected total nucleated and CD34+ cells were 4.4x107/kg and 1.6x105/kg, respectively. All patients received TCF, with TBI 2Gy (86%), TBI 4Gy (12%) and TBI 6Gy (2%). Rabitt ATG (rATG) was used as part of RIC in 82 patients (12.4%) with a median total dose of rATG (Fresenius®) of 20mg/kg (5-60) and rATG (Genzyme®) of 8mg/kg (5-15). GVHD prophylaxis consisted of cyclosporine A (CsA)+ mycophenolate mofetil (MMF) in 91%, Csa alone±other in 9%. The median follow-up was 36.3 months. When compared to patients not receiving rATG-TCF, patients given rATG-TCF had more MDS/CML (30% vs 20%, p 51 years, positive CMV serology, MDS/CML, advanced disease status, year of transplant, HLA 4/6 and ABO incompatibility). In the final MV models, use of rATG was associated with decreased incidence of aGVHD (HR=0.31, 95%, CI=0.17-0.55, p<0.0001), higher incidence of NRM (HR=1.68, 95% CI=1.16-2.43, p=0.0009) and decreased OS (HR=1.69, 95% CI=1.19-2.415, p=0.003), however it was not associated with engraftment, chronic GVHD and relapse. In rATG-RIC-group, the main cause of death was transplantation related in 51% of cases. Death related to infections was 72% in the rATG-RIC group compared to 39% in the non rATG group. In conclusion, in this retrospective and multicentre analysis, use of rATG as part of TCF regimen, was associated with decreased incidence of acute GVHD, however with increased NRM and decreased OS, probably related to the higher incidence of infections. Despite the retrospective design of our study, we suggest that in UCBT for adults with hematological malignancies given a TCF regimen, systematic use of rATG might be a matter of concern. In addition, timing and dose of rATG are still open questions and only randomized studies may address this issue. View this table: Disclosures: Yakoub-Agha: Genzyme: Honoraria, Research Funding. [1]: #T1
Early Parenteral Administration of Ceftiofur has Gender-Specific Short- and Long-Term Effects on the Fecal Microbiota and Growth in Pigs from the Suckling to Growing Phase

Simple Summary Antibiotics are commonly used in prevention and therapy of bacterial diseases in pig production. Although the main target of antibiotics are the pathogenic bacteria, they often disrupt the commensal gut microbiota as a whole, leading to intestinal disturbances. These detrimental effects have been well established for oral administration of antibiotics, whereas knowledge about potential disturbing effects of single parenteral antibiotic treatments on the gut microbiota development is limited. In this research, the impact of a single antibiotic injection on the first day of life on the maturation of the fecal microbiome and host growth performance was evaluated from the suckling to the growing phase. Results showed that a single antibiotic injection early in life influenced the bacterial community development in the short- and long-term and that this disturbance in the bacterial community was sex-specific. Present results further demonstrated that changes in the bacterial ecosystem of the gut may impair the growth performance of the growing pig. Thus, the results of the present study emphasize the importance of a proper and strict use of antibiotics in swine herds. Abstract Using ceftiofur during the first days of life is a common preventative strategy against several bacterial diseases in pig production. This study aimed to evaluate short- and long-term effects of early use of ceftiofur on the fecal microbiota development in suckling and growing pigs. Sixty-four piglets from eight litters were assigned to the antibiotic (AB; n = 32) or control group (control; n = 32). Twelve hours postpartum (day 0) AB piglets received an intramuscular injection of ceftiofur (5.0 mg/kg body weight) or a placebo. DNA was extracted from fecal samples collected on days 0, 12, 28, and 97 for deep-sequencing of the 16S rRNA gene. The AB administration disturbed the maturational changes in the fecal microbiome, whereby effects were sex-specific. Sex-related differences in AB metabolism in females and males may have caused these diverging AB-effects on the fecal microbiota. Especially the loss of bacterial diversity and of certain taxa in female AB pigs may have contributed to the decreased body weight of these females on day 97 of life. Taken together, this study showed that an AB injection with ceftiofur 12 h postpartum markedly affected the successional changes in the fecal microbiota composition in male and female pigs, with long-term consequences for host performance.
Maternal Dietary Fiber Composition during Gestation Induces Changes in Offspring Antioxidative Capacity, Inflammatory Response, and Gut Microbiota in a Sow Model

To study the effects of maternal dietary fiber composition during gestation on offspring antioxidant capacity, inflammation, and gut microbiota composition, we randomly assigned 64 gilts to four treatments and administered diets with an insoluble/soluble fiber ratio of 3.89 (R1), 5.59 (R2), 9.12 (R3), and 12.81 (R4). Sow samples (blood and feces at gestation 110) and neonatal samples (blood, liver, and colonic contents) were collected. The results showed that sows and piglets in R1 and R2 had higher antioxidant enzyme activity and lower pro-inflammatory factor levels than those in R3 and R4. Moreover, piglets in R1 and R2 had higher liver mRNA expression of Nrf2 and HO-1 and lower NF-κB than piglets in R4. Interestingly, maternal fiber composition not only affected the production of short-chain fatty acids (SCFAs) in sow feces but also influenced the concentrations of SCFAs in the neonatal colon. Results of high-throughput sequencing showed that piglets as well as sows in R1 and R2 had microbial community structures distinct from those in R3 and R4. Therefore, the composition of dietary fiber in pregnancy diet had an important role in improving antioxidant capacity and decreasing inflammatory response of mothers and their offspring through modulating the composition of gut microbiota.
Hyperarousal captured in increased number of arousal events during pre‐REM periods in individuals with frequent nightmares

The aim of this study was to investigate hyperarousal in individuals with frequent nightmares (NM participants) by calculating arousal events during nocturnal sleep. We hypothesized an increased number of arousals in NM participants compared with controls, especially during those periods where the probability of spontaneous arousal occurrence is already high, such as non‐rapid eye movement to rapid eye movement transitions (pre‐rapid eye movement periods). Twenty‐two NM participants and 23 control participants spent two consecutive nights in our sleep laboratory, monitored by polysomnography. Arousal number and arousal length were calculated only for the second night, for 10 min before rapid eye movement (pre‐rapid eye movement) and 10 min after rapid eye movement (post‐rapid eye movement) periods, as well as non‐rapid eye movement and rapid eye movement phases separately. Repeated‐measures ANOVA model testing revealed significant Group (NM participants, controls) × Phase (pre‐rapid eye movement, post‐rapid eye movement) interaction in case of the number of arousals. Furthermore, post hoc analysis showed a significantly increased number of arousals during pre‐rapid eye movement periods in NM participants, compared with controls, a difference that disappeared in post‐rapid eye movement periods. We propose that focusing the analyses of arousals specifically on state transitory periods offers a unique perspective into the fragile balance between the sleep‐promoting and arousal systems. This outlook revealed an increased number of arousals in NM participants, reflecting hyperarousal during pre‐rapid eye movement periods.
The Hospital Readmissions Reduction Program and Readmissions for Chronic Obstructive Pulmonary Disease, 2006-2015.

RATIONALE In October 2012, the initial phase of the Hospital Readmission Reduction Program (HRRP) imposed financial penalties on hospitals with higher than expected risk-adjusted 30-day readmission rates for Medicare beneficiaries with congestive heart failure, myocardial infarction, and pneumonia. We hypothesized that these penalties may also be associated with decreased readmissions for chronic obstructive pulmonary disease (COPD) in the general population before COPD became a target condition (October 2014). OBJECTIVE To determine if implementation of the initial financial penalties for other conditions was associated with a decrease in hospital readmissions for COPD. METHODS We used population-level data to examine patients readmitted for any reason or for COPD within 30 days after an initial hospitalization for COPD. The data source was seven states in the State Inpatient Database. The pre-implementation period included calendar years 2006-2012. The post-implementation period included 2013-2015. Using interrupted time series, the level change was examined, which reflected the difference between the expected and actual readmission rates in 2013. The difference in slopes between the pre- and post-implementation periods was also examined. RESULTS We identified 805,764 hospitalizations for COPD from 904 hospitals. Overall, 26% of patients had primary insurance other than Medicare. After the intervention, patients had lower rates of all-cause 30-day readmissions (level change -0.93%, 95% CI -1.44, -0.43, P=0.004), which was driven by fewer early readmissions (0-7 days). The post-implementation slope became positive; the difference in slopes was 0.39% (95% CI 0.28, 0.50, P<0.001). Patients also had lower rates of COPD-related readmissions (level decrease -0.52%, 95% CI -0.93, -0.12, P=0.02), which was due to decreases in both early and late (8-30 days) readmissions. The post-implementation slope was negative; the difference in slopes was -0.21% (95% CI -0.35, -0.07, P=0.009). CONCLUSIONS In patients with COPD and any insurance status, there was an association between the initial phase of the HRRP and a decrease in both all-cause and COPD-related readmissions even before COPD became a target diagnosis. The large amount of money at risk to hospitals likely resulted in broad behavioral change. Future research is needed to test which levers can effectively reduce readmission rates for COPD.
Smartphone-Based Health Program for Improving Physical Activity and Tackling Obesity for Young Adults: A Systematic Review and Meta-Analysis

The need for physical activity for health promotion is recognized, yet young adults still perform insufficient physical activity. Smartphone health programs can be applied easily without time and space constraints, and various mobile health programs based on smartphone applications have recently been developed and applied. This study aimed to measure the effects of mobile smartphone-based health programs on physical activity and obesity outcomes in young adults through a systematic review and meta-analysis. We searched publications in English through electronic databases up to May 2019. Studies were included that provided interventions to improve physical activity using smartphone applications for young adults. After assessing study quality, data were extracted and synthesized concerning whether smartphone interventions affect health outcomes including physical activity and weight using Meta-Analysis software. Four randomized controlled studies and a quasi-experimental study were analyzed. They provided information related to health management, diet, physical activity, and personalized feedback using smartphone applications. The meta-analysis showed that smartphone-based health interventions significantly affect weight loss and increase physical activity. This study provides modest evidence for using smartphone health programs to improve young adults’ physical activity, weight control, and body mass index (BMI). Future research is needed to understand long-term effects and the reliability of increasing physical activity through smartphone health programs.
Synthesis and Evaluation of Saccharide-Based Aliphatic and Aromatic Esters as Antimicrobial and Antibiofilm Agents †

A small library of sugar-based (i.e., glucose, mannose and lactose) monoesters containing hydrophobic aliphatic or aromatic tails were synthesized and tested. The antimicrobial activity of the compounds against a target panel of Gram-positive, Gram-negative and fungi was assessed. Based on this preliminary screening, the antibiofilm activity of the most promising molecules was evaluated at different development times of selected food-borne pathogens (E. coli, L. monocytogenes, S. aureus, S. enteritidis). The antibiofilm activity during biofilm formation resulted in the following: mannose C10 > lactose biphenylacetate > glucose C10 > lactose C10. Among them, mannose C10 and lactose biphenylacetate showed an inhibition for E. coli 97% and 92%, respectively. At MICs values, no toxicity was observed on Caco-2 cell line for all the examined compounds. Overall, based on these results, all the sugar-based monoesters showed an interesting profile as safe antimicrobial agents. In particular, mannose C10 and lactose biphenylacetate are the most promising as possible biocompatible and safe preservatives for pharmaceutical and food applications.
Ecotin, a microbial inhibitor of serine proteases, blocks multiple complement dependent and independent microbicidal activities of human serum

Ecotin is a serine protease inhibitor produced by hundreds of microbial species, including pathogens. Here we show, that ecotin orthologs from Escherichia coli, Yersinia pestis, Pseudomonas aeruginosa and Leishmania major are potent inhibitors of MASP-1 and MASP-2, the two key activator proteases of the complement lectin pathway. Factor D is the key activator protease of another complement activation route, the alternative pathway. We show that ecotin inhibits MASP-3, which is the sole factor D activator in resting human blood. In pathway-specific ELISA tests, we found that all ecotin orthologs are potent lectin pathway inhibitors, and at high concentration, they block the alternative pathway as well. In flow cytometry experiments, we compared the extent of complement-mediated opsonization and lysis of wild-type and ecotin-knockout variants of two E. coli strains carrying different surface lipopolysaccharides. We show, that endogenous ecotin provides significant protections against these microbicidal activities for both bacteria. By using pathway specific complement inhibitors, we detected classical-, lectin- and alternative pathway-driven complement attack from normal serum, with the relative contributions of the activation routes depending on the lipopolysaccharide type. Moreover, in cell proliferation experiments we observed an additional, complement-unrelated antimicrobial activity exerted by heat-inactivated serum. While ecotin-knockout cells are highly vulnerable to these activities, endogenous ecotin of wild-type bacteria provides complete protection against the lectin pathway-related and the complement-unrelated attack, and partial protection against the alternative pathway-related damage. In all, ecotin emerges as a potent, versatile self-defense tool that blocks multiple antimicrobial activities of the serum. These findings suggest that ecotin might be a relevant antimicrobial drug target.
Advanced Glycation End Products (AGEs) May Be a Striking Link Between Modern Diet and Health

The Maillard reaction is a simple but ubiquitous reaction that occurs both in vivo and ex vivo during the cooking or processing of foods under high-temperature conditions, such as baking, frying, or grilling. Glycation of proteins is a post-translational modification that forms temporary adducts, which, on further crosslinking and rearrangement, form permanent residues known as advanced glycation end products (AGEs). Cooking at high temperature results in various food products having high levels of AGEs. This review underlines the basis of AGE formation and their corresponding deleterious effects on the body. Glycated Maillard products have a direct association with the pathophysiology of some metabolic diseases, such as diabetes mellitus type 2 (DM2), acute renal failure (ARF), Alzheimer’s disease, dental health, allergies, and polycystic ovary syndrome (PCOS). The most glycated and structurally abundant protein is collagen, which acts as a marker for diabetes and aging, where decreased levels indicate reduced skin elasticity. In diabetes, high levels of AGEs are associated with carotid thickening, ischemic heart disease, uremic cardiomyopathy, and kidney failure. AGEs also mimic hormones or regulate/modify their receptor mechanisms at the DNA level. In women, a high AGE diet directly correlates with high levels of androgens, anti-Müllerian hormone, insulin, and androstenedione, promoting ovarian dysfunction and/or infertility. Vitamin D3 is well-associated with the pathogenesis of PCOS and modulates steroidogenesis. It also exhibits a protective mechanism against the harmful effects of AGEs. This review elucidates and summarizes the processing of infant formula milk and the associated health hazards. Formulated according to the nutritional requirements of the newborn as a substitute for mother’s milk, formula milk is a rich source of primary adducts, such as carboxy-methyl lysine, which render an infant prone to inflammation, dementia, food allergies, and other diseases. We therefore recommend that understanding this post-translational modification is the key to unlocking the mechanisms and physiology of various metabolic syndromes.
Soluble Sugar and Lipid Readjustments in the Yarrowia lipolytica Yeast at Various Temperatures and pH

Microorganisms cope with a wide range of environmental challenges using different mechanisms. Their ability to prosper at extreme ambient pH and high temperatures has been well reported, but the adaptation mechanism often remains unrevealed. In this study, we addressed the dynamics of lipid and sugar profiles upon different cultivation conditions. The results showed that the cells grown at various pH and optimal temperature contained mannitol as the major cytosol sugar alcohol. The elevated temperature of 38 °C led to a two- to three-fold increase in total cytosol sugars with concurrent substitution of mannitol for trehalose. Lipid composition in the cells at optimal temperature changed insignificantly at any pH tested. The increase in the temperature caused some drop in the storage and membrane lipid levels, remarkable changes in their composition, and the degree of unsaturated fatty acids. It was shown that the fatty acid composition of some membrane phospholipids varied considerably at changing pH and temperature values. The data showed a pivotal role and flexibility of the sugar and lipid composition of Y. lipolytica W29 in adaptation to unfavorable environmental conditions.
Menopause-Specific Quality of Life among Emirati Women

To investigate the quality of life (QOL) of menopausal Emirati women aged 40–64 years and determine its relationship with their sociodemographic characteristics. A community-based cross-sectional study was conducted on 70 Emirati women using multistage stratified clustered random sampling. The participants were interviewed face-to-face using a structured questionnaire comprising sociodemographic variables, reproductive characteristics, and the Menopause-Specific Quality of Life (MENQOL) questionnaire. The most common symptom among the study participants was ‘aching in the muscles’. The participants had a moderate level of bothersome symptoms; in addition, vasomotor symptoms were reported by 61%, while sexual symptoms were only reported by one-third of the participants. There were no significant differences between the menopausal status in any of the four domains of the MENQOL questionnaire. Additionally, there were no significant differences between the mean scores of the four MENQOL domains and all predictors. This study highlights the importance of educating women about menopause and its symptoms.