Miracle-dz/UniFAR-FTUs huggingface dataset:
Metabolic reprogramming of myeloid-derived suppressor cells (MDSC) in cancer

ABSTRACT MDSC undergo metabolic reprogramming in the tumor resulting in an increased fatty acid β oxidation that supports their immunosuppressive functions. Fatty acid oxidation inhibitors, used to treat coronary disease, significantly delayed tumor growth and had a significantly increased antitumor effect when combined with adoptive cell therapy or low dose chemotherapy.
Breastfeeding intention and practice in an urban minority population: relationship to maternal depressive symptoms and mother–infant closeness

Current literature shows that predictors of breastfeeding practice vary depending on women's ethnic background. This study examines predictors of planning to breastfeeding and of successful breastfeeding initiation and persistence, including the relationship to maternal depressive symptoms, social support, and mothers' perception of closeness to their infants, in a sample of low‐income African American and Hispanic women in the urban Northeast. Detailed interviews were conducted in the early third trimester, at 2 weeks following delivery, and 3 months postpartum. Rates of intention to breastfeed were similar for Hispanic and African American women. Among Hispanics, greater identification with Hispanic culture was associated with increases in the likelihood of planning to breastfeed. A smaller proportion of Hispanic women persisted, especially among those women who supplemented with formula. For all women, we found no relationship between breastfeeding practice and either social support or depressive symptoms. Mothers' perception of closeness to their infants was greater among breastfeeders compared to bottlefeeders.
Preventive dental utilization for Medicaid-enrolled children in Iowa identified with intellectual and/or developmental disability.

OBJECTIVES To compare preventive dental utilization for children with intellectual and/or developmental disability (IDD) and those without IDD and to identify factors associated with dental utilization. METHODS We analyzed Iowa Medicaid dental claims submitted during calendar year (CY) 2005 for a cohort of children ages 3-17 who were eligible for Medicaid for at least 11 months in CY 2005 (n = 107,605). A protocol for identifying IDD children was developed by a group of dentists and physicians with clinical experience in treating children with disabilities. Utilization rates were compared for the two groups. Crude and covariate-adjusted odds ratios were estimated using conditional logistic regression modeling. RESULTS A significantly higher proportion of non-IDD children received preventive care than those identified as IDD (48.6 percent versus 46.1 percent; P < 0.001). However, the final model revealed no statistically significant difference between the two groups. Factors such as older age, not residing in a dental Health Professional Shortage Area, interaction with the medical system, and family characteristics increased one's likelihood of receiving preventive dental care. CONCLUSION Although IDD children face additional barriers to receiving dental care and may be at greater risk for dental disease, they utilize preventive dental services at the same rate as non-IDD children. Clinical and policy efforts should focus on ensuring that all Medicaid-enrolled children receive need-appropriate levels of preventive dental care.
Impact of Comorbidities on Racial/Ethnic Disparities in Hypertension in the United States

Background. Racial/ethnic disparities in hypertension (HTN) prevalence continue to persist in United States. We aimed in this study to examine the racial/ethnic disparities in hypertension prevalence and to determine whether or not health disparities may be explained by racial/ethnic disparities in co-morbidities. Materials and Methods. A cross-sectional design was used to examine the prevalence of hypertension among African Americans (AAs), Caucasians, and Hispanics in the National Health Interview Survey, 2003. The overall sample comprised 30, 852 adults. Results. There was a statistically significant racial/ethnic variability in hypertension prevalence, with AA/Blacks with the highest prevalence, (3), . Hypertension was associated with co-morbidities, age, education, physical inactivity, marital status, income, sex, alcohol, and cigarette consumption, but not insurance. Relative to Caucasians, AAA/Blacks were 43% more likely while Hispanics were 40% less likely to report being diagnosed with high blood pressure, prevalence odds ratio (POR) = 1.43, 99% CI, 1.25–1.64, , and POR = 0.60, 99% CI, 0.55–0.66, respectively. After adjustment for the relevant covariates including co-morbidities, racial/ethnic disparities in hypertension persisted; thus compared to Caucasians, African Americans were 61% more likely to be told by their health care providers that they were hypertensive, adjusted prevalence odds ratio (APOR) = 1.61, 99% CI, 1.39–1.86, . In contrast, Hispanics were 27% less likely to be diagnosed with hypertension compared to Caucasians, APOR = 0.73, 99% CI, 0.68–0.79, . Conclusions. There was racial/ethnic variability in hypertension prevalence in this large sample of non-institutionalized US residents, with the highest prevalence of hypertension observed among African Americans. These disparities were not removed after controlling for relevant covariates including co-morbidities.
The immune checkpoint ligand PD-L1 is upregulated in EMT-activated human breast cancer cells by a mechanism involving ZEB-1 and miR-200

ABSTRACT PD-L1 expression and regulation by mesenchymal tumor cells remain largely undefined. Here, we report that among different EMT-activated MCF7 human breast cancer cell clones, PD-L1 was differentially upregulated in MCF7 sh-WISP2, MCF7–1001/2101, and MDA-MB-231 cells but not in MCF7 SNAI1 and MCF7 SNAI1–6SA cells. Mechanistic investigations revealed that siRNA silencing of ZEB-1, but not SNAI1, TWIST, or SLUG and overexpression of miR200 family members in MCF7 sh-WISP2 cells strongly decreased PD-L1 expression. Thus, we propose that PD-L1 expression in EMT-activated breast cancer cells depends on the EMT-TF involved in EMT activation. Interestingly, siRNA-mediated targeting of PD-L1 or antibody-mediated PD-L1 block restored the susceptibility of highly resistant MCF7 sh-WISP2 and MCF7–2101 cells to CTL-mediated killing. Additionally, these results provide a novel preclinical rationale to explore EMT inhibitors as adjuvants to boost immunotherapeutic responses in subgroups of patients in whom malignant progression is driven by different EMT-TFs.
Preclinical efficacy and safety of the Ty21a vaccine strain for intravesical immunotherapy of non-muscle-invasive bladder cancer

ABSTRACT Intravesical Bacillus-Calmette-Guérin (BCG) immunotherapy can reduce recurrence/progression of non-muscle-invasive bladder cancer (NMIBC), although significant adverse events and treatment failure argue for alternative options. Here, we examined whether another attenuated live vaccine, Vivotif/Ty21a, used since more than 30 y against typhoid fever, may be safely used intravesically to improve bladder-tumor treatment. Mice-bearing MB49 orthotopic bladder-tumors treated with intravesical Ty21a or BCG were compared for survival and bacteria recovery. Both Ty21a and BCG enhanced mice survival when treating just after tumor implantation for 4 weeks (p = 0.008 and 0.04, respectively), but only Ty21a was effective when treating once mice with larger already established bladder-tumors (p = 0.0003). In contrast to BCG, no Ty21a bacteria survived in mouse bladder, human urothelial cell-lines or human peripheral blood mononuclear cells. However, Ty21a was as potent as BCG to induce tumor-cell death in vitro. In a human, 3D-bladder-tissue ex-vivo assay, Ty21a bacteria, still not surviving, induced a panel of cytokines associated with effective BCG-treatment in patient's urine. Overall, our pre-clinical data demonstrate that intravesical Ty21a is more effective than BCG for bladder-tumor treatment. Absence of surviving Ty21a bacteria and the excellent safety-record of the typhoid vaccine support its testing in NMIBC patients.
Maternal microchimerism is prevalent in cord blood in memory T cells and other cell subsets, and persists post-transplant

ABSTRACT Among reported advantages of umbilical cord blood (CB) in transplantation is lower leukemia relapse probability. Underlying cellular mechanisms of graft-vs.-leukemia (GVL) are thought to include a prominent role for T cells. Cells of the CB's mother, maternal microchimerism (MMc), were recently strongly, but indirectly, implicated in this GVL benefit. We assayed MMc directly and hypothesized benefit accrues from CB maternal T cells. MMc was quantified in 51 CBs and, within memory T, naïve T, B, NK cells, and monocytes in 27 CBs. Polymorphism-specific quantitative-PCR assays targeted maternal genotypes non-shared with CBs. Overall MMc was common and often at substantial levels. It was present in 52.9% of CB and in 33.3–55.6% of tested subsets. Remarkably, MMc quantities were greater in memory T cells than other subsets (p < 0.001). Expressed as genome equivalents (gEq) per 105 total gEq tested (gEq/105), memory T cell MMc averaged 850.2 gEq/105, while other subset mean quantities were 13.8–30.1 gEq/105. After adjustment for proportionality in CB, MMc remained 6–17 times greater in memory T, and 3–9 times greater in naïve T, vs. non-T-cell subsets. Further, CB-origin MMc was detected in vivo in a patient up to 6 mo post-transplantation, including among T cells. Overall, results revealed levels and phenotypes of CB MMc with potential relevance to CB transplantation and, more broadly, to offspring health.
Immune classifications with cytotoxic CD8+ and Th17 infiltrates are predictors of clinical prognosis in glioblastoma

ABSTRACT Background: Interest is growing on immune cells involvement in central nervous system tumors such as glioblastoma. Even if a few reports highlighted that immune classifications could have a prognostic value, no paradigm has been clearly yet established on large and homogeneous cohorts. The aim of our study was to analyze the prognostic role of the in situ immune response of cytotoxic T cells (i.e., CD8+), Foxp3 cells, Th17 and tumor-associated macrophages in glioblastoma on two independent large and homogeneous cohorts. Methods: We worked on two large homogenous cohorts of patients having glioblastoma who underwent standard radiochemotherapy. The first cohort of 186 patients was analyzed using IHC procedures (CD8+, IL-17A, FoxP3 and CD163) of surgery pieces. We next worked with transcriptomic data available online and used metagene strategy analysis for the second cohort of 525 patients. Results: Cytotoxic CD8+ lymphocytes and Foxp3 cells were associated with a good prognosis, while Th17 were associated with a poor clinical outcome. These data were confirmed with transcriptomic analysis. Moreover, we showed for the first time a strong link between angiogenesis and Th17 metagenes expressions in glioblastoma. Conclusions: Our study shows that glioblastoma bearing patients can be classified on the immune infiltrate aspects. Beyond this prognostic role of immune biomarkers, subsequent classifications could definitely help clinicians to handle targeted therapy administration and immunotherapeutic interventions.
Leukotriene B4-receptor-1 mediated host response shapes gut microbiota and controls colon tumor progression

ABSTRACT Inflammation and infection are key promoters of colon cancer but the molecular interplay between these events is largely unknown. Mice deficient in leukotriene B4 receptor1 (BLT1) are protected in inflammatory disease models of arthritis, asthma and atherosclerosis. In this study, we show that BLT1−/− mice when bred onto a spontaneous tumor (ApcMin/+) model displayed an increase in the rate of intestinal tumor development and mortality. A paradoxical increase in inflammation in the tumors from the BLT1−/−ApcMin/+ mice is coincidental with defective host response to infection. Germ-free BLT1−/−ApcMin/+ mice are free from colon tumors that reappeared upon fecal transplantation. Analysis of microbiota showed defective host response in BLT1−/− ApcMin/+ mice reshapes the gut microbiota to promote colon tumor development. The BLT1−/−MyD88−/− double deficient mice are susceptible to lethal neonatal infections. Broad-spectrum antibiotic treatment eliminated neonatal lethality in BLT1−/−MyD88−/− mice and the BLT1−/−MyD88−/−ApcMin+ mice are protected from colon tumor development. These results identify a novel interplay between the Toll-like receptor mediated microbial sensing mechanisms and BLT1-mediated host response in the control of colon tumor development.
Platelet-mediated shedding of NKG2D ligands impairs NK cell immune-surveillance of tumor cells

ABSTRACT Platelets promote metastasis, among others by coating cancer cells traveling through the blood, which results in protection from NK cell immune-surveillance. The underlying mechanisms, however, remain to be fully elucidated. Here we report that platelet-coating reduces surface expression of NKG2D ligands, in particular MICA and MICB, on tumor cells, which was mirrored by enhanced release of their soluble ectodomains. Similar results were obtained upon exposure of tumor cells to platelet-releasate and can be attributed to the sheddases ADAM10 and ADAM17 that are detectable on the platelet surface and in releasate following activation and at higher levels on platelets of patients with metastasized lung cancer compared with healthy controls. Platelet-mediated NKG2DL-shedding in turn resulted in impaired “induced self” recognition by NK cells as revealed by diminished NKG2D-dependent lysis of tumor cells. Our results indicate that platelet-mediated NKG2DL-shedding may be involved in immune-evasion of (metastasizing) tumor cells from NK cell reactivity.
Synthesis and cation distribution in the new bismuth oxyhalides with the Sillén-Aurivillius intergrowth structures.

About 20 new compounds with the Sillén-Aurivillius intergrowth structure, Me(1)Me(2)Bi3Nb2O11X (Me(1) = Pb, Sr, Ba; Me(2) = Ca, Sr, Ba; X = Cl, Br, I), have been prepared. They are composed of stacking of [ANb2O7] perovskite blocks, fluorite-type [M2O2] blocks and halogen sheets. The cation distribution between the fluorite and perovskite layers has been studied for Ba2Bi3Nb2O11I, Ca1.25Sr0. 75Bi3Nb2O11Cl, BaCaBi3Nb2O11Br and Sr2Bi3Nb2O11Cl. The smaller Me cations tend to reside in the perovskite block while the larger ones are situated in the fluorite-type block. The distribution of the elements was confirmed for BaCaBi3Nb2O11Br using energy dispersive X-ray analysis combined with scanning transmission electron microscopy (STEM-EDX). An electron diffraction study of this compound reveals a local symmetry lowering caused by weakly correlated rotation of NbO6 octahedra. Based on our findings, we suggest a new stability criterion for mixed-layer structures, which is that net charges of any two consecutive layers do not compensate for each other and only the whole layer sequence is electroneutral.
Mortality in patients with myalgic encephalomyelitis and chronic fatigue syndrome

ABSTRACT Background: There is a dearth of research examining mortality in individuals with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS). Some studies suggest there is an elevated risk of suicide and earlier mortality compared to national norms. However, findings are inconsistent. Objective: This study sought to determine if patients are reportedly dying earlier than the overall population from the same cause. Methods: Family, friends, and caregivers of deceased patients were recruited. This study analyzed data including cause and age of death for 56 individuals. Results: The findings suggest patients in this sample are at a significantly increased risk of earlier all-cause (M = 55.9 years) and cardiovascular-related (M = 58.8 years) mortality, and they had a directionally lower age of death for suicide (M = 41.3 years) and cancer (M = 66.3 years) compared to the overall U.S. population [M = 73.5 (all-cause), 77.7 (cardiovascular), 47.4 (suicide), and 71.1 (cancer) years of age]. Conclusions: Results suggest there is an increase in risk for earlier mortality in patients. Due to sample size and over-representation of severely ill patients, the findings should be replicated to determine if the directional differences for suicide and cancer mortality are significantly different from the overall population.
Clinical criteria versus a possible research case definition in chronic fatigue syndrome/myalgic encephalomyelitis

ABSTRACT Background: The Institute of Medicine (IOM) recently developed clinical criteria for what had been known as chronic fatigue syndrome. Given the broad nature of the clinical IOM criteria, there is a need for a research definition that would select a more homogenous and impaired group of patients than the IOM clinical criteria. At the present time, it is unclear what will serve as the research definition. Purpose: The current study focused on a research definition which selected homebound individuals who met the four IOM criteria, excluding medical and psychiatric co-morbidities. Methods: Our research criteria were compared to those participants meeting the IOM criteria. Those not meeting either of these criteria sets were placed in a separate group defined by six or more months of fatigue. Data analyzed were from the DePaul Symptom Questionnaire and the 36-item Short-Form Health Survey (SF-36). Due to unequal sample sizes and variances, Welch’s F tests and Games-Howell post-hoc tests were conducted. Results: Using a large database of over 1000 patients from several countries, we found that those meeting a more restrictive research definition were even more impaired and more symptomatic than those meeting criteria for the other two groups. Conclusion: Deciding on a particular research case definition would allow researchers to select more comparable patient samples across settings, and this would represent one of the most significant methodologic advances for this field of study.
Incidence of Epstein–Barr virus in Syrian women with breast cancer: A tissue microarray study

Epstein–Barr virus (EBV) has been recently shown to be present in human breast cancer worldwide, which could play an important role in the initiation and progression of this cancer. In this regard, we aimed to explore the prevalence of EBV in 108 breast cancer tissues from Syrian women using polymerase chain reaction (PCR) and tissue microarray (TMA) analysis. We found that EBV is present in 56 (51.85%) of breast cancers samples. Additionally, we report that the expression of LMP1 gene of EBV is associated with a cancer invasive phenotype in the majority of the cancer samples. These data imply that EBV is present in breast cancer worldwide including Syria and its presence is associated with more aggressive cancer phenotype. Thus, future investigations are needed to elucidate the exact role of EBV in breast carcinogenesis and metastasis.
Cunninghamella bertholletiae endocarditis: A case report and review of human Cunninghamella infections

Cunninghamella bertholletiae is an opportunistic fungal organism of the order Mucorales that is found in soil and is a rare cause of human disease. The few reported cases of C. bertholletiae have predominantly involved immunocompromised hosts and have been associated with very poor outcomes. To date, therapeutic options have included surgical debridement and high-dose amphotericin B deoxycholate, which have shown very limited efficacy. We report a case of C. bertholletiae endocarditis in an immunosuppressed patient. The patient was treated with amphotericin B followed by amphotericin B plus posaconazole, an investigational medication with in vitro activity against some agents of mucormycosis. To our knowledge, this is the third case of C. bertholletiae endocarditis reported in the literature and the second reported use of posaconazole for the treatment of mucormycosis.
Adolescent ADHD and family environment - an epidemiological and clinical study of ADHD in the Northern Finland 1986 Birth Cohort

The aim of the study was to deepen understanding of the concept of participant steering and to find out what participant steering is like in practical implementation of the social and health care development project. Participant steering refers to the operation of persons involved in the planning organisation of the development project. Participant steering is a new theoretical concept that has been formed during this research process. A qualitative case study approach was used in this study. The social and health care development project related to the Administrative Experiment of the Kainuu Region was chosen as the object of the study. Keywords: project management, public health administration, regional cooperation (International Journal of Circumpolar Health 66:4 2007)
EFFECT OF REINFORCEMENT OF VISUAL ACUITY IN MYOPIC ADULTS*

&NA; In two experiments, attempts were made to improve visual acuity through reinforcement. In Experiment I, four myopic subjects were given five blocks of 24 trials in a conditioning task. The target stimuli were slides of Landolt rings, with 14 different sizes (increasing on a logarithmic scale) and 12 different stimuli representing each size. Trial blocks of contingent social approval for a correct response were alternated with noncontingent blocks in which approval was delivered randomly. Results permitted the inference that contingent approval resulted in increased acuity. In Experiment II, essentially the same task was used to compare the performance of three groups of subjects (each N=20): contingent reinforcement, noncontingent response, and no‐response control. Results showed a nonsignificant increase in acuity and a significant decrease in refractive error. Possible directions for further research are discussed, and ethical considerations are noted.
Defining Clinical Research Nursing Practice: Results of a Role Delineation Study

Clinical research nursing is a specialty nursing practice focused on the care of research subjects and implementation of clinical research. A five‐dimensional model (Clinical Practice [CP], Study Management, Care Coordination and Continuity, Contributing to the Science [CS], Human Subjects Protection) has been validated nationally to represent the domain of clinical research nursing practice. The purpose of this study was to describe the frequency and importance of activities within each dimension as performed by nurses in clinical research and to describe differences between roles. One thousand and four nurses from the NIH Intramural Campus in Bethesda, Maryland, were invited to participate in an anonymous web‐based survey. Participants (N = 412) were predominantly female (90%) with ≥11 years research experience (70%). Two hundred eighty‐eight respondents (70%) identified themselves as clinical research nurses (CRNs) and 74 (18%) as research nurse coordinators (RNCs). CP activities were reported most frequent and important whereas CS activities were least frequent and important. CRN and RNC activity frequency differed across all dimensions (p < 0.001) with CRNs reporting significantly higher levels of CP activities and significantly lower levels in other dimensions. Delineating specialty activities and practice across roles enhances the understanding of nurses’ role in clinical research and provides groundwork for role‐based training. Clin Trans Sci 2011; Volume 4: 421–427