Miracle-dz/UniFAR-FTUs huggingface dataset:
Association between inhibited binding of folic acid to folate receptor alpha in maternal serum and folate-related birth defects in Norway.

BACKGROUND Folic acid intake during pregnancy can reduce the risk of neural tube defects (NTDs) and perhaps also oral facial clefts. Maternal autoantibodies to folate receptors can impair folic acid binding. We explored the relationship of these birth defects to inhibition of folic acid binding to folate receptor α (FRα), as well as possible effects of parental demographics or prenatal exposures. METHODS We conducted a nested case-control study within the Norwegian Mother and Child Cohort Study. The study included mothers of children with an NTD (n = 11), cleft lip with or without cleft palate (CL/P, n= 72), or cleft palate only (CPO, n= 27), and randomly selected mothers of controls (n = 221). The inhibition of folic acid binding to FRα was measured in maternal plasma collected around 17 weeks of gestation. On the basis of prior literature, the maternal age, gravidity, education, smoking, periconception folic acid supplement use and milk consumption were considered as potential confounding factors. RESULTS There was an increased risk of NTDs with increased binding inhibition [adjusted odds ratio (aOR) = 1.4, 95% confidence interval (CI) 1.0-1.8]. There was no increased risk of oral facial clefts from inhibited folic acid binding to FRα (CL/P aOR = 0.7, 95% CI 0.6-1.0; CPO aOR = 1.1, 95% CI 0.8-1.4). No association was seen between smoking, folate supplementation or other cofactors and inhibition of folic acid binding to FRα. CONCLUSIONS Inhibition of folic acid binding to FRα in maternal plasma collected during pregnancy was associated with increased risk of NTDs but not oral facial clefts.
Christian tourism to the holy land: pilgrimage during security crisis

As a growing niche market, religious tourism has been vastly understudied in the academic literature (Olsen & Timothy, 2006). This lack of attention is particularly acute when it comes to statistical data. Because of this, Christian Tourism to the Holy Land is a welcome addition to the academic literature on religious tourism. The premise of Christian Tourism to the Holy Land is based on a failed study of the motivations and characteristics of religious Christian pilgrims to the Holy Land in 2000. When the authors’ survey pool dried up due to the political conflict that erupted later that year, it was decided instead to explore the reasons behind why some pilgrims continued to come even during politically tense times. As such, this book explores simultaneously a small segment of the religious tourism market as well as issues pertaining to geographies of fear. Chapter 1 serves as the theoretical foundation of the book, looking briefly at the literature on pilgrimage, the pilgrimage-tourism divide, and the history of Christian pilgrimage to the Holy Land. In Chapter 2 the authors review the literature pertaining to tourism and issues of safety and security and also review key political military crises that have affected the tourism industry in Israel from 1967 to 2004. Chapter 3 briefly outlines the research methodology of the study, which is then further discussed in the following three chapters. In Chapter 4, the authors discuss the behavioural aspects of both the Roman Catholic and Protestant pilgrims studied, examining such variables as their country of origin, their motivations for travelling to the Holy Land, and their desired expectations from their trip. Chapter 5 investigates the pilgrims’ attitudes and perceptions of the Holy Land, including their political attitudes towards the Holy Land, their knowledge about the current state of the Israeli–Palestinian conflict, as well as their feelings and attitudes about the security issues in the Holy Land. Chapter 6 moves into discussing the organisational frameworks of Roman Catholic and Protestant pilgrimage to the Holy Land, the role of tour guides in the pilgrimage trek, the sacred locations Roman Catholics and Protestants visit while in the Holy Land, the effects of safety and security issues on their chosen sites, and the satisfaction of their pilgrimage journeys. Chapter 7 summarises the three previous chapters and suggests that following Cohen’s (1979) familiar typology of tourist experiences, there are three types of pilgrims who come to the Holy Land: existential pilgrims, experiential existential pilgrims, and tourist pilgrims. Chapter 8 revisits security and safety issues in tourism and specifically expands on lessons that can be learned from the past and current political crises in the Holy Land when it comes to crises management strategies in the tourism economic sector. There are a few problems that readers of this book will notice when flipping through its pages. First, while the literature review does touch briefly upon some of the key issues
Current status and future directions of cancer immunotherapy

In the past decades, our knowledge about the relationship between cancer and the immune system has increased considerably. Recent years' success of cancer immunotherapy including monoclonal antibodies (mAbs), cancer vaccines, adoptive cancer therapy and the immune checkpoint therapy has revolutionized traditional cancer treatment. However, challenges still exist in this field. Personalized combination therapies via new techniques will be the next promising strategies for the future cancer treatment direction.
Thermal history and gape of individual Mytilus californianus correlate with oxidative damage and thermoprotective osmolytes

ABSTRACT The ability of animals to cope with environmental stress depends – in part – on past experience, yet knowledge of the factors influencing an individual's physiology in nature remains underdeveloped. We used an individual monitoring system to record body temperature and valve gaping behavior of rocky intertidal zone mussels (Mytilus californianus). Thirty individuals were selected from two mussel beds (wave-exposed and wave-protected) that differ in thermal regime. Instrumented mussels were deployed at two intertidal heights (near the lower and upper edges of the mussel zone) and in a continuously submerged tidepool. Following a 23-day monitoring period, measures of oxidative damage to DNA and lipids, antioxidant capacities (catalase activity and peroxyl radical scavenging) and tissue contents of organic osmolytes were obtained from gill tissue of each individual. Univariate and multivariate analyses indicated that inter-individual variation in cumulative thermal stress is a predominant driver of physiological variation. Thermal history over the outplant period was positively correlated with oxidative DNA damage. Thermal history was also positively correlated with tissue contents of taurine, a thermoprotectant osmolyte, and with activity of the antioxidant enzyme catalase. Origin site differences, possibly indicative of developmental plasticity, were only significant for catalase activity. Gaping behavior was positively correlated with tissue contents of two osmolytes. Overall, these results are some of the first to clearly demonstrate relationships between inter-individual variation in recent experience in the field and inter-individual physiological variation, in this case within mussel beds. Such micro-scale, environmentally mediated physiological differences should be considered in attempts to forecast biological responses to a changing environment. Highlighted Article: Variation in thermal experience and behavior contributes to inter-individual physiological variation within intertidal mussel beds, providing valuable insight into physiological plasticity and variable costs of defending against environmental stress.
Ecological guild and enzyme activities of rhizosphere soil microbial communities associated with Bt‐maize cultivation under field conditions in North West Province of South Africa

Insecticidal proteins expressed by genetically modified Bt maize may alter the enzymatic and microbial communities associated with rhizosphere soil. This study investigated the structure and enzymatic activity of rhizosphere soil microbial communities associated with field grown Bt and non‐Bt maize. Rhizosphere soil samples were collected from Bt and non‐Bt fields under dryland and irrigated conditions. Samples were subjected to chemical tests, enzyme analyses, and next generation sequencing. Results showed that nitrate and phosphorus concentrations were significantly higher in non‐Bt maize dryland soils, while organic carbon was significantly higher in non‐Bt maize irrigated field soil. Acid phosphatase and β‐glucosidase activities were significantly reduced in soils under Bt maize cultivation. The species diversity differed between fields and Bt and non‐Bt maize soils. Results revealed that Actinobacteria, Proteobacteria, and Acidobacteria were the dominant phyla present in these soils. Redundancy analyses indicated that some chemical properties and enzyme activities could explain differences in bacterial community structures. Variances existed in microbial community structures between Bt and non‐Bt maize fields. There were also differences between the chemical and biochemical properties of rhizosphere soils under Bt and non‐Bt maize cultivation. These differences could be related to agricultural practices and cultivar type.
Adoptive Transfer of Vaccine-Induced Peripheral Blood Mononuclear Cells to Patients with Metastatic Melanoma following Lymphodepletion1

Cancer vaccines can induce the in vivo generation of tumor Ag-specific T cells in patients with metastatic melanoma yet seldom elicit objective clinical responses. Alternatively, adoptive transfer of autologous tumor-infiltrating lymphocytes (TIL) can mediate tumor regression in 50% of lymphodepleted patients, but are logistically and technically difficult to generate. In this study, we evaluated the capability of vaccine-induced PBMC to mediate tumor regression after transfer to patients receiving the same chemotherapy-induced lymphodepletion used for TIL transfer therapy. Autologous PBMC from nine gp100-vaccinated patients with metastatic melanoma were stimulated ex vivo with the gp100:209–217(210M) peptide and transferred in combination with high-dose IL-2 and cancer vaccine. Transferred PBMC contained highly avid, gp100:209–217 peptide-reactive CD8+ T cells. One week after transfer, lymphocyte counts peaked (median of 14.3 × 103 cells/μl; range of 0.9–59.7 × 103 cells/μl), with 56% of patients experiencing a lymphocytosis. gp100:209–217 peptide-specific CD8+ T cells persisted at high levels in the blood of all patients and demonstrated significant tumor-specific IFN-γ secretion in vitro. Melanocyte-directed autoimmunity was noted in two patients; however, no patient experienced an objective clinical response. These studies demonstrate the feasibility and safety of using vaccine-induced PBMC for cell transfer, but suggests that they are not as effective as TIL in adoptive immunotherapy even when transferred into lymphodepleted hosts.
Contribution and pathways of diazotroph-derived nitrogen to zooplankton during the VAHINE mesocosm experiment in the oligotrophic New Caledonia lagoon

In oligotrophic tropical and subtropical oceans, where strong stratification can limit the replenishment of surface nitrate, dinitrogen (N-2) fixation by diazotrophs can represent a significant source of nitrogen (N) for primary production. The VAHINE (VAriability of vertical and tropHIc transfer of fixed N-2 in the south-wEst Pacific) experiment was designed to examine the fate of diazotroph-derived nitrogen (DDN) in such ecosystems. In austral summer 2013, three large ( similar to aEuro parts per thousand aEuro-50aEuro-m(3)) in situ mesocosms were deployed for 23 days in the New Caledonia lagoon, an ecosystem that typifies the low-nutrient, low-chlorophyll environment, to stimulate diazotroph production. The zooplankton component of the study aimed to measure the incorporation of DDN into zooplankton biomass, and assess the role of direct diazotroph grazing by zooplankton as a DDN uptake pathway. Inside the mesocosms, the diatom-diazotroph association (DDA) het-1 predominated during days 5-15 while the unicellular diazotrophic cyanobacteria UCYN-C predominated during days 15-23. A Trichodesmium bloom was observed in the lagoon (outside the mesocosms) towards the end of the experiment. The zooplankton community was dominated by copepods (63aEuro-% of total abundance) for the duration of the experiment. Using two-source N isotope mixing models we estimated a mean similar to aEuro parts per thousand aEuro-28aEuro-% contribution of DDN to zooplankton nitrogen biomass at the start of the experiment, indicating that the natural summer peak of N-2 fixation in the lagoon was already contributing significantly to the zooplankton. Stimulation of N-2 fixation in the mesocosms corresponded with a generally low-level enhancement of DDN contribution to zooplankton nitrogen biomass, but with a peak of similar to aEuro parts per thousand aEuro-73aEuro-% in mesocosm 1 following the UCYN-C bloom. qPCR analysis targeting four of the common diazotroph groups present in the mesocosms (Trichodesmium, het-1, het-2, UCYN-C) demonstrated that all four were ingested by copepod grazers, and that their abundance in copepod stomachs generally corresponded with their in situ abundance. N-15(2) labelled grazing experiments therefore provided evidence for direct ingestion and assimilation of UCYN-C-derived N by the zooplankton, but not for het-1 and Trichodesmium, supporting an important role of secondary pathways of DDN to the zooplankton for the latter groups, i.e. DDN contributions to the dissolved N pool and uptake by nondiazotrophs. This study appears to provide the first evidence of direct UCYN-C grazing by zooplankton, and indicates that UCYN-C-derived N contributes significantly to the zooplankton food web in the New Caledonia lagoon through a combination of direct grazing and secondary pathways.
Phase II Study of Alemtuzumab (CAMPATH-1) in Patients with HTLV-1–Associated Adult T-cell Leukemia/lymphoma

Purpose: Therapeutic regimens for adult T-cell leukemia/lymphoma (ATL) are limited with unsatisfactory results, thereby warranting development of novel therapies. This study investigated antitumor activity and toxicity of alemtuzumab with regard to response, duration of response, progression-free survival, and overall survival in patients with human T-cell lymphotropic virus-1 (HTLV-1)-associated ATL. Experimental Design: Twenty-nine patients with chronic, acute, and lymphomatous types of ATL were enrolled in a single-institution, nonrandomized, open-label phase II trial wherein patients received intravenous alemtuzumab 30 mg three times weekly for a maximum of 12 weeks. Results: Twenty-nine patients were evaluable for response and toxicity. The overall objective response was 15 of 29 patients [95% confidence interval (CI), 32.5%–70.6%]. The 15 patients who responded manifested a median time to response of 1.1 months. Median response duration was 1.4 months for the whole group and 14.5 months among responders. Median progression-free survival was 2.0 months. Median overall survival was 5.9 months. The most common adverse events were 2 with vasovagal episodes (7%) and 3 with hypotensive episodes (10%), leukopenia (41%) grade 3 and (17%) grade 4, lymphocytopenia (59%) grade 3, neutropenia (31%) grade 3, anemia (24%), and thrombocytopenia (10%). All patients developed cytomegalovirus antigenemia (CMV). Three were symptomatic and all responded to antiviral therapy. Grade 3 or 4 infections were reported in 4 (14%) of patients. Conclusions: Alemtuzumab induced responses in patients with acute HTLV-1–associated ATL with acceptable toxicity, but with short duration of responses. These studies support inclusion of alemtuzumab in novel multidrug therapies for ATL. Clin Cancer Res; 23(1); 35–42. ©2016 AACR.
Massive accidental overdose of hydroxyurea in a young child with sickle cell anemia

The Pediatric Hydroxyurea Phase III Clinical Trial (BABY HUG) confirmed safety and efficacy of hydroxyurea therapy for infants with sickle cell anemia. Treatment was associated with reduction in rates of pain, acute chest syndrome, hospitalizations, and blood transfusions; improved hematologic values; and, perhaps, preservation of organ function. During the study, a 2‐year‐old ingested at one time an entire 35‐day supply of hydroxyurea (612 mg/kg body weight). Despite a serum level of 7,756 µM 4 hours post‐ingestion, the only toxicity was transient mild myelosuppression. With wider usage of hydroxyurea anticipated, conservative management of future overdoses seems reasonable (ClinicalTrials.gov NCT00006400). Pediatr Blood Cancer 2012; 59: 170–172. © 2011 Wiley Periodicals, Inc.
Support for Gestalt versus Business-As-Usual theories of insight depends on operational definition of insight

SUPPORT FOR GESTALT VERSUS BUSINESS-AS-USUAL THEORIES OF INSIGHT DEPENDS ON OPERATIONAL DEFINITION OF INSIGHT Kimberly Diane Lee Old Dominion University, 2015 Director: Dr. Ivan K. Ash Some theories propose that insight involves automatic processes that are responsible for restructuring. Other theories postulate that the mechanisms surrounding restructuring are controlled and effortful. The current study tested these theories by comparing different methodology and operational definitions that have been used in previous research to investigate the nature of “Aha! ” experiences and impasse in insightful problem solving. One hundred two undergraduate psychology students from Old Dominion University completed working memory tasks, six classic insight problems, and gave initial problem representation ratings for the insight problems before solution attempt. Using a thinkaloud protocol, we assessed the occurrence of impasse during the problem solving phase. After solving each problem, participants completed self-reported, measures of the Aha! experience—solution confidence, how sudden a solution appeared, and the effort required. Results demonstrated distinctly different response patterns between selfreported ratings of insight and the empirically coded measure of impasse when compared with all other variables of interest. This suggests that the Aha! ratings lack construct validity as an assessment of insight. Further, we replicated contradictory working memory correlations found in previous research with the self-report ratings and impasse coding, suggesting that discrepancies in the literature were the result of how insight was assessed. These findings call into question previous research utilizing self-report Aha! ratings.
Daily Wear Contact Lenses Manufactured in Etafilcon A Are Noninferior to Two Silicone Hydrogel Lens Types With Respect to Hypoxic Stress

Purpose: This study hypothesized that a traditional high-water contact lens of moderate oxygen transmissibility (Dk/t) is noninferior to common silicone hydrogel (SH) lenses worn for daily wear with respect to measures of hypoxic stress. Methods: Thirty-six habitual contact lens wearers completed wear of three lens types worn in a randomized order: etafilcon A (ACUVUE 2, control), lotrafilcon B (Air Optix Aqua), and comfilcon A (Biofinity). Central corneal thickness (CT) and limbal hyperemia were measured >2 hr after waking and after 6 to 8 hr of wear on days 1 and 7. Endothelial bleb formation was measured on day 1 of each lens type. Noninferiority of etafilcon A, with respect to the other two lens types, was assumed if the following difference margins of equivalence were met: <1.5% for corneal swelling, <0.5 grade for limbal hyperemia, and <1% area of endothelial blebs. Outcomes were modeled using generalized linear mixed modeling techniques. Results: All lenses showed reductions in least-square mean estimates of CT on both days: etafilcon A −0.26% at day 1 and −0.31% at day 7; lotrafilcon B −1.11% at day 1 and −1.06% at day 7; comfilcon A −0.63% at day 1 and −0.84% at day 7. The difference in mean swelling between etafilcon A and lotrafilcon B was 0.85% at day 1 (95% confidence interval [0.4%–1.3%]) and 0.75% at day 7 (0.3%–1.2%). The difference in mean swelling between etafilcon A and comfilcon A was 0.37% at day 1 (−0.1% to 0.8%) and 0.53% at day 7 (0.1%–1.0%). For limbal redness, etafilcon A fell within 0.1 grade of lotrafilcon B and 0.18 grade of comfilcon A. For endothelial bleb formation, etafilcon A fell within 0.45% of lotrafilcon B and 0.23% of comfilcon A. Conclusion: The etafilcon A control lens resulted in corneal deswelling throughout the day as did the SH lens types. Limbal hyperemia and endothelial bleb formation with all lenses were negligible, and noninferiority assumptions were met between the lens types for all outcomes. Equivalence of etafilcon A with respect to the two SH lenses for three measures of hypoxic stress was demonstrated.
Bmc Infectious Diseases Influenza Activity in Europe during Eight Seasons (1999–2007): an Evaluation of the Indicators Used to Measure Activity and an Assessment of the Timing, Length and Course of Peak Activity (spread) across Europe

Background: The European Influenza Surveillance Scheme (EISS) has collected clinical and virological data on influenza since 1996 in an increasing number of countries. The EISS dataset was used to characterise important epidemiological features of influenza activity in Europe during eight winters (1999–2007). The following questions were addressed: 1) are the sentinel clinical reports a good measure of influenza activity? 2) how long is a typical influenza season in Europe? 3) is there a west-east and/or south-north course of peak activity ('spread') of influenza in Europe?
Chemokine Receptor Ccr2 Is Critical for Monocyte Accumulation and Survival in West Nile Virus Encephalitis

West Nile virus (WNV) is a re-emerging pathogen responsible for outbreaks of fatal meningoencephalitis in humans. Previous studies have suggested a protective role for monocytes in a mouse model of WNV infection, but the molecular mechanisms have remained unclear. In this study, we show that genetic deficiency in Ccr2, a chemokine receptor on Ly6chi inflammatory monocytes and other leukocyte subtypes, markedly increases mortality due to WNV encephalitis in C57BL/6 mice; this was associated with a large and selective reduction of Ly6chi monocyte accumulation in the brain. WNV infection in Ccr2+/+ mice induced a strong and highly selective monocytosis in peripheral blood that was absent in Ccr2−/− mice, which in contrast showed sustained monocytopenia. When a 1:1 mixture of Ccr2+/+ and Ccr2−/− donor monocytes was transferred by vein into WNV-infected Ccr2−/− recipient mice, monocyte accumulation in the CNS was not skewed toward either component of the mixture, indicating that Ccr2 is not required for trafficking of monocytes from blood to brain. We conclude that Ccr2 mediates highly selective peripheral blood monocytosis during WNV infection of mice and that this is critical for accumulation of monocytes in the brain.