Miracle-dz/UniFAR-FTUs huggingface dataset:
Neurotoxicity of a Biopesticide Analog on Zebrafish Larvae at Nanomolar Concentrations

Despite the ever-increasing role of pesticides in modern agriculture, their deleterious effects are still underexplored. Here we examine the effect of A6, a pesticide derived from the naturally-occurring α-terthienyl, and structurally related to the endocrine disrupting pesticides anilinopyrimidines, on living zebrafish larvae. We show that both A6 and an anilinopyrimidine, cyprodinyl, decrease larval survival and affect central neurons at micromolar concentrations. Focusing on a superficial and easily observable sensory system, the lateral line system, we found that defects in axonal and sensory cell regeneration can be observed at much lower doses, in the nanomolar range. We also show that A6 accumulates preferentially in lateral line neurons and hair cells. We examined whether A6 affects the expression of putative target genes, and found that genes involved in apoptosis/cell proliferation are down-regulated, as well as genes reflecting estrogen receptor activation, consistent with previous reports that anilinopyrimidines act as endocrine disruptors. On the other hand, canonical targets of endocrine signaling are not affected, suggesting that the neurotoxic effect of A6 may be due to the binding of this compound to a recently identified, neuron-specific estrogen receptor.
Role of nitrite in regulation of fetal cephalic circulation in sheep

Recent evidence in adult humans demonstrates that nitrite, at physiological concentrations, can be converted into vasodilating amounts of NO, thus constituting an alternative to NO production by NO synthases. Nitrite reacts with deoxyhaemoglobin to produce NO, a reaction proposed to mediate the vasodilating effects of nitrite. We have demonstrated previously that the rate of this reaction is ∼2‐fold faster with fetal haemoglobin than adult haemoglobin. Thus, we hypothesized that nitrite would be a potent vasodilator in the cephalic vasculature served by the carotid artery in the fetal sheep. In conflict with human adult forearm studies, we find that nitrite is not a vasodilator in the fetal sheep cephalic vasculature, despite the fact that nitrite is converted to NO more efficiently by fetal haemoglobin. The results suggest that the vasodilatory effects of nitrite are age‐ and species‐specific, and that the reaction of nitrite with deoxyhaemoglobin is not rate limiting with respect to its ability to decrease vascular tone.
Lens opacities among physicians occupationally exposed to ionizing radiation--a pilot study in Finland.

OBJECTIVES The aim of this study was to estimate the prevalence of lens opacities among physicians occupationally exposed to radiation - overall and by occupational factors - and to assess the feasibility of a large-scale study for risk assessment. METHODS Based on a nationwide registry of 1312 physicians, mostly radiologists with occupational exposure to ionizing radiation, 120 subjects were invited to participate, of which 59 (49%) consented. The inclusion criteria included (i) age 45-70 years, (ii) cumulative recorded radiation dose >10 mSv, and (iii) duration of work with dose monitoring >15 years. The participants completed a questionnaire regarding occupational history and other risk factors for lens opacities. A full ophthalmological examination was performed. Lenticular changes were graded using the Lens Opacities Classification System, version II (LOCS II), and the Nidek EAS-1000 Scheimpflug slit-imaging videophotography system. RESULTS Lens opacities were detected in 42% [95% confidence interval (95% CI) 29-55] of the 57 physicians without prior cataract surgery. Nuclear opacities were found in 14% (95% CI 6-26), cortical in 7% (95% CI 2-19), and posterior subcapsular in 5% (95% CI 1-15) of the subjects. The prevalence of lens opacities increased with age, smoking, and cumulative recorded radiation dose. After controlling for age, gender, and smoking, the excess odds ratio for any lens opacity was 0.13 (95% CI -0.02-0.28) per 10 mSv of cumulative radiation dose. CONCLUSIONS Our preliminary results show cortical and posterior subcapsular lens opacities among physicians exposed to occupational radiation, consistent with recent studies on low dose radiation exposure. A full study with an unexposed reference group for risk estimation is warranted.
Risk Factors for Disseminated Histoplasmosis in a Cohort of HIV-Infected Patients in French Guiana

Disseminated histoplasmosis is the first AIDS-defining infection in French Guiana. A retrospective cohort study studied predictive factors of disseminated histoplasmosis in HIV-infected patients between 1996 and 2008. Cox proportional hazards models were used. The variables studied were age, sex, last CD4/CD8 count, CD4 nadir, herpes or pneumocystosis, cotrimoxazole and fluconazole use, antiretroviral treatment and the notion of recent initiation of HAART. A total of 1404 patients were followed for 6833 person-years. The variables independently associated with increased incidence of disseminated histoplasmosis were CD4 count<50 per mm3, CD4 count between 50 and 200 per mm3, a CD4 nadir <50 per mm3, CD8 count in the lowest quartile, herpes infection, and recent antiretroviral treatment initiation (less than 6 months). The variables associated with decreased incidence of histoplasmosis were antiretroviral treatment for more than 6 months, fluconazole treatment, and pneumocystosis. There were 13.5% of deaths at 1 month, 17.5% at 3 months, and 22.5% at 6 months after the date of diagnosis of histoplasmosis. The most important predictive factors for death within 6 months of diagnosis were CD4 counts and antiretroviral treatment. The present study did not study environmental/occupational factors but provides predictive factors for disseminated histoplasmosis and its outcome in HIV patients in an Amazonian environment during the HAART era.
Pancreastatin activates pertussis toxin‐sensitive guanylate cyclase and pertussis toxin‐insensitive phospholipase C in rat liver membranes

We have recently found the calcium dependent glycogenolytic effect of pancreastatin on rat hepatocytes and the mobilization of intracellular calcium. To further investigate the mechanism of action of pancreastatin on liver we have studied its effect on guanylate cyclase, adenylate cyclase, and phospholipase C, and we have explored the possible involvement of GTP binding proteins by measuring GTPase activity as well as the effect of pertussis toxin treatment of plasma liver membranes on the pancreastatin stimulated GTPase activity and the production of cyclic GMP and myo‐inositol 1,4,5‐triphosphate.
HIT on the Psychometric Approach

Traditionally, identity and supervenience have been proposed in philosophy of mind as metaphysical accounts of how mental activities (fully understood, as they might be at the end of science) relate to brain processes. Kievet et al. (this issue) suggest that to be relevant to cognitive neuroscience, these philosophical positions must make empirically testable claims and be evaluated accordingly—they cannot sit on the sidelines, awaiting the hypothetical completion of cognitive neuroscience. We agree with the authors on the importance of rendering these positions relevant to ongoing science. We disagree, however, with their proposal that a metaphysical relationship (identity or supervenience) should “serve as a means to conceptually organize and guide the analysis of neurological and behavioral data” (p. 69). Instead, we advance a different view of the goals of cognitive neuroscience and of the proper means of relating metaphysics and explanation. Our central objection to the psychometric approach deployed by Kievet et al. is that the formal models only account for correlations between variables (measurements) and do not aid in explaining phenomena. Cognitive neuroscience is concerned with the latter. We develop this point in the next section, in which we present what we find to be problematic in their proposed models. In the Identity Claims and Mechanistic Explanations in Cognitive Neuroscience section, we advance an account of what is required to explain phenomena: (a) providing an adequate description of a phenomenon, and (b) characterizing the mechanism responsible for it. In doing so we characterize a version of the identity theory—heuristic identity theory (HIT), which figures centrally in developing such explanations—and illustrate its role in what we take to be a prototypical example of research in cognitive neuroscience. Finally, in the Levels, Mechanisms and Identity Claims section, we turn to how levels and interlevel relations should be construed in a metaphysical account that fits the mission of cognitive neuroscience.
Pathogenesis, diagnosis, and management of Kikuchi-Fujimoto disease.

BACKGROUND Kikuchi-Fujimoto disease (KFD) is a rare lymphohistiocytic disorder with an unknown etiopathogenesis. This disease is misdiagnosed as malignant lymphoma in up to one-third of cases and is associated with the development of systemic lupus erythematosus (SLE). METHODS The medical literature between the years 1972 and 2014 was searched for KFD, and the data were collected and analyzed regarding the epidemiology, clinical presentations, diagnosis, management, and suggested diagnostic and treatment algorithms. RESULTS Although KFD has been reported in other ethnic groups and geographical areas, it is more frequently diagnosed in young women of Asian descent. Patients with the disease typically present with rapidly evolving tender cervical lymphadenopathy, night sweats, fevers, and headache. Diagnosis is based on histopathological examination. Excisional lymph node biopsy is essential for a correct diagnosis. Apoptotic coagulation necrosis with karyorrhectic debris and the proliferation of histiocytes, plasmacytoid dendritic cells, and CD8(+) T cells in the absence of neutrophils are characteristic cytomorphology features. Interface dermatitis at the onset of KFD may be a marker for the subsequent evolution of SLE. The natural course of the disease is typically benign. Short courses of steroids, nonsteroidal anti-inflammatory drugs, or hydroxychloroquine can be administered to patients with more severe symptoms. CONCLUSIONS Although KFD was described more than 40 years ago, the etiology of this disease remains unsolved. Infectious or autoimmune processes were proposed but have not been definitively confirmed. Clinical presentation with systemic B symptoms and adenopathy may lead to an erroneous diagnosis of malignant lymphoma. The introduction of modern methods into hematopathology, including immunohistochemistry, flow cytometry, and molecular clonality studies, has decreased the probability of misdiagnosis. Until reliable prognostic markers are available, patients with KFD should have continued long-term follow-up care due to their increased risk of SLE.
Gene Expression Profiling Identifies HOXB4 as a Direct Downstream Target of GATA-2 in Human CD34+ Hematopoietic Cells

Aplastic anemia is characterized by a reduced hematopoietic stem cell number. Although GATA-2 expression was reported to be decreased in CD34-positive cells in aplastic anemia, many questions remain regarding the intrinsic characteristics of hematopoietic stem cells in this disease. In this study, we identified HOXB4 as a downstream target of GATA-2 based on expression profiling with human cord blood-derived CD34-positive cells infected with control or GATA-2 lentiviral shRNA. To confirm the functional link between GATA-2 and HOXB4, we conducted GATA-2 gain-of-function and loss-of-function experiments, and HOXB4 promoter analysis, including luciferase assay, in vitro DNA binding analysis and quantitative ChIP analysis, using K562 and CD34-positive cells. The analyses suggested that GATA-2 directly regulates HOXB4 expression through the GATA sequence in the promoter region. Furthermore, we assessed GATA-2 and HOXB4 expression in CD34-positive cells from patients with aplastic anemia (n = 10) and idiopathic thrombocytopenic purpura (n = 13), and demonstrated that the expression levels of HOXB4 and GATA-2 were correlated in these populations (r = 0.6573, p<0.01). Our results suggested that GATA-2 directly regulates HOXB4 expression in hematopoietic stem cells, which may play an important role in the development and/or progression of aplastic anemia.
Late Paleozoic to Triassic arc magmatism north of the Sverdrup Basin in the Canadian Arctic: Evidence from detrital zircon U-Pb geochronology

Paleozoic and Mesozoic tectonic reconstructions of the Arctic regions have been a subject of debate in recent years. The Permian emergence of a landmass north of the Sverdrup Basin in the Canadian Arctic led to the shedding of northerly derived detritus, an event that followed volcanism and basin inversion pulses that began in the late Pennsylvanian. However, the mechanisms for these events and the Paleozoic to Mesozoic paleogeography of this region remain controversial. New detrital zircon U-Pb geochronology results from Permian to Lower Triassic strata from northern Axel Heiberg and Ellesmere islands constrain the magmatic events within this northern landmass and its implications for the tectonic regime of the Sverdrup Basin and adjacent domains. Permian to lowermost Triassic strata along the northern margin of the Sverdrup Basin contain zircons derived from Silurian to Devonian rocks (420–350 Ma), Timanian-aged basement (700–500 Ma), and a Permian syndepositional source (300–250 Ma). Coeval strata in the southern margin are dominated by zircons formed during the Taconic, Scandian, and post-Scandian phases of the Appalachian and Caledonian orogenies, respectively (480–400 Ma). The detrital zircon signatures of the analyzed strata on the northern margin of the Sverdrup Basin record continuous magmatism within the northern landmass from latest Carboniferous (ca. 300 Ma) to at least earliest Triassic (ca. 250 Ma) time. These results are indicative of ongoing subduction and development of a magmatic arc off the northern margin of Laurentia, with the Sverdrup Basin potentially located in the backarc region of a proto-Pacific convergent margin involving parts of Arctic Alaska, Chukotka, and the Chukchi Shelf. The hypothesized onset of subduction in latest Carboniferous time and closure of this backarc basin in the latest Permian to earliest Triassic provides an explanation for the shift in stress regimes in the Sverdrup Basin that led to basin inversion and volcanism episodes. Therefore, the data presented here supports a backarc to retroarc setting for the Sverdrup Basin and the possibility of a convergent margin regime for the northern edge of Laurentia during the late Paleozoic to Triassic, contrasting with the generally accepted rift and passive margin settings. LITHOSPHERE; v. 10; no. 3; p. 426–445; GSA Data Repository Item 2018093 | Published online 23 March 2018 https://doi.org/10.1130/L683.1
The impact of macular pigment augmentation on visual performance using different carotenoid formulations.

PURPOSE To investigate changes in macular pigment optical density (MPOD) and visual performance following supplementation with different macular carotenoid formulations. METHODS Thirty-six subjects (19 male, 17 female; mean SD, age 51 13 years) were recruited into this single-masked placebo-controlled study, and were randomly assigned to one of the following three intervention (supplementation) groups: (1) group 1 (20 mg lutein [L] and 2 mg zeaxanthin [Z]); (2) group 2 (10 mg L, 2 mg Z, and 10 mg meso-zeaxanthin [MZ]); and group 3 (placebo). Outcomes measures included visual performance and MPOD response. Data were collected at baseline, at 3 months, and at 6 months. RESULTS At 3 and 6 months, a statistically significant increase in MPOD was found at all eccentricities (other than the most peripheral 3° location) in group 2 (P < 0.05 for all), whereas no significant increase in MPOD was demonstrable at any eccentricity for subjects in groups 1 and 3. Statistically significant improvements in visual performance measures including visual acuity and contrast sensitivity with and without glare were observed for group 2 only. Only mesopic contrast sensitivity at one spatial frequency improved significantly by 6 months (P < 0.05) for group 1. No improvements in any parameters of visual performance were observed for subjects supplemented with placebo (P > 0.05 for all). CONCLUSIONS These results suggest that supplementation with all three macular carotenoids potentially offered advantages over preparations lacking MZ, both in terms of MPOD response and visual performance enhancement.
Multi-source localization in reverberant environments by ROOT-MUSIC and clustering

Localization of acoustic sources in reverberant environments by microphone arrays remains a challenging task in audio signal processing. As a matter of fact, most assumptions of commonly adopted models are not met in real applications. Moreover, in practical systems it is not convenient or possible to employ sophisticated and costly architectures, that require precise synchronization and fast data shuffling among sensors. In this paper, a new robust multi-step procedure for speaker localization in reverberant rooms is introduced and described. The new approach is based on a disturbed harmonics model of time delays in the frequency domain and employs the well-known ROOT-MUSIC algorithm, after a preliminary distributed processing of the received signals. Candidate source positions are then estimated by clustering of raw TDOA estimates. Main features of the proposed approach, compared to previous solutions, are the capability of tracking multiple speakers and the high accuracy of the closed form TDOA estimator.
Catastrophic Valley Entrenchment and Debris Fan Formation in the Bluefields River, Westmoreland Jamaica

Little is known about the geomorphic response of Jamaican rivers to climate, geology, and human disturbance. The southwestern coast of Jamaica received a record of 32 cm of rain on June 12, 1979. Reports indicated that valley areas formed temporary lakes, overtopped small dams, and produced debris flows. This study investigates the effects of this extreme flooding on the geomorphology of the present-day Bluefields River near Belmont, Westmoreland Jamaica. The river drains 4.9 km 2 of limestone uplands and mountain slopes. This study evaluates evidence from longitudinal profiles, multiple cross-sections, Colonial maps, historical aerial photographs, oral histories, and sedimentological analysis to identify previous channel bed elevations and evaluate current channel morphology. The Bluefields River was entrenched by nearly 9 meters along its middle and lower reaches. In addition, Goat Gulley, its major tributary, was also incised along its lower and upper segments. Debris flows formed a large debris fan extending over 150 m out into Bluefields Bay. About 70% of the 1979 fan volume still remains today. While Colonial maps indicate that a delta fan always existed at the river mouth, the shoreline configuration was similar from the late 1700s to before the flood with little expression of the debris fan as now present. Therefore, the return period for this type of hydro-geomorphic event is >300 years. While causes are mostly related to climate and geology factors, human modification of the landscape may have contributed to increased rates and extent of channel incision, thus increasing sediment delivery. Bluefields Bay is now a fish sanctuary and further studies of sediment inputs to the bay over different timescales may be important for maintaining a healthy fishery.
Cyclosporin A inhibits caspase-independent death of NGF-deprived sympathetic neurons

Opening of the permeability transition pore (PTP) has been implicated as an important mitochondrial event that occurs during apoptosis. We examined the role of the PTP in the well-characterized cell death of rat sympathetic neurons deprived of nerve growth factor (NGF) in vitro. Removal of NGF causes these neurons to undergo either a classic apoptotic cell death or, when treated with a broad-spectrum caspase inhibitor such as boc-aspartyl(OMe)-fluoromethylketone (BAF), a delayed, nonapoptotic cell death. The PTP inhibitor, cyclosporin A (CsA), blocked commitment-to-die in the presence of BAF, as defined by the ability of NGF readdition to rescue cells, but had little effect on commitment-to-die in the absence of BAF. CsA did not have trophic effects on BAF-saved cells, but did block the decrease in mitochondrial membrane potential. These data suggest that PTP opening is a critical event in caspase-independent, nonapoptotic (but not caspase-dependent, apoptotic) death of NGF-deprived rat sympathetic neurons.
The regulation of central and peripheral circadian clocks in humans

Many circadian rhythms are controlled by the central clock of the suprachiasmatic nucleus of the hypothalamus, as well as clocks located in other brain regions and most peripheral tissues. These central and peripheral clocks are based on clock genes and their protein products. In recent years, the expression of clock genes has started to be investigated in human samples, primarily white blood cells, but also skin, oral mucosa, colon cells, adipose tissue as well as post‐mortem brain tissue. The expression of clock genes in those peripheral tissues offers a way to monitor human peripheral clocks and to compare their function and regulation with those of the central clock, which is followed by markers such as melatonin, cortisol and core body temperature. We have recently used such an approach to compare central and peripheral rhythms in subjects under different lighting conditions. In particular, we have monitored the entrainment of the clock of blood cells in subjects undergoing a simulated night shift protocol with bright light treatment, known to efficiently reset the central clock. This line of research will be helpful for learning more about the human circadian system and to find ways to alleviate health problems of shift workers, and other populations experiencing altered circadian rhythms.
Improvement in DCIS Detection Rates by MRI Over Time in a High‐Risk Breast Screening Study

Abstract: Although magnetic resonance imaging (MRI) is much more sensitive than mammography for detecting early invasive breast cancer, in many high‐risk screening studies MRI was less sensitive than mammography for detecting ductal carcinoma in situ (DCIS). We reviewed our experience detecting DCIS in our single center study of annual MRI, mammography, ultrasound and clinical breast examination (CBE) for screening very high‐risk women. All cases of DCIS ± microinvasion and invasive cancer were compared in two time frames: before (period A) and after (period B) July 2001—when we acquired expertise in the detection of DCIS with MRI—with respect to patient demographics, method of detection, and rates of detection of invasive cancer and DCIS. In period A there were 15 cases (3.1% of 486 screens) in 223 women, of which 2 (13%) were DCIS—one with microinvasion—neither detected by MRI. In period B there were 29 cases (3.3% of 877 screens) in 391 women, of which 10 (34%) were DCIS ± microinvasion (p = 0.04), all 10 detected by MRI but only one by mammography. No DCIS cases were detected by ultrasound or CBE. Specificity was lower in period B than in period A but acceptable. The ability to detect DCIS with screening MRI improves significantly with experience. MRI‐guided biopsy capability is essential for a high‐risk screening program. In experienced centers the increased sensitivity of MRI relative to mammography is at least as high for DCIS as it is for invasive breast cancer.