Miracle-dz/UniFAR-FTUs huggingface dataset:
Heterogeneity of Immune Markers in Hemophagocytic Lymphohistiocytosis: Comparative Study of 9 Familial and 14 Familial Inheritance‐Unproved Cases

Purpose Although immune dysfunction is suspected in patients with hemophagocytic lymphohistiocytosis (HLH), the difference between immune dysfunction in patients with familial ery-throphagocytic lymphohistiocytosis (FEL) and familial inheritance-unproved lymphohistiocytosis (FIU) remains unknown. The aim of this study was to determine useful markers to distinguish patients with FEL from those with FIU. Patients and Methods Clinical features and laboratory findings, especially natural killer (NK) cell activity and the relative frequencies of peripheral blood mononuclear cell (PBMC) subsets, and serum levels of interferon-γ and soluble interleukin-2 receptor were compared in 9 patients with FEL and 14 age-matched patients with FIU. Twenty-seven healthy infants served as controls. The treatment and outcome were also compared for patients with FEL and FIU. Results Comparison between patients with FEL and FIU revealed significantly lower NK activity in those with FEL (p = 0.03) but failed to show any significant differences in PBMC subsets, except that the percentage of CD3+ T cells was higher in patients with FEL (p = 0.02). CD4− and CD8-dominant phenotypes were characteristic findings in both groups of patients, although increased CD19+ B cells were restricted to patients with FIU. NK activity was deficient (< 5%) in four of the seven patients with FEL tested but in only one of eight patients with FIU. By comparison to values for age-matched controls, the percentages of CD3+, CD3+DR+ and CD45RO+ PBMCs in patients with FEL were significantly high (p < 0.05) and those of CD19+ and CD45RA+ subsets were lower than normal. Among patients with FIU, PBMC subsets included significantly reduced CD3+, CD4+, CD45RA+, and CD4+CD45RA+. In this small series, the outcome of patients with FEL and FIU treated with chemotherapy was not significantly different at the time of evaluation. Conclusions These results indicate considerable immune heterogeneity among patients with HLH younger than 2 years. Although NK activity was useful but not diagnostic, determination of PBMC subsets and patterns of cytokine expression was not helpful in distinguishing patients with FEL from those with FIU, suggesting that the immune responses characteristic of these diseases may reflect different triggering factors, including viruses. The impact of this immune heterogeneity on patients' outcome remains to be determined.
Graph Structure Learning from Unlabeled Data for Event Detection

Processes such as disease propagation and information diffusion often spread over some latent network structure which must be learned from observation. Given a set of unlabeled training examples representing occurrences of an event type of interest (e.g., a disease outbreak), our goal is to learn a graph structure that can be used to accurately detect future events of that type. Motivated by new theoretical results on the consistency of constrained and unconstrained subset scans, we propose a novel framework for learning graph structure from unlabeled data by comparing the most anomalous subsets detected with and without the graph constraints. Our framework uses the mean normalized log-likelihood ratio score to measure the quality of a graph structure, and efficiently searches for the highest-scoring graph structure. Using simulated disease outbreaks injected into real-world Emergency Department data from Allegheny County, we show that our method learns a structure similar to the true underlying graph, but enables faster and more accurate detection.
Nucleosome Interactions and Stability in an Ordered Nucleosome Array Model System*

Although it is well established that the majority of eukaryotic DNA is sequestered as nucleosomes, the higher-order structure resulting from nucleosome interactions as well as the dynamics of nucleosome stability are not as well understood. To characterize the structural and functional contribution of individual nucleosomal sites, we have developed a chromatin model system containing up to four nucleosomes, where the array composition, saturation, and length can be varied via the ordered ligation of distinct mononucleosomes. Using this system we find that the ligated tetranucleosomal arrays undergo intra-array compaction. However, this compaction is less extensive than for longer arrays and is histone H4 tail-independent, suggesting that well ordered stretches of four or fewer nucleosomes do not fully compact to the 30-nm fiber. Like longer arrays, the tetranucleosomal arrays exhibit cooperative self-association to form species composed of many copies of the array. This propensity for self-association decreases when the fraction of nucleosomes lacking H4 tails is systematically increased. However, even tetranucleosomal arrays with only two octamers possessing H4 tails recapitulate most of the inter-array self-association. Varying array length shows that systems as short as dinucleosomes demonstrate significant self-association, confirming that relatively few determinants are required for inter-array interactions and suggesting that in vivo multiple interactions of short runs of nucleosomes might contribute to complex fiber-fiber interactions. Additionally, we find that the stability of nucleosomes toward octamer loss increases with array length and saturation, suggesting that in vivo stretches of ordered, saturated nucleosomes could serve to protect these regions from histone ejection.
Phase II Study of the Histone Deacetylase Inhibitor Romidepsin in Relapsed Small Cell Lung Cancer (Cancer and Leukemia Group B 30304)

Introduction: Treatment of small cell lung cancer (SCLC) is initially gratifying with most patients responding to platinum-based chemotherapy. Treatment of relapsed disease gives much lower response rates of short duration. We undertook this study of the protein deacetylase inhibitor Romidepsin in chemosensitive recurrent SCLC based on preclinical data that suggested this to be an active target. Methods: Patients had recurrent chemosensitive SCLC (relapse ≥90 days since completion of platinum-based chemotherapy). Treatment was administered as weekly infusions of Romidepsin at 13 mg/m2 for 3 of 4 weeks. We designed a two-stage phase II study targeting a response rate of 30% (<10% response would be uninteresting and ≥30% worthy of further study). Results: Sixteen patients (10 male, 6 female) were accrued to the first stage of this study. Most (11 patients, 69%) presented with extensive-stage SCLC, and all had received prior chemotherapy, with 11 having received prior radiation. Eastern Cooperative Oncology Group performance status was excellent with 0 in 6 patients (38%) and 1 in 10 patients. No objective responses were seen, and stable disease was the best response seen in 3 patients (19%). Toxicity was modest with 3 patients suffering grade 3 toxicity (lymphopenia, insomnia, nausea, vomiting, and hyponatremia) and one patient with grade 4 thrombocytopenia. Median progression-free survival was 1.8 months, and median overall survival was 6 months. Conclusion: Romidepsin given on a weekly schedule in patients with chemosensitive, recurrent SCLC was inactive and will not be pursued further in this setting.
Plasma Carotenoids and Retinol and Overall and Breast Cancer Risk: A Nested Case-Control Study

Experimental studies suggest that carotenoids and retinol may play a role in carcinogenesis, but epidemiological evidence is lacking. We investigated the prospective associations between plasma concentrations of major carotenoids and retinol, and overall and breast cancer risk. A nested case-control study included all first incident cancer cases diagnosed in the SU.VI. MAX cohort between 1994 and 2002 (n = 159 cases, 1 matched control/case). Baseline plasma concentrations of carotenoids and retinol were measured by high-performance liquid chromatography. Conditional logistic regression was used to assess odds ratios for an increase of 0.1 μmol/L [odds ratio (OR)] and 95% confidence intervals (CI). Plasma β-carotene (OR = 0.95, 95% CI = 0.90–0.99, Ptrend = 0.04) and β-cryptoxanthin concentrations (OR = 0.89, 95% CI = 0.81–0.99, Ptrend = 0.03) were inversely associated with overall cancer risk. Plasma β-cryptoxanthin concentration was inversely associated with breast cancer risk (OR = 0.83, 95% CI = 0.71–0.96, Ptrend = 0.02). The OR between plasma lycopene concentration and overall cancer risk was 1.07 (0.99–1.15), Ptrend = 0.06. This association turned significant (Ptrend = 0.01) when excluding cancer cases diagnosed during the first year of follow-up. This prospective study suggests an inverse association between plasma concentrations of β-cryptoxanthin and both overall and breast cancer risk, and an inverse association between β-carotene and overall cancer risk. The direct association between lycopene concentration and cancer risk deserves further investigation.
Krüppel-Like Factor 5 Mediates Proinflammatory Cytokine Expression in Lipopolysaccharide-Induced Acute Lung Injury through Upregulation of Nuclear Factor-κB Phosphorylation In Vitro and In Vivo

Acute lung injury (ALI) is associated with an inflammation-mediated process, and the transcription factor, Krüppel-like factor 5 (KLF5), might play a crucial role in inflammatory lung disease. In this study, we evaluated KLF5, reactive oxygen species (ROS), and inflammatory responses in a lipopolysaccharide- (LPS-) induced ALI model to elucidate the role of KLF5 in ALI. Our data indicated that LPS upregulates proinflammatory cytokine expression in human bronchial epithelial cells in a dose-dependent manner. We observed upregulated KLF5 protein expression in human bronchial epithelial cells exposed to LPS, with peak expression 1 h after LPS treatment, and subsequent upregulation of p65 protein expression and p65 phosphorylation at Ser276. These results indicate that KLF5 mediates proinflammatory cytokine expression by upregulating nuclear factor-kappaB (NF-κB) phosphorylation at p65 in response to LPS. LPS treatment also increased ROS production and simultaneously upregulated KLF5 expression and NF-κB translocation. N-acetylcysteine significantly reduced ROS levels and KLF5 and NF-κB translocation in nuclear extracts. Therefore, N-acetylcysteine pretreatment before LPS exposure reduces ROS, downregulates KLF5 expression, and subsequently reduces inflammatory responses by scavenging ROS. Overall, our study results indicate that KLF5 mediates proinflammatory cytokine expression through upregulation of NF-κB phosphorylation at p65 in LPS-induced ALI.
Mobile Learning as a Method of Ubiquitous Learning: Students’ Attitudes, Readiness, and Possible Barriers to Implementation in Higher Education

The purpose of this study was to explore the attitudes and level of readiness, and possible barriers to implementing Mobile Learning as a part of ubiquitous learning. In addition, the study attempted to find out to what extent students are interested in mobile learning. It also aimed to answer the question regarding the readiness of college students to use mobile learning technologies. Furthermore, the level of students experience in electronic learning was examined. The study was conducted to gather valuable data about are the possible advantages and disadvantages of mobile learning, and the barriers do students expect facing when implementing the mobile learning technologies. To answer the research questions, a questionnaire was administered to 1000 college students, with some of them being interviewed for in-depth information. The findings of the study showed that students had highly positive attitudes toward mobile learning, and they had the necessary technical knowledge to implement mobile learning. However, students were found to have very little experience in electronic and mobile learning. Students have mentioned some advantages of mobile learning among which was the possibility of learning outside the classroom and at any time. Some disadvantages were mentioned such as the fact that students might become annoyed with receiving too many text messages per day. Finally, students listed some barriers they expect to face the implementation of mobile learning. The study concluded with suggestions for future research and recommendations to university officials to better implement mobile learning.
Opioid actions on single nucleus raphe magnus neurons from rat and guinea‐pig in vitro.

1. Intracellular recordings were made from neurons of the nucleus raphe magnus (NRM) from rat (n = 128) and guinea‐pig (n = 115). Two types of cells were found in each, primary (103 in rat, 27 in guinea‐pig) and secondary cells (25 in rat, 88 in guinea‐pig). 2. Primary cells had input resistances of 186 +/‐ 9 M omega (n = 9) in rat and 255 +/‐ 50 M omega (n = 11) in guinea‐pig. The action potential in each was about 1.5 ms in duration. Synaptic potentials were evoked by focal electrical stimulation and consisted of both gamma‐aminobutyric acid (GABA) and excitatory amino acid components. 3. Morphine, [Met5]enkephalin (ME) and [D‐Ala2,N‐Me‐Phe4, Gly5‐ol]enkephalin (DAMGO) depressed the amplitude of the GABA‐mediated synaptic potential by a maximum of 50‐65% and had little effect on the excitatory amino acid‐mediated synaptic potential. There was no effect of these opioids on the resting membrane potential or input resistance of primary cells in rat or guinea‐pig. 4. Secondary cells had short duration action potentials (less than 1 ms) and an input resistance of 354 +/‐ 47 M omega in rat (n = 6) and 290 +/‐ 40 M omega in guinea‐pig (n = 15). The synaptic potential observed in the cells of this group was mediated by activation of only excitatory amino acid receptors. 5. ME hyperpolarized and/or abolished the spontaneous firing in sixteen out of twenty‐four neurons in the secondary group from rat and eight out of eighty‐four neurons from guinea‐pig. ME induced an outward current at ‐60 mV that reversed polarity at potentials more negative than ‐92 +/‐ 3 mV in rat (n = 6) and ‐98 +/‐ 2 mV in guinea‐pig (n = 18). The reversal potential of the opioid current was shifted to less negative potentials when the external potassium concentration was increased, as predicted by the Nernst equation. 6. The morphology of the two types of cells were distinguishable in that primary cells were oval (29 x 18 microns in rat; 36 x 19 microns in guinea‐pig) with two to four thick tapering dendrites that branched within 50 microns of the cell body. Secondary cells were generally round or oval (about 24 x 13 microns in rat; 27 x 17 microns in guinea‐pig) with two to five thin non‐tapering dendrites. (ABSTRACT TRUNCATED AT 400 WORDS)
Reliable and Efficient Download Delivery with Raptor Codes

In this work we address reliable file delivery over mobile broadcast networks using Raptor Codes. We assume a point-to-multipoint (broadcast) transmission, where original source symbols are protected by additional parity symbols. Despite the good performance of Raptor codes, reliable delivery cannot be guaranteed due to the statistics in heterogeneous receiver environments. Therefore, a second phase, where individual users are allowed to complete their delivery by performing individual repair sessions, must be conducted. Our main contribution are two algorithms, one allowing to find a minimum set of source symbols to be requested in the post-delivery, and one allowing to find a sufficient number of consecutive repair symbols, guaranteeing successful recovery. These post-repair methods fully exploit the properties of these codes. Selected simulations verify the good performance of file distribution with Raptor codes as well as the algorithms for file repair in case of file distribution to more than one user.
Pesticides and prostate cancer: a review of epidemiologic studies with specific agricultural exposure information

Prostate cancer is the most commonly diagnosed cancer in US men, and the second most commonly diagnosed cancer among men worldwide. Although pesticides have been implicated in studies of prostate cancer among farmers, meta-analyses have found heterogeneity across studies, and a number of exposures and lifestyle factors may be unique to farmers. The purpose of this paper is to review the epidemiologic literature to evaluate the hypothesis that agricultural exposure to pesticides is causally associated with prostate cancer risk. We analyzed the eight cohort studies and five case–control studies that quantified and/or evaluated agricultural exposure to particular pesticide classes or chemicals. Despite sporadic positive findings, these studies did not show consistently increased risks to support a causal association between agricultural pesticide use and prostate cancer. Studies using an ‘external’ comparison group must be interpreted in the context of confounding by differences in prostate-specific antigen screening intensity. Furthermore, most studies did not adjust for potential confounders other than age and time period. It is clearly not possible to exonerate any particular pesticide as a putative cause of prostate cancer – to do so would require an inverse empirical association with an upper confidence limit below the null value. Existing evidence does not point to any pesticide as satisfying widely used guidelines for establishing causation: a strong, exposure-dependent and demonstrably unconfounded, unbiased association, documented in several studies.
Model structure analysis to estimate basic immunological processes and maternal risk for parvovirus B19

After a steep monotone rise with age, the seroprevalence profiles for human parvovirus B19 (PVB19) display a decrease or plateau between the ages of 20 and 40, in each of 5 European countries. We investigate whether this phenomenon is induced by waning antibodies for PVB19 and, if this is the case, whether secondary infections are plausible, or whether boosting may occur. Several immunological scenarios are tested for PVB19 by fitting different compartmental dynamic transmission models to serological data using data on social contact patterns. The social contact approach has already been shown informative to estimate transmission rates and the basic reproduction number for infections transmitted predominantly through nonsexual social contacts. Our results show that for 4 countries, model selection criteria favor the scenarios allowing for waning immunity at an age-specific rate over the assumption of lifelong immunity, assuming that the transmission rates are directly proportional to the contact rates. Different views on the evolution of the immune response to PVB19 infection lead to altered estimates of the age-specific force of infection and the basic reproduction number. The scenarios which allow for multiple infections during one lifetime predict a higher frequency of PVB19 infection in pregnant women and of associated fetal deaths. When prevaccination serological data are available, the framework developed in this paper could prove worthwhile to investigate these different scenarios for other infections as well, such as cytomegalovirus.
Auditory-verbal analysis in aphasia

ABSTRACT Background: Comprehension deficits are more pervasive in aphasic syndromes than initially believed. They affect differentially distinct levels of auditory-verbal comprehension. Current evidence from functional imaging studies in healthy subjects indicates that distinct levels of auditory-verbal analysis involve specific networks. Aims: The aim of this study is (1) to assess the different levels of auditory-verbal analysis with real-time monitoring tasks in patients with aphasia, (2) to compare the performance profiles across aphasia types, (3) to analyse patterns of dissociations vs. co-occurrence at specific levels, and (4) to establish correlations between disturbances at specific levels of auditory-verbal analysis and sites of lesions. Methods & Procedures: Forty-two right-handed patients with aphasia associated with a first unilateral left-hemispheric lesion underwent tests monitoring (1) phonetic-phonological, (2) lexical, (3) morphosyntactic, (4) semantic-pragmatic (at sentence level), and (5) linguistic prosody processing. Anatomo-clinical correlations were established by means of voxel-based lesion-symptom mapping. Outcomes & Results: Widespread deficits at multiple levels occurred across aphasic syndromes. In a given patient, more levels tended to be impaired in Wernicke’s and global aphasia than in Broca’s or conduction aphasia. Syllable and word processing double-dissociated behaviourally and partially anatomically. Morphosyntactic deficits were always accompanied by semantic-pragmatic deficits. Anatomo-clinical correlations implicated the dorsal auditory stream in syllable discrimination, the ventral stream in semantic processing at lexical level and in linguistic prosody and both streams in lexical frequency effect. Basal ganglia were implicated in syntactic and semantic processing at sentence level. Conclusions: At prelexical and lexical levels, syllable and word processing appear to be independent of each other. At sentence level, parsing of syntactic structure appears to be necessary for successful semantic-pragmatic analysis. Thus, the fine-grained evaluation of auditory-verbal processing capacities and of the integrity of specialised processing networks in brain-damaged patients provides a sensitive diagnostic tool.
Assessing Mental Imagery to Evaluate Topographical Disorientation: Group Study and Preliminary Normative Data

There is currently no specific neuropsychological test assessing spatial orientation abilities, despite the fact that navigational deficits are heavily incapacitating in daily life. This lack of a specific test is probably due to theoretical vagueness of concepts in this field and important interindividual differences in spatial cognition. Here we propose a new standardized test assessing a fundamental component of spatial orientation—namely, mental imagery: Adequate mental visualization of the environment is indeed a necessary step in finding one’s way. Two conditions of mental imagery were proposed to a group of 58 patients with a right cerebral lesion and to a control group (N = 117). The 1st condition assessed global, categorical imagery; the 2nd evaluated precise, metric imagery. We evaluated performance of the 2 groups in the 2 conditions and the impact of sociodemographic variables (age, gender, education). Results show that the right-lesioned patients presented difficulties in mental imagery, especially in the metric condition. Moreover, the data indicate a global impact of age and a milder effect of education on mental imagery abilities. Although sample sizes are sometimes small, preliminary normative data are given; already in the present form, they are usable and informative in assessing mental imagery, and more generally, spatial orientation, in a clinical practice.
Narratives of Fear in Syria

Scholarship on Syria has traditionally been limited by researchers' difficulty in accessing the reflections of ordinary citizens due to their reluctance to speak about politics. The 2011 revolt opened exciting opportunities by producing an outpouring of new forms of self-expression, as well as encouraging millions to tell their stories for the first time. I explore what we can learn from greater attention to such data, based on thick descriptive analysis of original interviews with 200 Syrian refugees. I find that individuals' narratives coalesce into a collective narrative emphasizing shifts in political fear. Before the uprising, fear was a pillar of the state's coercive authority. Popular demonstrations generated a new experience of fear as a personal barrier to be surmounted. As rebellion militarized into war, fear became a semi-normalized way of life. Finally, protracted violence has produced nebulous fears of an uncertain future. Study of these testimonials aids understanding of Syria and other cases of destabilized authoritarianism by elucidating lived experiences obscured during a repressive past, providing a fresh window into the construction and evolution of national identity, and demonstrating how the act of narration is an exercise in meaning making within a revolution and itself a revolutionary practice.