Miracle-dz/UniFAR-FTUs huggingface dataset:
Reconstitution of the cellular immune response after autologous peripheral blood stem cell transplantation in patients with non‐Hodgkin's lymphoma

Peripheral blood stem cell (PBSC) transplants may be depleted of lymphoid progenitors, thereby disabling the cellular immune response against viral pathogens after autologous PBSC transplantation (PBSCT). To monitor the cellular immune reconstitution after autologous PBSCT, we investigated the cytolytic activity (CLA) of peripheral blood T lymphocytes against Epstein–Barr virus (EBV) in 13 patients with non‐Hodgkin‘s lymphoma or multiple myeloma. The individual EBV‐directed CLA (EBV‐CLA) was determined by calculating the number of cytolytic effector cells in 106 T cells needed to lyse 25% of autologous EBV‐transformed B‐lymphoblastoid cells, expressed as lytic units (LU25). During the first 6 months after PBSCT, the EBV‐CLA was only 14.6% of the response of healthy controls (median 4.8 vs. 32.9 LU25). Thereafter, the EBV‐CLA increased to 28.15 LU25 (median) or 86% of healthy controls. Monthly follow‐up analyses in five selected patients showed that the EBV‐CLA was barely detectable at 4 weeks and recovered at 8–12 weeks after PBSCT in four out of five patients. Effector cells consisted mostly of CD8‐positive T lymphocytes, with small CD4‐ and CD3/CD56‐positive lymphocyte fractions. These results suggest that the reconstitution of the cellular immune response against EBV takes 8–12 weeks after autologous PBSCT.
Small Dense Low-Density Lipoprotein-Cholesterol Concentrations Predict Risk for Coronary Heart Disease: The Atherosclerosis Risk in Communities (ARIC) Study

Objective—To investigate the relationship between plasma levels of small dense low-density lipoprotein-cholesterol (sdLDL-C) and risk for incident coronary heart disease (CHD) in a prospective study among Atherosclerosis Risk in Communities (ARIC) study participants. Approach and Results—Plasma sdLDL-C was measured in 11 419 men and women of the biracial ARIC study using a newly developed homogeneous assay. A proportional hazards model was used to examine the relationship among sdLDL-C, vascular risk factors, and risk for CHD events (n=1158) for a period of ≈11 years. Plasma sdLDL-C levels were strongly correlated with an atherogenic lipid profile and were higher in patients with diabetes mellitus than non–diabetes mellitus (49.6 versus 42.3 mg/dL; P<0.0001). In a model that included established risk factors, sdLDL-C was associated with incident CHD with a hazard ratio of 1.51 (95% confidence interval, 1.21–1.88) for the highest versus the lowest quartile, respectively. Even in individuals considered to be at low cardiovascular risk based on their LDL-C levels, sdLDL-C predicted risk for incident CHD (hazard ratio, 1.61; 95% confidence interval, 1.04–2.49). Genome-wide association analyses identified genetic variants in 8 loci associated with sdLDL-C levels. These loci were in or close to genes previously associated with risk for CHD. We discovered 1 novel locus, PCSK7, for which genetic variation was significantly associated with sdLDL-C and other lipid factors. Conclusions—sdLDL-C was associated with incident CHD in ARIC study participants. The novel association of genetic variants in PCSK7 with sdLDL-C and other lipid traits may provide new insights into the role of this gene in lipid metabolism.
Human Rvb1/Tip49 Is Required for the Histone Acetyltransferase Activity of Tip60/NuA4 and for the Downregulation of Phosphorylation on H2AX after DNA Damage

ABSTRACT The role of chromatin-remodeling factors in transcription is well established, but the link between chromatin-remodeling complexes and DNA repair remains unexplored. Human Rvb1 and Rvb2 are highly conserved AAA+ ATP binding proteins that are part of various chromatin-remodeling complexes, such as Ino80, SNF2-related CBP activator protein (SRCAP), and Tip60/NuA4 complexes, but their molecular function is unclear. The depletion of Rvb1 increases the amount and persistence of phosphorylation on chromatin-associated H2AX after the exposure of cells to UV irradiation or to mitomycin C, cisplatin, camptothecin, or etoposide, without increasing the amount of DNA damage. Tip60 depletion, but not Ino80 or SRCAP depletion, mimics the effect of Rvb1 depletion on H2AX phosphorylation. Rvb1 is required for the histone acetyltransferase (HAT) activity of the Tip60 complex, and histone H4 acetylation is required prior to the dephosphorylation of phospho-H2AX. Thus, Rvb1 is critical for the dephosphorylation of phospho-H2AX due to the role of Rvb1 in maintaining the HAT activity of Tip60/NuA4, implicating the Rvb1-Tip60 complex in the chromatin-remodeling response of cells after DNA damage.
Botulinum toxin‐a treatment reduces human mechanical pain sensitivity and mechanotransduction

The mechanisms underlying the analgesic effects of botulinum toxin serotype A (BoNT‐A) are not well understood. We have tested the hypothesis that BoNT‐A can block nociceptor transduction. Intradermal administration of BoNT‐A to healthy volunteers produced a marked and specific decrease in noxious mechanical pain sensitivity, whereas sensitivity to low‐threshold mechanical and thermal stimuli was unchanged. BoNT‐A did not affect cutaneous innervation. In cultured rodent primary sensory neurons, BoNT‐A decreased the proportion of neurons expressing slowly adapting mechanically gated currents linked to mechanical pain transduction. Inhibition of mechanotransduction provides a novel locus of action of BoNT‐A, further understanding of which may extend its use as an analgesic agent. Ann Neurol 2014;75:591–596
The tropicalization of temperate marine ecosystems: climate-mediated changes in herbivory and community phase shifts

Climate-driven changes in biotic interactions can profoundly alter ecological communities, particularly when they impact foundation species. In marine systems, changes in herbivory and the consequent loss of dominant habitat forming species can result in dramatic community phase shifts, such as from coral to macroalgal dominance when tropical fish herbivory decreases, and from algal forests to ‘barrens’ when temperate urchin grazing increases. Here, we propose a novel phase-shift away from macroalgal dominance caused by tropical herbivores extending their range into temperate regions. We argue that this phase shift is facilitated by poleward-flowing boundary currents that are creating ocean warming hotspots around the globe, enabling the range expansion of tropical species and increasing their grazing rates in temperate areas. Overgrazing of temperate macroalgae by tropical herbivorous fishes has already occurred in Japan and the Mediterranean. Emerging evidence suggests similar phenomena are occurring in other temperate regions, with increasing occurrence of tropical fishes on temperate reefs.
Engineering Efficient Paging Algorithms

In the field of online algorithms, paging is a well-studied problem. LRU is a simple paging algorithm that incurs few cache misses and supports efficient implementations. Algorithms outperforming LRU in terms of cache misses exist but are in general more complex and thus not automatically better, since their increased runtime might annihilate the gains in cache misses. In this article, we focus on efficient implementations for the OnOPT class described in Moruz and Negoescu [2012], particularly on an algorithm in this class, denoted RDM, that was shown to typically incur fewer misses than LRU. We provide experimental evidence on a wide range of cache traces showing that our implementation of RDM is competitive to LRU with respect to runtime. In a scenario incurring realistic time penalties for cache misses, we show that our implementation consistently outperforms LRU, even if the runtime of LRU is set to zero.
Book Review: Solidarity in Europe. The History of an Idea

each case, with a common set of issues structuring each chapter: welfare state development in a historical perspective; poverty trends and anti-poverty policies; debates and initiatives in the field of minimum income. However, given the expected relevance of family solidarity in these countries and the incidence of child poverty, one wishes there were more specific attention paid to family policies, which are a weak part of the Mediterranean safety net. Ferrera’s introduction offers a general overview of the specific features of Southern European welfare states, while a final chapter addresses developments in Eastern and Southern-eastern Europe following the fall of communism, on the basis of the hypothesis that the experience of Southern European countries might be a useful point of reference for them. Although this chapter is, given limited knowledge about the welfare state pattern(s) in these countries, interesting in itself, the rationale for inserting it in this book is suggestive but not fully argued. The characteristics of Southern welfare states, particularly the widespread presence of the informal economy and the role attributed to extended family solidarity, explain why it has been so difficult in these countries to argue for, and to introduce, minimum income provisions. The risk of fraud is higher where the informal sector is large, particularly when coupled with reduced administrative capacity and a tradition of clientelism. That the introduction of a universal meanstested measure of income support for the poor has proved more difficult in Greece and Italy can be related to the fact that in these two countries there is also a criminal sector within the informal economy. The risk is thus not only that of financial fraud, but also of subsidizing workers in the criminal economy. Portugal and Spain are the successful cases. In each, some kind of minimum income provision was introduced in the 1990s and both countries, particularly Portugal, were active in the EU debate in this field. Anti-poverty policies are part of the public debate and National Action Plans are used as a governance instrument. With its ‘variable geometry’ of provisions, the Spanish case is, however, also an illustration of the challenges such a policy faces in countries with a highly decentralized administrative structure. Decentralization can also help one to understand the Italian case, where the debate on minimum income policy intersected with – and was ultimately superseded by – constitutional reforms. The Portuguese case also highlights the ‘good reasons’ of those who oppose the introduction of such measures in countries where there is a high national but also regional concentration of poverty. The risk is of functional overload, with assistance becoming the ‘only game in town’: a problem also faced in southern Italy during the experimentation with an RMI. Although all the authors share the persuasion that minimum income is a crucial item in the still inefficient social safety nets in the Southern countries, they honestly and clearly expose the multiple difficulties these face in introducing it.
Controlling Dengue with Vaccines in Thailand

Background Dengue is a mosquito-borne infectious disease that constitutes a growing global threat with the habitat expansion of its vectors Aedes aegyti and A. albopictus and increasing urbanization. With no effective treatment and limited success of vector control, dengue vaccines constitute the best control measure for the foreseeable future. With four interacting dengue serotypes, the development of an effective vaccine has been a challenge. Several dengue vaccine candidates are currently being tested in clinical trials. Before the widespread introduction of a new dengue vaccine, one needs to consider how best to use limited supplies of vaccine given the complex dengue transmission dynamics and the immunological interaction among the four dengue serotypes. Methodology/Principal Findings We developed an individual-level (including both humans and mosquitoes), stochastic simulation model for dengue transmission and control in a semi-rural area in Thailand. We calibrated the model to dengue serotype-specific infection, illness and hospitalization data from Thailand. Our simulations show that a realistic roll-out plan, starting with young children then covering progressively older individuals in following seasons, could reduce local transmission of dengue to low levels. Simulations indicate that this strategy could avert about 7,700 uncomplicated dengue fever cases and 220 dengue hospitalizations per 100,000 people at risk over a ten-year period. Conclusions/Significance Vaccination will have an important role in controlling dengue. According to our modeling results, children should be prioritized to receive vaccine, but adults will also need to be vaccinated if one wants to reduce community-wide dengue transmission to low levels.
Toward a Theory of Self-Directed Learning: a Study of Experts Without Formal Training

The authors analyzed the biographies of twenty acknowledged experts with out formal training beyond high school in search of commonalities that might suggest ways people become effectively self-directed in learning and accom plishment. Of the 154 characteristics identified, the fifty rated as most im portant were examined. They outline a pattern of education that is sharply focussed, active, experiential, self-directed, situational, and often personally challenging. They indicate a personality that is both traditional and radical, and they suggest a life theme of gathering purpose and drive. The authors transform their analyses into fourteen hypotheses about education, about a form of schooling that would prepare students for a life of self-directed learning and attainment.
Teachers' views of their pupils with profound and multiple learning difficulties

This paper explores the perceptions of a small group of teachers of pupils with profound and multiple learning disabilities (PMLD) in north‐eastern England. The focus of the paper is their views of their pupils who have PMLD. A total of 14 teachers were interviewed, both individually and in small groups over a four‐year period. This paper stems from the individual interviews, which were validated at the group interview stage. Through the interviews we hear how neurological, developmental and co‐existence issues help shape teachers’ views of their pupils. Thirty years ago this group of pupils received their education from the Department of Health; today they are in schools and we hear the teachers in this project reflect on their students’ learning needs in positive and professional ways. What emerges through this research is the need for teacher educators to support professional development experiences that enable teachers to integrate the distinct perspectives of parents and the more contemporary theories of disability into their understandings of this group of learners. In this way, teachers of pupils with PMLD would build upon their professional knowledge base to include wider parental and societal perspectives.
Puerto Rican Children's Codeswitching and their Performance on Receptive Vocabulary Instruments and a Nonverbal Cognitive Measure

Analyses of Puerto Rican bilingualism reveal the unique role of Spanish/English codeswitching in their communication. In the present study, 34 bilingual students (aged 9 to 13 years) of both sexes were administered forms of the Test de Vocabulario en Imágenes Peabody—Adaptación Hispanoamericana (TVIP-H) (Dunn, Padilla, Lugo & Dunn, 1986) and Peabody Picture Vocabulary Test-Revised (PPVT-R) (Dunn & Dunn, 1981), along with translations of both aforementioned tests. The Standard Progressive Matrices (SPM) (Raven, 1958) was administered as a nonverbal cognitive measure. Standard scores were recorded; then, a separate set of combined scores was derived for the TVIP-H and PPVT-R and their respective translations, in which the student was given credit for items answered incorrectly in one language but correctly in the other. Standard scores were also recorded for the SPM. Results revealed significant mean differences between the TVIP-H monolingual vocabulary tests and its respective combined/bilingual scores. Both combined/bilingual instruments' results positively correlated with the nonverbal measure. These findings suggest that the influence of codeswitching/bilingualism on verbal tests must be accounted for with this population.
Game-Based Learning in e-Learning Environments

Society today is changing at a great pace, driven by thegrowth rate of Information and Communication Technolo-gies (ICT). Present day educational structures, put in placein the late 19th century and the first half of the 20th cen-tury, are based on the classical idea of encyclopaedic knowl-edge and a simplistic view of education as the mere directtransmission of that knowledge [1]. But now the industrialage has been overtaken by the information age, in which anew model of society (the Information Society) requiresnew skills and competencies. Learners today need trainingthat covers topics such as the development of cognitiveskills, problem solving skills, information retrieval and fil-tering, and the acquisition of knowledge in new domains.And this not only requires the development of new skills,but also calls for new ways of interacting with information.Learners today are used to receiving information from vari-ous sources in parallel, in rich and attractive multimediaformats, in a participative and interactive manner and al-ways at great speed. The TV generation has given way tothe generation of the Internet, videogames, and mobile com-munications. In many cases the slower, more structured,unidirectional approach of a class (or even of a digital docu-ment) is totally at variance with modern learners’ normalway of doing things and arouses a sense of antagonism anddemotivation.Meanwhile, videogames have been developing in recentyears until they are now one of the most important branchesof the entertainment industry, and the idea of using themfor educational purposes has been gaining more and moreground [2]. The very elements that we blame for distractingour learners may be the ideal vehicle to reach them. How-
Lycium barbarum Extracts Protect the Brain from Blood-Brain Barrier Disruption and Cerebral Edema in Experimental Stroke

Background and Purpose Ischemic stroke is a destructive cerebrovascular disease and a leading cause of death. Yet, no ideal neuroprotective agents are available, leaving prevention an attractive alternative. The extracts from the fruits of Lycium barbarum (LBP), a Chinese anti-aging medicine and food supplement, showed neuroprotective function in the retina when given prophylactically. We aim to evaluate the protective effects of LBP pre-treatment in an experimental stroke model. Methods C57BL/6N male mice were first fed with either vehicle (PBS) or LBP (1 or 10 mg/kg) daily for 7 days. Mice were then subjected to 2-hour transient middle cerebral artery occlusion (MCAO) by the intraluminal method followed by 22-hour reperfusion upon filament removal. Mice were evaluated for neurological deficits just before sacrifice. Brains were harvested for infarct size estimation, water content measurement, immunohistochemical analysis, and Western blot experiments. Evans blue (EB) extravasation was determined to assess blood-brain barrier (BBB) disruption after MCAO. Results LBP pre-treatment significantly improved neurological deficits as well as decreased infarct size, hemispheric swelling, and water content. Fewer apoptotic cells were identified in LBP-treated brains by TUNEL assay. Reduced EB extravasation, fewer IgG-leaky vessels, and up-regulation of occludin expression were also observed in LBP-treated brains. Moreover, immunoreactivity for aquaporin-4 and glial fibrillary acidic protein were significantly decreased in LBP-treated brains. Conclusions Seven-day oral LBP pre-treatment effectively improved neurological deficits, decreased infarct size and cerebral edema as well as protected the brain from BBB disruption, aquaporin-4 up-regulation, and glial activation. The present study suggests that LBP may be used as a prophylactic neuroprotectant in patients at high risk for ischemic stroke.
Impact of consumer health informatics applications.

OBJECTIVE The objective of the report is to review the evidence on the impact of consumer health informatics (CHI) applications on health outcomes, to identify the knowledge gaps and to make recommendations for future research. DATA SOURCES We searched MEDLINE, EMBASE, The Cochrane Library, Scopus, and CINAHL databases, references in eligible articles and the table of contents of selected journals; and query of experts. METHODS Paired reviewers reviewed citations to identify randomized controlled trials (RCTs) of the impact of CHI applications, and all studies that addressed barriers to use of CHI applications. All studies were independently assessed for quality. All data was abstracted, graded, and reviewed by 2 different reviewers. RESULTS One hundred forty-six eligible articles were identified including 121 RCTs. Studies were very heterogeous and of variable quality. Four of five asthma care studies found significant positive impact of a CHI application on at least one healthcare process measure. In terms of the impact of CHI on intermediate health outcomes, significant positive impact was demonstrated in at least one intermediate health outcome of; all three identified breast cancer studies, 89 percent of 32 diet, exercise, physical activity, not obesity studies, all 7 alcohol abuse studies, 58 percent of 19 smoking cessation studies, 40 percent of 12 obesity studies, all 7 diabetes studies, 88 percent of 8 mental health studies, 25 percent of 4 asthma/COPD studies, and one of two menopause/HRT utilization studies. Thirteen additional single studies were identified and each found evidence of significant impact of a CHI application on one or more intermediate outcomes. Eight studies evaluated the effect of CHI on the doctor patient relationship. Five of these studies demonstrated significant positive impact of CHI on at least one aspect of the doctor patient relationship. In terms of the impact of CHI on clinical outcomes, significant positive impact was demonstrated in at least one clinical outcome of; one of three breast cancer studies, four of five diet, exercise, or physical activity studies, all seven mental health studies, all three identified diabetes studies. No studies included in this review found any evidence of consumer harm attributable to a CHI application. Evidence was insufficient to determine the economic impact of CHI applications. CONCLUSIONS Despite study heterogeneity, quality variability, and some data paucity, available literature suggests that select CHI applications may effectively engage consumers, enhance traditional clinical interventions, and improve both intermediate and clinical health outcomes.
Metamodeling applied to a measurement system

Measurement processes, specifically in software engineering, are of great importance to organizations' success. Important data for cost and time estimates only can be obtained by systematic measurement. However, to measurements get good results, it is important collect data from the organization itself. These data should be recorded in a database. In this sense, this paper will present a proposal for metamodeling that allows the user define their owns measurement metrics without changing the application source code.
Part‐time parent, part‐time child: Visiting after divorce

Abstract Patterns ousiting between non‐custodial parent and child after divorce are described, as studied in a five‐year clinical research project investigating the experience and effects of divorce on 131 children and adolescents from 60 divorcing families. The changed yet significant role of the part‐time parent is discussed in the context of the extraordinary continuity in contact for many parents and their children following divorce.