Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation and Proposal for Optimalization of Neurophysiological Tests in Migraine: Part 1—Electrophysiological Tests

Neurophysiological testing has become a valuable tool for investigating brain excitability and nociceptive systems in headache disorders. Previous reviews have suggested that most neurophysiological tests have limited value for headache diagnosis, but a vast potential for exploring the pathophysiology of headaches, the central effects of certain pharmacological treatments and phenotype-genotype correlations. Many protocols, however, lack standardization. This meta-analytical review of neurophysiological methods in migraine was initiated by a task force within the EUROHEAD project (EU Strep LSHM-CT-2004-5044837-Workpackage 9). Most of the neurophysiological approaches that have been used in headache patients are reviewed, i.e. evoked potentials, nociception-specific blink reflex, single-fibre electromyography, neuroimaging methods (functional MRI, PET, and voxel-based morphometry) and the nitroglycerin attack-provoking test. For each of them, we summarize the results, analyse the methodological limitations and propose recommendations for improved methodology and standardization of research protocols. The first part is devoted to electrophysiological methods, the second to neuroimaging techniques and the NTG test.
Higher expression of Toll-like receptors 2, 3, 4, and 8 in ocular Behcet's disease.

PURPOSE To investigate the role of Toll-like receptors (TLRs) 2, 3, 4, and 8 in the pathogenesis of Behcet's disease (BD). METHODS Sixteen patients with active ocular BD and 16 healthy volunteers were included in this study. Total RNA was isolated from PBMCs to determine mRNA levels of TLRs, including TLR2, TLR3, TLR4, and TLR8. Cell surface receptor activity of these TLRs was investigated by FACS analysis. Monocytes and naïve T cells from patients and controls were cultured with or without TLR ligands, such as LPS, PGN, R848, or PolyI:C. Culture supernatants were collected and IL-17, IL-1β, and IL-23 were analyzed by ELISA. RESULTS A markedly higher expression at the mRNA and protein level of TLR2, TLR3, TLR4, and TLR8 was observed in active BD patients as compared with controls. Significantly higher levels of IL-1β and IL-23 were detected in the supernatants of monocytes stimulated with LPS or PGN. A significantly higher level of IL-17 was observed in the supernatants of naïve T cells and monocytes stimulated with LPS or PGN in BD patients as compared with controls. Upon stimulation with R848 or PolyI:C, the levels of IL-17 in the supernatants of naïve T cells and monocytes and IL-23 levels in the supernatants of monocytes were not different between BD patients and controls. CONCLUSIONS A higher expression of TLRs may be involved in the pathogenesis of BD.
Personal risk factors for first-time low back pain.

STUDY DESIGN A prospective study of personal risk factors for first-time low back pain. OBJECTIVES To construct and validate a multivariate model to predict low back pain. SUMMARY OF BACKGROUND DATA Various physical and psychological factors have been reported to increase the risk of low back pain, but conflicting results may be attributable to inaccurate "clinical" measures and to poorly validated statistical models. METHODS A total of 403 health care workers aged 18-40 years volunteered for the study. None had any history of "serious" back pain requiring medical attention or time off work. The volunteers completed the following questionnaires: the modified somatic perception questionnaire, the Zung depression scale, and the Health Locus of Control. Anthropometric factors were quantified using standard techniques. The 3Space Isotrak device (Polhemus, VT) was used to measure lumbar curvature and hip and lumbar spine mobility. Leg and back strength and back muscle fatiguability were measured in functional postures. Postal follow-up questionnaires, sent after 6, 12, 18, 24, 30, and 36 months, inquired about back pain, and multivariate logistic regression was used to identify risk factors at each follow-up. RESULTS The response rate fell from 99% at 12 months to 90% at 36 months, at which time 90 volunteers reported "serious" back pain and 266 reported "any" back pain. The following were consistent predictors of serious back pain: reduced range of lumbar lateral bending, a long back, reduced lumbar lordosis, increased psychological distress, and previous nonserious low back pain. Only the latter three were consistent predictors of "any" back pain. Physical factors had the most influence in a sub-population of volunteers who were new to the job. CONCLUSIONS Personal risk factors explained up to 12% of first-time low back pain.
Community-Based Research in Graduate Education: Implementing Program Decisions Across the Disciplines

Community-Based Research (CBR) has been recognized as a significant reform agent within graduate education. This article explores the decisions involved in implementing a CBR model into graduate education programs. It uses the doctoral program in educational leadership at the University of Hartford as an example of how CBR can be employed to support the development of leadership, collaborative, and research competencies for graduate students, particularly in the area of school practice. The article concludes by highlighting particular decision points and recommendations for graduate faculty and community members to consider for assuring equitable partnerships in CBR.
High-speed holographic microscopy of malaria parasites reveals ambidextrous flagellar waveforms

Significance Cilia and flagella are ubiquitous in eukaryotes, enabling cells to move and pump fluid. Understanding how flagella beat is critical in understanding medical “ciliopathies” (e.g., hydrocephalus, male and female infertility). We introduce a unique flagellar model system: the male microgametes of the malaria parasite Plasmodium berghei. These microorganisms are isolated swimming flagella, unencumbered by large structures such as a cell body (as in Chlamydomonas algae). We measure their 3D beating patterns using high-speed holographic microscopy and find a surprising diversity of waveforms. Structural chirality (handedness) in the flagellum is not manifested in the beat patterns. This interrupts the link between the molecular structure of the flagellum and its dynamics, which was believed to break left-right symmetry in developing embryos. Axonemes form the core of eukaryotic flagella and cilia, performing tasks ranging from transporting fluid in developing embryos to the propulsion of sperm. Despite their abundance across the eukaryotic domain, the mechanisms that regulate the beating action of axonemes remain unknown. The flagellar waveforms are 3D in general, but current understanding of how axoneme components interact stems from 2D data; comprehensive measurements of flagellar shape are beyond conventional microscopy. Moreover, current flagellar model systems (e.g., sea urchin, human sperm) contain accessory structures that impose mechanical constraints on movement, obscuring the “native” axoneme behavior. We address both problems by developing a high-speed holographic imaging scheme and applying it to the (male) microgametes of malaria (Plasmodium) parasites. These isolated flagella are a unique, mathematically tractable model system for the physics of microswimmers. We reveal the 3D flagellar waveforms of these microorganisms and map the differential shear between microtubules in their axonemes. Furthermore, we overturn claims that chirality in the structure of the axoneme governs the beat pattern [Hirokawa N, et al. (2009) Ann Rev Fluid Mech 41:53–72], because microgametes display a left- or right-handed character on alternate beats. This breaks the link between structural chirality in the axoneme and larger scale symmetry breaking (e.g., in developing embryos), leading us to conclude that accessory structures play a critical role in shaping the flagellar beat.
Whole genome structural analysis of Caribbean hair sheep reveals quantitative link to West African ancestry

Hair sheep of Caribbean origin have become an important part of the U.S. sheep industry. Their lack of wool eliminates a number of health concerns and drastically reduces the cost of production. More importantly, Caribbean hair sheep demonstrate robust production performance even in the presence of drug-resistant gastrointestinal nematodes, a rising concern to the industry. Despite the growing importance of hair sheep in the Americas their genetic origins have remained speculative. Prior to this report no genetic studies were able to identify a unique geographical origin of hair sheep in the New World. Our study clarifies the African and European ancestry of Caribbean hair sheep. Whole-genome structural analysis was conducted on four established breeds of hair sheep from the Caribbean region. Using breeds representing Africa and Europe we establish an objective measure indicating Caribbean hair sheep are derived from Iberian and West African origins. Caribbean hair sheep result from West African introgression into established ecotypes of Iberian descent. Genotypes from 47,750 autosomal single nucleotide polymorphism markers scored in 290 animals were used to characterize the population structure of the St. Croix, Barbados Blackbelly, Morada Nova, and Santa Ines. Principal components, admixture, and phylogenetic analyses results correlate with historical patterns of colonization and trade. These patterns support co-migration of these sheep with humans.
Lessons in Primate Heat Tolerance: A Commentary Based on the “Human Zoo” Experience

Current enclosure designs for nonhuman primates emphasize cognitive and psychological well being (Hosey, 2005). The equal importance of physical environment was made apparent to us during the 2007 Human Zoo Project, which aimed to promote community awareness of Great Ape conservation, at Adelaide Zoo. To gain an experience of zoo exhibit conditions, four groups of six human participants spent a week in an outdoor enclosure that previously housed orangutans. A universal and immediate complaint made by participants was heat discomfort despite access to a spa pool, hammock, iced drinking water, shade sail, and sheltering palm trees (Figure 1). Although arguably this could be attributed to lack of acclimatization, given the temperature variability in outdoor environments (Figure 2, upper panel), heat familiarization would have been unlikely to influence thermal comfort (Parsons, 2002; Spagnolo & de Dear, 2003). The degree of thermal stress came as a surprise because apes had been housed in the enclosure for decades, and thermal issues had not been evident from prior observation. However, behavioral indicators of thermal stress may have been misattributed to psychological rather than physical factors. This realization has led our group to investigate thermoreg-
Are you ready? Exploring readiness to engage in exercise among people living with HIV and multimorbidity in Toronto, Canada: a qualitative study

Objectives Our aim was to explore readiness to engage in exercise among people living with HIV and multimorbidity. Design We conducted a descriptive qualitative study using face-to-face semistructured interviews with adults living with HIV. Setting We recruited adults (18 years or older) who self-identified as living with HIV and 2 or more additional health-related conditions from a specialty hospital in Toronto, Canada. Participants 14 participants with a median age of 50 years and median number of 9 concurrent health-related conditions participated in the study. The majority of participants were men (64%) with an undetectable viral load (71%). Outcome measures We asked participants to describe their readiness to engage in exercise and explored how contextual factors influenced their readiness. We analysed interview transcripts using thematic analysis. Results We developed a framework to describe readiness to engage in exercise and the interplay of factors and their influence on readiness among adults with HIV and multimorbidity. Readiness was described as a diverse, dynamic and fluctuating spectrum ranging from not thinking about exercise to routinely engaging in daily exercise. Readiness was influenced by the complex and episodic nature of HIV and multimorbidity comprised of physical impairments, mental health challenges and uncertainty from HIV and concurrent health conditions. This key factor created a context within which 4 additional subfactors (social supports, perceptions and beliefs, past experience with exercise, and accessibility) may further hinder or facilitate an individual's position along the spectrum of readiness to exercise. Conclusions Readiness to engage in exercise among people living with HIV is a dynamic and fluctuating construct that may be influenced by the episodic nature of HIV and multimorbidity and 4 subfactors. Strategies to facilitate readiness to exercise should consider the interplay of these factors in order to enhance physical activity and subsequently improve health outcomes of people with HIV and multimorbidity.
Sequential developmental changes in holoprosencephalic mouse embryos exposed to ethanol during the gastrulation period.

BACKGROUND Prenatal exposure to ethanol induces holoprosencephalic malformations in both humans and laboratory animals. However, its teratogenic window for inducing holoprosencephaly is narrow, and the teratogenic mechanism is not well understood. In the present study, we examined the morphological changes in the craniofacial structures of mouse embryos/fetuses at intervals following ethanol treatment and evaluated gene expression patterns in the embryos. METHODS Pregnant C57BL/6J mice were given two doses of ethanol (30 mg/kg in total) on the morning (7:00 and 11:00 AM) of day 7. The fetuses were observed at E10.5 and E15.5 grossly and/or histologically. The expression of Shh and Nkx2.1 gene transcripts was examined at E8.5 by in situ hybridization. RESULTS Gross and histological abnormalities of the brain and face were found in ethanol-exposed fetuses, and their midline structures were most frequently affected. The midline commissural fibers were often lacking in ethanol-exposed fetuses, even in those cases without external gross malformations. In situ hybridization revealed down-regulation of Shh and Nkx2.1 genes in ethanol-exposed embryos. CONCLUSIONS The results indicate that ethanol may perturb the expression of some developmental genes at a critical stage of embryonic development and induce holoprosencephaly and other midline craniofacial malformations, including histological brain abnormalities.
Toward fabrication of graphene based devices: Graphene transfer, processing, and characterization

The current work presents our group's progress toward a graphene transfer and graphene-Si junctions. We perform graphene transfer from copper to SiO2/Si and Si substrate using electrochemical delamination. We processed and characterized graphene on SiO2/Si and Si Finally we manufactured several junctions with graphene-Si. The I-V curve is symmetric with respect to the bias voltage, therefore one can infer that there is no Schottky contact at the interface. For larger bias voltages, the I-V characteristics are non-linear of second order.
ACCOUNTING DISCLOSURE PRACTICES IN THE UNITED-STATES AND THE UNITED-KINGDOM

This paper examines the frequency and timing of accounting disclosures made by domestic and foreign firms listing securities in either the United States, the United Kingdom, or both. We examine differences in disclosure rules between the two jurisdictions and in firms' compliance with these disclosure rules. We also investigate the association between the frequency and timing of our sample firms' accounting disclosures and five factors which vary both within and between jurisdictions: interactions between voluntary and mandatory disclosure; investor demand for information; domicile and the effects of being foreign; firm size; and U.S. exchange listing. The New York Stock Exchange (NYSE) and the Securities and Exchange Commission (SEC) are currently debating whether to relax accounting and disclosure rules for internationally traded firms relative to those of domestic firms (Siconolfi and Salwen [1992]). Evidence on factors that influence what, when, and where firms choose to disclose should be an important input to policy decisions about changes in
The role of seed coat thickness in resistance/susceptibility of legumes to cowpea beetle (Callosobruchus maculatus) infestation

The role of seed coat thickness in the resistance/susceptibility of V. unguiculata (black-eyed beans, Cultivar: Black-eyed peas) against infestation by the bruchid beetle C. maculatus (F.), was investigated. Decoated V. unguiculata beans were individually coated in one to four of previously removed seed coats or one layer of Phaseolus vulgaris (Red Kidney Beans-British Type) seed coat, before being offered to non-virgin C. maculatus females to oviposit on. Following incubation for several weeks, the total adult emergence was then used to determine egg-adult survival and the seed coat thickness for both types of beans was measured. The seed coat of P. vulgaris was approximately three times thicker than that of V. unguiculata. The survival of larvae in the four coats V. unguiculata treatment was similar to that of P. vulgaris seed coat, which showed the high correlation of seed coat thickness with V. unguiculata beans resistance to C. maculatus.
Alternative Models for Spatial Choice

A family of surrogate spatial interaction models is developed and tested. The family consists of eight separate but related models: four classes with two models per class. The surrogate models differ from conventional models with respect to structure, numbers of parameters, and computational complexity. The first section of the paper draws the distinction between conventional and surrogate spatial interaction models. The second section presents the family of surrogate models being considered. The third section of the paper is devoted to an empirical test of the models in analyzing data from three spatial systems: an outdoor recreation system, a university enrollment system, and a professional society system. Issues relevant to selecting the most appropriate class of model are discussed.
Chronic inflammation associated with hepatitis C virus infection perturbs hepatic transforming growth factor β signaling, promoting cirrhosis and hepatocellular carcinoma

Many patients with chronic hepatitis caused by hepatitis C virus (HCV) infection develop liver fibrosis with high risk for hepatocellular carcinoma (HCC), but the mechanism underling this process is unclear. Conversely, transforming growth factor beta (TGF‐β) activates not only TGF‐β type I receptor (TβRI) but also c‐Jun N‐terminal kinase (JNK), which convert the mediator Smad3 into two distinctive phosphoisoforms: C‐terminally phosphorylated Smad3 (pSmad3C) and linker‐phosphorylated Smad3 (pSmad3L). Whereas the TβRI/pSmad3C pathway suppresses epithelial cell growth by upregulating p21WAF1 transcription, JNK/pSmad3L‐mediated signaling promotes extracellular matrix deposition, partly, by upregulating plasminogen activator inhibitor 1 (PAI‐1). We studied the domain‐specific Smad3 phosphorylation in biopsy specimens representing chronic hepatitis, cirrhosis, or HCC from 100 patients chronically infected with HCV, and correlated Smad3 phosphorylation with clinical course. As HCV‐infected livers progressed from chronic hepatitis through cirrhosis to HCC, hepatocytic pSmad3L/PAI‐1 increased with fibrotic stage and necroinflammatory grade, and pSmad3C/p21WAF1 decreased. Of 14 patients with chronic hepatitis C with strong hepatocytic pSmad3L positivity, 8 developed HCC within 12 years; only 1 of 12 showing little pSmad3L positivity developed HCC. We further sought molecular mechanisms in vitro. JNK activation by the pro‐inflammatory cytokine interleukin‐1β stimulated the pSmad3L/PAI‐1 pathway in facilitating hepatocytic invasion, in the meantime reducing TGF‐β‐dependent tumor‐suppressive activity by the pSmad3C/p21WAF1 pathway. Conclusion: These results indicate that chronic inflammation associated with HCV infection shifts hepatocytic TGF‐β signaling from tumor‐suppression to fibrogenesis, accelerating liver fibrosis and increasing risk for HCC. (HEPATOLOGY 2007;46:48–57.)
R&D Investments and Credit Lines

Abstract Using data for 939 publicly listed firms from 17 European countries over the period from 2004 to 2013, we investigate the effect of used credit lines on R&D investments, controlling for other determinants of R&D investments, i.e., cash flows, cash holdings, sales growth, equity financing, and Tobin's Q. Our estimation results, based on the system-GMM method, show that used credit lines have a positive and significant impact on R&D investments. In addition, we find that this impact is more pronounced for small and young firms than for large and mature firms. These results show that firms use credit lines as part of their liquidity management tools for supporting their R&D investments. Finally, we provide evidence that European firms in bank-based countries increased their use of credit lines for financing their R&D investments during the financial crisis of 2007–2009, while the link between R&D investments and used credit lines became weaker during the European sovereign debt crisis of 2010–2013.
Na-H Exchanger Isoform-2 (NHE2) Mediates Butyrate-dependent Na+ Absorption in Dextran Sulfate Sodium (DSS)-induced Colitis*

Background: Defective Na+ absorption is the primary cause of diarrhea in inflamed colon such as ulcerative colitis (UC). Results: Butyrate stimulates Na+ and water absorption in dextran sulfate sodium-induced inflamed colon. Conclusion: Na-H exchanger-2 (NHE2) is activated and mediates butyrate-dependent Na+ absorption in inflamed colon. Significance: Butyrate-dependent Na+ absorption would be a potential target to control UC-associated diarrhea. Diarrhea associated with ulcerative colitis (UC) occurs primarily as a result of reduced Na+ absorption. Although colonic Na+ absorption is mediated by both epithelial Na+ channels (ENaC) and Na-H exchangers (NHE), inhibition of NHE-mediated Na+ absorption is the primary cause of diarrhea in UC. As there are conflicting observations reported on NHE expression in human UC, the present study was initiated to identify whether NHE isoforms (NHE2 and NHE3) expression is altered and how Na+ absorption is regulated in DSS-induced inflammation in rat colon, a model that has been used to study UC. Western blot analyses indicate that neither NHE2 nor NHE3 expression is altered in apical membranes of inflamed colon. Na+ fluxes measured in vitro under voltage clamp conditions in controls demonstrate that both HCO3−-dependent and butyrate-dependent Na+ absorption are inhibited by S3226 (NHE3-inhibitor), but not by HOE694 (NHE2-inhibitor) in normal animals. In contrast, in DSS-induced inflammation, butyrate-, but not HCO3−-dependent Na+ absorption is present and is inhibited by HOE694, but not by S3226. These observations indicate that in normal colon NHE3 mediates both HCO3−-dependent and butyrate-dependent Na+ absorption, whereas DSS-induced inflammation activates NHE2, which mediates butyrate-dependent (but not HCO3−-dependent) Na+ absorption. In in vivo loop studies HCO3−-Ringer and butyrate-Ringer exhibit similar rates of water absorption in normal rats, whereas in DSS-induced inflammation luminal butyrate-Ringer reversed water secretion observed with HCO3−-Ringer to fluid absorption. Lumen butyrate-Ringer incubation activated NHE3-mediated Na+ absorption in DSS-induced colitis. These observations suggest that the butyrate activation of NHE2 would be a potential target to control UC-associated diarrhea.