Miracle-dz/UniFAR-FTUs huggingface dataset:
Integrin alpha 2 beta 1 is upregulated in fibroblasts and highly aggressive melanoma cells in three-dimensional collagen lattices and mediates the reorganization of collagen I fibrils

The ability of cultured human fibroblasts to reorganize and contract three dimensional collagen I gels is regarded as an in vitro model for the reorganization of connective tissue during wound healing. We investigated whether adhesion receptors of the integrin family are involved. It was found that synthesis and transcription of the alpha 2 beta 1 integrin (but not of alpha 1 beta 1 or alpha 3 beta 1) is selectively upregulated when fibroblasts are seeded into type I collagen gels. Time course experiments revealed that high synthetic levels of alpha 2 beta 1 parallel the gel contraction process and return to "baseline" levels after the contraction has subsided. Furthermore, function-blocking mAbs directed to the alpha 2 and beta 1 chain of integrins inhibited gel contraction. Remodelling of connective tissue can be important for tumor cells during invasion and formation of metastases. Therefore, we tested human melanoma cell lines for this function. Five out of nine melanoma lines contracted collagen gels in vitro. Among these, two highly aggressive melanoma cell lines (MV3 and BLM) most efficiently contracted gels almost reaching the rate of normal adult fibroblasts. In these cells, synthesis of alpha 2 beta 1 was also significantly upregulated when seeded into collagen I gels. Moreover, function blocking anti-alpha 2 in conjunction with anti-beta 1 chain mAbs completely inhibited gel contraction for several days. Other melanoma cells (530) with lower metastatic potential which were not able to contract gels, showed no induction of alpha 2 beta 1 synthesis in gel culture. Our results suggest an important role of integrin alpha 2 beta 1 in the contraction of collagen I by normal diploid fibroblasts during wound healing and in the reorganization of collagen matrices by highly aggressive human melanoma cells.
Effects of tetrabrombisphenol A on DNA integrity, oxidative stress, and sterlet (Acipenser ruthenus) spermatozoa quality variables

The sperm of sterlet (Acispenser ruthenus) was used to investigate the effect of the xenobiotic tetrabrombisphenol A (TBBPA) on sperm quality variables (ATP content, spermatozoa motility, and velocity), DNA integrity, and oxidative stress indices. Sperm was diluted to obtain a spermatozoa density of 5 × 108 cells/mL and exposed for 2 h to final concentrations of TBBPA (0.5, 1.75, 2.5, 5, and 10 μg/L). The oxidative stress indices, including lipid peroxidation, carbonyl derivatives of proteins, and antioxidant activity were significantly higher with increased concentrations of TBBPA. There was significantly less intracellular ATP in sperm samples at TBBPA concentrations of 2.5 μg/L and above. Spermatozoa velocity and percent motile sperm were significantly lower at each sampling time post‐activation compared to controls. DNA damage expressed as percent DNA in Tail and Olive Tail moment was significantly higher with exposures ≥2.5 μg/L TBBPA. The results demonstrated that TBBPA and other xenobiotics can induce reactive oxygen species stress in fish spermatozoa, which could impair the sperm quality, DNA integrity, ATP content, and the antioxidant defense system. This study confirmed that fish spermatozoa can be used in in vitro assays for monitoring residual pollution in aquatic environments. © 2014 Wiley Periodicals, Inc. Environ Toxicol 30: 735–745, 2015.
Glycemic index and dietary fiber and the risk of type 2 diabetes.

OBJECTIVE To examine associations between type 2 diabetes and fiber, glycemic load (GL), dietary glycemic index (GI), and fiber-rich foods. RESEARCH DESIGN AND METHODS This was a prospective study of 36,787 men and women aged 40-69 years without diabetes. For all self-reported cases of diabetes at 4-year follow-up, confirmation of diagnosis was sought from medical practitioners. Case subjects were those who reported diabetes at follow-up and for whom there was no evidence that they did not have type 2 diabetes. Data were analyzed with logistic regression, adjusting for country of birth, physical activity, family history of diabetes, alcohol and energy intake, education, 5-year weight change, sex, and age. RESULTS Follow-up was completed by 31,641 (86%) participants, and 365 cases were identified. The odds ratio (OR) for the highest quartile of white bread intake compared with the lowest was 1.37 (95% CI 1.04-1.81; P for trend = 0.001). Intakes of carbohydrate (OR per 200 g/day 0.58, 0.36-0.95), sugars (OR per 100 g/day 0.61, 0.47-0.79), and magnesium (OR per 500 mg/day 0.62, 0.43-0.90) were inversely associated with incidence of diabetes, whereas intake of starch (OR per 100 g/day 1.47, 1.06-2.05) and dietary GI (OR per 10 units 1.32, 1.05-1.66) were positively associated with diabetes. These relationships were attenuated after adjustment for BMI and waist-to-hip ratio. CONCLUSIONS Reducing dietary GI while maintaining a high carbohydrate intake may reduce the risk of type 2 diabetes. One way to achieve this would be to substitute white bread with low-GI breads.
Mass-gathering Events: The Role of Advanced Nurse Practitioners in Reducing Referrals to Local Health Care Agencies

Abstract Introduction The introduction of advanced practitioner roles has challenged the traditional boundaries of health care. While studies have been undertaken to understand the role of physicians in respect of mass-gathering medicine, the role of advanced nurse practitioners (ANPs) has not been investigated. Problem Does the presence of an ANP reduce the referral rates of patients presenting for medical care at mass-gathering events to external health care resources? Methods A prospective observational study was undertaken to determine whether the presence of an ANP would reduce the patient referral rate to external health care services by first aiders and paramedics working within an event medical team. Patients identified as requiring referral were reviewed by an ANP as part of the on-site medical provision for four mass-gathering events in the south of England. Additionally, information was gathered identifying which patients would have been transported to hospital by ambulance compared to those actually transported following ANP review. Statistical analysis was undertaken for three key measures (referrals to all local health resources, referrals to hospital-based acute services, and transfers to hospital by ambulance). Results A rounded total of 842,000 people attended four mass-gathering events held over 14 days. Of these, 652 presented for medical care, many self-referring. Using a one-tailed Fisher’s Exact Test and Phi analysis, this study demonstrated statistically significant reductions in the overall referral of patients to all external health care resources (P<.001; φ=0.44), to the emergency department (ED; P<.001; φ=0.43), and a reduction in ambulance transport (P<.001; φ=0.42). Effect size analysis demonstrated a medium-sized effect evident for all of the above, which was also demonstrated in economic terms. The event medical team would have referred 105 (16.3%) of the 652 patient presentations to external health care services; 47 (7.2%) would have been transported by ambulance. In comparison, the ANP referred 23 patients (3.5%) with 11 (1.7%) being transported by ambulance. It also was noted that the first aiders and paramedics could be more selective in their referral habits that were focused primarily on the ED. Conclusions Appropriately trained and experienced ANPs working within event medical teams have a positive impact on referral rates from mass-gathering events. KempAE. Mass-gathering events: the role of advanced nurse practitioners in reducing referrals to local health care agencies. Prehosp Disaster Med. 2016;31(1):58–63.
Sinonasal Neuroendocrine Carcinoma Presenting as a Nasopharyngeal Mass

sinonasal cavities are exceedingly uncommon and difficult to diagnose by conventional histologic examination. NEC are small cell neoplasms that show positive immunoreaction to neuroendocrine markers and lack of olfactory maturation.1 The English-language literature consists of small series and isolated case reports, many of which are poorly documented, therefore retrospective analysis of published cases is difficult. In addition, a critical review of these reports indicates that some of the lesions described exhibited clinical or pathological features consistent with other diagnosis, and in particular with olfactory neuroblastoma (ON). 2 In this article, we describe a single case of NEC of the sinonasal cavities that clinically presented as a tumor of the nasopharynx.
Cerebrovascular, Neuronal, and Behavioral Effects of Long‐Term Ca2+ Channel Blockade in Aging Normotensive and Hypertensive Rat Strains

The pathogenesis of essential hypertension is not fully understood, but most of the cardiovascular, metabolic, neurogenic, and humoral abnormalities are explained by dysfunctions in the control of intracellular Ca2+ concentrations in the cells of the vascular wall. Most theories of disturbed calcium regulation focus on the calcium concentration within vascular smooth muscle cells. The implications of hypertension for the increased calcium content of aging arteries seem to be clear, but were only studied in the peripheral circulation; hypertension prominently augments the aging-related accumulation of calcium in the vessel wall. Although the contribution of calcium overload in hypertensive cerebrovascular damage is well documented, it is not clear yet if hypertension per se is the main cause of hypertension-associated calcium-dependent cerebral damage. Thus far, the hypotensive effects of most calcium antagonists were extensively described, and their efficacy in stroke prevention was proven. Earlier studies indicated that chronic administration of nimodipine revealed a protective effect in the occurrence of strokes in SHR-SP rats, yielding a decreased mortality rate. Because nimodipine did not lower the extremely high blood pressure of these animals, the mechanisms behind such nimodipine-induced stroke prevention may be attributed to a direct cerebrovascular and/or neuronal action of nimodipine. Hypertension is generally considered a vascular pathologic condition, and most research has been directed towards the influences of hypertension on large peripheral arteries such as the aorta and coronary artery. The influence of the CNS on the regulation of cardiovascular system and blood pressure regulation was described in detail, and the role of the CNS in hypertension also was the subject of study. The increased risk of stroke in hypertensive subjects generated numerous studies on the precise nature of compromised cerebrovascular functioning under hypertensive conditions. Few data are available on Ca2+ alterations in cerebral neurons during hypertension. Honda et al. demonstrated that voltage-dependent Ca2+ uptake was higher in cortical synaptosomes from SHR than form normotensive animals and suggested that an important alteration in Ca2+ channel characteristics may occur in SHR brain synaptosomes. Although the density of L-type calcium channels was shown to be higher in the hippocampus of SHR rats, others reported that the number of L-type calcium channels was significantly lower in the brain of SHR rats than WKY normotensive controls. The latter data suggest that hypertension may be associated with similar alterations in neuronal calcium homeostasis as demonstrated for aging in normotensive subjects. (ABSTRACT TRUNCATED AT 400 WORDS)
Grazer diversity interacts with biogenic habitat heterogeneity to accelerate intertidal algal succession.

Environmental heterogeneity contributes to coexistence by allowing species with different traits to persist when different species perform best at different times or places. This interaction between niche differences and environmental variability may also help explain relationships between biodiversity and ecosystem functioning, but few data are available to rigorously evaluate this hypothesis. We assessed how a biologically relevant aspect of environmental heterogeneity interacts with species diversity to determine ecosystem processes in a natural rocky intertidal community. We used field removals to factorially manipulate biogenic habitat heterogeneity (barnacles, bare rock, and plots that were 50/50 mixes of the two habitat types) and gastropod grazer species richness and then tracked algal community succession and recovery over the course of 1 yr. We found that herbivore diversity, substrate heterogeneity, and their interaction played unique roles in the peak abundance and timing of occurrence of different algal functional groups. Early successional microalgae were most heavily grazed in diverse herbivore assemblages and those with barnacles present, which was likely due to complementary feeding strategies among all three grazers. In contrast, late successional macroalgae were strongly influenced by the presence of a habitat generalist limpet. In this herbivore's absence, heterogeneous habitats (i.e., mixtures of bare rock and barnacles) experienced the greatest algal accumulation, which was partly a result of complementary habitat use by the remaining herbivores. The complex way habitat identity and heterogeneity altered grazer-algal interactions in our study suggests species' differences and environmental heterogeneity both separately and interactively contribute to the relationship between biodiversity and ecosystem functions.
Absence of Neuroplastin-65 Affects Synaptogenesis in Mouse Inner Hair Cells and Causes Profound Hearing Loss

The Neuroplastin gene encodes two synapse-enriched protein isoforms, Np55 and Np65, which are transmembrane glycoproteins that regulate several cellular processes, including the genesis, maintenance, and plasticity of synapses. We found that an absence of Np65 causes early-onset sensorineural hearing loss and prevented the normal synaptogenesis in inner hair cells (IHCs) in the newly identified mouse mutant pitch. In wild-type mice, Np65 is strongly upregulated in the cochlea from around postnatal day 12 (P12), which corresponds to the onset of hearing. Np65 was specifically localized at the presynaptic region of IHCs. We found that the colocalization of presynaptic IHC ribbons and postsynaptic afferent terminals is greatly reduced in pitch mutants. Moreover, IHC exocytosis is also reduced with mutant mice showing lower rates of vesicle release. Np65 appears to have a nonessential role in vision. We propose that Np65, by regulating IHC synaptogenesis, is critical for auditory function in mammals. SIGNIFICANCE STATEMENT In the mammalian cochlea, the sensory inner hair cells (IHCs) encode auditory information. They do this by converting sound wave-induced mechanical motion of their hair bundles into an electrical current. This current generates a receptor potential that controls release of glutamate neurotransmitter from their ribbon synapses onto the auditory afferent fiber. We show that the synapse-enriched protein Np65, encoded by the Neuroplastin gene, is localized at the IHC presynaptic region. In mutant mice, absence of Np65 causes early-onset sensorineural hearing loss and prevents normal neurotransmitter release in IHCs and colocalization of presynaptic ribbons with postsynaptic afferents. We identified Neuroplastin as a novel deafness gene required for ribbon synapse formation and function, which is critical for sound perception in mammals.
Ti/Au Die Backside Metallization for Flip Chip Heat Spreader Attachment

In this paper, a heat spreader attachment with indium solder for high-power flip chip-in-package application was investigated. The Cu heat spreader was metallized with Ni/Au and the flip chip die backside metallization was Ti/Au. A low voiding attachment process was achieved with vacuum soldering. The Au thin film was converted into AuIn2 completely after initial soldering, but no intermetallic compund (IMC) formation between Ti and In was observed. The attachment had good mechanical strength as measured by shear testing. The shear strength was not degraded significantly after multiple lead free solder reflows or with thermal aging at 120°C. For thermal shock cycle test (-40°C to 85°C), die with Ti/Au (2000 A¿ of Au) metallization had early partial delamination. The effect of Au thickness on mechanical strength was further evaluated. Assemblies (Cu on Si) with Ti/Au (2000 A¿) die had lower shear strength compared with Ti/Au (3000 A¿) and Ti/Au (4000 A¿ ) die. The pull strength (Si on Si) increased with increasing gold thickness. Thermal shock testing (-40°C to 85°C) for assemblies with Ti/Au 3000 A¿ along with Ti/Ni/Au (control) did not show early delamination and had similar performance after 2000 cycles.
SemMedDB: a PubMed-scale repository of biomedical semantic predications

SUMMARY Effective access to the vast biomedical knowledge present in the scientific literature is challenging. Semantic relations are increasingly used in knowledge management applications supporting biomedical research to help address this challenge. We describe SemMedDB, a repository of semantic predications (subject-predicate-object triples) extracted from the entire set of PubMed citations. We propose the repository as a knowledge resource that can assist in hypothesis generation and literature-based discovery in biomedicine as well as in clinical decision-making support. AVAILABILITY AND IMPLEMENTATION The SemMedDB repository is available as a MySQL database for non-commercial use at http://skr3.nlm. nih.gov/SemMedDB. An UMLS Metathesaurus license is required. CONTACT kilicogluh@mail.nih.gov.
Cellular origin and ultrastructure of membranes induced during poliovirus infection

Poliovirus RNA replicative complexes are associated with cytoplasmic membranous structures that accumulate during viral infection. These membranes were immunoisolated by using a monoclonal antibody against the viral nonstructural protein 2C. Biochemical analysis of the isolated membranes revealed that several organelles of the host cell (lysosomes, trans-Golgi stack and trans-Golgi network, and endoplasmic reticulum) contributed to the virus-induced membranous structures. Electron microscopy of infected cells preserved by high-pressure freezing revealed that the virus-induced membranes contain double lipid bilayers that surround apparently cytosolic material. Immunolabeling experiments showed that poliovirus proteins 2C and 3D were localized to the same membranes as the cellular markers tested. The morphological and biochemical data are consistent with the hypothesis that autophagy or a similar host process is involved in the formation of the poliovirus-induced membranes.
Women's perspectives on human papillomavirus self‐sampling in the context of the UK cervical screening programme

Testing for human papillomavirus (HPV) is being incorporated into the cervical screening programme, with the probable future introduction of HPV as a primary test and a possibility of HPV self‐sampling. In anticipation of this development, we sought to inform future policy and practice by identifying potential barriers to HPV self‐sampling.
Multiple Equilibrium Problem and Non-Canonical Correlation Devices

A correlated equilibrium for a normal form game is a mediator whose recommendations the players find optimal to follow obediently. A (direct) correlation device or a mediator however may face the multiple equilibrium problem as the obedient strategy profile may be dominated by some other Nash equilibrium in the extended game. This paper addresses the question whether it is possible to avoid this problem by considering non-canonical correlation devices. The paper presents three different non-canonical correlation devices (one with and two without a sunspot) to understand this problem for a parametric version of the Chicken game.
Automated software remodularization based on move refactoring: a complex systems approach

Modular design is a desirable characteristic of complex software systems that can significantly improve their comprehensibility, maintainability and thus quality. While many software systems are initially created in a modular way, over time modularity typically degrades as components are reused outside the context where they were created. In this paper, we propose an automated strategy to remodularize software based on move refactoring, i.e. moving classes between packages without changing any other aspect of the source code. Taking a complex systems perspective, our approach is based on complex networks theory applied to the dynamics of software modular structures and its relation to an n-state spin model known as the Potts Model. In our approach, nodes are probabilistically moved between modules with a probability that nonlinearly depends on the number and module membership of their adjacent neighbors, which are defined by the underlying network of software dependencies. To validate our method, we apply it to a dataset of 39 Java open source projects in order to optimize their modularity. Comparing the source code generated by the developers with the optimized code resulting from our approach, we find that modularity (i.e. quantified in terms of a standard measure from the study of complex networks) improves on average by 166+-77 percent. In order to facilitate the application of our method in practical studies, we provide a freely available Eclipse plug-in.
AGE AND GENDER DIFFERENCES IN GONIAL ANGLE, RAMUS HEIGHT AND BIGONIAL WIDTH IN DENTATE SUBJECTS

The aim of this study was to investigate the influence of age and gender differences (three mandibular parameters gonial angle, ramus height and bigonial width) in dentate Jordanian subjects using digital panoramic radiography. A total of 209 (103 males and 106 females) dentate subjects aged 11 and 69 (mean: 33.51±14.5) years participated in this study. The data were obtained by using an interview, clinical and radiographic examination. Gonial angles, ramus heights (on both sides) and bigonial widths were recorded using panoramic radiograph and measured digitally for each subject. The mean values were calculated and compared between male and female subjects and between different age groups using SPSS (V. 17). Level of significance was set at 0.05. The results of the study showed that males had higher values of the parameters compared to females. The differences in bigonial width and ramus height were statistically significant (p<0.0001). Gonial angles and bigonial widths increased with increasing age, however, ramus height increased from 11-29 years then decreased with increasing age. The morphology of the mandible changed as a consequence of age and between genders, which can be expressed as a widening of the gonial angle, increasing of the bigonial width and shortening of the ramus.