Miracle-dz/UniFAR-FTUs huggingface dataset:
Early Life Adversity and Inflammation in African Americans and Whites in the Midlife in the United States Survey

Objectives: To determine whether early life adversity (ELA) was predictive of inflammatory markers and to determine the consistency of these associations across racial groups. Methods: We analyzed data from 177 African Americans and 822 whites aged 35 to 86 years from two preliminary subsamples of the Midlife in the United States biomarker study. ELA was measured via retrospective self-report. We used multivariate linear regression models to examine the associations between ELA and C-reactive protein, interleukin-6, fibrinogen, endothelial leukocyte adhesion molecule-1, and soluble intercellular adhesion molecule-1, independent of age, gender, and medications. We extended race-stratified models to test three potential mechanisms for the observed associations. Results: Significant interactions between ELA and race were observed for all five biomarkers. Models stratified by race revealed that ELA predicted higher levels of log interleukin-6, fibrinogen, endothelial leukocyte adhesion molecule-1, and soluble intercellular adhesion molecule-1 among African Americans (p < .05), but not among whites. Some, but not all, of these associations were attenuated after adjustment for health behaviors and body mass index, adult stressors, and depressive symptoms. Conclusions: ELA was predictive of high concentrations of inflammatory markers at midlife for African Americans, but not whites. This pattern may be explained by an accelerated course of age-related disease development for African Americans. BMI = body mass index; CRP = C-reactive protein; CVD = cardiovascular diseases; E-selectin = endothelial leukocyte adhesion molecule-1; ELA = early life adversity; GCRC = general clinical research center; IL = interleukin; MIDUS = Midlife in the U.S. survey; SEP = socioeconomic position; sICAM-1 = soluble intercellular adhesion molecule-1.
Distributive Justice and the Regulation of Fertility Centers: An Analysis of the Fertility Clinic Success Rate and Certification Act

The right to conceive and bear children has been protected both in law and in policy. Human society has from its earliest time valued children and defended procreation as a basic right. Modern health technology offers the possibility of conception to the estimated 2.5 million infertile couples who may wish to have children. For these persons, infertility treatment offers the hope of having children, an activity deemed basic and essential in human society. In general, the state has been reluctant to directly interfere in the reproductive decisions of individuals. However, the state may act to increase or reduce access to reproductive services in a variety of ways. For example, recent legislation regulating fertility clinics affects the distribution of assisted reproductive technology (ART) in the United States. The purpose of this paper is to describe this legislation, project its probable effects on the distribution of ART services, and analyze these effects based on distributive theories of justice.
High Sodium Chloride Diets Injure Arteries and Raise Mortality Without Changing Blood Pressure

High NaCI diets often increase blood pressure and thereby accelerate lesions in arterial walls. Could high NaCI diets increase arterial lesions without raising blood pressure? To test this, 100 uninephrectomized Dahl salt-resistant (DR) rats (highly resistant to NaCI hypertension) were administered deoxycorticosterone acetate (DOCA) (250 mg/kg) in silicone implants and drinking water containing 1% NaCI for 6 weeks. Then the DOCA and saline were removed, and the rats were allowed to recover for 4 weeks. Intra-arterial mean blood pressures on all rats allowed division of the rats into two matched groups, each group with an average blood pressure of 160 mm Hg. One group continued on a 03% NaCI diet, whereas the other group began an 8% NaCI diet for 8 weeks. After 5 weeks on these two diets, the intra-arterial blood pressure averaged 158 mm Hg in both groups. Thus, the 8% NaCI diet produced no further increase in blood pressure in the DR rats. Nevertheless, after 8 weeks on the 8% NaCI diet, 53% of the rats (26 of 49) had died; whereas in the group on the 03% NaCI diet, not one rat (0 of 51) had died (p < 0.000001). After 7 more weeks on the 8% NaCI diet, all the rats in this group had died. The chief cause of death in the group of rats on the 8% NaCI diet was likely cerebral infarction because small cerebral infarcts were observed in rats that died on this diet Uremia, congestive failure, cerebral hemorrhage, and arrhythmia were not likely causes of death. Thus, it appears that a high NaCI diet in mildly hypertensive DR rats can greatly accelerate cerebral arterial disease with brain infarction and very high mortality, even when the high NaCI diet causes no increase in blood pressure whatsoever. Seemingly, salt's infamy goes beyond blood pressure. It is even possible that “salt-resistant” hypertensive humans could reduce vascular complications by adhering to a low NaCI diet.
Illumination Invariant Novel Approaches for Face Recognition

Most of current identification and verification systems like access control and surveillance require reliable person identification technique. The primary goal of such systems is that resources are accessed only by legitimate users. Inefficient person identification systems may become vulnerable thereby allowing impostors. Under these circumstances biometric systems such as automated face recognition finds its immense application. In this paper, we investigate the use of five novel approaches for learning low- dimensional representation of a face image using the concept of transmutation and its variants. Experiments were conducted on two standard datasets namely ORL and Grimace and comparisons among the proposed algorithms have been carried out. The results revealed that transmutation method outperforms its variants. 
Characterization of the Council of Emergency Medicine Residency Directors' standardized letter of recommendation in 2011-2012.

OBJECTIVES The Council of Emergency Medicine Residency Directors (CORD) introduced the standardized letter of recommendation (SLOR) in 1997, and it has become a critical tool for assessing candidates for emergency medicine (EM) training. It has not itself been evaluated since the initial studies associated with its introduction. This study characterizes current SLOR use to evaluate whether it serves its intended purpose of being standardized, concise, and discriminating. METHODS This retrospective, multi-institutional study evaluated letters of recommendation from U.S. allopathic applicants to three EM training programs during the 2011-2012 Electronic Residency Application Service (ERAS) application cycle. Distributions of responses to each question on the SLOR were calculated, and the free-text responses were analyzed. Two pilots, performed on five applicants each, assisted in developing a strategy for limiting interrater reliability. RESULTS Each of the three geographically diverse programs provided a complete list of U.S. allopathic applicants to their program. Upon randomization, each program received a list of coded applicants unique to their program randomly selected for data collection. The number of applicants was selected to reach a goal of approximately 200 SLORs per site (n = 602). Among this group, comprising 278 of 1,498 applicants (18.6%) from U.S. allopathic schools, a total of 1,037 letters of recommendation were written, with 724 (69.8%) written by emergency physicians. SLORs represented 57.9% (602/1037) of all LORs (by any kind of author) and 83.1% (602/724) of letters written by emergency physicians. Three hundred ninety-two of 602 SLORs had a single author (65.1%). For the question on "global assessment," students were scored in the top 10% in 234 of 583 of applications (40.1%; question not answered by some), and 485 of 583 (83.2%) of the applicants were ranked above the level of their peers. Similarly, >95% of all applicants were ranked in the top third compared to peers, for all but one section under "qualifications for emergency medicine. " For 405 of 602 of all SLORs (67.2%), one or more questions were left unanswered, while 76 of all SLORs (12.6%) were "customized" or changed from the standard template. Finally, in 291 of 599 of SLORs (48.6%), the word count was greater than the recommended maximum of 200 words. CONCLUSIONS Grade inflation is marked throughout the SLOR, limiting its ability to be discriminating. Furthermore, template customization and skipped questions work against the intention to standardize the SLOR. Finally, it is not uncommon for comments to be longer than guideline recommendations. As an assessment tool, the SLOR could be more discerning, concise, and standardized to serve its intended purpose.
Electrical Characteristics and Microstructures of Pr6O11-Doped Bi4Ti3O12 Ceramics

The electrical properties of Pr6O11-doped bismuth titanates (BixPryTi3O12, BPT) ceramics prepared by a conventional ceramic technique have been investigated. At applied d.c. field below 200V/mm, the current-voltage curve of Pr-doped samples exhibit negative differential resistance behavior. The conducting filamentary model has been used to explain the negative differential resistance phenomenon in Pr-doped bismuth titanates. The impedance spectrum indicates that Pr-doped sample consists of semiconducting grain and moderately insulating grain boundary regions. XRD, SEM and EPMA analyses reveal crystalline phase characterized by a Bi-layered perovskite structure of Bi4Ti3O12 and the distribution of every element is uniform. Pr-doped samples exhibit randomly oriented and plate-like morphology.
High-Efficiency Self-Adjusting Switched Capacitor DC-DC Converter with Binary Resolution

Switched-Capacitor Converters (SCC) suffer from a fundamental power loss deficiency which make their use in some applications prohibitive. The power loss is due to the inherent energy dissipation when SCC operate between or outside their output target voltages. This drawback was alleviated in this work by developing two new classes of SCC providing binary and arbitrary resolution of closely spaced target voltages. Special attention is paid to SCC topologies of binary resolution. Namely, SCC systems that can be configured to have a no-load output to input voltage ratio that is equal to any binary fraction for a given number of bits. To this end, we define a new number system and develop rules to translate these numbers into SCC hardware that follows the algebraic behavior. According to this approach, the flying capacitors are automatically kept charged to binary weighted voltages and consequently the resolution of the target voltages follows a binary number representation and can be made higher by increasing the number of capacitors (bits). The ability to increase the number of target voltages reduces the spacing between them and, consequently, increases the efficiency when the input varies over a large voltage range. The thesis presents the underlining theory of the binary SCC and its extension to the general radix case. Although the major application is in step-down SCC, a simple method to utilize these SCC for step-up conversion is also described, as well as a method to reduce the output voltage ripple. In addition, the generic and unified model is strictly applied to derive the SCC equivalent resistor, which is a measure of the power loss. The theoretical predictions are verified by simulation and experimental results.
The embryonic type of SPP1 transcriptional regulation is re-activated in glioblastoma

Osteopontin (SPP1, a secreted phosphoprotein 1) is primarily involved in immune responses, tissue remodelling and biomineralization. However, it is also overexpressed in many cancers and regulates tumour progression by increasing migration, invasion and cancer stem cell self-renewal. Mechanisms of SPP1 overexpression in gliomas are poorly understood. We demonstrate overexpression of two out of five SPP1 isoforms in glioblastoma (GBM) and differential isoform expression in glioma cell lines. Up-regulated SPP1 expression is associated with binding of the GLI1 transcription factor to the promoter and OCT4 (octamer-binding transcription factor 4) to the first SPP1 intron of the SPP1 gene in human glioma cells but not in non-transformed astrocytes. GLI1 knockdown reduced SPP1 mRNA and protein levels in glioma cells. GLI1 and OCT4 are known regulators of stem cell pluripotency. GBMs contain rare cells that express stem cell markers and display ability to self-renew. We reveal that SPP1 is overexpressed in glioma initiating cells defined by high rhodamine 123 efflux, sphere forming capacity and stemness marker expression. Forced differentiation of human glioma spheres reduced SPP1 expression. Knockdown of SPP1, GLI1 or CD44 with siRNAs diminished sphere formation. C6 glioma cells stably depleted of Spp1 displayed reduced sphere forming capacity and downregulated stemness marker expression. Overexpression of the wild type Spp1, but not Spp1 lacking a Cd44 binding domain, rescued cell ability to form spheres. Our findings show re-activation of the embryonic-type transcriptional regulation of SPP1 in malignant gliomas and point to the importance of SPP1-CD44 interactions in self-renewal and pluripotency glioma initiating cells.
Genetics of Cardiac Arrhythmias and Sudden Cardiac Death

Abstract: This presentation deals with the molecular substrates of the inherited diseases leading to genetically determined cardiac arrhythmias and sudden death. In the first part of this article the current knowledge concerning the molecular basis of cardiac arrhythmias will be summarized. Second, we will discuss the most recent evidence showing that the picture of the molecular bases of cardiac arrhythmias is becoming progressively more complex. Thanks to the contribution of molecular genetics, the genetic bases, pathogenesis, and genotype‐phenotype correlation of diseases—such as the long QT syndrome, the Brugada syndrome, progressive cardiac conduction defect (Lenegre disease), catecholaminergic polymorphic ventricular tachycardia, and Andersen syndrome—have been progressively unveiled and shown to have an extremely high degree of genetic heterogeneity. The evidence supporting this concept is outlined, with particular emphasis on the growing complexity of the molecular pathways that may lead to arrhythmias and sudden death, in terms of the relationships between genetic defect(s) and genotype(s), as well as gene‐to‐gene interactions. The current knowledge is reviewed, focusing on the evidence that a single clinical phenotype may be caused by different genetic substrates and, conversely, a single gene may cause very different phenotypes acting through different pathways.
Adalimumab for maintenance treatment of Crohn’s disease: results of the CLASSIC II trial

Background: Adalimumab induced clinical remission after four weeks in patients with active Crohn’s disease in the CLASSIC I trial. Objective: To evaluate long term efficacy and safety of adalimumab maintenance therapy in Crohn’s disease in a follow-on randomised controlled trial (CLASSIC II). Methods: In the preceding CLASSIC I trial, 299 patients with moderate to severe Crohn’s disease naive to tumour necrosis factor antagonists received induction therapy with adalimumab 40 mg/20 mg, 80 mg/40 mg, or 160 mg/80 mg, or placebo, at weeks 0 and 2. In all, 276 patients from CLASSIC I enrolled in CLASSIC II and received open-label adalimumab 40 mg at weeks 0 (week 4 of CLASSIC I) and 2; 55 patients in remission at both weeks 0 and 4 were re-randomised to adalimumab 40 mg every other week, 40 mg weekly, or placebo for 56 weeks. Patients not in remission at both weeks 0 and 4 were enrolled in an open-label arm and received adalimumab 40 mg every other week. With non-response or flare, these patients could have their dosages increased to 40 mg weekly. Patients in the randomised arm with continued non-response or disease flare could switch to open-label adalimumab 40 mg every other week and again to 40 mg weekly. The primary end point was maintenance of remission (CDAI <150) in randomised patients through week 56. Results: Of 55 patients randomised at week 4, 79% who received adalimumab 40 mg every other week and 83% who received 40 mg weekly were in remission at week 56, v 44% for placebo (p<0.05). In all, 204 patients entered the open-label arm. Of these, 93 (46%) were in clinical remission at week 56. Adalimumab was generally well-tolerated in all patients. Conclusions: Adalimumab induced and maintained clinical remission for up to 56 weeks in patients with moderate to severe Crohn’s disease naive to anti-TNF treatment.
Effect of an epidermal growth factor receptor tyrosine kinase inhibitor on actin remodeling in an in vitro bladder cancer carcinogenesis model

Alteration of actin remodeling is a marker of malignant-associated field defect and a potential surrogate biomarker for chemoprevention trials. We tested erlotinib, a specific tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR), on actin remodeling in a bladder carcinogenic model consisting of untransformed HUC-PC cells and transformed MC-T11 cells, both derived from the same normal human urothelial clone immortalized by SV40. Erlotinib had a selective growth inhibitory and actin remodeling effect on MC-T11 cells over HUC-PC cells, as examined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and immunofluorescence labeling with laser scan cytometer analysis, respectively. The IC50 of untransformed HUC-PC cells was significantly higher than that of transformed MC-T11 cells (P < 0.05, t test). The actin remodeling effect was more prominent at lower dosage levels (1/8-1/4 of IC50), which was accompanied by an increased cell adhesion and decreased motility. At higher dosage levels (1/2 of IC50), erlotinib induced a decreased adhesion and anoikis (detachment-associated apoptosis). The transformed MC-T11, but not HUC-PC, showed a weak constitutive EGFR phosphorylation activity, which was inhibited by erlotinib in a dose-response manner. However, on epidermal growth factor stimulation, both cell lines showed a similar dose-response inhibitory effect on phosphorylated EGFR and mitogen-activated protein kinase (MAPK; P44/P42) activities, and MAPK inhibitor PD98059 showed no specific effect on erlotinib-induced actin remodeling, suggesting that pathways other than MAPK (P44/P42) may be responsible for erlotinib-induced actin remodeling. The findings provide evidence to support erlotinib-based bladder cancer chemoprevention and using actin remodeling as a marker for erlotinib-based intervention trials. [Mol Cancer Ther 2006;5(7):1754–63]
Increased Pro-Inflammatory Cytokines, C-Reactive Protein and Nerve Growth Factor Expressions in Serum of Patients with Interstitial Cystitis/Bladder Pain Syndrome

Objective The etiology and pathogenesis of interstitial cystitis/bladder pain syndrome (IC/BPS) are unclear. Chronic inflammation is considered the main pathology of IC/BPS. This study measured the serum c-reactive protein (CRP), nerve growth factor (NGF) and pro-inflammatory cytokine/chemokine interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and IL-8 expression in patients with IC/BPS to elucidate the involvement of systemic inflammation in IC/BPS. Methods Serum samples were collected from 30 IC/BPS patients and 26 control subjects. The concentrations of serum nerve growth factor (NGF), IL-1β, IL-6, TNF-α, and IL-8 were quantified using a bead-based, human serum adipokine panel kit. Serum C-reactive protein (CRP) was also assessed. Differences of serum CRP, NGF, IL-1β, IL-6, TNF-α, and IL-8 levels between the IC/BPS patients and controls were compared, and correlations between CRP and pro-inflammatory cytokines and chemokine were also evaluated. Results The results showed that CRP level (p = 0.031), NGF (p = 0.015) and pro-inflammatory cytokines/chemokine IL-1β, IL-6, TNF-α, and IL-8 levels were significantly higher in the patients with IC/BPS than among controls (all p<0.001). Significant associations were observed between IL-1β and IL-8 (p<0.001), IL-6 and CRP (p = 0.01), IL-6 and IL-8 (p = 0.02), and IL-6 and TNF-α (p = 0.03). Conclusion Increased pro-inflammatory cytokines/chemokine (IL-1β, IL-6, TNF-α, and IL-8) expression in the sera of IC/BPS patients implies not only mast cell activation, but also that other inflammatory mediators play important roles in the pathogenesis of IC/BPS. Thus, for some patients, IC/BPS is considered a chronic inflammatory disease.
The role of peptide YY in gastrointestinal diseases and disorders

Peptide YY (PYY) is affected in several gastrointestinal diseases and disorders. Changes in PYY appear to be an adaptive response to alterations in pathophysiological conditions caused by the disease. This applies to gastrointestinal diseases/disorders such as irritable bowel syndrome, inflammatory bowel disease, celiac disease, systemic sclerosis, and post-intestinal resection. By contrast, the changes in PYY in chronic idiopathic slow transit constipation (CST) seem to be of a primary nature, and may be one etiological factor of the disease. Abnormalities in PYY seem to contribute to the development of symptoms present in irritable bowel syndrome, inflammatory bowel disease, gastroenteropathy in long-standing diabetes and CST. The changes in PYY could, however, be favorable in some gastrointestinal disorders such as celiac disease, systemic sclerosis and post-intestinal resection state. Investigating changes in PYY in gastrointestinal diseases/disorders could be beneficial in clinical practice, where a receptor agonist or an antagonist can be used as a drug, depending on the condition. Similar to other neuroendocrine peptides/amines of the gut, PYY has broad physiological/pharmacological effects: it can bind to and activate several receptors with independent actions. Thus, in order to use PYY as a drug, receptor-specific agonists or antagonists need to be developed.
Inhibiting Subthalamic D5 Receptor Constitutive Activity Alleviates Abnormal Electrical Activity and Reverses Motor Impairment in a Rat Model of Parkinson's Disease

Burst firing has been reported as a pathological activity of subthalamic nucleus (STN) neurons in Parkinson's disease. However, the origin of bursts and their causal link with motor deficits remain unknown. Here we tested the hypothesis that dopamine D5 receptors (D5Rs), characterized by a high constitutive activity, may contribute to the emergence of burst firing in STN. We tested whether inhibiting D5R constitutive activity depresses burst firing and alleviates motor impairments in the 6-OHDA rat model of Parkinson's disease. Intrasubthalamic microinjections of either an inverse agonist of D5Rs, flupenthixol, or a D2R antagonist, raclopride, were applied. Behavioral experiments, in vivo and in vitro electrophysiological recordings, and ex vivo functional neuroanatomy studies were performed. Using [5S]GTPγ binding autoradiography, we show that application of flupenthixol inhibits D5R constitutive activity within the STN. Furthermore, flupenthixol reduced evoked burst in brain slices and converted pathological burst firing into physiological tonic, single-spike firing in 6-OHDA rats in vivo. This later action was mimicked by calciseptine, a Cav1 channel blocker. Moreover, the same treatment dramatically attenuated motor impairment in this model and normalized metabolic hyperactivity in both STN and substantia nigra pars reticulata, the main output structure of basal ganglia in rats. In contrast, raclopride as well as saline did not reverse burst firing and motor deficits, confirming the selective action of flupenthixol on D5Rs. These results are the first to demonstrate that subthalamic D5Rs are involved in the pathophysiology of Parkinson's disease and that administering an inverse agonist of these receptors may lessen motor symptoms.