Miracle-dz/UniFAR-FTUs huggingface dataset:
Biaxial mechanical properties of passive and tetanized canine diaphragm.

The architecture, vascular supply, and ease of tetanization make the diaphragm an ideal structure in which to assess multidimensional mechanical properties of active and passive striated muscle. We developed an isolated, perfused canine diaphragm preparation suitable for the assessment of biaxial stress-strain relations in both the resting state and during tetanization. Each of 33 specimens had a wide, flat region (approximately 3 x 3 cm) wherein there was a single predominant fiber direction. Simultaneous, equal stretchings were imposed in the fiber and perpendicular cross-fiber directions over the same strain ranges in both the passive state and during tetanic contraction. Highly nonlinear behavior was seen in the passive state with a limit of extensibility in both directions. The specimens were also markedly anisotropic, with the cross-fiber direction being stiffer than the fiber direction (slopes of the regression line for the stresses in each direction averaged 3.97). Moreover, 31 of the 33 specimens were stiffer in the cross-fiber direction, one was isotropic, and one was stiffer in the fiber direction. During tetanization, the extent and distribution of anisotropy were significantly altered (regression slope averaged 1.08, and 18 specimens were now either isotropic or stiffer in the fiber direction). Disrupting the membranes covering each surface increased extensibility and decreased the anisotropy, thereby suggesting that these membranes bear most of the passive load and contribute greatly to the cross-fiber stiffness and anisotropy of the intact diaphragm. Both before and after disruption of the surface membranes, there was still a consistent increase in cross-fiber stress during tetanization, implying active force generation perpendicular to the fiber direction. (ABSTRACT TRUNCATED AT 250 WORDS)
Impaired performance on the angle board test is induced in a model of painful whiplash injury but is only transient in a model of cervical radiculopathy

Although clinical studies report motor impairment associated with some painful injuries of the neck, assessment of motor function in animal models has been largely limited only to studies of direct trauma to the nervous system. The incline plane test was modified to evaluate motor function in two rodent pain models of facet joint distraction (FJD) and nerve root compression (NRC) injury (n = 5/group). Sham groups were also included as controls. Motor function was measured using the modified inclined plane test with rats facing downward before surgery (baseline) and following surgery on days corresponding to when mechanical sensitivity is established and remains elevated. Mean baseline values of the board angle inducing slip for FJD (45.8 ± 3.1°) was significantly greater (p = 0.014) than that for NRC (43.5 ± 2.5°), but baseline measurements did not vary for either group over time. No changes in motor function were found for shams. Motor function after FJD significantly decreased (p < 0.001) at days 1 and 7 after injury. In contrast, at day 1 after NRC injury, slip occurred at significantly lower (p = 0.0016) incline angles, but returned to baseline levels by day 7. These results show motor function impairment is induced following painful FJD and suggest the incline plane test offers utility to evaluate functional deficits in painful injuries. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:562–566, 2011
Novel corticosteroid-binding globulin variant that lacks steroid binding activity.

BACKGROUND Corticosteroid-binding globulin (CBG) is the principal carrier for glucocorticoids in the circulation and a regulator of their bioavailability. Inherited CBG deficiencies are rarely reported, and only three causative mutations in four families have been described. PATIENTS, METHODS, AND RESULTS In a 26-yr-old female with hypotension, fatigue, and undetectable total serum cortisol at presentation, we have identified a novel homozygous c.776g>t transversion in exon 3 of the CBG (SERPINA6) gene. This results in a p.Gly237Val substitution that is predicted to influence the positioning of two β-sheets that constitute part of the CBG steroid-binding site. Two siblings were also homozygous for the variant, whereas her mother and an unaffected sibling were heterozygous. No other symptomatic family members were identified apart from the proband. Individuals homozygous for the variant had serum CBG levels below the reference range when measured by RIA, but CBG was unmeasurable in cortisol-binding capacity assays. In the same individuals, we observed very low baseline and stimulated total serum cortisol levels but normal free serum and salivary cortisol and plasma ACTH. In a study of ultradian cortisol pulsatility, increased pulse frequency was only observed in the proband. CONCLUSION We describe a novel CBG variant that lacks steroid binding activity. All mutant homozygotes have very low total serum cortisol, but normal free serum cortisol levels. The only biochemical feature to distinguish the symptomatic subject was increased cortisol pulsatility, and we suggest that this may influence glucocorticoid signaling and contribute to symptoms previously associated with CBG deficiency.
Comparative analysis of novel Long Life Routing Methods in Mobile Networks

In this study we propose two novel ABR extended Long Life Routing Methods called Alternative enhancement for Enhanced Associativity Based Routing (AEABR) and Associativity Tick Averaged ABR (ATAABR) methods which are also modifications of Associativity Based Routing (ABR). Comparison of these associativity based long Life routing algorithms in Mobile Networks are done for route speeds, life times and outage times Since ABR at most focuses on power strength, it will be preferable in most systems to establish long life routes from source to destination considering the power constraints. It is shown in this paper that, the novel algorithms that we propose provide better life time, link speeds and outage time results than EABR (Enhanced Associativity Based Routing) method and other relay selection algorithms taken into consideration in this work. It's illustrated that the performance of EABR method, is really better than other relay selection algorithms for number of Route reconstructions (RRC) or relay changes and Connected Status Percentage (CSP). On the other hand it has also been illustrated that AEABR and ATAABR improve the connection stability of EABR by keeping the connection outage time at lower levels where ATAABR require less modification on algorithm and needs less computation time. AEABR improves either connection outage times or number of RRC. During this analysis message overhead and bandwidth wastage of each algorithm is also investigated. The proposed algorithms can be used in designing a unicast mobile network having power constraints to provide longer path life and lower number of route reconstructions.
Measures of Morbidity in Clinical Studies with Recurrent Skeletal Complications

Abstract Double-blind placebo-controlled clinical trials in metastatic bone disease considered counts of morbid events as the clinical outcome measure. These (recurrent) skeletal events were derived from a composite endpoint based on the necessity of medical interventions against bone pain or incident fractures. The trials were conducted for regulatory approval of therapy with bisphosphonates and were intended to demonstrate that an active treatment reduces the occurrence of skeletal events. The advanced morbidity of the patients led to a substantial amount of premature discontinuations, because of early death or because of progression of the basic disease. In some trials the discontinuations were unbalanced between treatment arms, where there were more dropouts under placebo. These effects contribute to a high portion of patients with no morbidity events. This background presents difficulties for the task of defining statistics that validly quantify skeletal morbidity in these trials while keeping the necessary simplicity so as to be accepted by health authorities and a clinical audience. Guided by this regulatory context, this paper compares the performance of five (simple) approaches to quantifying skeletal morbidity. Key criteria are bias and validity under different dropout scenarios, as well as the capability to demonstrate treatment effects. Based on theoretical considerations, two simulation studies, and real data results, a morbidity measure in the form of a smoothed rate was favored: this is a rate estimate in the individual patient of the form (y + c)(T + d)−1, where y is the count of events, T is the patient's observation time, and c, d are constants to be appropriately chosen. This morbidity measure performed well in the simulation studies and showed a wanted insensitivity to dropout patterns. It outperforms the simple rate y/T due to the high portion of patients without events. Rates of this type were used before in the quantal bioassay and have a strong relationship to Bayesian approaches. Hence, these measures represent a good approach to handle the inherent difficulties of morbid event data in severely diseased patient populations, still offering sufficient simplicity.
Insulin-like Growth Factor I-mediated Activation of the Transcription Factor cAMP Response Element-binding Protein in PC12 Cells

IGF-I is known to support growth and to prevent apoptosis in neuronal cells. Activation of the nuclear transcription factor cAMP response element-binding protein (CREB) has emerged as a central determinant in neuronal functions. In the present investigation, we examined the IGF-I-mediated phosphorylation and transcriptional activation of CREB in rat pheochromocytoma (PC12) cells, a cellular model for neuronal differentiation, and defined three distinct postreceptor signaling pathways important for this effect including the p38 mitogen-activated protein kinase (MAPK) pathway. CREB phosphorylation at serine 133 and its transcriptional activation as measured by a CREB-specific Gal4-CREB reporter and the neuroendocrine-specific gene chromogranin A was induced 2–3.3-fold by insulin-like growth factor (IGF)-I. This activation was significantly blocked (p < 0.001) by the dominant negative K-CREB or by mutation of the CRE site. IGF-I stimulated chromogranin A gene expression by Northern blot analysis 3.7-fold. Inhibition of MAPK kinase with PD98059, PI 3-kinase with wortmannin, and p38 MAPK with SB203580 blocked IGF-I-mediated phosphorylation and transcriptional activation of CREB by 30–50% (p < 0.001). Constitutively active and dominant negative regulators of the Ras and PI 3-kinase pathways confirmed the contribution of these pathways for CREB regulation by IGF-I. Cotransfection of PC12 cells with p38β and constitutively active MAPK kinase 6 resulted in enhanced basal as well as IGF-I-stimulated chromogranin A promoter. IGF-I activated p38 MAPK, which was blocked by the inhibitor SB203580. This is the first description of a p38 MAPK-mediated nuclear signaling pathway for IGF-I leading to CREB-dependent neuronal specific gene expression.
Reliability of dual- vs single-volume reconstruction of three-dimensional digital subtraction angiography for follow-up evaluation of endovascularly treated intracranial aneurysms

Introduction Single-volume reconstruction of three-dimensional (3D) digital subtraction angiography (DSA) can be effectively used for aneurysm assessment and planning of endovascular embolization. Unfortunately, post-embolization follow-up angiographic images can be obscured by artifact. The dual-volume reconstruction technique was developed in order to reduce artifact and enhance the visualization of the aneurysm, the parent vessel and side branches, and endovascular devices. The purpose of this study was to compare the reliability of dual- vs single-volume reconstruction of 3D DSA in evaluation of follow-up images after endovascular embolization of intracranial aneurysms. Method Four cerebrovascular neurosurgeons independently and blindly reviewed 20 randomly selected dual-and single-volume reconstructions of 3D DSAs demonstrating cerebral aneurysms treated with primary coil embolization, stent-assisted coil embolization, or Pipeline embolization. Five images were repeated for each modality (single and dual volume) in order to assess intra-rater reliability. The intraclass correlation coefficient was calculated as a measure of the overall inter-rater agreement. Cohen’s kappa value was used to assess repeat measurement consistency for each rater. Results Overall inter-rater agreement using dual- and single-volume reconstruction was 0.81 and 0.75, respectively. Dual-volume reconstruction resulted in superior agreement in assessing location, occlusion status, position of aneurysm recanalization or residual, status of nearby branches, presence of coil migration and presence of intravascular devices (stent or Pipeline). Conclusion Three-dimensional reconstruction is an important complementary imaging technique in evaluating the angioarchitecture of aneurysms and recanalization after endovascular embolization. Dual-volume reconstruction imaging was associated with superior inter- and intra-rater reliability.
Concurrent and prospective associations between physical activity, walking and mental health in older women

Background Leisure-time physical activity (LTPA) shows promise for reducing the risk of poor mental health in later life, although gender- and age-specific research is required to clarify this association. This study examined the concurrent and prospective relationships between both LTPA and walking with mental health in older women. Methods Community-dwelling women aged 73–78 years completed mailed surveys in 1999, 2002 and 2005 for the Australian Longitudinal Study on Women's Health. Respondents reported their weekly minutes of walking, moderate LTPA and vigorous LTPA. Mental health was defined as the number of depression and anxiety symptoms, as assessed with the Goldberg Anxiety and Depression Scale (GADS). Multivariable linear mixed models, adjusted for socio-demographic and health-related variables, were used to examine associations between five levels of LTPA (none, very low, low, intermediate and high) and GADS scores. For women who reported walking as their only LTPA, associations between walking and GADS scores were also examined. Women who reported depression or anxiety in 1999 were excluded, resulting in data from 6653 women being included in these analyses. Results Inverse dose–response associations were observed between both LTPA and walking with GADS scores in concurrent and prospective models (p<0.001). Even low levels of LTPA and walking were associated with lowered scores. The lowest scores were observed in women reporting high levels of LTPA or walking. Conclusion The results support an inverse dose–response association between both LTPA and walking with mental health, over 3 years in older women without depression or anxiety.
The effects of single lung transplantation in rats with monocrotaline‐induced pulmonary hypertension

Abstract Acute haemodynamic change after single lung transplantation for primary pulmonary hypertension was evaluated using a rat transplantation model. Inbred Fisher 344 rats were administered with 40 mg/kg monocrotaline in order to induce pulmonary hypertension. The rats whose mean pulmonary arterial pressure (PAP) was over 30.0 mmHg received a left lung isograft from a normal donor after right heart catheterization. In the control group, PAP increased after single lung transplantation. On the other hand, in the pulmonary hypertensive group, PAP was significantly decreased 60 min after the transplantation, but 3 and 6 h after the transplantation, the PAP significantly increased again. On the day after the operation, it again decreased significantly. Left‐to‐right lung blood flow ratio was significantly increased in rats with pulmonary hypertension compared to rats with normal pulmonary pressure on both the 1st and 3rd postoperative days. The oedema of the grafted lung was more severe in the pulmonary hypertensive group than in the control group in the acute phase. In conclusion, single lung transplantation for pulmonary hypertension shifted pulmonary blood perfusion to the grafted lung and this shift made pulmonary oedema of the grafts more severe in the acute phase. These oedematous changes, which were more pronounced in the grafts in the pulmonary hypertensive rats, might have contributed to the transient rise in PAP in those rats after single lung transplanation.
Cancer-Initiating Cells from Colorectal Cancer Patients Escape from T Cell–Mediated Immunosurveillance In Vitro through Membrane-Bound IL-4

Cancer-initiating cells (CICs) that are responsible for tumor initiation, propagation, and resistance to standard therapies have been isolated from human solid tumors, including colorectal cancer (CRC). The aim of this study was to obtain an immunological profile of CRC-derived CICs and to identify CIC-associated target molecules for T cell immunotherapy. We have isolated cells with CIC properties along with their putative non-CIC autologous counterparts from human primary CRC tissues. These CICs have been shown to display “tumor-initiating/stemness” properties, including the expression of CIC-associated markers (e.g., CD44, CD24, ALDH-1, EpCAM, Lgr5), multipotency, and tumorigenicity following injection in immunodeficient mice. The immune profile of these cells was assessed by phenotype analysis and by in vitro stimulation of PBMCs with CICs as a source of Ags. CICs, compared with non-CIC counterparts, showed weak immunogenicity. This feature correlated with the expression of high levels of immunomodulatory molecules, such as IL-4, and with CIC-mediated inhibitory activity for anti-tumor T cell responses. CIC-associated IL-4 was found to be responsible for this negative function, which requires cell-to-cell contact with T lymphocytes and which is impaired by blocking IL-4 signaling. In addition, the CRC-associated Ag COA-1 was found to be expressed by CICs and to represent, in an autologous setting, a target molecule for anti-tumor T cells. Our study provides relevant information that may contribute to designing new immunotherapy protocols to target CICs in CRC patients.
In an Idealized World: Can Discrepancies Across Self-Reported Parental Care and High Betrayal Trauma During Childhood Predict Infant Attachment Avoidance in the Next Generation?

Adult caregivers’ idealization of their parents as assessed by the Adult Attachment Interview is a risk factor for the intergenerational transmission of the insecure-avoidant attachment style. This study evaluated a briefer screening approach for identifying parental idealization, testing the utility of prenatal maternal self-report measures of recalled betrayal trauma and parental care in childhood to predict observationally assessed infant attachment avoidance with 58 mother–infant dyads 18 months postpartum. In a logistic regression that controlled for maternal demographics, prenatal psychopathology, and postnatal sensitivity, the interaction between women's self-reported childhood high betrayal trauma and the level of care provided to them by their parents was the only significant predictor of 18-month infant security versus avoidance. Results suggest that betrayal trauma and recalled parental care in childhood can provide a means of identifying caregivers whose infant children are at risk for avoidant attachment, potentially providing an efficient means for scientific studies and clinical intervention aimed at preventing the intergenerational transmission of attachment problems.
Novel cyclic azo‐bridged analogs of gonadotropin‐releasing hormone

Five linear analogs of GnRH containing a p‐aminophenylalanine (Pap) residue in their sequence and their six corresponding azo‐bridged cyclic derivatives were synthesized. The precyclic peptides were prepared on solid‐support, while azo‐cyclization was performed in solution by diazotization of the p‐aminophenylalanine residue followed by intramolecular coupling of the formed diazo salt with either tyrosine or histidine side chains present in the sequence. All peptides were examined for their binding ability to the GnRH receptor expressed on rat pituitary membranes and for their LH‐release activity from dispersed rat pituitary cells. Linear analogs 1 i.e [Pap5] GnRH and 3, i.e. [Tyr3, Pap5] GnRH, were found to bind to the GnRH receptors only slightly less avidly than native GnRH. Their cyclization, however, led to a marked reduction in the binding capacity, i.e. from IC50 of 10−9 M to the 10−7 M range, and in biopotency, i.e. LH‐release. All other linear and cyclic peptides were found to bind selectively to the GnRH receptor only in the low µM range. Only peptide 1 was found comparable to native GnRH in respect to LH‐release activity and thus may potentially be a good agonist of the parent peptide. Peptides 1–4, the most potent GnRH receptor binders, were examined for their conformational properties using CD. Cyclic‐azo peptides 2 and 4 were further evaluated by NMR spectroscopy in solution combined with molecular modeling. The structural information obtained explains in part the GnRH‐like biological activity observed. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.
Abdominal Bloating in Employed Adults: Prevalence, Risk Factors, and Association With Other Bowel Disorders

BACKGROUND AND AIMS:Bloating is common, but its significance as a marker of underlying disease has not been defined. We report on risk factors for bloating, its relationship to physical activity and quality of life (QOL), and its predictive value for functional bowel disorders.METHODS:This is a cross-sectional population-based study of 1,069 employees of the Veterans Affairs Black Hills Health Care System. The validated Bowel Disease Questionnaire was used to identify subjects with abdominal bloating and other bowel disorders. The association of bloating with QOL was assessed using the SF36 (Short-Form 36) questionnaire. Physical activity was assessed using the modified Baecke questionnaire.RESULTS:The response rate was 72% (723 of 1,069). Bloating was reported by 21% of all subjects (95% confidence interval [CI] 17.7–23.7), 64% with irritable bowel syndrome (IBS), 35% with non-IBS constipation, 23% with non-IBS diarrhea, and 42% with dyspepsia. Functional bloating (i.e., bloating in the absence of other bowel disorders) was reported by 7% of subjects (95% CI 5.2–9.0). Of those with bloating, 28% had IBS, 25% non-IBS constipation, 8% non-IBS diarrhea, and 30% dyspepsia. The positive and negative predictive values of bloating in the diagnosis of functional bowel disorder were 66% and 87%, respectively. The only risk factors were smoking and high-dose aspirin. Bloating was not associated with physical activity. QOL on all subscales of SF36 was lower in subjects with bloating than those without bloating.CONCLUSIONS:Bloating is a common symptom in otherwise healthy adults, and is often associated with but not predictive of functional bowel disorders. Smoking and high-dose aspirin are associated with bloating while physical activity is not.