Miracle-dz/UniFAR-FTUs huggingface dataset:
Profiles of neuromuscular diseases. Duchenne muscular dystrophy.

One hundred and sixty-two patients with Duchenne muscular dystrophy (DMD) were followed over a 10-yr period to provide a profile of impairment and disability. The median height and weight of DMD boys were normally distributed before ages 9-10, but during the second decade height was markedly reduced, and weight was no longer normally distributed. Younger boys gained more weight than normals, whereas older individuals actually showed weight loss. Manual muscle test (MMT) measurements showed loss of strength in a fairly linear fashion from ages 5-13 yr, -0.25 MMT units per year. Upper extremity muscles were stronger than lower extremity muscles, proximal muscle groups were weaker than distal muscle groups, and extensor muscles were weaker than flexor muscles. There was no side dominance. There was a change in the rate of strength loss at 14-15 yr, and the decline slowed to only -0.06 MMT units per year. Although MMT and quantitative strength measurement profiles were similar, the latter were far more sensitive. In general, by the time strength declined to MMT grade 4, isometrically measured strength was 40-50% of normal control values. Joint contractures were rare before age 9, increased in frequency and severity with age, and were present in most individuals older than 13. Lower extremity contractures were strongly related to onset of wheelchair reliance, but there was no association between muscle imbalance around a joint. The prevalence of scoliosis increased between ages 11 and 16, with about 50% of the boys acquiring scoliosis between ages 12 and 15, corresponding to the onset of the adolescent growth spurt. Wheelchair reliance and scoliosis were both age-related. Percent predicted forced vital capacity declined at different yearly rates: ages 7-10, -0.3%; ages 10-20, -8.5%; after age 20, -6.2%. There was a direct relationship between percent predicted FVC and MMT scores. Decreased airway pressures, especially maximal expiratory pressure, appeared earlier than reductions in FVC but followed the same pattern. Thirty percent of the DMD boys had a history of respiratory complications, and the frequency increased with age. Spine deformity did not have a significant additive effect on the age-related decrement in pulmonary function. There was a high occurrence (79%) of abnormal electrocardiograms with age-related progression of some abnormalities, but only 30% of the patients had a history of cardiovascular complications. Functional level grades and timed motor performance measurements had a nonlinear relationship with strength and age. (ABSTRACT TRUNCATED AT 400 WORDS)
Advances in clinical next-generation sequencing: target enrichment and sequencing technologies

ABSTRACT The huge parallel sequencing capabilities of next generation sequencing technologies have made them the tools of choice to characterize genomic aberrations for research and diagnostic purposes. For clinical applications, screening the whole genome or exome is challenging owing to the large genomic area to be sequenced, associated costs, complexity of data, and lack of known clinical significance of all genes. Consequently, routine screening involves limited markers with established clinical relevance. This process, referred to as targeted genome sequencing, requires selective enrichment of the genomic areas comprising these markers via one of several primer or probe-based enrichment strategies, followed by sequencing of the enriched genomic areas. Here, the authors review current target enrichment approaches and next generation sequencing platforms, focusing on the underlying principles, capabilities, and limitations of each technology along with validation and implementation for clinical testing.
Assessing the strength and integrity of an intervention.

PURPOSE/OBJECTIVES To evaluate the strength and integrity of a pilot behavioral intervention designed to assist mothers with breast cancer and their children. RESEARCH APPROACH A single-group analysis of the strength and integrity characteristics of an intervention developed for a pilot research study. SETTING Homes of study participants in an urban area. PARTICIPANTS Seven households with a mother and father and one household with a single mother. METHODOLOGIC APPROACH Observer-reported checklists, audiorecorded intervention session data, and structured interview data obtained from study participants. MAIN RESEARCH VARIABLES Strength of the intervention included dimensions such as the theoretical foundation, competence of the interventionist, and specificity to the breast cancer experience in the family. Intervention integrity consisted of adherence by the interventionist and participants to the intervention plan. FINDINGS The strength of the intervention was determined to be an asset. Careful planning had included a framework, a defined set of scripted sessions, a competent interventionist, and content specific to the breast cancer experience. In regard to integrity, the protocol content was delivered as scripted. Improvements in the dosage and purity dimensions were found to be needed. Homework assignments and in-session skill-building approaches with the mothers were refined. CONCLUSIONS An intervention can be examined carefully for strength and integrity with established criteria to determine improvements needed. INTERPRETATION A clinical research protocol can be improved through an assessment of an intervention's strength and integrity.
Predicting aggregate returns using valuation ratios out-of-sample

It is well established that valuation ratios (indicators of the fi nancial market situation) provide, in-sample, relevant signals regarding future returns on assets. Specifi cally, periods of high prices, relative to dividends, are proceeded by years of low returns; and periods of low prices, relative to dividends, precede years of high returns. This pattern of predictability is pervasive across fi nancial markets. In this paper, we assess the ability of valuation ratios to predict out-of-sample aggregate returns for the stock and the housing markets in the U.S. We fi nd that there is statistical evidence supporting the extension of the in-sample results to an out-of-sample framework. The dividend-price ratio and the rent-price ratio display a signifi cant ability for predicting in real-time stock and housing returns, respectively. Nevertheless, we note that these fi ndings may be sample dependent. Especially for the stock market, the sample’s ending data, including the recent fi nancial crisis, may be responsible for the good results.
A dual mode channel decoder for 3GPP2 mobile wireless communications

This paper presents a turbo and Viterbi decoder single chip for 3GPP2 standard. The turbo decoding with a maximum block length of 20,730 and Viterbi decoding with various coding rates are implemented to provide maximum 4.52 Mb/s and 5.26 Mb/s data rates respectively. The memory access is reduced by the input caching scheme. And the system complexity is lowered by the efficient interleaver design. This chip is fabricated in a 0.18 /spl mu/m six-metal standard CMOS process, and the measured power dissipation is 83 mW while decoding a 3.1 Mb/s turbo encoded data stream with six iterations for each block.
Serum thyrotropin-receptor autoantibodies levels after I therapy in Graves' patients: effect of pretreatment with methimazole evaluated by a prospective, randomized study.

OBJECTIVE Radioiodine therapy (131I) in hyperthyroid Graves' disease is generally followed by a transitory increase in levels of thyrotropin receptors antibodies (TRAb). Immunosuppressive effects of antithyroid drugs are still a matter of debate. In this study we evaluated the effect of methimazole pretreatment on the TRAb boost induced by 131I. DESIGN A randomized, prospective clinical trial. METHODS 61 patients were randomly assigned to receive 131I alone (32 patients) or 131I plus pretreatment with methimazole (30 mg/day; 29 patients). Serum TRAb levels were measured on the day of 131I dosing (D0), and at 1, 3, 6 and 12 months after 131I administration. RESULTS The mean serum TRAb levels decreased significantly from baseline to D0 in patients treated with methimazole (80.8 vs 48.8 U/l; P<0.05). After 131I treatment, TRAb levels increased at 3 months (48.8 to 60 U/l; 19%) and they were still elevated at 6 months compared with D0 values (99.9 U/l; 105%). Thereafter, TRAb levels decreased to baseline values (47.8 U/l) at 12 months. In hyperthyroid patients, TRAb levels increased significantly from D0 to 1 month (45.0 to 78 U/l; 73%) reaching their highest levels at 3 months (225 U/l; 400%). After this, we observed a progressive decrease to the baseline levels at 12 months (40.0 U/l). The course of TRAb levels after 131I treatment was significantly different between the two groups (P<0.05). Multiple regression analysis identified serum TRAb levels on D0 as independent predictors of TRAb increment after 131I therapy (r2=0.34; P=0.001). A higher increment in serum TRAb levels was associated with hypothyroidism after 1 year of follow-up. CONCLUSION Methimazole pretreatment attenuates the 131I-induced rise in serum TRAb levels. The effects of methimazole could be attributed to a direct immunomodulatory action or may be due to its effects on the control of hyperthyroidism, which is a known cause of immune dysregulation.
The role of the medial supramammillary nucleus in the control of hippocampal theta activity and behaviour in rats

The medial supramammillary nucleus (mSUM) controls the frequency of hippocampal theta activity, completely in anaethsetized rats and partially in free‐moving rats. mSUM could therefore influence hippocampal contributions to cognition and emotion. Using chemical lesions of mSUM in rats, we tested whether mSUM is involved in controlling several hippocampal‐dependent functions: (i) defensive behaviour (open field, fear conditioning); (ii) behavioural inhibition (fixed interval schedule, differential reinforcement of low rates schedule); and (iii) spatial learning (water maze). Theta frequency was measured in all these tasks. mSUM lesions produced a pattern of changes in motivated/emotional behaviours (hyperactivity in defensive and operant tasks) similar to the pattern produced by hippocampal lesions, but had no significant effect on spatial learning. mSUM lesion decreased theta frequency modestly (by ≈ 0.4 Hz) in behaving rats if the amount of movement was unchanged. There was not always a parallel between changes in theta frequency and behaviour; behaviours changed despite unchanged theta in defensive tasks and learning changed little despite a lower frequency of theta in the water maze task. This suggests that mSUM function impacts on emotional behaviour more than cognition, and can modulate theta and behaviour independently.
Examination of a sociocultural model of disordered eating among male and female adolescents.

OBJECTIVES The study tests a version of Stice's (1994) sociocultural model of disordered eating that was modified to incorporate social comparisons. Additionally, it examines how self-reported body-mass index and perceived weight status influence associations within the model. METHOD Questionnaires were administered in a state secondary school; the sample consisted of 250 female and 257 male adolescents aged 11-16 years. RESULTS The results supported the sociocultural model among both male and female adolescents. Perceived pressure to lose weight was directly associated with eating behaviour, as well as indirectly associated through social comparisons, internalization and body dissatisfaction. However, social comparisons were most strongly related to body dissatisfaction among adolescents who perceived themselves as overweight. CONCLUSIONS The findings indicate that models of eating disordered behaviour, developed for adolescent girls, are also appropriate for understanding this behaviour among male adolescents. The results suggest that social comparisons represent a useful addition to Stice's (1994) original model and a potentially fruitful target for interventions.
Evaluation of Lumbar Lordosis: A Prospective and Retrospective Study

Two lordotic angles were measured on roentgenograms of 973 adults in a prospective and retrospective review. The majority of the films were taken because of lumbar complaints. The mean lumbosacral (LS) angle (L2- Sacrum) was 45.05° ±. 85°. The mean lumbolumbar (LL) angle (L2–L5) was 29.96° ±. 74°. Only minor differences were found between a standardized (prospective) and a nonstandardized (retrospective) group. There was a statistically significant difference between men and women with both LS and LL angles, but no racial differences were observed. A “routine” supine lateral lumbar spine roentgenogram is a very accurate means of measuring lordotic angles. A lordotic angle of less than 23° defines hypolordosis and more than 68°, hyperlordosis.
Transforming Growth Factor-β1-mediated Inhibition of the flk-1/KDR Gene Is Mediated by a 5′-Untranslated Region Palindromic GATA Site*

The angiogenic effects of vascular endothelial growth factor are mediated predominantly by the FLK-1/KDR receptor. An understanding of the transcriptional control mechanisms underlyingflk-1/KDR expression should provide insight into the molecular basis of angiogenesis. In this study, we show that transforming growth factor-β1 (TGF-β1) down-regulates expression of the endogenous flk-1/KDR gene in endothelial cells. In transient transfection assays, this effect was mapped to a palindromic GATA site in the 5′-untranslated region. In electrophoretic mobility shift assays, the palindromic GATA site was shown to bind to two molecules of GATA protein. Moreover, DNA-GATA interactions were inhibited by TGF-β1. Finally, in cotransfection assays, transactivation of the flk-1/KDRpromoter by GATA-1 or GATA-2 was attenuated in TGF-β1-treated cells. Taken together, these results suggest that the TGF-β-1-mediated inhibition of theflk-1/KDR gene is mediated by a 5′-untranslated region palindromic GATA site.
Tracking the estrogen receptor in neurons: Implications for estrogen-induced synapse formation

Estrogens (E) and progestins regulate synaptogenesis in the CA1 region of the dorsal hippocampus during the estrous cycle of the female rat, and the functional consequences include changes in neurotransmission and memory. Synapse formation has been demonstrated by using the Golgi technique, dye filling of cells, electron microscopy, and radioimmunocytochemistry. N-methyl-d-aspartate (NMDA) receptor activation is required, and inhibitory interneurons play a pivotal role as they express nuclear estrogen receptor alpha (ERα) and show E-induced decreases of GABAergic activity. Although global decreases in inhibitory tone may be important, a more local role for E in CA1 neurons seems likely. The rat hippocampus expresses both ERα and ERβ mRNA. At the light microscopic level, autoradiography shows cell nuclear [3H]estrogen and [125I]estrogen uptake according to a distribution that primarily reflects the localization of ERα-immunoreactive interneurons in the hippocampus. However, recent ultrastructural studies have revealed extranuclear ERα immunoreactivity (IR) within select dendritic spines on hippocampal principal cells, axon terminals, and glial processes, localizations that would not be detectable by using standard light microscopic methods. Based on recent studies showing that both types of ER are expressed in a form that activates second messenger systems, these findings support a testable model in which local, non-genomic regulation by estrogen participates along with genomic actions of estrogens in the regulation of synapse formation.
Follicle Stimulating Hormone-Induced DNA Synthesis in the Granulosa Cells of Hamster Preantral Follicles Involves Activation of Cyclin-Dependent Kinase-4 Rather Than Cyclin D2 Synthesis1

Abstract Although cyclin D2 mRNA synthesis precedes gonadotropin-induced DNA synthesis in quiescent granulosa cells in culture, it is unclear whether a similar mechanism exists for the granulosa cells of growing preantral follicles in cyclic animals. The objective was to evaluate whether the synthesis of cyclin D2 protein was a prerequisite for FSH-induced DNA synthesis in the granulosa cells of intact preantral follicles of cyclic hamsters. Preantral follicles from cyclic hamsters were cultured in the presence or absence of FSH, and cell cycle parameters were examined. FSH stimulated cyclin-dependent kinase (CDK)-4 activity by 2 h and DNA synthesis by 4 h without altering the levels of cyclin D2 in the granulosa cells. The FSH effect was mimicked by epidermal growth factor administered in vivo. Although FSH increased the levels of cyclin D2 mRNA, it also stimulated the degradation of cyclin D2 as well as p27Kip1 and p19INK4 proteins. FSH activation of CDK4 was mediated by cAMP and ERK-1/2. In contrast to granulosa cells in intact follicles, FSH or cAMP significantly increased cyclin D2 protein levels in cultured granulosa cells but failed to induce DNA synthesis. Collectively, these data suggest that granulosa cells of preantral follicles, which are destined to enter the S phase during the estrous cycle, contain necessary amounts of cyclin D2 and other G1 phase components. FSH stimulation results in the formation and activation of the cyclin D2/CDK4 complex leading to DNA synthesis. This mechanism may be necessary for rapid movement of follicles from preantral to antral stages during the short duration of the murine estrous cycle.
Frontotemporoparietal asymmetry and lack of illness awareness in schizophrenia

Introduction: Lack of illness awareness or anosognosia occurs in both schizophrenia and right hemisphere lesions due to stroke, dementia, and traumatic brain injury. In the latter conditions, anosognosia is thought to arise from unilateral hemispheric dysfunction or interhemispheric disequilibrium, which provides an anatomical model for exploring illness unawareness in other neuropsychiatric disorders, such as schizophrenia. Methods: Both voxel‐based morphometry using Diffeomorphic Anatomical Registration through Exponentiated Lie Algebra (DARTEL) and a deformation‐based morphology analysis of hemispheric asymmetry were performed on 52 treated schizophrenia subjects, exploring the relationship between illness awareness and gray matter volume. Analyses included age, gender, and total intracranial volume as covariates. Results: Hemispheric asymmetry analyses revealed illness unawareness was significantly associated with right < left hemisphere volumes in the anteroinferior temporal lobe (t = 4.83, P = 0.051) using DARTEL, and the dorsolateral prefrontal cortex (t = 5.80, P = 0.003) and parietal lobe (t = 4.3, P = 0.050) using the deformation‐based approach. Trend level associations were identified in the right medial prefrontal cortex (t = 4.49, P = 0.127) using DARTEL. Lack of illness awareness was also strongly associated with reduced total white matter volume (r = 0.401, P < 0.01) and illness severity (r = 0.559, P < 0.01). Conclusion: These results suggest a relationship between anosognosia and hemispheric asymmetry in schizophrenia, supporting previous volume‐based MRI studies in schizophrenia that found a relationship between illness unawareness and reduced right hemisphere gray matter volume. Functional imaging studies are required to examine the neural mechanisms contributing to these structural observations. Hum Brain Mapp, 2013. © 2012 Wiley Periodicals, Inc.
Management of congestive heart failure: how well are we doing?

The reasons for this are multifactorial. In one study, patients followed by cardiologists were more likely to be prescribed an ACE inhibitor than were those managed by primary care physicians, in part because the primary care physicians were less likely to perform imaging procedures that document left ventricular dysfunction. 11 In another study, patients with renal failure were less likely than other patients to be prescribed an ACE inhibitor, for fear of worsening renal function. 9 Sig
The role of mathematical modelling in the development of recommendations in the 2013 WHO consolidated antiretroviral therapy guidelines

Despite the exponential growth in the literature on modelling and simulation studies of impact and cost-effectiveness in different aspects of healthcare, there is no clear consensus on the appropriate role of modelling in the development of recommendations in clinical guidelines. This is compounded both by the lack of a standardised approach to assess the quality of modelling, and lack of clarity on its positioning within the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) method for decision-making in the development of WHO guidelines, that considers both evidence from systematic reviews of randomized clinical trials (RTCs) or observational studies, together with stakeholder values and preferences, resource use, and feasibility issues. In the development of the 2013 WHO Consolidated Guidelines on the use of Antiretroviral drugs for treating and preventing HIV infection, a series of modelling projects were undertaken to inform the recommendations on eligibility criteria for ART initiation, and approaches to monitoring for treatment response. We report our experiences, challenges encountered, and several key considerations to guide the future use of modelling in the development of WHO guidelines. These are: (1) Transparency in the conduct and reporting of model inputs and results; (2) The need for agreed standards for critical appraisal and use of modelling data in healthcare policy making; (3) recognition that modelling of cost-effectiveness is only one component of decision-making in development of WHO recommendations and in priority-setting; (4) The need for closer interaction and an ongoing dialogue between modellers and model end-users or decision-makers; (5) the important role of WHO in convening and facilitating comparative assessment of multiple models; and (6) The need to optimize research and data collection to inform modelling studies.
Effects of nickel-oxide nanoparticle pre-exposure dispersion status on bioactivity in the mouse lung

Abstract Nanotechnology is emerging as one of the world's most promising new technologies. From a toxicology perspective, nanoparticles possess two features that promote their bioactivity. The first involves physical–chemical characteristics of the nanoparticle, which include the surface area of the nanoparticle. The second feature is the ability of the nanoparticle to traverse cell membranes. These two important nanoparticle characteristics are greatly influenced by placing nanoparticles in liquid medium prior to animal exposure. Nanoparticles tend to agglomerate and clump in suspension, making it difficult to reproducibly deliver them for in vivo or in vitro experiments, possibly affecting experimental variability. Thus, we hypothesize that nanoparticle dispersion status will correlate with the in vivo bioactivity/toxicity of the particle. To test our hypothesis, nano-sized nickel oxide was suspended in four different dispersion media (phosphate-buffered saline (PBS), dispersion medium (DM), a combination of dipalmitoyl-phosphatidyl choline (DPPC) and albumin in concentrations that mimic diluted alveolar lining fluid), Survanta®, or pluronic (Pluronic F-68). Well-dispersed and poorly dispersed suspensions were generated in each media by varying sonication time on ice utilizing a Branson Sonifer 450 (25W continuous output, 20 min or 5 min, respectively). Mice (male, C57BL/6J, 7-weeks-old) were given 0–80 µg/mouse of nano-sized nickel oxide in the different states of dispersion via pharyngeal aspiration. At 1 and 7 d post-exposure, mice underwent whole lung lavage to assess pulmonary inflammation and injury as a function of dispersion status, dose and time. The results show that pre-exposure dispersion status correlates with pulmonary inflammation and injury. These results indicate that a greater degree of pre-exposure dispersion increases pulmonary inflammation and cytotoxicity, as well as decreases in the integrity of the blood–gas barrier in the lung.