Miracle-dz/UniFAR-FTUs huggingface dataset:
Distractive Properties of a Threaded Interbody Fusion Device: An In Vivo Model

Study Design. Twenty sheep underwent anterior lumbar interbody fusions with either a threaded titanium interbody fusion device (cage, n = 8), autogenous iliac crest dowel graft (autograft, n = 6), or interbody decortication only (sham, n = 6). Two sheep had misplaced cages and were excluded. Sheep were killed after 6 months. Objectives. To determine whether this model is useful for examining the distractive and fixation properties of interbody fusion cages. Summary of Background Data. Interbody fusion cages are used in anterior lumbar interbody fusion procedures to provide immediate intersegmental fixation and to distract and preserve interbody height. The process of physiologic anchorage by bone ingrowth into such devices is under investigation. Methods. Sheep were radiographed immediately after surgery and 2, 4, and 6 months after surgery. Interbody distraction and angulation were measured with a digital photo image analyzer at each time point. After the sheep were killed, stiffness to flexion, extension, and lateral bending moments were measured. Twelve untreated cadaver spines were also tested for comparison. Results. After surgery, interbody distraction successfully occurred in cage and autograft‐implanted sites. Loss of interbody height ensued, however, in all groups during the first 2 months. Percentage loss of height was lowest in cage sites. By 6 months, only cage sites remained distracted beyond normal. Fusions in all groups were stiffer than untreated spines. Autograft sites were stiffer than cage sites to lateral bending. Sham sites were stiffer than cage and autograft sites to flexion, but this likely resulted from complete intervertebral collapse. Conclusion. Despite early subsidence, interbody fusion cages successfully distracted and preserved interbody spaces. This model is useful for investigating methods of improving distraction and stabilization.
Controlling the kinetics of interferon transgene expression for improved gene therapy

Interferon (IFN) gene based therapy has been studied for the treatment of many diseases such as viral infections, cancer and allergic diseases. Non-viral vectors, like plasmid DNA, are promising ways for delivering IFN genes, because of their low immunogenicity and toxicity compared with viral vectors. Potent therapeutic effects of IFN gene transfer will depend on the level and duration of transgene expression after in vivo administration. Therefore, controlling the kinetics of transgene expression of IFNs is a rational approach for improved gene therapy. The design and optimization of plasmid vectors, as well as their route/method of administration, is the key to obtaining high and persistent transgene expression. In this review, we aim to present experimental evidence about the relationships among the properties of plasmid vectors expressing IFNs, the kinetics of transgene expression, and therapeutic effects as well as safety issues.
Proposal of a nest box for the reproduction of wild rabbits (Oryctolagus cuniculus) in cages

This paper reports on the design of a nest box consisting of two compartments for the breeding in cages of wild rabbits(Oryctolagus cuniculus). The first compartment was a chamber measuring on the inside 17×23×20 cm (base and height), conforming to the small body size of the wild rabbit and similar to its breeding burrows. A plastic tray was placed inside the chamber, in which the doe could build her nest. The other part of the nest box was a tunnel with an inner cross-section of 9×8 cm leading to the nesting chamber and designed to make the doe enter the nest slowly. The does made considerable use of the boxes as nesting places since, out of a total number of 41 births, 85.4% of the does gave birth to all of their kits inside the nest box, and in 71.4% of these cases the does suckled their litters there. No differences were found in the use of the nest box between does born in breeding burrows and those born in the nest boxes tested here. It was concluded that this nest box is appropriate for breeding captive wild rabbits.
Clinical Applications of Intraspinal Microstimulation

Intraspinal microstimulation is a neuroprosthetic approach for activating specific spinal reflexes using penetrating electrodes chronically implanted into spinal cord. Artificial control of spinally mediated functions, such as arm and leg movement or bladder voiding, may be necessary in spinal cord injury, multiple sclerosis, cerebral palsy, amyotrophic lateral sclerosis, and spina bifida, when the brain becomes disconnected from spinal cord and a person loses control over these functions. Animal studies indicate the feasibility of efficient control of bladder voiding and limb movement. Development of novel microstimulation electrodes focuses on reduction of electrode dimensions for improved targeting efficiency, decreased tissue trauma, improved biocompatibility, and long-term safety and reliability of applied stimulation. Clinical usefulness of existing devices is limited by a lack of highly integrated and biocompatible neuroprosthetic systems, comprising high-density electrode arrays and integrated electronics for pulse generation and stimulation site addressing. Future developments will require a coordinated effort in the areas of neural prosthetic engineering, applied neurophysiology, neurosurgery, physical therapy, and rehabilitation. In the long term, clinical applications of intraspinal microstimulation may include treatments of such spinal cord-related disabilities, such as bladder and bowel emptying, sexual function, hand and arm control, and even walking. These treatments can address the long-standing needs of paralyzed patients aimed at improving their medical, psychological, social, and work-related conditions.
Systemic exposure, tolerability, and efficacy of pimecrolimus cream 1% in atopic dermatitis patients

Aims: To measure pimecrolimus blood concentrations and to evaluate tolerability and efficacy in children and infants treated topically for atopic dermatitis with pimecrolimus cream 1% for three weeks. Methods: Three open label, non-controlled, multiple topical dose studies were conducted in children aged 8–14 years (study A, ten patients), and in infants aged 8–30 months (study B, eight patients) and 4–11 months (study C, eight patients). Pimecrolimus blood concentrations were determined on days 4 and 22 of treatment, and at end of study. Efficacy was assessed using the Eczema Area and Severity Index (EASI). Results: Pimecrolimus blood concentrations were consistently low, typically (81%) below 1 ng/ml, with more than half of the measurements below the assay limit of quantitation (0.5 ng/ml) in studies A and B. The highest blood concentration measured throughout the three studies was 2.6 ng/ml. The cream was well tolerated, locally and systemically. The most common adverse event suspected to be related to study medication was a transient mild to moderate stinging sensation at the application site in 5/26 patients. There was no indication of any systemic adverse effect. The patients responded well to therapy with a rapid onset of action, usually within four days. Median reductions of EASI from baseline at day 22 were 55% (study A), 63% (study B), and 83% (study C). Conclusion: Three weeks treatment of children and infants with extensive atopic dermatitis, using pimecrolimus cream 1% twice daily, is well tolerated and results in minimal systemic exposure, at which no systemic effect is expected.
Strong Influence of Eddy Length on Boreal Summertime Extreme Precipitation Projections

Previous research has shown that projected changes in the horizontal eddy length of ascending anomalies likely drive subtropical changes in large‐scale ascent during extreme precipitation events (extreme ascent), which in turn strongly influence regional projections of extreme precipitation. Here we present evidence that this eddy length effect extends into the Northern Hemisphere extratropics during the summer season. This is shown by analyzing output from a large ensemble of the Canadian Earth System Model version 2 as well as models participating in the Coupled Model Intercomparison Project phase 5. As found previously, the changes in eddy length are associated with changes in an effective stability quantity that combines dry and moist effects. It is shown that the change of extreme ascent associated with a projected change of eddy length agrees with expectations based on analysis of internal variability of extreme ascent and eddy length during the historical period.
The Role of Unequal Crossover in Alpha-Satellite DNA Evolution: A Computational Analysis

Human DNA consists of a large number of tandem repeat sequences. Such sequences are usually called satellites, with the primary example being the centromeric alpha-satellite DNA. The basic repeat unit of the alpha-satellite DNA is a 171 bp monomer. Arbitrary monomer pairs usually have considerable sequence divergence (20-40%). However, with the exception of peripheral alpha-satellite DNA, monomers can be grouped into blocks of k-monomers (4 < or = k < or = 20) between which the divergence rate is much smaller (e.g., 5%). Perhaps the simplest and best understood mechanism for tandem repeat array evolution is unequal crossover. Although it is possible that alpha-satellite sequences developed as a result of subsequent unequal crossovers only, no formal computational framework seems to have been developed to verify this possibility. In this paper, we develop such a framework and report on experiments which imply that pericentromeric alpha-satellite segments (which are devoid of higher order structure) are evolutionarily distinct from the higher order repeat segments. It is likely that the higher order repeats developed independently in distinct regions of the genome and were carried into their current locations through an unknown mechanism of transposition.
An Evolution-Based Approach to De Novo Protein Design and Case Study on Mycobacterium tuberculosis

Computational protein design is a reverse procedure of protein folding and structure prediction, where constructing structures from evolutionarily related proteins has been demonstrated to be the most reliable method for protein 3-dimensional structure prediction. Following this spirit, we developed a novel method to design new protein sequences based on evolutionarily related protein families. For a given target structure, a set of proteins having similar fold are identified from the PDB library by structural alignments. A structural profile is then constructed from the protein templates and used to guide the conformational search of amino acid sequence space, where physicochemical packing is accommodated by single-sequence based solvation, torsion angle, and secondary structure predictions. The method was tested on a computational folding experiment based on a large set of 87 protein structures covering different fold classes, which showed that the evolution-based design significantly enhances the foldability and biological functionality of the designed sequences compared to the traditional physics-based force field methods. Without using homologous proteins, the designed sequences can be folded with an average root-mean-square-deviation of 2.1 Å to the target. As a case study, the method is extended to redesign all 243 structurally resolved proteins in the pathogenic bacteria Mycobacterium tuberculosis, which is the second leading cause of death from infectious disease. On a smaller scale, five sequences were randomly selected from the design pool and subjected to experimental validation. The results showed that all the designed proteins are soluble with distinct secondary structure and three have well ordered tertiary structure, as demonstrated by circular dichroism and NMR spectroscopy. Together, these results demonstrate a new avenue in computational protein design that uses knowledge of evolutionary conservation from protein structural families to engineer new protein molecules of improved fold stability and biological functionality.
Continuous performance test and schizophrenia: a test of stimulus-response compatibility, working memory, response readiness, or none of the above?

OBJECTIVE Abnormalities of attention are considered the fundamental deficits in cognitive function manifested by patients with schizophrenia. The authors administered variations of two types of cognitive tasks to patients with schizophrenia (N=20) and normal comparison subjects (N=30) to test four possible cognitive mechanisms that might account for such abnormalities. METHOD Variations of the Continuous Performance Test were used to test the four mechanisms. Stimulus-response mapping was explored by comparing results on a task in which subjects were to make a response if the word "nine" was preceded by the word "one" with results on a task in which the required response was made explicit by the stimulus (the word "ready" followed by the word "press"). The building up of a prepotent response tendency was tested by manipulating the probability with which the cue and imperative stimulus appeared (17% or 50%). The amount of working memory required to maintain contextual information was tested by using different delay intervals (1000 msec and 3000 msec). The extent to which problems in vigilance might be attributable to problems in the "motoric" component of response readiness was operationalized by having subjects perform a secondary motor task concurrent with the attentional task. RESULTS Patients with schizophrenia performed significantly worse than the normal comparison subjects on all tasks. However, none of the four manipulations of the Continuous Performance Test tasks had a differential impact on the patients' performance speed or accuracy. In contrast, there was a significant interaction of group, delay interval, and target probability in which patients made disproportionately more omission errors at short delay intervals and at low target probabilities. CONCLUSIONS The findings may call into question the explanatory power of certain well-known contemporary mechanistic accounts of performance on the Continuous Performance Test in patients with schizophrenia. The findings suggest that a difficulty in rapidly encoding information (i.e., constructing a representation) in certain "unengaging" situations may be at the core of deficits on tasks associated with this attentional test.
Executive Function in Charge Syndrome

This study addressed the presence of executive dysfunction in children with CHARGE syndrome, a genetic disorder with multiple physical anomalies and severe challenging behaviors. Ninety-eight children were included in the study. More than half received clinically significant scores on the Behavior Rating Inventory of Executive Function (BRIEF; Gioia et al., 2000) scales of Shift, Monitor, and the Behavioral Regulation Index, with additional high scores on Inhibit and the Global Executive Composite. Associations were found with the age the child first walked, scores on the Autism Behavior Checklist (ABC; Krug et al., 1993), and being classified as deafblind. Difficulties with making transitions and flexible problem solving, monitoring their work and their effect on others, and acting on impulse, may be related to the behavioral difficulties exhibited by children with CHARGE. Interventions targeting improved self-regulation may help to manage this challenging behavior.
A recurrent polyalanine expansion in the transcription factor FOXL2 induces extensive nuclear and cytoplasmic protein aggregation

Blepharophimosis syndrome is an autosomal dominant disease characterised by eyelid malformations, associated or not with premature ovarian failure. It is caused by mutations in the FOXL2 gene, which encodes a forkhead transcription factor containing a polyalanine (polyAla) domain of 14 alanines. Expansions of the polyAla tract from 14 to 24 residues account for 30% of the reported mutations and lead mainly to isolated palpebral defects. We have transfected COS-7 cells with DNA constructs driving the expression of the wildtype and mutant FOXL2 proteins fused to the green fluorescent protein. The polyAla expansion was found to induce the formation of intranuclear aggregates and a mislocalisation of the protein due to extensive cytoplasmic aggregation. These findings were confirmed by immunofluorescence. Co-transfection experiments suggest that the wildtype and mutant proteins can co-aggregate. We propose that the mechanism for the molecular pathogenesis of the polyAla expansions of FOXL2 may be its mislocalisation concomitant with its inclusion into nuclear aggregates. This may diminish the pool of active protein. Potential effects of aggregation on cell viability are under study.
Quantification of Mitochondrial Acetylation Dynamics Highlights Prominent Sites of Metabolic Regulation*

Background: Lysine acetylation, a prevalent post-translational modification, alters mitochondrial metabolism in response to nutrient changes. Results: Quantitative proteomics distinguishes dynamic and static acetylation sites, highlighting 48 likely regulatory sites of thousands identified. Conclusion: Acetylation of Acat1 lysine 260, a highly dynamic site, reversibly inhibits enzyme activity. Significance: Quantitative, state-specific proteomic analyses accelerate the functional characterization of acetylation in mitochondrial remodeling. Lysine acetylation is rapidly becoming established as a key post-translational modification for regulating mitochondrial metabolism. Nonetheless, distinguishing regulatory sites from among the thousands identified by mass spectrometry and elucidating how these modifications alter enzyme function remain primary challenges. Here, we performed multiplexed quantitative mass spectrometry to measure changes in the mouse liver mitochondrial acetylproteome in response to acute and chronic alterations in nutritional status, and integrated these data sets with our compendium of predicted Sirt3 targets. These analyses highlight a subset of mitochondrial proteins with dynamic acetylation sites, including acetyl-CoA acetyltransferase 1 (Acat1), an enzyme central to multiple metabolic pathways. We performed in vitro biochemistry and molecular modeling to demonstrate that acetylation of Acat1 decreases its activity by disrupting the binding of coenzyme A. Collectively, our data reveal an important new target of regulatory acetylation and provide a foundation for investigating the role of select mitochondrial protein acetylation sites in mediating acute and chronic metabolic transitions.
22q13.3 deletion syndrome: Clinical and molecular analysis using array CGH

The 22q13.3 deletion syndrome results from loss of terminal segments of varying sizes at 22qter. Few genotype–phenotype correlations have been found but all patients have mental retardation and severe delay, or absence of, expressive speech. We carried out clinical and molecular characterization of 13 patients. Developmental delay and speech abnormalities were common to all and comparable in frequency and severity to previously reported cases. Array‐based comparative genomic hybridization showed the deletions to vary from 95 kb to 8.5 Mb. We also carried out high‐resolution 244K array comparative genomic hybridization in 10 of 13 patients, that defined the proximal and distal breakpoints of each deletion and helped determine the size, extent, and gene content within the deletion. Two patients had a smaller 95 kb terminal deletion with breakpoints within the SHANK3 gene while three other patients had a similar 5.5 Mb deletion implying the recurrent nature of these deletions. The two largest deletions were found in patients with ring chromosome 22. No correlation could be made with deletion size and phenotype although complete/partial SHANK3 was deleted in all patients. There are very few reports on array comparative genomic hybridization analysis on patients with the 22q13.3 deletion syndrome, and we aim to accurately characterize these patients both clinically and at the molecular level, to pave the way for further genotype–phenotype correlations. © 2010 Wiley‐Liss, Inc.
Health Behaviors as Mediators for the Effect of Partner Abuse on Infant Birth Weight

BackgroundIntimate partner abuse of pregnant women has been linked to the delivery of low-birth-weight infants. Also, abused pregnant women have reported a greater prevalence of substance abuse, poor nutrition, and demographic risk factors for poor birth outcomes. These factors may play a role in the reported relation between intimate partner violence and birth weight. ObjectivesTo explore the role of substance abuse (smoking, alcohol, and drug use) and weight gain of less than 15 pounds during pregnancy as potential mediators of the relation between recent partner abuse and infant birth weight, and to investigate the role of demographic risk factors as potential moderators for the impact of abuse on birth weight. MethodsData were extracted on abuse screening results, demographics, birth outcomes, and a range of medical and obstetric risks and complications from the medical records of 1,969 women who had been screened by clinicians for domestic abuse during pregnancy. Hypotheses were tested using multiple regression analysis. ResultsRecent physical or psychological abuse had a small but significant effect on birth weight in this sample. Smoking and low weight gain were weak but significant mediators of the relation between recent abuse and infant birth weight. Single marital status was the strongest demographic predictor of decreased birth weight. No moderator effects were found. ConclusionsAlthough prospective studies are warranted, nursing care to reduce smoking and promote adequate weight gain in all women along with support for women’s efforts to seek safety from abuse may help to improve birth outcomes and promote maternal well-being.
What research we no longer need in neurodegenerative disease at the end of life: The case of research in dementia

A complete silence. That was what we got back from the European experts who had been energetically discussing research priorities in palliative care in neurodegenerative disease (ND) until a short while ago.1 The chair, an entertaining professor with good manners, must have felt the unease and quickly refocused the group to their task. But, wasn’t this the best question of all day? What research we no longer need? As scientists able to consider different perspectives, shouldn’t we have some idea of what research is, by contrast, no longer necessary? Palliative care research and research with people who have ND and are at the end of their life is, by definition, difficult. Making choices is a sensitive issue, but funds are limited. Therefore, we take a counterpoint to the research agenda recently reported by European Union (EU) Joint Programme – Neurodegenerative Disease Research (JPND),1 and consider whether there are studies we no longer need or are low priority, taking the example of dementia.
Assessing Factor Structure and Convergent Validity of the Work Regulatory Focus Scale

This study assessed the factor structure of the Work Regulatory Focus Scale, which includes work-related prevention and promotion as dimensions of regulatory focus. To examine the concurrent validity, these dimensions were correlated with the prevention and promotion subscales of the Chronic Regulatory Focus Questionnaire. Using computer-assisted telephone interviews, data were collected from 237 full-time working people in Hong Kong, with a response rate of 72.9%. A confirmatory factor analysis indicated that the two-factor model of the Work Regulatory Focus Scale fit the data adequately. Fit indices improved after two of the items with low factor loadings on the promotion focus dimension were excluded from the analysis, which left 10 items in the scale. Pearson correlations between work-related regulatory focus subscales and chronic regulatory focus subscales were low but significant (range, .19−.39). The mean score differences between regulatory focus subscales were mostly in the expected direction, providing convergent validity evidence. The implications of these findings and suggestions for future research on the validity of the scale were discussed.