Miracle-dz/UniFAR-FTUs huggingface dataset:
High-dosage ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A: results of a randomized, double-masked, controlled trial.

IMPORTANCE No current medications improve neuropathy in subjects with Charcot-Marie-Tooth disease type 1A (CMT1A). Ascorbic acid (AA) treatment improved the neuropathy of a transgenic mouse model of CMT1A and is a potential therapy. A lower dosage (1.5 g/d) did not cause improvement in humans. It is unknown whether a higher dosage would prove more effective. OBJECTIVE To determine whether 4-g/d AA improves the neuropathy of subjects with CMT1A. DESIGN A futility design to determine whether AA was unable to reduce worsening on the CMT Neuropathy Score (CMTNS) by at least 50% over a 2-year period relative to a natural history control group. SETTING Three referral centers with peripheral nerve clinics (Wayne State University, Johns Hopkins University, and University of Rochester). PARTICIPANTS One hundred seventy-four subjects with CMT1A were assessed for eligibility; 48 did not meet eligibility criteria and 16 declined to participate. The remaining 110 subjects, aged 13 to 70 years, were randomly assigned in a double-masked fashion with 4:1 allocation to oral AA (87 subjects) or matching placebo (23 subjects). Sixty-nine subjects from the treatment group and 16 from the placebo group completed the study. Two subjects from the treatment group and 1 from the placebo group withdrew because of adverse effects. INTERVENTIONS Oral AA (4 g/d) or matching placebo. MAIN OUTCOMES AND MEASURES Change from baseline to year 2 in the CMTNS, a validated composite impairment score for CMT. RESULTS The mean 2-year change in the CMTNS was -0.21 for the AA group and -0.92 for the placebo group, both better than natural history (+1.33). This was well below 50% reduction of CMTNS worsening from natural history, so futility could not be declared (P > .99). CONCLUSIONS AND RELEVANCE Both treated patients and those receiving placebo performed better than natural history. It seems unlikely that our results support undertaking a larger trial of 4-g/d AA treatment in subjects with CMT1A. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00484510.
A Psychoeducational Relaxation Group for Pain and Stress Management in the Nursing Home

Abstract The quality of life for elderly nursing home residents is profoundly impacted by pain and stress. Traditional treatment models have been medically oriented, often relying entirely on pharmacological approaches. The nursing home resident as an active participant in the healing process is often overlooked, and yet recent research has indicated that elderly patients with chronic pain can benefit from the use of alternative, non-pharmacological approaches. A psychoeducational group therapy program for chronic pain, anxiety and distress, modeled on the Mindfulness-Based Stress Reduction Program at the UMass Medical Center, was introduced into a 514-bed academic nursing home. Group members practiced breathing exercises, meditation, visualization, and guided imagery. Music and aromatherapy were also utilized to provide a calming milieu. In addition, group tasks focused on reframing responses to difficult situations and empowering the residents. Members are taught to practice techniques in response to pa.
Modelling the effect of race surface and racehorse limb parameters on in silico fetlock motion and propensity for injury

BACKGROUND The metacarpophalangeal joint (fetlock) is the most commonly affected site of racehorse injury, with multiple observed pathologies consistent with extreme fetlock dorsiflexion. Race surface mechanics affect musculoskeletal structure loading and injury risk because surface forces applied to the hoof affect limb motions. Race surface mechanics are a function of controllable factors. Thus, race surface design has the potential to reduce the incidence of musculoskeletal injury through modulation of limb motions. However, the relationship between race surface mechanics and racehorse limb motions is unknown. OBJECTIVE To determine the effect of changing race surface and racehorse limb model parameters on distal limb motions. STUDY DESIGN Sensitivity analysis of in silico fetlock motion to changes in race surface and racehorse limb parameters using a validated, integrated racehorse and race surface computational model. METHODS Fetlock motions were determined during gallop stance from simulations on virtual surfaces with differing average vertical stiffness, upper layer (e.g. cushion) depth and linear stiffness, horizontal friction, tendon and ligament mechanics, as well as fetlock position at heel strike. RESULTS Upper layer depth produced the greatest change in fetlock motion, with lesser depths yielding greater fetlock dorsiflexion. Lesser fetlock changes were observed for changes in lower layer (e.g. base or pad) mechanics (nonlinear), as well as palmar ligament and tendon stiffness. Horizontal friction and fetlock position contributed less than 1° change in fetlock motion. MAIN LIMITATIONS Simulated fetlock motions are specific to one horse's anatomy reflected in the computational model. Anatomical differences among horses may affect the magnitude of limb flexion, but will likely have similar limb motion responses to varied surface mechanics. CONCLUSIONS Race surface parameters affected by maintenance produced greater changes in fetlock motion than other parameters studied. Simulations can provide evidence to inform race surface design and management to reduce the incidence of injury.
Heart rate variability parameters in horses distinguish atrial fibrillation from sinus rhythm before and after successful electrical cardioversion

BACKGROUND Atrial fibrillation (AF) is the most common pathological arrhythmia in horses. After successful treatment, recurrence is common. Heart rate monitors are easily applicable in horses and some devices offer basic heart rate variability (HRV) calculations. If HRV can be used to distinguish between AF and sinus rhythm (SR), this could become a monitoring tool for horses at risk for recurrence of AF. OBJECTIVES The purpose of this study was to assess whether in horses AF (before cardioversion) and SR (after cardioversion) can be differentiated based upon HRV parameters. STUDY DESIGN Cohort study with internal controls. METHODS Six HRV parameters were determined in 20 horses, both in AF and in SR, at rest (2- and 5-min and 1- and 4-h recordings) and during exercise (walk and trot, 2-min recordings). Time-domain (standard deviation of the NN intervals, root mean squared successive differences in NN intervals and triangular index), frequency domain (low/high frequency ratio) and nonlinear parameters (standard deviation of the Poincaré plot [SD]1 and SD2) were used. Statistical analysis was done using paired Wilcoxon signed rank tests and receiver operating characteristic curves. RESULTS HRV was higher during AF compared to SR. Results for the detection of AF were good (area under the receiver operating characteristic curve [AUC] 0.8-1) for most HRV parameters. Root mean squared successive differences in NN intervals and SD1 yielded the best results (AUC 0.9-1). Sensitivity and specificity were high for all parameters at all recordings, but highest during exercise. Although AUCs improved with longer recordings, short recordings were also good (AUC 0.8-1) for the detection of AF. In horses with frequent second degree atrioventricular block, HRV at rest is increased and recordings at walk or trot are recommended. MAIN LIMITATIONS Animals served as their own controls and there was no long-term follow-up to identify AF recurrence. CONCLUSIONS AF (before cardioversion) and SR (after cardioversion) could be distinguished with HRV. This technique has promise as a monitoring tool in horses at risk for AF development.
Physical Fitness and Exercise Endurance Measured by Oxygen Uptake Kinetics in Stroke Patients

Hemiparetic stroke patients have both decreased oxygen consumption and low endurance to exercise. This study examined their physical fitness to quantify the initial deficit and change in oxygen uptake kinetics (VO2 kinetics) during inpatients rehabilitation following stroke. Twenty-nine ambulatory hemiparetic stroke patients were treated in an 8-week program of low intensity aerobic exercise. They undertook a bicycle ergometer test with gas analysis before and after the exercise program to obtain maximum oxygen uptake (VO2 peak), maximum work load (max WR), and VO2 kinetics data. The time constant (τon) and O2 deficit on constant load after exercise training were significantly lower than those in initial measurement by 17% and 10%, respectively. On the incremental load, VO2 peak and max WR were significantly increased by 16% and 17% respectively and ΔVO 2/ΔWR was decreased by 11%. These results show that low-intensity endurance training produces energy efficiency of oxygen uptake kinetics and improves the physical fitness of ambulatory hemiparetic stroke patients.
Investigating the opinions of donkey owners and veterinary surgeons towards pain and analgesia in donkeys

Summary The aim of this questionnaire-based study was to identify which analgesics are currently prescribed to donkeys in clinical practice and to collect opinions from veterinary surgeons and donkey owners on the importance of different pain-related behaviours in donkeys. Questionnaires were completed by 143 veterinary surgeons and 93 donkey owners. Phenylbutazone, flunixin, detomidine and butorphanol were reported as the most frequently used analgesics in donkeys. Most veterinary surgeons reported administering these drugs at the horse dose rate and dosing interval, which may be inappropriate in the donkey. Four pain-related behaviours were identified as very important by veterinary surgeons and owners: dullness for colic-associated pain, keeping the foot lifted, and lameness for foot and limb pain and inability to chew properly for head and dental pain. This is a more limited behavioural repertoire than has recently been identified to be associated with pain in the donkey and suggests that the respondents were reporting perceived wisdom as to what people think are the behavioural signs associated with pain or were not interpreting pain-related behaviours correctly.
IDH mutation in glioma: new insights and promises for the future.

IMPORTANCE Over the past 4 years, our understanding of gliomagenesis and the practice of neuro-oncology have been radically changed by the discovery of mutations involving the isocitrate dehydrogenase (IDH) enzymes. IDH mutation has been found to be an inciting event in gliomagenesis and to have a profound effect on the molecular and genetic route of oncogenic progression and on clinical outcome. OBJECTIVES To review the role of IDH enzymes in normal physiology and describe aberrations in the IDH pathway that are associated with gliomagenesis, to review recent work examining the effect of IDH-targeted therapy in cancers harboring IDH mutation, and to determine how this work has expanded our understanding of the role of IDH in the development and progression of glioma. EVIDENCE REVIEW A systematic review of the literature dating from 2008, when IDH mutation was discovered to be clinically significant in glioma, to 2013 was performed using the PubMed database. The following search terms were used: IDH, IDH1, IDH2, and isocitrate dehydrogenase, in conjunction with glioma or leukemia. The search was limited to articles published in English. Further hand searching was performed using a review of the pertinent references from the identified publications. All identified original articles were investigated for content and critiqued by Z.T. and S.D. FINDINGS IDH mutation is an early event in gliomagenesis and has significant implications for glioma progression and tumor behavior. Early evidence suggests that IDH may be a therapeutic target in IDH-mutant gliomas. CONCLUSIONS AND RELEVANCE IDH mutation is a central and defining event in the development and progression of glioma and may be a key target for future therapies for these types of neoplasms.
COMPARATIVE ANALYSES OF SEX‐RATIO VARIATION IN DIOECIOUS FLOWERING PLANTS

Dioecious plant species commonly exhibit deviations from the equilibrium expectation of 1:1 sex ratio, but the mechanisms governing this variation are poorly understood. Here, we use comparative analyses of 243 species, representing 123 genera and 61 families to investigate ecological and genetic correlates of variation in the operational (flowering) sex ratio. After controlling for phylogenetic nonindependence, we examined the influence of growth form, clonality, fleshy fruits, pollen and seed dispersal vector, and the possession of sex chromosomes on sex‐ratio variation. Male‐biased flowering sex ratios were twice as common as female‐biased ratios. Male bias was associated with long‐lived growth forms (e.g., trees) and biotic seed dispersal and fleshy fruits, whereas female bias was associated with clonality, especially for herbaceous species, and abiotic pollen dispersal. Female bias occurred in species with sex chromosomes and there was some evidence for a greater degree of bias in those with heteromorphic sex chromosomes. Although the role of interactions among these correlates require further study, our results indicate that sex‐based differences in costs of reproduction, pollen and seed dispersal mechanisms and sex chromosomes can each play important roles in affecting flowering sex ratios in dioecious plants.
UNDERSTANDING THE BASIS OF DIMINISHED GENE FLOW BETWEEN HYBRIDIZING CHROMOSOME RACES OF THE HOUSE MOUSE

Speciation may be promoted in hybrid zones if there is an interruption to gene flow between the hybridizing forms. For hybridizing chromosome races of the house mouse in Valtellina (Italy), distinguished by whole‐arm chromosomal rearrangements, previous studies have shown that there is greater interruption to gene flow at the centromeres of chromosomes that differ between the races than at distal regions of the same chromosome or at the centromeres of other chromosomes. Here, by increasing the number of markers along race‐specific chromosomes, we reveal a decay in between‐race genetic differentiation from the centromere to the distal telomere. For the first time, we use simulation models to investigate the possible role of recombination suppression and hybrid breakdown in generating this pattern. We also consider epistasis and selective sweeps as explanations for isolated chromosomal regions away from the centromere showing differentiation between the races. Hybrid breakdown alone is the simplest explanation for the decay in genetic differentiation with distance from the centromere. Robertsonian fusions/whole‐arm reciprocal translocations are common chromosomal rearrangements characterizing both closely related species and races within species, and this fine‐scale empirical analysis suggests that the unfitness associated with these rearrangements in the heterozygous state may contribute to the speciation process.
SINGLE‐GENE SPECIATION WITH PLEIOTROPY: EFFECTS OF ALLELE DOMINANCE, POPULATION SIZE, AND DELAYED INHERITANCE

Single‐gene speciation is considered to be unlikely, but an excellent example is found in land snails, in which a gene for left‐right reversal has given rise to new species multiple times. This reversal might be facilitated by their small population sizes and maternal effect (i.e., “delayed inheritance,” in which an individual's phenotype is determined by the genotype of its mother). Recent evidence suggests that a pleiotropic effect of the speciation gene on antipredator survival may also promote speciation. Here we theoretically demonstrate that, without a pleiotropic effect, in small populations the fixation probability of a recessive mutant is higher than a dominant mutant, but they are identical for large populations and sufficiently weak selection. With a pleiotropic effect that increases mutant viability, a dominant mutant has a higher fixation probability if the strength of viability selection is sufficiently greater than that of reproductive incompatibility, whereas a recessive mutant has a higher fixation probability otherwise. Delayed inheritance increases the fixation probability of a mutant if viability selection is sufficiently weaker than reproductive incompatibility. Our results clarify the conflicting effects of viability selection and positive frequency‐dependent selection due to reproductive incompatibility and provide a new perspective to single‐gene speciation theory.
THE ROLE OF INBREEDING DEPRESSION AND MATING SYSTEM IN THE EVOLUTION OF HETEROSTYLY

We investigated the role of morph‐based differences in the expression of inbreeding depression in loss of the mid‐styled morph from populations of tristylous Oxalis alpina. The extent of self‐compatibility (SC) of reproductive morphs, the degree of self‐fertilization, and the magnitude of inbreeding depression were investigated in three populations of O. alpina differing in their tristylous incompatibility relationships. All three populations exhibited significant inbreeding depression. In two populations with highly modified tristylous incompatibility, manifested as increased reciprocal compatibility between short‐ and long‐styled morphs, substantial SC and self‐fertilization of mid‐styled morphs were detected, and expected to result in expression of inbreeding depression in the progeny of mid‐styled morphs in the natural populations. In contrast, significant self‐fertility of the mid‐styled morph was absent from the population with typical tristylous incompatibility, and no self‐fertilization could be detected. Although self‐fertilization and expression of inbreeding depression should result in selection against the mid‐styled morph in the later stages of the transition from tristyly to distyly, in O. alpina selection against the mid‐styled morph in the early phases of the evolution of distyly is likely due to genic selection against mid‐alleles associated with modified tristylous incompatibility, rather than expression of inbreeding depression.
EVALUATING PATTERNS OF CONVERGENT EVOLUTION AND TRANS‐SPECIES POLYMORPHISM AT MHC IMMUNOGENES IN TWO SYMPATRIC STICKLEBACK SPECIES

The immunologically important major histocompatibility complex (MHC) harbors some of the most polymorphic genes in vertebrates. These genes presumably evolve under parasite‐mediated selection and frequently show inconsistent allelic genealogies, where some alleles are more similar between species than within species. This phenomenon is thought to arise either from convergent evolution under parallel selection or from the preservation of ancient allelic lineages beyond speciation events (trans‐species polymorphism, TSP). Here, we examine natural populations of two sympatric stickleback species (Gasterosteus aculeatus and Pungitius pungitius) to investigate the contribution of these two mechanisms to the evolution of inconsistent allelic genealogies at the MHC. Overlapping parasite taxa between the two host species in three different habitats suggest contemporary parallel selection on the MHC genes. Accordingly, we detected a lack of species‐specific phylogenetic clustering in the immunologically relevant antigen‐binding residues of the MHC IIB genes which contrasted with the rest of the coding and noncoding sequence. However, clustering was not habitat‐specific and a codon‐usage analysis revealed patterns of similarity by descent. In this light, common descent via TSP, in combination with intraspecies gene conversion, rather than convergent evolution is the more strongly supported scenario for the inconsistent genealogy at the MHC.
BODY AND LIMB SIZE DISSOCIATION AT THE ORIGIN OF BIRDS: UNCOUPLING ALLOMETRIC CONSTRAINTS ACROSS A MACROEVOLUTIONARY TRANSITION

The origin of birds and powered flight is a classic major evolutionary transition. Research on their origin often focuses on the evolution of the wing with trends of forelimb elongation traced back through many nonavian maniraptoran dinosaurs. We present evidence that the relative forelimb elongation within avian antecedents is primarily due to allometry and is instead driven by a reduction in body size. Once body size is factored out, there is no trend of increasing forelimb length until the origin of birds. We report that early birds and nonavian theropods have significantly different scaling relationships within the forelimb and hindlimb skeleton. Ancestral forelimb and hindlimb allometric scaling to body size is rapidly decoupled at the origin of birds, when wings significantly elongate, by evolving a positive allometric relationship with body size from an ancestrally negative allometric pattern and legs significantly shorten by keeping a similar, near isometric relationship but with a reduced intercept. These results have implications for the evolution of powered flight and early diversification of birds. They suggest that their limb lengths first had to be dissociated from general body size scaling before expanding to the wide range of fore and hindlimb shapes and sizes present in today's birds.
EVALUATING A SIMPLE APPROXIMATION TO MODELING THE JOINT EVOLUTION OF SELF‐FERTILIZATION AND INBREEDING DEPRESSION

A comprehensive understanding of plant mating system evolution requires detailed genetic models for both the mating system and inbreeding depression, which are often intractable. A simple approximation assuming that the mating system evolves by small infrequent mutational steps has been proposed. We examine its accuracy by comparing the evolutionarily stable selfing rates it predicts to those obtained from an explicit genetic model of the selfing rate, when inbreeding depression is caused by partly recessive deleterious mutations at many loci. Both models also include pollen limitation and pollen discounting. The approximation produces reasonably accurate predictions with a low or moderate genomic mutation rate to deleterious alleles, on the order of U = 0.02–0.2. However, for high mutation rates, the predictions of the full genetic model differ substantially from those of the approximation, especially with nearly recessive lethal alleles. This occurs because when a modifier allele affecting the selfing rate is rare, homozygous modifiers are produced mainly by selfing, which enhances the opportunity for purging nearly recessive lethals and increases the marginal fitness of the allele modifying the selfing rate. Our results confirm that explicit genetic models of selfing rate and inbreeding depression are required to understand mating system evolution.
Perception And Attitude About Breast And Cervical Cancer Screening Among Muslim Women In A Midwest University Campus

Yeasmeen, Tahira. M.P.H. , Purdue University, December 2013. Perception and Attitude about Breast and Cervical Cancer Screening among Muslim Women in a Midwest University Campus. Major Professor: Gerald C. Hyner. Early detection of breast and cervical cancer through mammograms and Pap smears can improve survival rates. Muslim women in the United States are faced with traditional beliefs and diverse socioeconomic and cultural backgrounds that may affect their knowledge and perceptions about these cancer screening practices. The objective of this study is to determine the overall health status and participation rates, knowledge, and perceptions about, and barriers to, breast and cervical cancer screening among a controlled population of Muslim women. Data were collected from Muslim women residing at or near Purdue University and the Greater Lafayette area via an online questionnaire survey. Characteristics related to cancer screenings were determined using frequency distributions and logistic regression models were developed to determine barriers and facilitators to screening participation. Factors such as a physician’s referral, self-efficacy, at least one physical examination in the last two years in the United States, health status perception, regular physical checkups, a graduate degree, a higher income level, and being between 31–40 years of age were positively related to