Miracle-dz/UniFAR-FTUs huggingface dataset:
Treatment of refractory myositis: a randomized crossover study of two new cytotoxic regimens.

OBJECTIVE To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis. METHODS Thirty patients with refractory myositis, of whom 25 had an inadequate or no response to previous cytotoxic therapy, were randomized to begin either a combination of weekly oral methotrexate and daily azathioprine (MTX/AZA) or intravenous methotrexate with leucovorin rescue (I.V. MTX) every 2 weeks for 6 months. Crossover to the alternate therapy occurred according to defined rules; evaluations of muscle strength and functional abilities were performed at the beginning, and after 3 and 6 months, of each treatment. RESULTS Of the 15 patients initially randomized to oral MTX/AZA, 8 improved with oral therapy and 1 improved with I.V. MTX during the crossover period. Of the 15 patients initially randomized to I.V. MTX therapy, 3 improved with the I.V. therapy and 4 with the oral combination during the crossover period. Although the study lacked the power to directly compare both treatments, intention-to-treat analysis showed a trend in favor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral combination therapy and 0.16 per patient-month with I.V. therapy (P = 0.09). CONCLUSION Combination oral MTX/AZA may benefit patients with treatment-resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. I.V. MTX with leucovorin rescue may also benefit some patients with refractory myositis.
Hypertrophy-type Resistance Training Improves Phase Angle in Young Adult Men and Women

Abstract The main purpose of the present study was to investigate the effect of a hypertrophy-type resistance training protocol on phase angle, an indicator of cellular integrity, in young adult men and women. 28 men (22.2±4.3 years, 67.8±9.0 kg and 174.2±6.8 cm) and 31 women (23.2±4.1 years, 58.7±12.1 kg and 162.7±6.4 cm) underwent a progressive RT for 16 weeks (2 phases, 8 weeks each), 3 times per week, consisting of 10 to 12 whole body exercises with 3 sets of 8–12 repetitions maximum. Phase angle, resistance, reactance and total body water (intra and extracellular water compartments) were assessed by bioimpedance spectroscopy (Xitron 4200 Bioimpedance Spectrum Analyzer). Total body water, intracellular water and phase angle increased significantly (P<0.05) in men (7.8, 8.3, and 4.3%, respectively) and women (7.6, 11.7, and 5.8% respectively), with no significant difference between sexes (P>0.05). Bioimpedance resistance decreased (P<0.05) similarly in both sex (men=−4.8%, women=−3.8%). The results suggest that regardless of sex, progressive RT induces an increase in phase angle and a rise in cellular hydration.
A Randomized, Double-Blind, Controlled Trial: Intradiscal Electrothermal Therapy Versus Placebo for the Treatment of Chronic Discogenic Low Back Pain

Study Design. A prospective, randomized, double-blind, placebo-controlled trial of intradiscal electrothermal therapy (IDET) for the treatment of chronic discogenic low back pain (CDLBP). Objectives. To test the safety and efficacy of IDET compared with a sham treatment (placebo). Summary of Background Data. In North America alone, more than 40,000 intradiscal catheters have been used to treat CDLBP. The evidence for efficacy of IDET is weak coming from retrospective and prospective cohort studies providing only Class II and Class III evidence. There is one study published with Class I evidence. This demonstrates statistically significant improvements following IDET; however, the clinical significance of these improvements is questionable. Methods. Patients with CDLBP who failed to improve following conservative therapy were considered for this study. Inclusion criteria included the presence of one- or two-level symptomatic disc degeneration with posterior or posterolateral anular tears as determined by provocative computed tomography (CT) discography. Patients were excluded if there was greater than 50% loss of disc height or previous spinal surgery. Fifty-seven patients were randomized with a 2:1 ratio: 38 to IDET and 19 to sham procedure (placebo). In all cases, the IDET catheter was positioned to cover at least 75% of the annular tear as defined by the CT discography. An independent technician connected the catheter to the generator and then either delivered electrothermal energy (active group) or did not (sham group). Surgeon, patient, and independent outcome assessor were all blinded to the treatment. All patients followed a standard postprocedural rehabilitation program. Independent statistical analysis was performed. Outcome Measures. Low Back Outcome Score (LBOS), Oswestry Disability Index (ODI), Short Form 36 questionnaire (SF-36), Zung Depression Index (ZDI), and Modified Somatic Perceptions Questionnaire (MSPQ) were measured at baseline and 6 months. Successful outcome was defined as: no neurologic deficit, improvement in LBOS of greater then 7 points, and improvement in SF-36 subsets (physical function and bodily pain) of greater than 1 standard deviation. Results. Baseline demographic data, initial LBOS, ODI, SF-36, ZDI, and MSPQ were similar for both groups. No neurologic deficits occurred. No subject in either arm showed improvement of greater than 7 points in LBOS or greater than 1 standard deviation in the specified domains of the SF-36. Mean ODI was 41.42 at baseline and 39.77 at 6 months for the IDET group, compared with 40.74 at baseline and 41.58 at 6 months for the placebo group. There was no significant change in ZDI or MSPQ scores for either group. Conclusions. The IDET procedure appeared safe with no permanent complications. No subject in either arm met criteria for successful outcome. Further detailed analyses showed no significant change in outcome measures in either group at 6 months. This study demonstrates no significant benefit from IDET over placebo.
Structural and thermodynamic analysis of the packing of two alpha-helices in bacteriophage T4 lysozyme.

Packing interactions in bacteriophage T4 lysozyme were explored by determining the structural and thermodynamic effects of substitutions for Ala98 and neighboring residues. Ala98 is buried in the core of T4 lysozyme in the interface between two alpha-helices. The Ala98 to Val (A98V) replacement is a temperature-sensitive lesion that lowers the denaturation temperature of the protein by 15 degrees C (pH 3.0, delta delta G = -4.9 kcal/mol) and causes atoms within the two helices to move apart by up to 0.7 A. Additional structural shifts also occur throughout the C-terminal domain. In an attempt to compensate for the A98V replacement, substitutions were made for Val149 and Thr152, which make contact with residue 98. Site-directed mutagenesis was used to construct the multiple mutants A98V/T152S, A98V/V149C/T152S and the control mutants T152S, V149C and A98V/V149I/T152S. These proteins were crystallized, and their high-resolution X-ray crystal structures were determined. None of the second-site substitutions completely alleviates the destabilization or the structural changes caused by A98V. The changes in stability caused by the different mutations are not additive, reflecting both direct interactions between the sites and structural differences among the mutants. As an example, when Thr152 in wild-type lysozyme is replaced with serine, the protein is destabilized by 2.6 kcal/mol. Except for a small movement of Val94 toward the cavity created by removal of the methyl group, the structure of the T152S mutant is very similar to wild-type T4 lysozyme. In contrast, the same Thr152 to Ser replacement in the A98V background causes almost no change in stability. Although the structure of A98V/T152S remains similar to A98V, the combination of T152S with A98V allows relaxation of some of the strain introduced by the Ala98 to Val replacement. These studies show that removal of methyl groups by mutation can be stabilizing (Val98----Ala), neutral (Thr152----Ser in A98V) or destabilizing (Val149----Cys, Thr152----Ser). Such diverse thermodynamic effects are not accounted for by changes in buried surface area or free energies of transfer of wild-type and mutant side-chains. In general, the changes in protein stability caused by a mutation depend not only on changes in the free energy of transfer associated with the substitution, but also on the structural context within which the mutation occurs and on the ability of the surrounding structure to relax in response to the substitution. (ABSTRACT TRUNCATED AT 400 WORDS)
Social Comparison, Envy, and Depression on Facebook: A Study Looking at the Effects of High Comparison Standards on Depressed Individuals

The co-occurrence of depression and envy is both plausible and empirically established. However, little is known about the mechanisms underlying this correlation. An account is proposed according to which low self-esteem in depressed individuals leads to upward social comparison and thus makes envy more likely. This effect should frequently occur in online social networks like Facebook because they allow for easy impression management and hence provide high comparison standards. In a quasi-experimental online study, depressed and nondepressed participants indicated their self-esteem and were then presented with specifically set up Facebook profiles that were either attractive or unattractive. Participants were asked to compare themselves to the profile owner and to report their resulting feelings of inferiority and envy. Depressed participants were more envious, especially after seeing the attractive profile. Envy was associated with higher self-reported inferiority and also correlated negatively with sel.
Effect of nutrition on androgenic activity and spermatogenesis in mammals

To define the nutrient requirements essential to the male organism for its normal reproductive function is by no means a simple matter. It is a problem of many aspects because the processes involved are subject to fluctuations even within a single species, according to climate, environmental conditions, food habits, and the age of sexual maturation. A further complication arises from the effects of so-called ‘nervous’, ‘stress’ or ‘conditioning’ factors which can alter the normal requirements of an individual for a specific nutrient by influencing the absorption of food, storage and utilization of metabolites in the tissues, and their excretion to such an extent that the result is ‘malnutrition’ in spite of adequate food composition (Ershoff, 1948). It must also be kept in mind that failures of reproduction brought about by ‘malnutrition’ may be aggravated by congenital anatomical as well as genetic factors. However, by far the greatest difficulty encountered in the appraisal of reproductive disorders due to ‘malnutrition’ is to distinguish between primary effects due to the lack of a specific dietary component such as a vitamin, a trace element, or an essential amino acid, and secondary effects arising from diminished appetite, inadequate food intake and, finally, inanition, all of which are sequelae of deficient diets. This is one of the reasons why pair-feeding is such an essential and important prerequisite for all experimental investigations on the relationship between nutrition and reproduction. The literature on the subject of nutritionally conditioned reproductive failures in the male is vast and abounds in observations on testicular atrophy, gynaecomastia, diminished libido and impotence, associated with such conditions as diabetes, hepatic cirrhosis, atrophic glossitis, gingivitis, seborrhea, keratosis of the eyelids and others; in this category belongs also the important study of Evans & Burr (1927) on degenerative and atrophic changes in the testes and male sterility, associated with deficiency of vitamins A and E. Together, these and similar studies represent an imposing total of valuable data which have been comprehensively reviewed from time to time, in particular by Biskind (1946), Hertz (1946), Samuels (1948)’ Russell (1948)’ Mason (1949), Ferrando (1953), Meites (1953)) Roche (1957), and more recently by Lutwak-Mann (1958).
ENHANCED ADAPTIVE CAPACITIES AFTER BRIEF TREATMENT FOR DEPRESSION

Using data from the National Institute of Mental Health-sponsored Treatment of Depression Collaborative Research Program, the authors examined predictors of the intensity of depressive symptoms after the brief treatment of depression. Multilevel modeling was applied to measures of depression and stress assessed at termination and at 6-, 12-, and 18-month follow-ups. The slope of depression on stress was used to index stress reactivity. Patients with high mean levels of stress experienced more intense depressive symptoms, but this effect was moderated by patients' reports of the extent to which they had acquired enhanced adaptive capacities (EACs) in treatment. Patients who reported high EAC early in the follow-up were more resilient in the face of stress than those with low EAC. Greater EACs were found for patients who received psychotherapy than medication or placebo and, across all treatments, for patients with a stronger therapeutic alliance. These findings suggest that treatments should be evaluated in terms of their impact on patients' developing adaptive capacities as well as the reduction of symptomatology.
Comprehensive eye evaluation algorithm

In recent years, several research groups have developed automatic algorithms to detect diabetic retinopathy (DR) in individuals with diabetes (DM), using digital retinal images. Studies have indicated that diabetics have 1.5 times the annual risk of developing primary open angle glaucoma (POAG) as do people without DM. Moreover, DM patients have 1.8 times the risk for age-related macular degeneration (AMD). Although numerous investigators are developing automatic DR detection algorithms, there have been few successful efforts to create an automatic algorithm that can detect other ocular diseases, such as POAG and AMD. Consequently, our aim in the current study was to develop a comprehensive eye evaluation algorithm that not only detects DR in retinal images, but also automatically identifies glaucoma suspects and AMD by integrating other personal medical information with the retinal features. The proposed system is fully automatic and provides the likelihood of each of the three eye disease. The system was evaluated in two datasets of 104 and 88 diabetic cases. For each eye, we used two non-mydriatic digital color fundus photographs (macula and optic disc centered) and, when available, information about age, duration of diabetes, cataracts, hypertension, gender, and laboratory data. Our results show that the combination of multimodal features can increase the AUC by up to 5%, 7%, and 8% in the detection of AMD, DR, and glaucoma respectively. Marked improvement was achieved when laboratory results were combined with retinal image features.
Lower Devonian faunas and palynomorphs from the Dornes Syncline (Central Iberian Zone, Portugal): stratigraphical and paleogeographical implications

In the Dornes syncline, southern Central Iberian Zone, Portugal, the uppermost levels of the Serra do Luacao Formation up to now have been considered to be of Pridoli-Lochkovian? age because they lie immediately under the Dornes Formation, which is of Pragian age and is well defined stratigraphically. New paleontological elements including benthic faunas and palynomorphs allow us to confirm that the top of the Serra do Luacao Formation is securely Lochkovian, for upper Lochkovian strata are present although relatively thin. The transition from the Serra do Luacao to the Dornes formations and their lithostratigraphical relationship are now clear: the terrigenous succession belongs to the Serra do Luacao Formation and the limestones represent the Dornes Formation. The benthic faunas clearly have North-Gondwanan affinities.
Renal transplant recipient attitudes toward steroid use and steroid withdrawal

Abstract: Although steroid avoidance and withdrawal in renal transplant recipients (RTR) are actively being evaluated by physicians, the attitudes of recipients toward steroid use have not been systematically studied in the modern era. We conducted a confidential written survey of single‐organ adult RTR pertaining to prednisone‐related side‐effects. Recipients were asked which drug they felt maximized graft life, which drug they wished to avoid if graft life was unaffected, and which drug they had most compliant with. They also rated 16 common immunosuppressive‐related side‐effects on a Likert scale with 1 meaning complete disagreement and 10 complete agreement with their own prednisone‐attributed experience. A comparison of responses based on RTR demographic characteristics was made by ANOVA or chi‐square analysis with Bonferroni correction. The questionnaire was completed by 223 recipients, of whom 93% were primary recipients, 57% were cadaveric organ recipients, and 69% were white people, 7% black people, and 23% Asian people. Age at transplant, age at survey and time since transplant were 41.5 ± 11, 47.5 ± 11 and 6.0 ± 5 yr, respectively. For the entire group, overall side‐effect profile for prednisone was rated as 6.1 ± 3 on the Likert scale, while efficacy was rated as 7.3 ± 3. If offered monotherapy, 67% preferred a calcineurin‐inhibitor (CI), 23% mycophenolate mofetil (MMF)/azathioprine (AZA), and 10% prednisone. When asked which drug they would like to discontinue, 19% chose CI, 16% MMF/AZA, and 65% prednisone. Most recipients felt that CI was the most efficacious drug (80%), followed by MMF/AZA (12%), and prednisone (8%). The side‐effects reported as most common were unacceptable weight gain (5.8 ± 3) and bone/joint disease (5.3 ± 3). The least common side‐effects were blood disorders (2.2 ± 2) and cancer (2.3 ± 2). Black people were more likely than non‐black people to report developing diabetes (p = 0.02), blood disorders (p = 0.003) and headaches (p = 0.003) as a result of prednisone use. Males reported more liver damage (p = 0.01) while females reported more body fat (p = 0.01) and fluid retention (p = 0.006). RTR >5 yr post‐transplant reported more infections (p = 0.008), skin/hair problems (p = 0.02), gastrointestinal irritation (p = 0.02), and bone disease (p = 0.02) compared with RTR <1 yr. Donor source and recipient age did not determine any responses. If given a ‘risk‐free’ choice, the majority of recipients prefer withdrawal of steroids over other agents. Demographic data may be used to predict prednisone‐related side‐effects and guide steroid use in this population. Study designs related to steroid withdrawal should account for patient preferences in this context.
The Impact of Learning Time on Academic Achievement

As schools aim to raise student academic achievement levels and districts wrangle with decreased funding, it is essential to understand the relationship between learning time and academic achievement. Using regression analysis and a data set drawn from California’s elementary school sites, we find a statistically significant and positive relationship between the number of instructional minutes in an academic year and school-site standardized test scores. Fifteen more minutes of school a day at a school site (or about an additional week of classes over an academic year) relates to an increase in average overall academic achievement of about 1%, and about a 1.5% increase in average achievement for disadvantaged students. This same increase in learning time yields the much larger 37% gain in the average growth of socioeconomically disadvantage achievement from the previous academic year. Placing this impact in the context of other influences found important to academic achievement, similar increases in achievement only occur with an increase of fully credentialed teachers by nearly 7 percentage points. These findings offer guidance regarding the use of extended learning time to increase academic performance. Moreover, they suggest caution in reducing instructional time as the default approach to managing fiscal challenges.
Arteriovenous malformations in the basal ganglia--surgical indications and approaches.

We present 18 cases of arteriovenous malformation (AVM) in the basal ganglia. The results of seven cases of definitive surgery are reported in detail and are compared with those of 10 nonsurgical and one nondefinitive surgical cases. Among those available for follow-up, three of the seven nonsurgical and one nondefinitive surgical patients died of rebleeding. On the other hand, all seven patients who underwent definitive surgery are doing well, and their signs and symptoms were not aggravated by surgery. AVMs in the basal ganglia are classified into four types according to site: lateral, medial, mixed, and anteroinferior in relation to the internal capsule. The nidus was totally removed in two medial and four lateral cases. Eight of the 11 nonsurgical and nondefinitive surgical cases were of the mixed type and most had large nidi, and those that were totally removed were small or medium-sized. The surgical accessibility of AVMs in the basal ganglia and the current surgical approaches are discussed in terms of their locations and sizes.
Oxidant-induced Activation of Type I Protein Kinase A Is Mediated by RI Subunit Interprotein Disulfide Bond Formation*

Here we demonstrate that type I protein kinase A is redoxactive, forming an interprotein disulfide bond between its two regulatory RI subunits in response to cellular hydrogen peroxide. This oxidative disulfide formation causes a subcellular translocation and activation of the kinase, resulting in phosphorylation of established substrate proteins. The translocation is mediated at least in part by the oxidized form of the kinase having an enhanced affinity for α-myosin heavy chain, which serves as a protein kinase A (PKA) anchor protein and localizes the PKA to its myofilament substrates troponin I and myosin binding protein C. The functional consequence of these events in cardiac myocytes is that hydrogen peroxide increases contractility independently of β-adrenergic stimulation and elevations of cAMP. The oxidant-induced phosphorylation of substrate proteins and increased contractility is blocked by the kinase inhibitor H89, indicating that these events involve PKA activation. In essence, type I PKA contains protein thiols that operate as redox sensors, and their oxidation by hydrogen peroxide directly activates the kinase.
Horizon Effects in Average Returns: The Role of Slow Information Diffusion

We characterize linkages between average returns calculated at different horizons. Theoretically, when stocks incorporate information slowly, average short-horizon returns are downward biased. Buy-and-hold strategies can amplify the effect. In contrast, existing theories analyze price noises that are independent of fundamentals, and buy-and-hold portfolio returns are unaffected. We document horizon effects as large as 10% annualized in daily and monthly style portfolios and international indices. Slow reaction to market information, identified by gradually declining lagged betas, is an important cause. These findings have natural consequences for performance evaluation.