Miracle-dz/UniFAR-FTUs huggingface dataset:
Real‐world use of pomalidomide and dexamethasone in double refractory multiple myeloma suggests benefit in renal impairment and adverse genetics: a multi‐centre UK experience

Myeloma patients who become refractory to immunomodulatory agents (IMiDs) and bortezomib have poor survival, with limited therapeutic options. Pomalidomide has shown improved survival and good tolerability in this patient cohort in clinical trials, but real world data are scarce. We retrospectively analysed all patients treated with pomalidomide at five UK centres between 2013 and 2016. Of 85 patients identified, 70 had sufficient information for response assessments. Median age was 66 years [40–89], 96·5% were refractory to IMiDs, 72·9% were refractory to both an IMiD and bortezomib and 92·9% were refractory to their last treatment. Of 45 patients with fluorescence in situ hybridization results 64% had adverse risk, 19 patients (22·4%) had an estimated glomerular filtration rate <45 ml/min. Grade ≥3 non‐haematological toxicities occurred in 42·4%, and grade ≥3 neutropenia and thrombocytopenia in 38% and 24% respectively, but only 18·8% had dose reductions. The overall response rate was 52·9%. At a median follow‐up of 13·2 months, median progression‐free survival was 5·2 months [95% confidence interval (CI) 4·150–6·238], and median overall survival was 13·7 months (95% CI 11·775–15·707). No significant difference was seen in response, survival or tolerability by renal function, age or cytogenetic risk. This real‐world data support the results seen in published clinical trials.
Principal Component and Linkage Analysis of Cardiovascular Risk Traits in the Norfolk Isolate

Objective(s): An individual’s risk of developing cardiovascular disease (CVD) is influenced by genetic factors. This study focussed on mapping genetic loci for CVD-risk traits in a unique population isolate derived from Norfolk Island. Methods: This investigation focussed on 377 individuals descended from the population founders. Principal component analysis was used to extract orthogonal components from 11 cardiovascular risk traits. Multipoint variance component methods were used to assess genome-wide linkage using SOLAR to the derived factors. A total of 285 of the 377 related individuals were informative for linkage analysis. Results: A total of 4 principal components accounting for 83% of the total variance were derived. Principal component 1 was loaded with body size indicators; principal component 2 with body size, cholesterol and triglyceride levels; principal component 3 with the blood pressures; and principal component 4 with LDL-cholesterol and total cholesterol levels. Suggestive evidence of linkage for principal component 2 (h2 = 0.35) was observed on chromosome 5q35 (LOD = 1.85; p = 0.0008). While peak regions on chromosome 10p11.2 (LOD = 1.27; p = 0.005) and 12q13 (LOD = 1.63; p = 0.003) were observed to segregate with principal components 1 (h2 = 0.33) and 4 (h2 = 0.42), respectively. Conclusion(s): This study investigated a number of CVD risk traits in a unique isolated population. Findings support the clustering of CVD risk traits and provide interesting evidence of a region on chromosome 5q35 segregating with weight, waist circumference, HDL-c and total triglyceride levels.
Short-Term Effects of a Ready-to-Drink Pre-Workout Beverage on Exercise Performance and Recovery

In a double-blind, randomized and crossover manner, 25 resistance-trained participants ingested a placebo (PLA) beverage containing 12 g of dextrose and a beverage (RTD) containing caffeine (200 mg), β-alanine (2.1 g), arginine nitrate (1.3 g), niacin (65 mg), folic acid (325 mcg), and Vitamin B12 (45 mcg) for 7-days, separated by a 7–10-day. On day 1 and 6, participants donated a fasting blood sample and completed a side-effects questionnaire (SEQ), hemodynamic challenge test, 1-RM and muscular endurance tests (3 × 10 repetitions at 70% of 1-RM with the last set to failure on the bench press (BP) and leg press (LP)) followed by ingesting the assigned beverage. After 15 min, participants repeated the hemodynamic test, 1-RM tests, and performed a repetition to fatigue (RtF) test at 70% of 1-RM, followed by completing the SEQ. On day 2 and 7, participants donated a fasting blood sample, completed the SEQ, ingested the assigned beverage, rested 30 min, and performed a 4 km cycling time-trial (TT). Data were analyzed by univariate, multivariate, and repeated measures general linear models (GLM), adjusted for gender and relative caffeine intake. Data are presented as mean change (95% CI). An overall multivariate time × treatment interaction was observed on strength performance variables (p = 0.01). Acute RTD ingestion better maintained LP 1-RM (PLA: −0.285 (−0.49, −0.08); RTD: 0.23 (−0.50, 0.18) kg/kgFFM, p = 0.30); increased LP RtF (PLA: −2.60 (−6.8, 1.6); RTD: 4.00 (−0.2, 8.2) repetitions, p = 0.031); increased BP lifting volume (PLA: 0.001 (−0.13, 0.16); RTD: 0.03 (0.02, 0.04) kg/kgFFM, p = 0.007); and, increased total lifting volume (PLA: −13.12 (−36.9, 10.5); RTD: 21.06 (−2.7, 44.8) kg/kgFFM, p = 0.046). Short-term RTD ingestion maintained baseline LP 1-RM (PLA: −0.412 (−0.08, −0.07); RTD: 0.16 (−0.50, 0.18) kg/kgFFM, p = 0.30); LP RtF (PLA: 0.12 (−3.0, 3.2); RTD: 3.6 (0.5, 6.7) repetitions, p = 0.116); and, LP lifting volume (PLA: 3.64 (−8.8, 16.1); RTD: 16.25 (3.8, 28.7) kg/kgFFM, p = 0.157) to a greater degree than PLA. No significant differences were observed between treatments in cycling TT performance, hemodynamic assessment, fasting blood panels, or self-reported side effects.
Concanavalin A induces autophagy in hepatoma cells and has a therapeutic effect in a murine in situ hepatoma model

Concanavalin A (ConA), a lectin with mannose specificity that can induce acute hepatic inflammation, was tested for its therapeutic effect against hepatoma. ConA is cytotoxic or inhibitory to hepatoma cells, which is mediated by the autophagic pathway through mitochondria. Once it was bound to cell membrane glycoproteins, the ConA was internalized and preferentially localized onto the mitochondria. The mitochondria membrane permeability changed, and an autophagic pathway including LC3‐II generation, double‐layer vesicle, BNIP3 induction, and acidic vesicular organelle formation was induced. Either 3‐MA or siRNA for BNIP3 and LC3, but neither beclin‐1 nor ATG 5, partially inhibited the ConA‐induced cell death. In addition to the autophagy induction, ConA is known to be a T cell mitogen. Using an in situ hepatoma model, ConA can exert an anti‐hepatoma therapeutic effect, inhibiting tumor nodule formation in the liver and prolonging survival. Conclusion: ConA can be considered as an anti‐hepatoma agent therapeutically because of its autophagic induction and immunomodulating activity. This dual function of ConA provides a novel mechanism for the biological effect of lectin. (HEPATOLOGY 2007;45:286–296.)
Orthopaedic management of cerebral palsy.

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High plasma retinol binding protein 4 (RBP4) is associated with systemic inflammation independently of low RBP4 adipose expression and is normalized by transplantation in nonobese, nondiabetic patients with chronic kidney disease

Objective Adipose‐secreted retinol binding protein 4 (RBP4) circulates in free (active) and transthyretin (TTR)‐bound forms and may be associated with obesity‐related inflammation. Potential involvement of plasma and adipose RBP4 in systemic inflammation in the absence of obesity and diabetes is unknown. Inflammation reduces survival in chronic kidney disease (CKD) [particularly in maintenance haemodialysis (MHD)], and plasma RBP4 may increase with renal dysfunction. We investigated (i) potential associations between RBP4 and inflammation in CKD and (ii) the role of adipose tissue in this putative interaction.
Asymmetric development of the nervous system

The human nervous system consists of seemingly symmetric left and right halves. However, closer observation of the brain reveals anatomical and functional lateralization. Defects in brain asymmetry correlate with several neurological disorders, yet our understanding of the mechanisms used to establish lateralization in the human central nervous system is extremely limited. Here, we review left‐right asymmetries within the nervous system of humans and several model organisms, including rodents, Zebrafish, chickens, Xenopus, Drosophila, and the nematode Caenorhabditis elegans. Comparing and contrasting mechanisms used to develop left‐right asymmetry in the nervous system can provide insight into how the human brain is lateralized. Developmental Dynamics 247:124–137, 2018. © 2017 Wiley Periodicals, Inc.
WISE-2005: exercise and nutrition countermeasures for upright VO2pk during bed rest.

PURPOSE Exercise prescriptions for spaceflight include aerobic and resistive countermeasures, yet few studies have evaluated their combined effects on exercise responses after real or simulated microgravity. We hypothesized that upright aerobic capacity (VO2pk) is protected during a 60-d bed rest (BR) in which intermittent (40%-80% pre-BR VO2pk) aerobic exercise (supine treadmill exercise against lower body negative pressure) was performed 2-4 d x wk(-1) and resistive exercise (inertial flywheel exercises) was performed 2-3 d x wk(-1). Further, we hypothesized that ingestion of an amino acid supplement that was shown previously to counteract muscle atrophy, would reduce the decline in VO2pk in nonexercising subjects during BR. METHODS Twenty-four healthy women (8 nonexercise controls (CON), 8 exercisers (EX), and 8 nonexercisers with nutritional supplementation (NUT)) underwent a 20-d ambulatory baseline period, 60 d of 6 degrees head-down tilt BR, and 21 d of ambulatory recovery. VO2pk was measured pre-BR and on the third day of recovery from BR (R3). RESULTS In the EX group, VO2pk (mean +/- SE) was not different from pre-BR (-3.3 +/- 1.2%) on R3, although it decreased significantly in the CON (-21.2 +/- 2.1%) and NUT (-25.6 +/- 1.6%) groups. CONCLUSIONS These results indicate that alternating aerobic and resistive exercise on most days during prolonged microgravity simulated by BR is sufficient to preserve or allow quick recovery of upright aerobic capacity in women but that a nutritional supplementation alone is not effective.
How does change occur following a theoretically based self-management intervention for type 2 diabetes

The purpose of this study was to test the extent that constructs from two theoretical models (self-regulatory theory and social cognitive theory) mediated change in outcomes following a self-management intervention. One hundred and twenty four individuals with type 2 diabetes who had participated in a randomised controlled trial of a diabetes self-management programme were analysed for the extent that illness beliefs and self-efficacy mediated change in self-management behaviours and illness specific quality of life. Exercise specific self-efficacy significantly mediated change in exercise at three months (B = .03; .01, p < .05) while monitoring specific self-efficacy mediated change in monitoring behaviour at both three (B = .04; .01, p < .01) and nine months follow-up (B = 5.97; 1.01, p < .01). Belief in control over diabetes mediated change in illness specific quality of life at three months (B = −.07; .28, p < .05) and nine months (B = .79; .28, p < .01) follow-ups, as well as change in exercise behaviour at immediately post-intervention (B = −.12; .17, p < .05). Behaviour-specific self-efficacy may have a stronger role in mediating self-management behaviours than illness beliefs; however, belief in control over diabetes may be important to manipulate for change in quality of life. This suggests different theoretical constructs may mediate change dependent on outcome.
Clinical Trial of Tailored Activity and Eating Newsletters With Older Rural Women

Background: Unhealthy diet and lack of physical activity increase rural midlife and older women's risk of chronic diseases and premature death, and they are behind urban residents in meeting Healthy People 2010 objectives. Objectives: The objective of this study was to compare a tailored intervention based on the Health Promotion Model with a generic intervention to increase physical activity and healthy eating among rural women. Methods: In a randomized-by-site, community-based, controlled, clinical trial, Wellness for Women, 225 women aged 50 to 69 years were recruited in two similar rural areas. Over 12 months, women received by mail either 18 generic newsletters or 18 newsletters computer tailored on Health Promotion Model behavior-specific cognitions (benefits, barriers, self-efficacy, and interpersonal support), activity, and eating. Outcomes at 6 and 12 months included behavioral markers and biomarkers of physical activity and eating. Data were analyzed by repeated-measures analysis of variance and chi-square tests (&agr; < .05). Results: Both groups significantly increased stretching and strengthening exercise and fruit and vegetable servings and decreased percentage of calories from fat, whereas only the tailored group increased moderate or greater intensity activity and decreased percentage of calories from saturated fat from baseline to 6 months. Both groups increased stretching and strengthening exercise, whereas only the tailored group increased moderate or greater intensity activity and fruit and vegetable servings and decreased percentage of calories from fat from baseline to 12 months. Both groups had several changes in biomarkers over the study. A higher proportion of women receiving tailored newsletters met Healthy People 2010 criteria for moderate or greater intensity activity, fruit and vegetable servings, and percentage of calories from fat at 12 months. Discussion: Mailed computer-tailored and generic print newsletters facilitated the adoption of change in both activity and eating over 6 months. Tailored newsletters were more efficacious in facilitating change over 12 months.
Self-Ratings of Physical Attractiveness in a Competitive Context: When Males are More Sensitive to Self-Perceptions Than Females

Abstract The authors investigated sex differences in the ratings of physical attractiveness in a competitive context. Participants in an Ultimatum Game experiment offered to split a sum of money with their opponents who could either accept or reject the offers; subsequently, physical attractiveness ratings (both self-ratings and of the other) were obtained. The authors found that male participants rated themselves higher on physical attractiveness when facing male opponents than when facing female ones; there was no such difference for the female participants. Furthermore, male participants' self-ratings of physical attractiveness were higher than the ratings provided by their corresponding male opponents. The authors discuss these findings using the tenets of evolutionary psychology pertaining to as male intra-sexual rivalry in competitive contexts.
Do I Trust You Online, and If So, Will I Buy? An Empirical Study of Two Trust-Building Strategies

This research investigates the effectiveness of various trust-building strategies to influence actual buying behavior in online shopping environments, particularly for first-time visitors to an Internet store that does not have an established reputation. Drawing from the literature on trust, we developed a model of how trust-building strategies could affect trust and the consequences of trust. We investigated two trust-building strategies: portal association (based on reputation categorization and trust transference) and satisfied customer endorsements (based on unit grouping, reputation categorization, and trust transference). A series of two studies was conducted at a large public university in Hong Kong. The first study employed a laboratory experiment to test the model in an online bookstore environment, using a real task that involves actual book purchases. Of the two strategies investigated, satisfied customer endorsement by similar peers, but not portal association, was found to increase consumers' trusting beliefs about the store. This, in turn, positively influenced consumers' attitudes toward the store and their willingness to buy from the store, which ultimately led to actual buying behaviors. To gather further insights on the two Web strategies investigated, a second study was conducted using a questionnaire survey approach. Overall, the findings corroborated those in the first study. Specifically, it shows that endorsements by similar (local, nonforeign) peers, but not by dissimilar (foreign) peers, were effective means of developing trust among first-time visitors to online stores.
Investigating Risk Factors for Chronicity: The Importance of Distinguishing Between Return-to-Work Status and Self-Report Measures of Disability

Objective: The objective of this study was to examine whether the outcome of psychosocial risk factor analyses varied as a function of whether the outcome variable was return-to-work status or self-reported functional disability. Methods: Participants were 255 workers who sustained a soft tissue injury to the back and participated in a community-based secondary prevention program. Assessment of psychologic risk factors (pain severity, pain catastrophizing, fear of movement/reinjury, depression) was conducted at pretreatment. Results: Logistic regression revealed that pain catastrophizing (odds ratio [OR], 0.53; 95% confidence interval [CI] = 0.32–0.88) and pain severity (OR, 0.65; 95% CI = 0.45–0.94) were significant predictors of return to work. However, when change in self-reported disability was used as the outcome variable, none of the psychosocial risk factors emerged as significant predictors. Conclusions: Given the important theoretical, clinical, and policy implications of the outcome of risk factor research, more research is needed to further clarify the respective advantages and limitations to using self-reported versus return to work-based measures of disability.
Transverse myelitis as the first manifestation of systemic lupus erythematosus or lupus-like disease: good functional outcome and relevance of antiphospholipid antibodies.

OBJECTIVE Transverse myelitis (TM) is a rare complication of systemic lupus erythematosus (SLE). Although usually a late manifestation of SLE, it can occur at presentation. We investigated the clinical presentation, treatment and outcome of 15 patients with TM as the presenting manifestation of SLE or lupus-like disease. METHODS All patients received corticosteroids, while 13 also received immunosuppressive therapy. Five patients were fully anticoagulated with warfarin. RESULTS A sensory level with spastic lower limb weakness and sphincter disturbance was the most common presentation: 14/15 patients had a thoracic or cervical sensory level. Cerebrospinal fluid examination showed high protein concentrations in 3 patients and oligoclonal bands in 8. Eleven of the 15 (73%) had antiphospholipid antibodies (aPL). Of the 15 patients, 3 had complete resolution of the symptoms, 6 had good functional improvements, 5 had good to fair outcome with some functional deficit, and one patient who received corticosteroids alone later died from pneumonia. CONCLUSION We describe 15 patients with TM as the presenting manifestation of SLE or lupus-like disease with a high prevalence of aPL. Our data support the view that early diagnosis and immunosuppressive therapy may be superior to corticosteroids alone in improving functional outcome. In those patients with aPL, antiplatelet agents and/or warfarin should also be considered.
The Effects of Experimenter Gender on State Social Physique Anxiety and Strength in a Testing Environment

Lamarche, L, Gammage, KL, and Gabriel, DA The effects of experimenter gender on state social physique anxiety and strength in a testing environment J Strength Cond Res 25(2): 533-538, 2011-Social influences can impact self-presentational concerns such as social physique anxiety (SPA), concerns over one's body being evaluated by others. In addition, social influences may also impact performance on a physical test. In a physical testing environment, one social factor that influences SPA and which may also influence the outcomes of a physical test is experimenter gender. The present study examined the influence of experimenter gender on SPA and actual muscle strength in an experimental testing environment. Male (n = 50) and female (n = 50) university students were randomly assigned to either a male or female experimenter. Before strength testing, state SPA (SPA-S) was assessed. Actual strength was represented by the score obtained during the maximum voluntary contraction (MVC) test. Two 2 × 2 (participant gender × gender of the experimenter) analyses of variance were conducted with SPA-S and strength as the dependent variables. For SPA-S, a significant main effect was found only for participant gender (F(1,95) = 14.08, p < 0.01, η2 = 0.13), with women scoring significantly higher than men. For MVC, there was a significant effect for participant gender (F(1,96) = 48.08, p < 0.001, η2 = 0.33), with men, as expected, having significantly higher strength values than women. Although the gender of the experimenter did not influence SPA-S or muscle strength, other forms of anxiety (e.g., fitness anxiety) may be relevant in this setting. Future research should also investigate other factors in the testing environment (e.g., type of task) that may be more influential on psychological or performance outcomes.