Miracle-dz/UniFAR-FTUs huggingface dataset:
Marine feeding areas and vertical movements of Atlantic salmon (Salmo salar) as inferred from recoveries of data storage tags

We released 598 Atlantic salmon (Salmo salar) hatchery smolts in a river in Iceland in 2005 and 2006 tagged with data storage tags recording temperature and (depth) continuously. Five salmon returned in 2006 and two in 2007, all spending 1 year at sea. The complete temperature and depth profiles of the whole ocean migration were measured. The salmon stayed close to the surface most of the time and showed diurnal behavior, staying at slightly deeper waters during day. The salmon were in temperatures from 6 to 15 °C, with warmer temperatures in the summer. We compared the fish-recorded temperature with sea surface temperature from an available National Oceanic and Atmospheric Administration database to locate the fish at different times. Utilizing the diurnal behavior of the salmon, we estimated solar noon each day during winter. Sea surface temperatures and diurnal activity were used to estimate daily locations using established Hidden Markov Model for fish geolocation. The salmon in the study stayed south.
Antiproliferative and proapoptotic activity of sunitinib on endothelial and anaplastic thyroid cancer cells via inhibition of Akt and ERK1/2 phosphorylation and by down-regulation of cyclin-D1.

CONTEXT Recent experimental evidence suggests a rationale for the use of multitarget tyrosine kinase inhibitors for the treatment of thyroid cancers. Sunitinib showed promising preliminary results against anaplastic thyroid cancer (ATC), and it has been used for some patients who are ineligible for clinical trials. OBJECTIVES The aims of this study were to investigate the in vitro and in vivo activity of sunitinib on ATC and on microvascular endothelial cells and the molecular mechanism for the observed sunitinib activity. METHODS Proliferation and apoptotic assays were performed on human dermal microvascular endothelial and on BRAF- or H-ras-mutated ATC cells (8305C and FB3, respectively) after in vitro exposure to sunitinib for 72 hours. Vascular endothelial growth factor receptor-2, epithelial growth factor receptor, ERK1/2, and Akt phosphorylation was quantified by ELISA and Western blot. Cyclin-D1 mRNA expression was evaluated by real-time PCR, and cyclin-D1 intracellular concentrations were measured by ELISA. 8305C tumor xenografts in nude mice were treated with sunitinib at 50 mg/kg/d (i.p.). RESULTS Antiproliferative and proapoptotic activity of sunitinib was observed in both endothelial and ATC cells. Phospho-vascular endothelial growth factor receptor-2 levels significantly decreased after sunitinib treatment in activated endothelial cells. Phospho-epidermal growth factor receptor, ERK1/2, and Akt phosphorylation was significantly inhibited by sunitinib treatment in endothelial and cancer cells, and cyclin-D1 mRNA and protein expression was inhibited. Sunitinib administration in vivo caused significant inhibition of tumor growth (P < .05). CONCLUSIONS Sunitinib is active in vitro and in vivo against activated endothelial and ATC cells via the inhibition of Akt and ERK1/2 phosphorylation and through the down-regulation of cyclin-D1.
Complex rhythmicity and age dependence of growth hormone secretion are preserved in patients with acromegaly: further evidence for a present hypothalamic control of pituitary somatotropinomas.

CONTEXT Traditionally, acromegaly is viewed as a disease resulting from GH hypersecretion from an autonomous pituitary somatotropinoma. OBJECTIVE To test the hypothesis that GH secretion in acromegaly is still subjected to normal hypothalamic control, we studied the daily rhythmicity of GH secretion in normal controls and patients with newly diagnosed, untreated acromegaly. DESIGN AND SETTING This was an observational inpatient study in the General Clinical Research Center at the University of Michigan. PATIENTS OR OTHER PARTICIPANTS One hundred four normal controls and 67 acromegalic patients were included in the study. INTERVENTION The intervention consisted of frequent blood sampling over 24 hours. MAIN OUTCOME MEASURE(S) We hypothesized that acromegalic patients would show rhythmicity, sexual dimorphism, and age-related decline of GH secretion similar to normal controls. RESULTS Both normal controls and the patients exhibited 3 major GH waves with the highest values at 12:00 pm, 5:00 pm, and 1:00 am (P < .001 for all). Both controls and patients exhibited a clear appearance of the nocturnal GH waves, irrespective of the gender (P < .001 for all). The amplitude of the maximal (nocturnal) GH secretory wave (1:00 am) as compared with the nadir GH secretion (9:00 am) was clearly different between the 2 groups, with a significantly smaller magnitude in acromegaly (P < .001). A subsequent subanalysis of both groups was performed separately for both genders. Similar to the entire groups, both controls and patients exhibited a clear appearance of the nocturnal GH waves, irrespective of the gender (P < .001 for all). Patients with clearly elevated GH values have shown an age-related decline of GH secretion (r = -0.35, P < .001), similar to controls. CONCLUSIONS The analysis of GH profiles in multiple patients with untreated acromegaly discloses the persistence of the hallmarks of the central control of GH regulation, ie, nictohemeral rhythmicity, sexual dimorphism, and an age-related decline of GH output.
The devil in the corner: A mixed-methods study of metaphor use by those with spinal cord injury-specific neuropathic pain.

OBJECTIVES Metaphorical expressions of persistent pain play an influential role in the modulation of pain. This may be particularly distressing for those with physical disabilities such as spinal cord injury (SCI). Neuropathic pain (NP) after SCI is often described using metaphorical expressions such as burning and electricity. This study explored the use of metaphors by those with NP after SCI. DESIGN A qualitative, semi-structured interview design was employed. METHODS Data were analysed using content analysis (CA) and interpretative phenomenological analysis to explore prevalence of metaphor use and its meaning. Sixteen individuals aged between 23 and 82 years, with chronic NP (persisting for 3 months or longer), arising from SCI were interviewed in their homes or on hospital wards (M = 10, F = 6). Interviews lasted between 40 and 120 min. RESULTS The results capture a range of metaphorical expressions embedded in participants' accounts. Three themes emerged: (1) pain as a personal attack, (2) the desire to be understood, and (3) conveying distress without adequate terminology. CA revealed that younger age, female gender, and outpatient status were associated with increased metaphor use. CONCLUSIONS This study highlights the power of metaphor in eliciting understanding of NP after SCI from others, whilst demonstrating the challenge of communicating NP. Cognitive treatment that incorporates image-based techniques with acceptance and mindfulness-based therapies may encourage adaptive responses to, and interpretation of, pain. This may subsequently reduce pain-related distress and catastrophizing. Statement of contribution What is already known on this subject? Neuropathic pain is often described with metaphorical language such as burning and crushing. For those with physical limitations, metaphor use may induce or exacerbate psychological distress. However, for those with spinal cord injuries, metaphor use has received little attention. What does this study add? Metaphor use is common in those with spinal cord injury, with differences across gender and age. Core metaphors used conceptualized pain as an attacker or likened pain to heat and burning. Such language may have benefits in terms of improved understanding and increased empathy, but may be reflective of catastrophic thinking.
Retest Reliability of Centre of Pressure Measures of Standing Balance in Healthy Older Women

Centre of pressure (COP) measurements have been frequently used in the evaluation of postural control, especially in the elderly. Despite this, the retest reliability of these measures has not been well investigated in this age group. This study investigated the retest reliability of COP measures using a force platform in 17 women with a mean age of 69.5 years. Results indicated low correlations between test occasions for static stance postures with Intra class Correlation Coefficients (ICCs) ranging between 0.27 and 0.55. In contrast, ICCs were high (between 0.81 and 0.92) for test conditions involving angular perturbation of the support surface. Investigation of test durations of 10 and 25 second length did not indicate any significant difference between these two test durations (p>0.05). The study also revealed no series effects using twelve consecutive 25 second tests on the force platform. These results support further investigation of dynamic standing balance in older women using the test protocol described in this study, including whether these tests are able to discriminate between fallers and non fallen, and their predictive validity.
Disuse impairs the muscle protein synthetic response to protein ingestion in healthy men.

BACKGROUND Disuse leads to rapid skeletal muscle atrophy, which brings about numerous negative health consequences. Muscle disuse atrophy is, at least in part, attributed to a decline in basal (postabsorptive) muscle protein synthesis rates. However, it remains to be determined whether muscle disuse also impairs the muscle protein synthetic response to dietary protein ingestion. PURPOSE We assessed muscle protein synthesis rates after protein ingestion before and after a period of disuse in humans. METHODS Twelve healthy young (24 ± 1 year) men underwent a 14-day period of one-legged knee immobilization by way of a full leg cast. Before and after the immobilization period, quadriceps cross-sectional area, muscle strength, skeletal muscle protein synthesis rates, and associated im (intramuscular) molecular signaling were assessed. Continuous infusions of l-[ring-²H₅]phenylalanine were applied to assess mixed-muscle protein fractional synthetic rates after the ingestion of 20 g dietary protein. RESULTS Immobilization led to an 8.4% ± 2.8% (P < .001) and 22.9% ± 2.6% (P < .001) decrease in quadriceps muscle cross-sectional area and strength, respectively. Immobilization resulted in a 31% ± 12% reduction in postprandial muscle protein synthesis rates (from 0.046% ± 0.004% to 0.032% ± 0.006% per hour; P < .05). These findings were observed without any discernible changes in the skeletal muscle phosphorylation status of mammalian target of rapamycin or p70 ribosomal protein S6 kinase. CONCLUSIONS A short period of muscle disuse impairs the muscle protein synthetic response to dietary protein intake in vivo in healthy young men. Thus, anabolic resistance to protein ingestion contributes significantly to the loss of muscle mass that is observed during disuse.
Differences in multiple-target visual search performance between non-professional and professional searchers due to decision-making criteria.

Professional visual searches, such as those conducted by airport security personnel, often demand highly accurate performance. As many factors can hinder accuracy, it is critical to understand the potential influences. Here, we examined how explicit decision-making criteria might affect multiple-target search performance. Non-professional searchers (college undergraduates) and professional searchers (airport security officers) classified trials as 'safe' or 'dangerous', in one of two conditions. Those in the 'one = dangerous' condition classified trials as dangerous if they found one or two targets, and those in the 'one = safe' condition only classified trials as dangerous if they found two targets. The data suggest an important role of context that may be mediated by experience; non-professional searchers were more likely to miss a second target in the one = dangerous condition (i.e., when finding a second found target did not change the classification), whereas professional searchers were more likely to miss a second in the one = safe condition.
Disruption of GIP/GIPR axis in human adipose tissue is linked to obesity and insulin resistance.

CONTEXT Glucose-dependent insulinotropic peptide (GIP) has a central role in glucose homeostasis through its amplification of insulin secretion; however, its physiological role in adipose tissue is unclear. OBJECTIVE Our objective was to define the function of GIP in human adipose tissue in relation to obesity and insulin resistance. DESIGN GIP receptor (GIPR) expression was analyzed in human sc adipose tissue (SAT) and visceral adipose (VAT) from lean and obese subjects in 3 independent cohorts. GIPR expression was associated with anthropometric and biochemical variables. GIP responsiveness on insulin sensitivity was analyzed in human adipocyte cell lines in normoxic and hypoxic environments as well as in adipose-derived stem cells obtained from lean and obese patients. RESULTS GIPR expression was downregulated in SAT from obese patients and correlated negatively with body mass index, waist circumference, systolic blood pressure, and glucose and triglyceride levels. Furthermore, homeostasis model assessment of insulin resistance, glucose, and G protein-coupled receptor kinase 2 (GRK2) emerged as variables strongly associated with GIPR expression in SAT. Glucose uptake studies and insulin signaling in human adipocytes revealed GIP as an insulin-sensitizer incretin. Immunoprecipitation experiments suggested that GIP promotes the interaction of GRK2 with GIPR and decreases the association of GRK2 to insulin receptor substrate 1. These effects of GIP observed under normoxia were lost in human fat cells cultured in hypoxia. In support of this, GIP increased insulin sensitivity in human adipose-derived stem cells from lean patients. GIP also induced GIPR expression, which was concomitant with a downregulation of the incretin-degrading enzyme dipeptidyl peptidase 4. None of the physiological effects of GIP were detected in human fat cells obtained from an obese environment with reduced levels of GIPR. CONCLUSIONS GIP/GIPR signaling is disrupted in insulin-resistant states, such as obesity, and normalizing this function might represent a potential therapy in the treatment of obesity-associated metabolic disorders.
Fasting serum taurine-conjugated bile acids are elevated in type 2 diabetes and do not change with intensification of insulin.

CONTEXT Bile acids (BAs) are newly recognized signaling molecules in glucose and energy homeostasis. Differences in BA profiles with type 2 diabetes mellitus (T2D) remain incompletely understood. OBJECTIVE The objective of the study was to assess serum BA composition in impaired glucose-tolerant, T2D, and normal glucose-tolerant persons and to monitor the effects of improving glycemia on serum BA composition in T2D patients. DESIGN AND SETTING This was a cross-sectional cohort study in a general population (cohort 1) and nonrandomized intervention (cohort 2). PATIENTS AND INTERVENTIONS Ninety-nine volunteers underwent oral glucose tolerance testing, and 12 persons with T2D and hyperglycemia underwent 8 weeks of intensification of treatment. MAIN OUTCOME MEASURES Serum free BA and respective taurine and glycine conjugates were measured by HPLC tandem mass spectrometry. RESULTS Oral glucose tolerance testing identified 62 normal-, 25 impaired glucose-tolerant, and 12 T2D persons. Concentrations of total taurine-conjugated BA were higher in T2D and intermediate in impaired- compared with normal glucose-tolerant persons (P = .009). Univariate regression revealed a positive association between total taurine-BA and fasting glucose (R = 0.37, P < .001), postload glucose (R = 0.31, P < .002), hemoglobin A1c (R = 0.26, P < .001), fasting insulin (R = 0.21, P = .03), and homeostatic model assessment-estimated insulin resistance (R = 0.26, P = .01) and an inverse association with oral disposition index (R = -0.36, P < .001). Insulin-mediated glycemic improvement in T2D patients did not change fasting serum total BA or BA composition. CONCLUSION Fasting taurine-conjugated BA concentrations are higher in T2D and intermediate in impaired compared with normal glucose-tolerant persons and are associated with fasting and postload glucose. Serum BAs are not altered in T2D in response to improved glycemia. Further study may elucidate whether this pattern of taurine-BA conjugation can be targeted to provide novel therapeutic approaches to treat T2D.
Skeletal muscle characteristics and motor performance after 2-year growth hormone treatment in adults with prader-willi syndrome.

CONTEXT In adults with Prader-Willi syndrome (PWS), abnormal body composition with decreased lean body mass and skeletal muscle (SM) volume has been related to altered GH secretion and may possibly contribute to greatly reduced motor capacity. OBJECTIVE The scope of the study was to test the hypothesis that GH treatment has favorable effects on SM characteristics and motor performance in adults with PWS. DESIGN, SETTING, AND PARTICIPANTS Fifteen obese PWS subjects (nine males and six females; age range, 19-35 y; body mass index, 37.7-59.9 kg/m(2)) were investigated before and after 12 (GH12) and 24 (GH24) months of GH treatment. MAIN OUTCOME MEASURES SM cross-sectional area and SM attenuation were determined with computed tomography at the lumbar and midthigh levels. Maximal isometric handgrip strength and isokinetic knee extension peak torque were measured. Motor performance was evaluated with different indoor walking tests, whereas exercise endurance was assessed with a treadmill incremental test to exhaustion. RESULTS A condition of severe GH deficiency was found in six patients (40%). GH treatment significantly increased lean body mass (GH12, P < .05; GH24, P < .05), reduced percentage of body fat (GH12, P < .05; GH24, P < .05), and augmented SM cross-sectional area and SM attenuation of both lumbar (GH12, P < .01; GH24, P < .001) and thigh muscles (GH24, P < .05). Handgrip strength increased by 7% at GH12 (P < .05) and by 13% at GH24 (P < .001). Peak torque of knee extension extrapolated at zero angular velocity was significantly higher at GH24 (P < .01), and exercise endurance rose by 13% (P < .05) and 17% (P < .05) before exhaustion at GH12 and GH24, respectively, whereas no change was detected with walking tests. No significant difference in the response to GH treatment was detected between patients with and without GH deficiency. CONCLUSION Long-term GH treatment in adult PWS patients improves body composition and muscle size and quality and increases muscle strength and exercise tolerance independently from the GH secretory status.
Effect of Pain Severity on Quadriceps Isokinetic Peak Torque in Knee Osteoarthritis

Objectives: to study the extent to which the pain severity in moderate knee osteoarthritis could affect the force production of the quadriceps in terms of eccentric and concentric isokinetic torque under different angular velocities. Methods: Sixty male patients diagnosed as moderate bilateral knee osteoarthritis according to Altman grade II were assigned to patient groups (group I; mild pain, group II; moderate pain and group III; sever pain) and twenty healthy subjects were assigned to healthy group. The peak torques of the eccentric and concentric contractions of the quadriceps at angular velocities of 40°/s and 120°/s in both knees were measured for all groups by using Biodex isokinetic dynamometer and pain severity was measured by using VAS. Results: A multiple measures analysis of variance revealed that there were no significant differences in the isokinetic peak torque values of quadriceps muscle between healthy group and group I in the following conditions; concentric contraction at angular velocity 120°/sec (p = 0.333) and eccentric contraction at both angular velocities 40°/sec (p = 0.158 ) and 120°/sec (p = 0.290). Otherwise, the isokinetic peak torque values of quadriceps muscle were significantly lower in group II and III in both concentric and eccentric contractions at both angular velocities. Conclusion Pain intensity has a negative uneven impact on isokinetic concentric and eccentric quadriceps peak torques in males with moderate knee osteoarthritis.
A multicenter phase 2 trial of pazopanib in metastatic and progressive medullary thyroid carcinoma: MC057H.

CONTEXT Pazopanib is a small molecule inhibitor of kinases principally including vascular endothelial growth factor receptors-1, -2, and -3; platelet-derived growth factor receptors-α and -β; and c-Kit. We previously reported a tumor response rate of 49% in patients with advanced differentiated thyroid cancer and 0% in patients with advanced anaplastic thyroid cancer. The present report details results of pazopanib therapy in advanced medullary thyroid cancer (MTC). OBJECTIVE, DESIGN, SETTING, PATIENTS, INTERVENTION, AND OUTCOME MEASURES: Having noted preclinical activity of pazopanib in MTC, patients with advanced MTC who had disease progression within the preceding 6 months were accrued to this multiinstitutional phase II clinical trial to assess tumor response rate (by Response Evaluation Criteria In Solid Tumors criteria) and safety of pazopanib given orally once daily at 800 mg until disease progression or intolerability. RESULTS From September 22, 2008, to December 11, 2011, 35 individuals (80% males, median age 60 y) were enrolled. All patients have been followed up until treatment discontinuation or for a minimum of four cycles. Eight patients (23%) are still on the study treatment. The median number of therapy cycles was eight. Five patients attained partial Response Evaluation Criteria In Solid Tumors responses (14.3%; 90% confidence interval 5.8%-27.7%), with a median progression-free survival and overall survival of 9.4 and 19.9 months, respectively. Side effects included treatment-requiring (new) hypertension (33%), fatigue (14%), diarrhea (9%), and abnormal liver tests (6%); 3 of 35 patients (8.6%) discontinued therapy due to adverse events. There was one death of a study patient after withdrawal from the trial deemed potentially treatment related. CONCLUSIONS Pazopanib has promising clinical activity in metastatic MTC with overall manageable toxicities.
Neuroscience and Biobehavioral Reviews the Basic Emotional Circuits of Mammalian Brains: Do Animals Have Affective Lives?

The primal affects are intrinsic brain value systems that unconditionally and automatically inform animals how they are faring in survival. They serve an essential function in emotional learning. The positive affects index " comfort zones " that support survival, while negative affects inform animals of circumstances that may impair survival. Affective feelings come in several varieties, including sensory, homeostatic, and emotional (which I focus on here). Primary-process emotional feelings arise from ancient caudal and medial subcortical regions, and were among the first subjective experiences to exist on the face of the earth. Without them, higher forms of conscious " awareness " may not have emerged in primate brain evolution. Because of homologous " instinctual " neural infrastructures, we can utilize animal brain research to reveal the nature of primary-process human affects. Since all vertebrates appear to have some capacity for primal affective feelings, the implications for animal-welfare and how we ethically treat other animals are vast.