julilili42/papers huggingface dataset:
Validation and reliability testing of a new, fully integrated gait analysis insole
2015-01-01

Abstract Background A new tool (OpenGo, Moticon GmbH) was introduced to continuously measure kinetic and temporospatial gait parameters independently through an insole over up to 4 weeks. The goal of this study was to investigate the validity and reliability of this new insole system in a group of healthy individuals. Methods Gait data were collected from 12 healthy individuals on a treadmill at two different speeds. In total, six trials of three minutes each were performed by every participant. Validation was performed with the FDM‐S System (Zebris). Complete sensor data were used for a within test reliability analysis of over 10000 steps. Intraclass correlation was calculated for different gait parameters and analysis of variance performed. Results Intraclass correlation for the validation was &gt;0.796 for temporospatial and kinetic gait parameters. No statistical difference was seen between the insole and force plate measurements (difference between means: 36.3 ± 27.19 N; p = 0.19 and 0.027 ± 0.028 s; p = 0.36). Intraclass correlation for the reliability was &gt;0.994 for all parameters measured. Conclusion The system is feasible for clinical trials that require step by step as well as grouped analysis of gait over a long period of time. Comparable validity and reliability to a stationary analysis tool has been shown.
Frailty, Inflammation and Immunosenescence
2015-01-01

Frailty is a still-evolving concept of a complex phenomenon. There are several algorithms and strategies for assessing frailty syndrome, but currently, no universally accepted definition or measurement protocol has been determined. Consequently, the biological cause(s) of frailty are also poorly defined. Much circumstantial experimental data point to the dysregulation of several key physiological systems, including the neuroendocrine, musculoskeletal, metabolic and immune/inflammatory systems, resulting from alterations in functional reserves. Immune dysregulation and inflammation as causes of frailty have gained some support from the results of longitudinal studies, but a true causal relationship has not been established. This chapter will describe the immune/inflammatory alterations found in frailty and their putative causal relationships with this state.
Chemotherapy and Chemoprevention by Thiazolidinediones
2015-01-01

Thiazolidinediones (TZDs) are synthetic ligands of Peroxisome-Proliferator-Activated Receptor gamma (PPAR<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M1"><mml:mrow><mml:mi>γ</mml:mi></mml:mrow></mml:math>). Troglitazone, rosiglitazone, and pioglitazone have been approved for treatment of diabetes mellitus type II. All three compounds, together with the first TZD ciglitazone, also showed an antitumor effect in preclinical studies and a beneficial effect in some clinical trials. This review summarizes hypotheses on the role of PPAR<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M2"><mml:mrow><mml:mi>γ</mml:mi></mml:mrow></mml:math>in tumors, on cellular targets of TZDs, antitumor effects of monotherapy and of TZDs in combination with other compounds, with a focus on their role in the treatment of differentiated thyroid carcinoma. The results of chemopreventive effects of TZDs are also considered. Existing data suggest that the action of TZDs is highly complex and that actions do not correlate with cellular PPAR<mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML" id="M3"><mml:mrow><mml:mi>γ</mml:mi></mml:mrow></mml:math>expression status. Effects are cell-, species-, and compound-specific and concentration-dependent. Data from human trials suggest the efficacy of TZDs as monotherapy in prostate cancer and glioma and as chemopreventive agent in colon, lung, and breast cancer. TZDs in combination with other therapies might increase antitumor effects in thyroid cancer, soft tissue sarcoma, and melanoma.
Enhanced Suicidal Erythrocyte Death Contributing to Anemia in the Elderly
2015-01-01

Background/Aims: Anemia, a common condition in the elderly, could result from impaired formation and/or from accelerated loss of circulating erythrocytes. The latter could result from premature suicidal erythrocyte death or eryptosis characterized by phosphatidylserine (PS) exposure at the erythrocyte surface. Triggers of eryptosis include increased cytosolic Ca2+-concentration ([Ca2+]i), oxidative stress and ceramide. The present study explored whether eryptosis is altered in elderly individuals and, if so, to identify underlying mechanisms. Methods: Blood was drawn from healthy young (n=11, age 31.3±1.7 years) and elderly (n=16, age 88.6±0.9 years) individuals. PS exposure was estimated from annexin V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, reactive oxygen species (ROS) from 2',7'dichlorodihydrofluorescein fluorescence, reduced glutathione (GSH) from mercury orange fluorescence and ceramide from FITC-conjugated antibody binding in flow cytometry. Measurements were made in erythrocytes from freshly drawn blood and in erythrocytes exposed in vitro for 24 h to plasma from young or elderly individuals. Results: Elderly individuals suffered from severe anemia (hemoglobin 10.5±0.3 g/100 ml) despite enhanced number of reticulocytes (2.3±0.2%). The percentage of PS-exposing erythrocytes was significantly higher in the elderly (2.5±0.2%) than in the young volunteers (1.3±0.1%). The increase in PS exposure was paralleled by significant increase of ROS and significantly decreased levels of reduced GSH. Erythrocyte [Ca2+]i, and ceramide abundance tended to be higher in the elderly, differences, however, not reaching statistical significance. Conclusions: The anemia of elderly individuals is mainly if not exclusively due to enhanced eryptosis, resulting at least in part from GSH deficiency and increased oxidative stress.
Rethinking the implications of numerical ratio effects for understanding the development of representational precision and numerical processing across formats.
2015-01-01

Numerical ratio effects are a hallmark of numerical comparison tasks. Moreover, ratio effects have been used to draw strong conclusions about the nature of numerical representations, how these representations develop, and the degree to which they generalize across stimulus formats. Here, we compute ratio effects for 1,719 children from Grades K-6 for each individual separately by computing not just the average ratio effect for each person, but also the variability and statistical magnitude (effect-size) of their ratio effect. We find that individuals' ratio effect-sizes in fact increase over development, calling into question the view that decreasing ratio effects over development indicate increasing representational precision. Our data also strongly caution against the use of ratio effects in inferring the nature of symbolic number representation. While 75% of children showed a statistically significant ratio effect for nonsymbolic comparisons, only 30% did so for symbolic comparisons. Furthermore, whether a child's nonsymbolic ratio effect was significant did not predict whether the same was true of their symbolic ratio effect. These results undercut the notions (a) that individuals' ratio effects are indicative of representational precision in symbolic numbers, and (b) that a common process generates ratio effects in symbolic and nonsymbolic formats. Finally, for both formats, it was the variability of an individual child's ratio effect (not its slope or even effect-size) that correlated with arithmetic ability. Taken together, these results call into question many of the long-held tenets regarding the interpretation of ratio effects-especially with respect to symbolic numbers.
p-hacking by post hoc selection with multiple opportunities: Detectability by skewness test?: Comment on Simonsohn, Nelson, and Simmons (2014).
2015-01-01

Simonsohn, Nelson, and Simmons (2014) have suggested a novel test to detect p-hacking in research, that is, when researchers report excessive rates of "significant effects" that are truly false positives. Although this test is very useful for identifying true effects in some cases, it fails to identify false positives in several situations when researchers conduct multiple statistical tests (e.g., reporting the most significant result). In these cases, p-curves are right-skewed, thereby mimicking the existence of real effects even if no effect is actually present.
Vitamin D-Rich Diet in Mice Modulates Erythrocyte Survival
2015-01-01

&lt;b&gt;&lt;i&gt;Background/Aims: &lt;/i&gt;&lt;/b&gt;Epidemiological evidence suggests that vitamin D deficiency is associated with anemia. The potent metabolite 1,25(OH)&lt;sub&gt;2&lt;/sub&gt; vitamin D&lt;sub&gt;3&lt;/sub&gt; [1,25(OH)&lt;sub&gt;2&lt;/sub&gt;D&lt;sub&gt;3&lt;/sub&gt;] activates various signaling cascades regulating a myriad of cellular functions including suicidal cell death or apoptosis. Suicidal death of erythrocytes or eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Stimulation of eryptosis may limit lifespan of circulating erythrocytes and thus cause anemia. In the present study, we explored the effect of a high vitamin D diet (10,000 I.U. vitamin D for 14 days) in mice on eryptosis. &lt;b&gt;&lt;i&gt;Methods: &lt;/i&gt;&lt;/b&gt;Plasma concentrations of erythropoietin were estimated using an immunoassay kit, blood count using an electronic hematology particle counter, relative reticulocyte numbers using Retic-COUNT® reagent, PS exposure at the cell surface from annexin V binding, cell volume from forward scatter, and cytosolic Ca&lt;sup&gt;2+&lt;/sup&gt; ([Ca&lt;sup&gt;2+&lt;/sup&gt;]&lt;sub&gt;i&lt;/sub&gt;) from Fluo3-fluorescence in FACS analysis. &lt;b&gt;&lt;i&gt;Results: &lt;/i&gt;&lt;/b&gt;Vitamin D treatment decreased mean corpuscular volume, reticulocyte count, and plasma erythropoietin levels. Vitamin D treatment slightly but significantly decreased forward scatter but did not significantly modify spontaneous PS exposure and [Ca&lt;sup&gt;2+&lt;/sup&gt;]&lt;sub&gt;i&lt;/sub&gt; of freshly drawn erythrocytes. Vitamin D treatment augmented the stimulation of PS exposure and cell shrinkage following exposure to hyperosmotic shock (addition of 550 mM sucrose) or energy depletion (glucose removal) without significantly modifying [Ca&lt;sup&gt;2+&lt;/sup&gt;]&lt;sub&gt;i&lt;/sub&gt;. &lt;b&gt;&lt;i&gt;Conclusions: &lt;/i&gt;&lt;/b&gt;The present observations point to a subtle effect of exogenous vitamin D supplementation on erythrocyte survival.
Triggering of Suicidal Erythrocyte Death by Ruxolitinib
2015-01-01

Background/Aims: The JAK1/JAK2 tyrosine kinase inhibitor ruxolitinib is widely used for the treatment of myeloproliferative neoplasm-associated myelofibrosis and other malignancies. Most important side effects include anemia. A common cause of anemia is accelerated suicidal death of erythrocytes or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Mechanisms contributing to the triggering of eryptosis include oxidative stress, Ca2+ entry with increase of cytosolic Ca2+ activity ([Ca2+]i), and activation of distinct kinases, such as p38 mitogen activated protein (MAP) kinase. The present study explored whether and how ruxolitinib induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca2+]i from Fluo3-fluorescence, and ROS formation from DCFDA dependent fluorescence. Results: A 48 hours exposure of human erythrocytes to ruxolitinib (25 μM) significantly increased the percentage of annexin-V-binding cells and significantly decreased forward scatter. Ruxolitinib did not significantly modify Fluo3-fluorescence and DCFDA fluorescence and the effect of ruxolitinib on annexin-V-binding was not significantly modified by removal of extracellular Ca2+. The effect of ruxolitinib on annexin-V-binding was, however, significantly blunted by the p38 MAP kinase inhibitor SB203580 and virtually abolished by the p38 MAP kinase inhibitor skepinone. Conclusion: Ruxolitinib triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part requiring p38 MAP kinase activity.
How the zebra got its stripes: a problem with too many solutions
2015-01-01

The adaptive significance of zebra stripes has thus far eluded understanding. Many explanations have been suggested, including social cohesion, thermoregulation, predation evasion and avoidance of biting flies. Identifying the associations between phenotypic and environmental factors is essential for testing these hypotheses and substantiating existing experimental evidence. Plains zebra striping pattern varies regionally, from heavy black and white striping over the entire body in some areas to reduced stripe coverage with thinner and lighter stripes in others. We examined how well 29 environmental variables predict the variation in stripe characteristics of plains zebra across their range in Africa. In contrast to recent findings, we found no evidence that striping may have evolved to escape predators or avoid biting flies. Instead, we found that temperature successfully predicts a substantial amount of the stripe pattern variation observed in plains zebra. As this association between striping and temperature may be indicative of multiple biological processes, we suggest that the selective agents driving zebra striping are probably multifarious and complex.
Stimulation of Suicidal Erythrocyte Death by PRIMA-1
2015-01-01

Background: The anticarcinogenic drug PRIMA-1 (p53 reactivation and induction of massive apoptosis 1) induces suicidal death of tumor cells, an effect in large part attributed to the up-regulation of the proapoptotic transcription factor p53. Erythrocytes are lacking gene transcription but are nevertheless able to enter eryptosis, a suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include increase of cytosolic Ca2+-activity ([Ca2+]i) and ceramide formation. The present study tested whether PRIMA-1 stimulates eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, ceramide abundance from binding of specific antibodies, and ROS formation from DCFDA fluorescence. Results: A 48 h exposure of human erythrocytes to PRIMA-1 (25 μM) significantly increased the percentage of annexin-V-binding cells without significantly influencing [Ca2+]i or forward scatter. PRIMA-1 (100 μM) induced annexin-V-binding was not significantly blunted by removal of extracellular Ca2+ or by the caspase-3 inhibitor zVAD. PRIMA-1 (100 μM) further increased the ceramide abundance at the cell surface and ROS formation. Conclusions: PRIMA-1 stimulates phosphatidylserine translocation at the erythrocyte cell membrane, an effect at least partially due to up-regulation of ceramide abundance and ROS formation.
Stimulation of Suicidal Erythrocyte Death by the Antimalarial Drug Mefloquine
2015-01-01

Background: The antimalarial drug mefloquine has previously been shown to stimulate apoptosis of nucleated cells. Similar to apoptosis, erythrocytes may enter suicidal death or eryptosis, which is characterized by cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, increase of cytosolic Ca2+-activity ([Ca2+]i), and ceramide. Methods: Phosphatidylserine abundance at the cell surface was estimated from annexin V binding, cell volume from forward scatter, reactive oxidant species (ROS) from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, [Ca2+]i from Fluo3-fluorescence, and ceramide abundance from specific antibody binding. Results: A 48 h treatment of human erythrocytes with mefloquine significantly increased the percentage of annexin-V-binding cells (≥5 μg/ml), significantly decreased forward scatter (≥5 μg/ml), significantly increased ROS abundance (5 μg/ml), significantly increased [Ca2+]i (7.5 μg/ml) and significantly increased ceramide abundance (10 μg/ml). The up-regulation of annexin-V-binding following mefloquine treatment was significantly blunted but not abolished by removal of extracellular Ca2+. Even in the absence of extracellular Ca2+, mefloquine significantly increased annexin-V-binding. Conclusions: Mefloquine treatment leads to erythrocyte shrinkage and erythrocyte membrane scrambling, effects at least partially due to induction of oxidative stress, increase of [Ca2+]i and up-regulation of ceramide abundance.
Clofazimine Induced Suicidal Death of Human Erythrocytes
2015-01-01

Background/Aims: The antimycobacterial riminophenazine clofazimine has previously been shown to up-regulate cellular phospholipase A2 and to induce apoptosis. In erythrocytes phospholipase A2 stimulates eryptosis, the suicidal erythrocyte death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Phospholipase A2 is in part effective by fostering formation of prostaglandin E2, which triggers Ca2+ entry. Stimulators of Ca2+ entry and eryptosis further include oxidative stress and energy depletion. The present study tested, whether and how clofazimine induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, cytosolic Ca2+ activity ([Ca2+]i) from Fluo3-fluorescence, reactive oxygen species (ROS) from 2′, 7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence, and cytosolic ATP level utilizing a luciferin-luciferase assay kit. Results: A 24-48 hours exposure of human erythrocytes to clofazimine (≥1.5 μg/ml) significantly increased the percentage of annexin-V-binding cells without appreciably modifying forward scatter. Clofazimine significantly increased [Ca2+]i, significantly decreased cytosolic ATP, but did not significantly modify ROS. The effect of clofazimine on annexin-V-binding was significantly blunted, but not fully abolished by removal of extracellular Ca2+, and by phospholipase A2 inhibitor quinacrine (25 μM). Clofazimine further augmented the effect of Ca2+ ionophore ionomycin (0.1 μM) on eryptosis. The clofazimine induced annexin-V-binding was, however, completely abrogated by combined Ca2+ removal and addition of quinacrine. Conclusion: Clofazimine stimulates phospholipid scrambling of the erythrocyte cell membrane, an effect in part dependent on entry of extracellular Ca2+, paralleled by cellular energy depletion and sensitive to phospholipase A2 inhibitor quinacrine.
Programmed Erythrocyte Death Following in Vitro Treosulfan Treatment
2015-01-01

Background/Aims: The cytotoxic drug Treosulfan is clinically used for the treatment of malignancy. A common side effect of Treosulfan treatment is anemia. Treosulfan is at least partially effective by triggering apoptosis of tumor cells. Similar to apoptosis of nucleated cells, erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and translocation of phosphatidylserine from the inner to the outer leaflet of the plasma membrane. Triggers of eryptosis include oxidative stress, Ca2+-entry and increase of cytosolic Ca2+-activity ([Ca2+]i). The present study explored whether Treosulfan stimulates eryptosis, which may contribute to development of anemia. Methods: Erythrocyte volume was estimated from forward scatter, phosphatidylserine abundance at the erythrocyte surface from Fluorescein isothiocyanate (FITC)-annexin-V-binding, [Ca2+]i from Fluo3 fluorescence and reactive oxygen species (ROS) from 2',7'-dichlorodihydrofluorescein diacetate (DCFDA)-fluorescence. Results: A 48 hours exposure of human erythrocytes to Treosulfan (800 μg/ml) significantly decreased erythrocyte forward scatter, increased the percentage of annexin-V-binding cells, increased [Ca2+]i, and increased ROS. The effect of Treosulfan on annexin-V-binding was virtually abrogated by removal of extracellular Ca2+. Conclusion: Treosulfan stimulates suicidal erythrocyte death or eryptosis at least in part by inducing oxidative stress and stimulating Ca2+ entry.
Lapatinib Induced Suicidal Death of Human Erythrocytes
2015-01-01

Background/Aims: The human epidermal growth factor receptors tyrosine kinase inhibitor lapatinib has been shown to trigger suicidal death or apoptosis of tumor cells and is thus used for the treatment of malignancy. Side effects of lapatinib include anemia, which could, at least in theory, result from stimulation of eryptosis, the suicidal death of erythrocytes which is characterized by cell shrinkage and phospholipid scrambling of the cell membrane leading to phosphatidylserine translocation to the erythrocyte surface. Mechanisms involved in the triggering of eryptosis include oxidative stress, increase of cytosolic Ca2+ activity ([Ca2+]i), and ceramide. The present study explored, whether lapatinib induces eryptosis. Methods: Phosphatidylserine exposure at the cell surface was estimated from annexin-V-binding, cell volume from forward scatter, [Ca2+]i from Fluo3-fluorescence, abundance of reactive oxygen species (ROS) from DCFDA dependent fluorescence, and ceramide abundance utilizing labelled specific antibodies. Results: A 48 hours exposure of human erythrocytes to lapatinib (≥ 1 μg/ml) significantly increased the percentage of annexin-V-binding cells, and significantly decreased forward scatter. Lapatinib (7.5 μg/ml) did not significantly modify DCFDA fluorescence and ceramide abundance. Lapatinib slightly, but significantly decreased Fluo3-fluorescence (≥ 5 μg/ml). Lapatinib (7.5 μg/ml) enhanced the annexin-V-binding in the presence of the Ca2+ ionophore ionomycin (1 μM) without significantly modifying Fluo3 fluorescence in the presence of ionomycin. The effect of lapatinib on forward scatter but not on annexin-V-binding was significantly blunted by removal of extracellular Ca2+. Conclusion: Lapatinib triggers cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect occurring despite decrease of cytosolic Ca2+ activity.