Miracle-dz/UniFAR-FTUs huggingface dataset:
Commentary—Prognosis in melanoma: the truth still lies in the node

revealed S100-positive staining. The other patient had brain metastases for which radiotherapy was given. At the last follow-up (28 months) he was alive with disease, without elevation of his serum S-100B. We hypothesize that progressive dedifferentiation leads to loss of ability of the melanoma cells to manufacture S-100B protein. Twelve of the 70 patients without recurrence had an elevated S-100B at a certain point in time. In all of them, the elevated S-100B value was reason to repeat this test and they all had a normal second value. Therefore, an increased S-100B without signs of recurrence warrants a second determination. A repeat S-100B that is normal obviates the need for further staging.
The Club-Level Road Cyclist: Injury, Pain, and Performance

Objective:The aims of this study were to (1) examine riding habits of injured cyclists, (2) identify factors related to seeking medical treatment, (3) investigate performance of recreational road cyclists compared with established norms regarding strength and flexibility measures, and (4) propose cycling-specific injury risk factors. Design:Observational and prospective study. Setting:Cycling store and bicycle distribution company. Participants:Sixty-three experienced road cyclists. Assessment of Risk Factors:Initial data collection included a questionnaire. A 2-week training diary and 8 weekly follow-up injury questionnaires were also collected. Main Outcome Measures:Training habits and injury history, bike fit, flexibility, and isometric, dynamic, and plyometric strength measures. Results:Participants were likely to have an injury at baseline, and chronic pain was common. Cyclists trained for an equal quantity of time irrespective of experiencing pain. Injury severity in terms of pain level and participant age were factors in seeking medical care. Our participants performed poorly on our testing protocol compared with available norms. Flexibility, strength, and bike fit measures did not predict injury. Previous injury predicted prospective injury. The knee and lumbar region were most frequently injured. Conclusions:Cycling is a sport in which injury risk and prevention need to be further studied. Cyclists are frequently injured but continue to participate in cycling at volumes equal to their healthy peers. Clinical Relevance:This study outlines a clinically reproducible cyclist assessment and discusses behaviors common to the cycling patient.
Maternal eating disorder history and toddlers’ neurodevelopmental outcomes: A brief report

ABSTRACT This study explored the neurodevelopmental outcomes of toddlers whose mothers have eating disorder histories and the contribution of maternal eating and comorbid psychopathology to the children’s cognitive functioning. Twenty-nine mothers with prenatal eating disorders and their toddlers (18–42 months old) were compared to a case-control matched group of mothers with no eating psychopathology and their toddlers. Measures included current maternal eating and co-occurring psychopathology, and a developmental assessment of each child. The children of mothers with eating disorders showed delayed mental and psychomotor development. Severity of maternal eating disorder symptoms emerged as a significant predictor of child development, but other maternal psychopathology did not. Findings suggest that maternal eating disorder history may play a unique role in the development of neurodevelopmental functions in their children.
Amyloid β and Alzheimer disease therapeutics: the devil may be in the details

Alzheimer disease (AD) is characterized by the progressive accumulation of amyloid β protein (Aβ) in areas of the brain serving cognitive functions such as memory and language. The first of two separate reports (see the related articles beginning on pages 415 and 440) reveals that intrinsic T cell reactivity to the self-antigen Aβ exists in many humans and increases with age. This finding has implications for the design of Aβ vaccines. The second report demonstrates that a number of FDA- approved nonsteroidal anti-inflammatory drugs are capable of lowering Aβ levels in mice. The work suggests that further testing of the therapeutic utility of these types of compounds for the potential treatment of AD is warranted.
Acceptance and psychological change at the higher levels of care: A naturalistic outcome study

ABSTRACT This naturalistic outcome study reports on psychological change among a large (N = 617), transdiagnostic sample of eating disordered adults treated at higher levels of care at a private facility. Patients were assessed at admission and discharge for eating disorder psychopathology, depression, personality, and acceptance. Effect sizes ranged from d = . 29 to d = 1.29, and the majority of participants (58.2%) were treatment responders, with BN patients showing a higher response rate than AN-R patients. Increased acceptance over the course of treatment was strongly associated with decreased eating disorder risk and may be an important factor in recovery.
Ambulatory Blood Pressure Variability Is Increased in Diabetic Hypertensives

The purpose of this study was to examine the possible difference in the 24-hr BP profile—including short-term BP variability, assessed as the standard deviation—between diabetic and non-diabetic hypertensives. We measured 24-hr ambulatory BP in 11 diabetic hypertensives (diabetic HT) and 10 non-diabetic hypertensives (non-diabetic HT) who were hospitalized for the educational program in our hospital and were under stable salt intake. Renal function and sleep apnea were also estimated. There were no significant differences in 24-hr systolic BP (141 mmHg vs. 135 mmHg, ns), daytime systolic BP (143 mmHg vs. 138 mmHg, ns), and nighttime systolic BP (135 mmHg vs. 130 mmHg, ns) between diabetic HT and non-diabetic HT. The values of 24‐hr HR (69.7 beats/min vs. 65.2 beats/min, ns) and 24-hr HR variability (9.9 beats/min vs. 10.1 beats/min, ns) were also similar between the groups. Interestingly, diabetic HT had a significantly greater 24-hr systolic and diastolic BP variability than non-diabetic HT (18.2 mmHg vs. 14.5 mmHg, p < 0.05; 11.5 mmHg vs. 9.6 mmHg, p < 0.05, respectively). The values for creatinine clearance, urinary protein excretion, and apnea-hypopnea index were similar between the groups. Bivariate linear regression analysis demonstrated that fasting blood glucose was the primary determinant of 24-hr diastolic BP variability (r = 0.661, p < 0.01). Multiple stepwise regression analysis revealed that fasting blood glucose was a significant and independent contributor to 24-hr systolic BP variability (r = 0.501, p < 0.05). Taken together, these results demonstrate that BP variability is increased in diabetic hypertensives. Furthermore, it is possible that an elevation of fasting blood glucose may contribute to the enhanced BP variability in hypertensives.
ITAM receptor‐mediated generation of reactive oxygen species in human platelets occurs via Syk‐dependent and Syk‐independent pathways

Background: Ligation of the platelet‐specific collagen receptor, GPVI/FcRγ, causes rapid, transient disulfide‐dependent homodimerization, and the production of intracellular reactive oxygen species (ROS) generated by the NADPH oxidase, linked to GPVI via TRAF4. Objectives: The aim of this study was to evaluate the role of early signaling events in ROS generation following engagement of either GPVI/FcRγ or a second immunoreceptor tyrosine‐based activation motif (ITAM)‐containing receptor on platelets, FcγRIIa. Methods and Results: Using an H2DCF‐DA‐based flow cytometric assay to measure intracellular ROS, we show that treatment of platelets with either the GPVI agonists, collagen‐related peptide (CRP) or convulxin (Cvx), or the FcγRIIa agonist 14A2, increased intraplatelet ROS; other platelet agonists such as ADP and TRAP did not. Basal ROS in platelet‐rich plasma from 14 healthy donors displayed little inter‐individual variability. CRP, Cvx or 14A2 induced an initial burst of ROS within 2 min followed by additional ROS reaching a plateau after 15–20 min. The Syk inhibitor BAY61‐3606, which blocks ITAM‐dependent signaling, had no effect on the initial ROS burst, but completely inhibited the second phase. Conclusions: Together, these results show for the first time that ROS generation downstream of GPVI or FcγRIIa consists of two distinct phases: an initial Syk‐independent burst followed by additional Syk‐dependent generation.
HOMA-Estimated Insulin Resistance Is Associated with Hypertension in Iranian Diabetic and Non-Diabetic Subjects

The relationship between insulin resistance (IR) and essential hypertension (HTN) is controversial. The aim of this study was to determine the association of IR estimated by homeostasis model assessment of insulin resistance (HOMA-IR) and HTN in a large sample of Iranian diabetic and non-diabetic population. A total of 2047 diabetic and non-diabetic individuals with or without HTN, aged 30–75 yrs, who were referred to a university general hospital between November 2004 and April 2007 were included in this study. Demographic data and anthropometric characteristics of participants were recorded. Fasting blood samples were collected, and fasting plasma glucose (FPG), serum creatinine, lipids, insulin, C-peptide and HbA1c were measured. HOMA-IR and HOMA derived Beta-cell function (HOMA-B) were also calculated. Age, sex and waist girth adjusted HOMA-IR values were compared between hypertensive and normotensive subjects. Hypertensive patients had significantly higher HOMA-IR than age-, sex-, and waist girth-adjusted normotensive individuals in both non-diabetic (2.163 ± 0.08 and 1.75 ± 0.03, p < 0.001) and diabetic (3.40 ± 0.10 and 3.07 ± 0.09, p < 0.05) groups. Multivariate logistic regression analysis showed that after adjustment for age, sex, waist girth, BMI, triglyceride, total cholesterol, FPG, and C-peptide, HOMA-IR was a significant independent predictor of HTN in all subjects (odds ratio = 1.117, CI 95% = 1.026–1.216, p < 0.05) and in diabetic and non-diabetic subjects separately (odds ratio = 1.102, CI 95% = 1.009–1.203, p < 0.05 and odds ratio = 1.328, CI 95% = 1.116–1.580, p < 0.01, respectively). In conclusion, this study showed that IR is associated with HTN in Iranian diabetic and non-diabetic subjects.
Structure, biosynthetic relationships and chemical synthesis of the icetexane diterpenoids.

Covering: up to 2009A detailed overview of the icetexane diterpenoid natural product family is presented. The structure, isolation and biological activity of these natural products is followed by an examination of their biosynthetic relationships and a comprehensive summary of the synthetic approaches to the icetexane family; 92 references are cited.
Seasonal variation of venous thrombosis: a consecutive case series within studies from Leiden, Milan and Tromsø

D. D . R I BE I RO, * P . BUCCIARELL I , S . K . BR AEKKAN,§– W. M. L I J FER ING ,* S . M. PASSAMONTI , E . E . BR ODIN ,§– F . R . ROSENDAAL ,* I . MART INELL I and J . -B . HA NSEN §– *Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands; Hematology, University Hospital, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil; Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Medicine and Medical Specialties, Fondazione IRCCS Ca Granda Ospedale Maggiore Policlinico and University of Milan, Milan, Italy; §Hematological research group (HERG), Department of Clinical Medicine, University of Tromsø, Tromsø; and –Division of Internal Medicine, University Hospital of North Norway, Tromsø, Norway
Internal rulers to assess fluorescent protein photoactivation efficiency

Photoactivatable fluorescent proteins (PA‐FPs) have been widely used to assess the dynamics of cell biological processes. In addition, PA‐FPs enabled single‐molecule based super‐resolution imaging (photoactivated localization microscopy) and thereby provided unprecedented structural insight. For the lack of tools, however, the fraction of PA‐FPs that is, actually being switched on to fluoresce, that is, the photoactivation efficiency, has been difficult to assess. Uncertainty about photoactivation efficiency has hampered an understanding of the absolute amount of PA‐FPs, that is, being examined. Here, we present internal rulers to assess photoactivation efficiencies of photoactivatable proteins. These internal rulers comprise a PA‐FP that is genetically directly coupled to a spectrally distinct always‐on fluorescent protein. Thus, these fluorescent proteins will be expressed in the bacterial and mammalian cell in a one‐to‐one ratio. With these tools, we describe photoactivation efficiencies of PA‐GFP and PA‐Cherry in intensity‐based ratiometric ensemble studies and on the single‐molecule level. In ratiometric ensemble studies, we show that photoactivation efficiency depends on how the PA‐FPs are exposed to 405 nm light. Using a laser‐scanning microscope, hundreds of iterative low‐level exposures are up to four times more efficient than a short high‐power exposure. Using wide‐field illumination, photoactivation was similarly efficient and instantaneous. These findings suggest that the repetitive or stochastic exposure to photons of 405 nm light results in more efficient photoactivation than a continuous flow of photons. Because of the differential photoactivation efficiency, it is crucial to assess photoactivation efficiency for any given experimental set‐up. The tools we provide can be applied to any genetically encoded photoactivatable protein. Determination of photoactivation efficiency is essential for an understanding of absolute molecule numbers in ensemble studies and, most importantly, quantitative superresolution imaging. © 2017 International Society for Advancement of Cytometry
Superoxide Dismutase, Catalase, and Guanase in Traumatic Brain Injury

Objectives:Reactive oxygen species generated after brain trauma trigger a cascade of events resulting in neuronal death. Despite numerous defenses, the brain is vulnerable to oxidative damage, mainly because of its high content of unsaturated fatty acids. The goal in this experimental study was to demonstrate the activities of antioxidant enzymes, namely, superoxide dismutase, catalase, and guanase, in plasma and brain tissue at 30 minutes and 60 minutes after brain trauma. Methods:Forty adult male Sprague-Dawley rats were used as subjects. Rats in group 1 were subjected to moderate head injury, whereas rats in group 2 were subjected to severe head injury. Eight rats served as a sham operated (control) group. Results:The results of this study showed that there is, in general, an increase in the activities of these 3 enzymes in plasma; however, in the brain tissue, we observed that guanase activities were decreased during the posttraumatic period. Conclusion:These alterations in enzyme activities suggest that lipid peroxidation ensues in the early period of trauma and that treatment strategies aimed to increase antioxidant enzyme activities may prevent the secondary mechanisms resulting in neuronal death.
Effects of Ramadan Intermittent Fasting on Middle-Distance Running Performance in Well-Trained Runners

Objective:To assess whether Ramadan intermittent fasting (RIF) affects 5000-m running performance and physiological parameters classically associated with middle-distance performance. Design:Two experimental groups (Ramadan fasting, n = 9, vs control, n = 9) participated in 2 experimental sessions, one before RIF and the other at the last week of fasting. Setting:For each session, subjects completed 4 tests in the same order: a maximal running test, a maximal voluntary contraction (MVC) of knee extensor, 2 rectangular submaximal exercises on treadmill for 6 minutes at an intensity corresponding to the first ventilatory threshold (VT1), and a running performance test (5000 m). Participants:Eighteen, well-trained, middle-distance runners. Main Outcome Measures:Maximal oxygen consumption, MVC, running performance, running efficiency, submaximal &OV0312;O2 kinetics parameters (&OV0312;O2, &OV0312;O2b, time constant τ, and amplitude A1) and anthropometric parameters were recorded or calculated. Results:At the end of Ramadan fasting, a decrease in MVC was observed (−3.2%; P < 0.00001; η2, 0.80), associated with an increase in the time constant of oxygen kinetics (+51%; P < 0.00007; η2, 0.72) and a decrease in performance (−5%; P < 0.0007; η2, 0.51). No effect was observed on running efficiency or maximal aerobic power. Conclusions:These results suggest that Ramadan changes in muscular performance and oxygen kinetics could affect performance during middle-distance events and need to be considered to choose training protocols during RIF.
Could Forearm Kinesio Taping Improve Strength, Force Sense, and Pain in Baseball Pitchers With Medial Epicondylitis?

Objective:To determine short-term effects of applied forearm Kinesio Taping (KT) on pain, wrist flexor strength, and force sense for baseball players with medial epicondylitis (ME). Design:Case-control repeated measures study. Setting:Clinical sports medicine research laboratory in a medical university. Participants:A group of 10 baseball players with ME (ME group) and another group of 17 healthy collegiate athletes (healthy group). Intervention:Three taping conditions were applied in both groups: (1) no taping applied, (2) placebo taping applied (PT), and (3) KT applied. Main Outcome Measures:Three variables were measured including maximal wrist flexor strength, related/absolute force sense errors, and pain scale (pressure pain and pain tolerance) under 3 taping conditions. Results:No significant relationship was found either in maximal wrist flexor strength or in related force sense errors between the 2 groups with taping applied, except absolute force sense errors (P = 0.037). Both the healthy group and the ME group in absolute force sense measurement significantly decreased the errors in PT and KT conditions. Also, the tolerance of pressure pain also improved in both the healthy group and the ME group when performing PT and KT conditions. Conclusions:Forearm KT may enhance absolute force sense and improve pain condition for both healthy athletes and athletes suffering from ME when placebo and KT applied. However, KT did not result in significant changes in maximal wrist flexor strength for either group.
Risk Assessment in the 21st Century: Changes Wrought by Changing Science

Krewski et al. (2009) have provided an admirably concise overview of the NRC (2007) report, Toxicity Testing in the 21st Century: A Vision and a Strategy. The full report is rich with insights and ideas, and I would urge readers of Risk Analysis to study its fuller development of the questions addressed by Krewski et al. The NRC Committee envisions not simply the advent of new testing technologies (although these will come) but a consequent shift in the questions that toxicology is able to address and therefore will seek to elucidate. The focus will shift away from apical endpoints in whole animals (with subsequent work attempting to explain underlying causes and to assess their potential operation in humans at environmental exposure levels) and toward detecting perturbation of normal physiology itself as the primary object of testing (with subsequent inferences about the disease processes in humans that might be affected). That is, the flow of inference is being reversed—no longer from ultimate effects backward to potential underlying causes but now from causes forward to their ultimate potential effects. The NRC report argues that this would be more efficient and better able to address concerns such as human relevance, sensitive subpopulations, and interindividual variability. It would be a mistake to regard testing for physiological perturbation as only the development of better biomarkers or predictors of traditional apical endpoints—the perturbations themselves are the object of the envisioned new paradigm in testing. Whether, how quickly, and by what means the NRC’s vision can be realized is a worthy topic of discussion. The vision supposes that our qualitative
Blast cell deficiency of CD11a as a marker of acute megakaryoblastic leukemia and transient myeloproliferative disease in children with and without Down syndrome

The classification of acute myeloid leukemia (AML) FAB subtype M7 relies on immunophenotypic assessment. CD41 is expressed throughout all stages of maturation of megakaryocytes and has therefore been described as a specific blast cell marker in AML M7 as well as in transient myeloproliferative disease (TMD) of patients with Down syndrome (DS). However, technical difficulties underlie the need for new markers for these entities.
Validation of cell‐based fluorescence assays: Practice guidelines from the International Council for Standardization of Haematology and International Clinical Cytometry Society

Bruce H. Davis (brucedavis@trilliumdx.com), Amar Dasgupta (adasgupta@srl.in), Steven Kussick (skussick@phenopath.com), Jin‐Yeong Han (jyhan@dau.ac.kr), Annalee Estrellado (Annalee.L.Estrellado@biogenidec.com), Patrick O'Neil (Patrick.Oneil@beckman.com), Bob Hoffman (bob-hoffman@comcast.net), Norman Purvis (norman.purvis@Nodality.com), Ben Hunsberger (bch@vsh.com), Horacio Vall (vallh@labcorp.com), David Kaplan (david.kaplan@case.edu), Lili Wang (lili.wang@nist.gov), Anna Porwit (anna.porwit@uhn.ca), Shabnam Tangri (Shabnam.Tangri@biogenidec.com), T. Vincent Shankey (Vincent.Shankey@Coulter.com), David Barnett (d.barnett@btconnect.com), Raul Louzao (raul.louzao@duke.edu), Peter Gambell (Peter.Gambell@petermac.org), Jitakshi De (jitakshi@gmail.com), Teri Oldaker (toldaker@cox.net), Curtis Hanson (cahanson@mayo.edu), Brent L. Wood (woodbl@u.washington.edu), Dragan Jevremovic, (jevremovic.dragan@mayo.edu), Marie C. Béné (mariechristine.bene@chu-nantes.fr), Ming Yan (ming_yan@bd.com), Patrick Jacobs (p.jacobs@beckman.com), Virginia Litwin (virginia.litwin@covance.com).
Development and Validation of a Computerized Visual Analog Scale for the Measurement of Pain in Patients With Patellofemoral Pain Syndrome

Objective:To develop a computerized visual analog scale (cVAS) system and determine if it could be used in place of the traditional 100-mm paper-based visual analog scale (pVAS) method for the measurement of pain in patients with patellofemoral pain syndrome (PFPS). Design:Descriptive laboratory study. Setting:Biomechanics laboratory. Participants:Thirty-six runners diagnosed with PFPS. Interventions:A cVAS system was custom-coded for this study. Participants completed both the cVAS survey and a pVAS survey that measured usual knee pain during running, walking, prolonged sitting, stair ascent, stair descent, and squatting movements. Thus, 216 paired measurements were made in total. Main Outcome Measures:Pearson correlation coefficients and slopes of the line of best fit were calculated to assess the relationship between cVAS and pVAS scores, and Bland–Altman plots were constructed to determine cVAS agreement to pVAS scores. Results:All cVAS measures were highly correlated to pVAS scores (all r values were >0.9), and slopes were always near 1.0. Bland–Altman plots demonstrated that there was good agreement between the 2 methods. Conclusions:The cVAS system that was developed is a valid method for measurement of pain in patients with PFPS. Further use of the cVAS for studies involving PFPS is supported.