Miracle-dz/UniFAR-FTUs huggingface dataset:
Regulation by S-Nitrosylation of Protein Post-translational Modification*

Protein post-translational modification by S-nitrosylation conveys a ubiquitous influence of nitric oxide on signal transduction in eukaryotic cells. The wide functional purview of S-nitrosylation reflects in part the regulation by S-nitrosylation of the principal protein post-translational modifications that play a role in cell signaling, including phosphorylation, acetylation, ubiquitylation and related modifications, palmitoylation, and alternative Cys-based redox modifications. In this minireview, we discuss the mechanisms through which S-nitrosylation exerts its broad pleiotropic influence on protein post-translational modification.
Russia's Crash of August 1998: Diagnosis and Prescription

A distinguished French specialist on the Soviet and Russian economies analyzes the financial, political, and institutional crises facing Russia in 1999. Discussion of the vulnerabilities of the economy prior to the crash of 1998 is followed by a suggested program for coping with the currency, banking, and public finance crises, and for building market institutions. Comparisons are drawn with the post-war experiences of France, Italy, and Japan. The article includes an extended critique of the assumptions underlying alternative interpretations and prescriptions.
Lack of correlation among the 3 outcomes describing SLE: disease activity, damage and quality of life.

OBJECTIVE The aim of the this study was to correlate three outcome measures in patients with SLE, namely disease activity, damage, and quality of life. METHODS One hundred and five SLE patients completed the Medical Outcome Survey (MOS) SF-20 during their regular clinic visit. Disease activity (SLEDAI) and damage (SLICC/ACR Damage Index) were assessed according to a standard protocol. Statistical analyses included the Pearson correlation coefficients, a logistic regression, and a linear regression analysis. RESULTS There was no correlation between the SLEDAI and SLICC/ACR DI. There was no correlation between the SLICC/ACR DI and any of the MOS domains by Pearson correlation. Although a statistical correlation was demonstrated between the SLEDAI score and the social functioning and health perception domains of the MOS SF-20, there were not clinically important. CONCLUSION Thus, the three outcomes of disease activity, accumulated damage, and health status remain important independent outcome measures in the assessment of prognosis in patients with SLE.
Early Detection of Breast Cancer in Countries with Limited Resources

Abstract: Breast cancer is commonly diagnosed at late stages in countries with limited resources. Efforts aimed at early detection can reduce the stage at diagnosis, potentially improving the odds of survival and cure, and enabling simpler and more cost‐effective treatment. Early detection of breast cancer entails both early diagnosis in symptomatic women and screening in asymptomatic women. Key prerequisites for early detection are ensuring that women are supported in seeking care and that they have access to appropriate, affordable diagnostic tests and treatment. We therefore propose the following sequential action plan: 1) promote the empowerment of women to obtain health care, 2) develop infrastructure for the diagnosis and treatment of breast cancer, 3) begin early detection efforts through breast cancer education and awareness, and 4) when resources permit, expand early detection efforts to include mammographic screening. Public education and awareness can promote earlier diagnosis, and these goals can be achieved in simple and cost‐effective ways, such as dissemination of messages through mass media. All women have the right to education about breast cancer, but it must be culturally appropriate and targeted and tailored to the specific population. When resources become available for screening, they should be invested in screening mammography, as it is the only modality that has thus far been shown to reduce breast cancer mortality. Clinical breast examination (CBE) and breast self‐examination (BSE) are important components of routine breast care in countries with access to mammography and are important for general breast health education in all countries. However, the evidence does not support the use of CBE and BSE as lifesaving screening methods at this time, recognizing that data from countries with very limited resource are lacking. When widespread screening is not possible, screening can begin in an institution, city, or region, or by targeting screening to women at highest risk. A pilot program can be an ideal way to define the best approach to screening. To succeed, early detection efforts must include the health care providers with whom women have contact; these providers may be physicians, nurses, midwives, traditional healers, or others. There are tremendous differences among and within countries, and a program to promote early detection must be tailored to each country's unique situation.
Antiphospholipid Syndrome and Thrombosis

Antiphospholipid antibodies [such as anticardiolipin antibodies (ACLA)] are strongly associated with thrombosis and appear to be the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagulable state remain unclear, several theories have been advanced. The most common thrombotic events associated with ACLA are deep vein thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome) or cerebrovascular/retinal vessel thrombosis (type III syndrome), and occasionally patients present with mixtures (type IV syndrome). Type V patients are those with antiphospholipid antibodies and fetal wastage syndrome. It is as yet unclear how many seemingly normal individuals who may never develop manifestations of antiphospholipid syndrome (type VI) harbor asymptomatic antiphospholipid antibodies. The relative frequency of ACLA in association with arterial and venous thrombosis strongly suggests that these should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I through VI) should be defined, if possible, as this may dictate both type and duration of both immediate and long-term anticoagulant therapy. Unlike those with ACLA, patients with primary lupus anticoagulant thrombosis syndrome usually suffer venous thrombosis. Because the activated partial thromboplastin time (aPTT) is unreliable in patients with lupus anticoagulant (prolonged in only about 40 to 50% of patients) and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests including ELISA for ACLA, the dRVVT for lupus anticoagulant, hexagonal phospholipid neutralization procedure, and B-2-GP-I (IgG, IgA, and IgM) should be immediately ordered when suspecting antiphospholipid syndrome or in individuals with otherwise unexplained thrombotic or thromboembolic events. If these are negative, in the appropriate clinical setting, subgroups should also be assessed. Finally, most patients with antiphospholipid thrombosis syndrome will fail warfarin therapy and, except for retinal vascular thrombosis, most will fail antiplatelet therapy, thus it is of major importance to make this diagnosis in order that patients can be treated with the most effective therapy for secondary prevention, low-molecular weight heparin (LMWH) or unfractionated heparin (UHF) in most instances.
Stroke Prevention in Atrial Fibrillation

New orally administered anticoagulants will simplify stroke-prevention strategies in patients with atrial fibrillation (AF). Novel anticoagulants, such as dabigatran etexilate, a direct thrombin inhibitor, and rivaroxaban, a direct factor Xa inhibitor, have been approved by the US Food and Drug Administration for the prevention of stroke and systemic embolism in patients with nonvalvular AF. In addition, the factor Xa inhibitor apixaban has been reported to be as effective as warfarin in a large, randomized clinical trial, and the efficacy of edoxaban is being assessed in a phase III warfarin comparison trial. This review discusses the limitations of vitamin K antagonist therapy for patients with AF and establishes the need for alternative, effective anticoagulation with an improved benefit–risk ratio for the prevention of stroke. Novel anticoagulants have the potential to provide convenient, effective stroke prophylaxis without many of the issues inherent in the use of traditional agents.
Costimulation Blockade in Autoimmunity and Transplantation: The CD28 Pathway

T cell activation is a complex process that requires multiple cell signaling pathways, including a primary recognition signal and additional costimulatory signals. TCR signaling in the absence of costimulatory signals can lead to an abortive attempt at activation and subsequent anergy. One of the best-characterized costimulatory pathways includes the Ig superfamily members CD28 and CTLA-4 and their ligands CD80 and CD86. The development of the fusion protein CTLA-4–Ig as an experimental and subsequent therapeutic tool is one of the major success stories in modern immunology. Abatacept and belatacept are clinically approved agents for the treatment of rheumatoid arthritis and renal transplantation, respectively. Future interventions may include selective CD28 blockade to block the costimulatory potential of CD28 while exploiting the coinhibitory effects of CTLA-4.
Mean Platelet Volume and Extent and Complexity of Coronary Artery Disease in Diabetic and Nondiabetic Patients With ST Elevation Myocardial Infarction

We investigated whether the mean platelet volume (MPV) is associated with the extent and complexity of coronary artery disease in patients with ST elevation myocardial infarction (STEMI). We prospectively included 912 STEMI patients (663 male and 249 female; mean age 58.7 ± 12.4 years) who underwent primary percutaneous coronary intervention. The patients were divided into 3 groups according to MPV tertiles. Highest SYNTAX score (SS) was observed in MPVhigh group compared with MPVmid and MPVlow groups (P < .001 for all). The SS of MPVmid group was higher than MPVlow group (P = .036). The MPV in diabetic STEMI patients was higher than in nondiabetic STEMI patients (P < .001). Multivariate linear regression analysis showed that the MPV was associated with diabetes (β = .115, P = .001), troponin level (β = .131, P = .001), platelet count (β = −.241, P < .001), and SS (β = .216, P < .001). The relation between MPV and SS in diabetic STEMI patients was stronger than for nondiabetic STEMI patients (r = .473, P < .001 vs r = .129, P = .001).
What "price" means when buying food: insights from a multisite qualitative study with Black Americans.

OBJECTIVES We explored the role of price in the food purchasing patterns of Black adults and youths. METHODS We analyzed qualitative data from interviews and focus groups with socioeconomically diverse, primarily female, Black adults or parents (n = 75) and youths (n = 42) in 4 US cities. Interview protocols were locality specific, but all were designed to elicit broad discussion of food marketing variables. We performed a conventional qualitative content analysis by coding and analyzing data from each site to identify common salient themes. RESULTS Price emerged as a primary influence on food purchases across all sites. Other value considerations (e.g., convenience, food quality, healthfulness of product, and family preferences) were discussed, providing a more complex picture of how participants considered the price of a product. CONCLUSIONS Food pricing strategies that encourage consumption of healthful foods may have high relevance for Black persons across income or education levels. Accounting for how price intersects with other value considerations may improve the effectiveness of these strategies.
Impaired modulation of sympathetic α‐adrenergic vasoconstriction in contracting forearm muscle of ageing men

Recent evidence indicates that older healthy humans demonstrate greater vasoconstrictor tone in their active muscles during exercise compared with young adults. Therefore, we tested the hypothesis that the normal ability of muscle contractions to blunt sympathetic α‐adrenergic vasoconstriction (functional sympatholysis) is impaired with age in healthy humans. We measured forearm blood flow (FBF; Doppler ultrasound) and calculated the forearm vascular conductance (FVC) responses to α‐adrenergic receptor stimulation during rhythmic handgrip exercise (15% maximum voluntary contraction) and during a control non‐exercise vasodilator condition (intra‐arterial adenosine infusion) in seven young (25 ± 2 years) and eight healthy older men (65 ± 2 year). FVC responses to intra‐arterial tyramine (evokes endogenous noradrenaline release), phenylephrine (α1‐agonist) and clonidine (α2‐agonist) were assessed. In young men, the vasoconstrictor responses to tyramine (−25 ± 1 versus−56 ± 6%), phenylephrine (−11 ± 4 versus−39 ± 4%) and clonidine (−12 ± 4 versus−38 ± 5%; all P < 0.005) were blunted during exercise compared with adenosine. In contrast, exercise did not significantly blunt the response to tyramine (−30 ± 2 versus−36 ± 7%; P= 0.4) or phenylephrine (−16 ± 2 versus−19 ± 3%; P= 0.3) in older men, but did attenuate the response to clonidine (−22 ± 3 versus−37 ± 6%; P < 0.05). The magnitude of functional sympatholysis, calculated as the difference in the vasoconstrictor responses during adenosine infusion and exercise, was significantly lower in older compared with young men in the presence of tyramine (−6 ± 7 versus−31 ± 6%), phenylephrine (−3 ± 3 versus−28 ± 4%) and clonidine (−15 ± 4 versus−26 ± 3%; all P < 0.05). We conclude that ageing is associated with impaired functional sympatholysis in the vascular beds of contracting forearm muscle in healthy men. These findings might help explain the greater skeletal muscle vasoconstrictor tone and reduced blood flow during large muscle dynamic exercise in older adults.
The Effects of Exercise-Induced Muscle Damage on Cycling Time-Trial Performance

Burt, DG and Twist, C. The effects of exercise-induced muscle damage on cycling time-trial performance. J Strength Cond Res 25(8): 2185-2192, 2011—Previous research has advocated that plyometric training improves endurance performance. However, a consequence of such a training is the immediate and prolonged appearance of exercise-induced muscle damage (EIMD). This study examined whether a single bout of plyometric exercise, designed to elicit muscle damage, affected cycling endurance performance. Seventeen participants were randomly assigned to either a muscle damage (n = 7 men, 1 woman) or nonmuscle damage (n = 8 men, 1 woman) group. Before and at 48 hours, participants were measured for perceived muscle soreness, peak isokinetic strength, and physiological, metabolic, and perceptual responses during 5-minute submaximal cycling at ventilatory threshold (VT) and a 15-minute time trial. Perceived muscle soreness and isokinetic strength (p < 0.05) were significantly altered in the muscle damage group after EIMD. No changes in heart rate or blood lactate were evident during submaximal exercise (p > 0.05). However, &OV0312;o2, &OV0312;E, and rating of perceived exertion (RPE) values were increased at VT in the muscle damage group at 48 hours after EIMD (p < 0.05). During the time trial, mean power output, distance covered, and &OV0312;o2 were lower in the muscle damage group at 48 hours after EIMD (p < 0.05). However, there was no change in RPE (p > 0.05), suggesting effort perception was unchanged during time-trial performance after EIMD. In conclusion, individuals using concurrent plyometric and endurance training programs to improve endurance performance should be aware of the acute impact of muscle-damaging exercise on subsequent cycling performance.
Swiss national community survey on functioning after spinal cord injury: Protocol, characteristics of participants and determinants of non-response.

OBJECTIVE To detail the protocol, recruitment, study population, response, and data quality of the first population-based community survey of the Swiss Spinal Cord Injury (SwiSCI) Cohort Study. DESIGN The survey consisted of 3 successive modules administered between September 2011 and March 2013. The first two modules queried demographics, lesion characteristics and key domains of functioning. The third module collected information on psychological personal factors and health behaviour; work integration; or health services and aging. PARTICIPANTS Community-dwelling persons with chronic spinal cord injury in Switzerland. METHODS Descriptive analyses of the recruitment process, participant characteristics, and correspondence between self-reported and clinical data. Determinants for participation and the impact of non-response on survey results were assessed. RESULTS Out of 3,144 eligible persons 1,549 participated in the first two modules (cumulative response rate 49.3%). Approximately three-quarters of participants were male, with a median age of 53 years, and 78% had traumatic spinal cord injury. Record-linkage with medical records demonstrated substantial agreement with self-reported demographic and lesion characteristics. A minimal non-response bias was found. CONCLUSIONS The community survey was effective in recruiting an unbiased sample, thus providing valuable information to study functioning, health maintenance, and quality of life in the Swiss SCI community.
α‐Adducin Translocates to the Nucleus upon Loss of Cell–Cell Adhesions

The F‐actin binding protein adducin plays an important role in plasma membrane stability, cell motility and cell–cell junctions. In this study, we demonstrate that α‐adducin is mainly localized in the nucleus of sparsely cultured epithelial cells, whereas it is localized at cell–cell junctions when the cells are grown to confluence. Disruption of cell–cell adhesions induces a nuclear translocation of α‐adducin. Conversely, α‐adducin is redistributed to the cytoplasm and cell–cell junctions in the process of establishing cell–cell adhesions. We identify that α‐adducin contains a bipartite nuclear localization signal (NLS) in its COOH‐terminal tail domain and a nuclear export signal in its neck region. The phosphorylation of α‐adducin at Ser716 that is immediately adjacent to the NLS appears to antagonize the function of the NLS. Moreover, we show that depletion of α‐adducin has adverse effects on cell–cell adhesions and, to our surprise, cell proliferation. The impaired cell proliferation is associated with mitotic defects characterized by disorganized mitotic spindles, aberrant chromosomal congregation/segregation and abnormal centrosomes. Taken together, our results not only reveal the mechanism for α‐adducin to shuttle between the cytoplasm and nucleus, but also highlight a potential role for α‐adducin in mitosis.
A novel multiscale nonlinear thresholding method for ultrasonic speckle suppressing

This paper presents a novel speckle suppression method for medical B-scan ultrasonic images. An original image is first separated into two parts with an adaptive filter. These two parts are then transformed into a multiscale wavelet domain and the wavelet coefficients are processed by a soft thresholding method, which is a variation of Donoho's (1995) soft thresholding method. The processed coefficients for each part are then transformed back into the space domain. Finally, the denoised image is obtained as the sum of the two processed parts. A computer-simulated image and an in vitro B-scan image of a pig heart have been used to test the performance of this new method. This technique effectively reduces the speckle noise, while preserving the resolvable details. It performs well in comparison to the multiscale thresholding technique without adaptive preprocessing and two other speckle-suppression methods.
Causes and Risk Factors for Liver Injury Following Bone Marrow Transplantation

Goals: A retrospective study of pretransplantation risk factors predisposing to liver injury following bone marrow transplantation (BMT). Background: Liver complications are a major cause of morbidity and mortality following BMT. Determination of the pretransplantation factors that are likely to lead to liver injury may allow earlier diagnosis after BMT and may possibly improve prognosis. Study: Medical records of BMT patients were reviewed, and results of serial liver function tests and HBV/HCV serology during the pre‐ and posttransplantation 1‐year period were noted. Presence of liver injury was defined as alanine aminotransferase levels twice the upper limit of normal. Forty‐four allogeneic and 17 autologous BMTs, performed between 1990 and 2000, were analyzed in the study. Results and Conclusion: One‐year survival was 77% (34 of 44 patients) for allogeneic BMT and 52% (9 of 17 patients) for autologous BMT. Seventy‐two percent (32 of 44) of allogeneic transplant recipients and 47% (8 of 17) of autologous transplant recipients had liver injury during the first year of BMT. The most frequent causes of liver injury were graft‐versus‐host disease and drug hepatotoxicity for allogeneic BMT and drug hepatotoxicity for autologous BMT. Fulminant hepatic failure occurred in one allogeneic transplant recipient who was a pretrans‐plantation HBV carrier and led to death. Multivariate regression analysis showed that pretransplantation HBV/HCV positivity and pretransplantation elevated liver enzyme levels of any cause were predictive risk factors for post‐BMT liver injury, and close follow‐up, early diagnosis, and treatment are highly recommended for BMT patients with these risk factors.
Implementation of Self-Directed Supports for Individuals with Intellectual and Developmental Disabilities: A Political Economy Analysis

Self-directed supports, as a method of service delivery, have grown from small pilot programs in a handful of states to at least one program in every state. For individuals with intellectual and developmental disabilities (IDD), self-direction presents unique opportunities to engage in selfdetermined behavior and shape the services upon which they rely. Although the evidence base for self-direction is relatively robust, there is a significant lack of information on how implementation of self-direction is faring on the national level. The purpose of this study is to understand how the political and economic factors within and across states have impacted the implementation of a self-directed service delivery system.