Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of Anti‐TNF‐α Treatment on Lipid Profile in Patients with Active Rheumatoid Arthritis

Abstract: Cardiovascular morbidity and mortality appear to be increased in rheumatoid arthritis (RA), which might be due to increased prevalence of risk factors for cardiovascular disease, such as an accelerated progression of atherosclerosis. Patients with active RA frequently show an atherogenic lipid profile, which has been linked with the inflammatory reaction. Tumor necrosis factor‐α (TNF‐α), a pivotal proinflammatory cytokine implicated in the pathogenesis of atherosclerosis in RA, may be involved in the development of the altered lipid profile observed in active RA. Our aim was to investigate the effects of anti‐TNF‐α treatment in combination with methotrexate (MTX) and corticosteroid therapy on lipid profile in patients with active RA. In this prospective study 34 consecutive RA patients were included (all women, mean age 51.6 ± 7.9 years, range 46–72 years) with active (defined as Disease Activity Index 28 joint score [DAS‐28], of at least 3.2) and refractory RA, in stable treatment with MTX (7.5–10 mg/week) and prednisone (7.5–10 mg/day) for 3 months. All patients received TNF‐α blockers (n= 16, etanercept 25 mg twice weekly; n= 14, infliximab 3 mg/kg on 0, 2, 6, and every 8 weeks thereafter; and finally, n= 4, adalimumab 40 mg every other week). Total cholesterol, high‐density lipoprotein cholesterol (HDL cholesterol), triglycerides (TG) and lipoprotein (a) [Lp(a)] levels and the atherogenic index (ratio cholesterol/HDL cholesterol) were measured at base line, and at 16 and 24 weeks. Results were as follows: The DAS‐28 was 6.9 ± 2.1 at base line and decreased to 4.6 ± 1.8 after 16 weeks, and further to 4.1 ± 1.3 after 24 weeks (both, P < 0.01). Following anti‐TNF‐α treatment, the mean levels of total cholesterol were 168 ± 24 mg/dL at base line and increased to 188 ± 28 mg/dL at 16 weeks (P < 0.01), and 197 ± 26 mg/dL at 24 weeks (P < 0.001). However, also the mean levels of HDL cholesterol were significantly higher than basal values after 16 and 24 weeks of treatment (34 ± 12 mg/dL versus 36 ± 18 mg/dL [P < 0.05] and 38 ± 14 mg/dL [P < 0.01], respectively). TG and Lp(a) levels, as well as the atherogenic index were not significantly changed. Interestingly, variations in disease activity were significantly and inversely correlated with HDL cholesterol levels. In conclusion: Short anti‐TNF‐α treatment was associated with a significant increase of both total cholesterol and HDL cholesterol levels, and correlated with decreased disease activity. The atherogenic index showed no changes during the study. Therefore, anti‐TNF‐α treatment might affect lipid profile in RA patients.
3-D Mesh Adaptation on Multiple Weak Discontinuities and Boundary Layers

This paper presents new developments within an anisotropic mesh adaptation methodology, made essentially by the introduction of a metric modification and a shock-filter model that allow crisp capturing of weak shocks, as well as boundary layers and wakes. Inviscid and laminar external flow tests are used to demonstrate the efficiency of the method.
Risk factors for nonvertebral fracture in obese older women.

CONTEXT A high prevalence of obesity has recently been reported in postmenopausal women with low trauma fracture, suggesting that higher bone mineral density (BMD) in obese individuals may not be protective against fracture. OBJECTIVE The aim of this study was to compare BMD and other risk factors for nonvertebral fracture in 1377 obese postmenopausal women. DESIGN Characteristics of obese women with and without incident nonvertebral fracture were investigated among the prospective cohort in the Study of Osteoporotic Fractures. SETTING The Study of Osteoporotic Fractures is a multicenter study of 9704 women (>99% Caucasian) aged 65 yr and over who were recruited between September 1986 and October 1988 from population-based listings at four U.S. clinical centers. MAIN OUTCOME MEASURE The main outcome measure was nonvertebral fracture. RESULTS BMD T-scores in the spine, femoral neck, and total hip were significantly lower in obese women who experienced fractures than in obese women without fracture: mean differences, -0.56 [95% confidence interval (CI) = -0.73 to -0.39], -0.46 (95% CI = -0.57 to -0.36), and -0.51 (95% CI = -0.62 to -0.39), respectively (P < 0.0001 for all). A previous history of fracture [odds ratio = 1.69 (95% CI = 1.33-2.14); P < 0.0001] and femoral neck BMD [1.62 (95% CI = 1.42-1.85) per sd decrease in BMD; P < 0.0001] were independently associated with incident nonvertebral fracture. CONCLUSIONS Obese postmenopausal women who sustain nonvertebral fractures have significantly lower BMD on average than obese women without fracture and are more likely to have a past history of fracture. Fractures in obese postmenopausal women thus exhibit some characteristics of fragility fractures.
A randomized trial of prophylactic palifermin on gastrointestinal toxicity after intensive induction therapy for acute myeloid leukaemia

Gastrointestinal toxicity, including oral mucositis, is a frequent complication of intensive combination chemotherapy for acute myeloid leukaemia (AML) and contributes substantially to treatment‐related mortality. We conducted a placebo‐controlled randomized trial to evaluate the efficacy of palifermin (keratinocyte growth factor), given at 60 μg/kg per daily IV for 3 d before and after chemotherapy, for mucosal protection in adult patients with previously untreated AML receiving induction therapy with idarubicin, high‐dose cytarabine and etoposide. Among 155 randomized patients, there was no statistically significant difference in the rate of grade 3 and 4 oral mucositis (primary study endpoint) between the two treatment arms (three in palifermin arm (4%), 8 in placebo arm (10%; P = 0·21); however, when considering the severity of oral mucositis (World Health Organization grade 0–4), there was evidence of reduced rates of higher grades of oral mucositis in the palifermin arm (P = 0·0007, test for trend). There was a statistically significantly lower rate of grades 3 and 4 gastrointestinal adverse events in the palifermin arm (21% vs. 44% in placebo arm; P = 0·003), mainly due to a reduction in severe diarrhoea (8% palifermin, 26% placebo; P = 0·01). Palifermin has activity as a mucosal protectant in AML patients receiving intensive chemotherapy. This trial is registered at ACTRN012605000095662.
Aromatase excess syndrome: identification of cryptic duplications and deletions leading to gain of function of CYP19A1 and assessment of phenotypic determinants.

CONTEXT Aromatase excess syndrome (AEXS) is a rare autosomal dominant disorder characterized by gynecomastia. Although cryptic inversions leading to abnormal fusions between CYP19A1 encoding aromatase and its neighboring genes have been identified in a few patients, the molecular basis remains largely unknown. OBJECTIVE The objective of the study was to examine the genetic causes and phenotypic determinants in AEXS. PATIENTS Eighteen affected males from six families participated in the study. RESULTS We identified three types of heterozygous genomic rearrangements, i.e. a 79,156-bp tandem duplication involving seven of 11 noncoding CYP19A1 exons 1, a 211,631-bp deletion involving exons 2-43 of DMXL2 and exons 5-10 of GLDN, and a 165,901-bp deletion involving exons 2-43 of DMXL2. The duplicated exon 1 functioned as transcription start sites, and the two types of deletions produced the same chimeric mRNA consisting of DMXL2 exon 1 and CYP19A1 coding exons. The DMXL2 exon 1 harbored a translation start codon, and the DMXL2/CYP19A1 chimeric mRNA was identified in only 2-5% of CYP19A1-positive transcripts. This was in contrast to the inversion-mediated chimeric mRNA that had no coding sequence on the fused exon 1 and accounted for greater than 80% of CYP19A1-positive transcripts. CYP19A1 was expressed in a limited number of tissues, whereas its neighboring genes involved in the chimeric mRNA formation were expressed widely. CONCLUSIONS This study provides novel mechanisms leading to gain of function of CYP19A1. Furthermore, it appears that clinical severity of AEXS is primarily determined by the tissue expression pattern of relevant genes and by the structural property of promoter-associated exons of chimeric mRNA.
The Arabic version of the Parental Stressor Scale: psychometric properties and Jordanian parents’ stress during child admission to PICU

This paper presents an exploration of the validity and reliability of the translated Arabic version of the original English version of the Parental Stressor Scale: Paediatric Intensive Care Unit (PSS: PICU) with a sample of Jordanian parents of children admitted to a paediatric intensive care unit. Three hundred and fifty parents were recruited to the study. The PSS: PICU was completed by parents within 15 minutes. Data were collected from parents (N = 350) from different governmental, private and educational hospitals in Amman, Jordan. Subscales measuring stress from Child’s Appearance, Procedures, Sights and Sounds, Staff Communication, Staff Behavior, Parental Role, and Child’s Behavior and Emotions showed a range of responses and showed good internal consistency. Parents in this study perceived stress from various sources during their child’s hospitalisation. The dimensions ranked most stressful in the PICU were procedures (mean = 3.8, standard deviation, SD = 1.11), the child’s behaviors and emotions (mean = 3.72, SD = 1.04) and child’s appearance (mean = 3.71, SD = 0.75). The least listed stressful items were behaviors of professional staff in the unit (mean = 2.19, SD = 0.73), and staff communication in the unit (mean = 2.25, SD = 0.81). The reported elevated levels of parental stress underscores the importance of ongoing screening for factors impacting on psychological well-being and the inclusion of this information in education and counseling strategies in the inpatient settings. Consideration of areas of parent education regarding stressful ICU environment, and children’s behavioral and emotional reaction to hospitalisation could help reduce stress for Jordanian parents.
Long‐acting recombinant factor IX Fc fusion protein (rFIXFc) for perioperative management of subjects with haemophilia B in the phase 3 B‐LONG study

In the phase 3 B‐LONG (Recombinant Factor IX Fc Fusion Protein [rFIXFc] in Subjects With Haemophilia B) study, rFIXFc demonstrated a prolonged half‐life compared with recombinant factor IX (rFIX), and safety and efficacy for prophylaxis and treatment of bleeding in subjects with moderately‐severe to severe haemophilia B. In this B‐LONG sub‐analysis, rFIXFc was evaluated for efficacy in subjects requiring major surgery. Dosing was investigator‐determined. Assessments included dosing, consumption, bleeding, transfusions and haemostatic response. A population pharmacokinetics model of rFIXFc was used to predict FIX activity. Twelve subjects underwent 14 major surgeries (including 11 orthopaedic surgeries); most subjects (11/12) received rFIXFc prophylaxis before surgery (range, ~2 weeks–12 months). Investigators/surgeons rated haemostatic responses as excellent (n = 13) or good (n = 1). In most surgeries (85·7%), haemostasis from the pre‐surgical dose until the end of surgery was maintained with a single rFIXFc infusion. Blood loss was consistent with similar surgeries in subjects without haemophilia. The strong correlation (R2 = 0·9586, P < 0·001) between observed and population pharmacokinetic model‐predicted FIX activity suggests surgery did not impact rFIXFc pharmacokinetics. No unique safety concerns or inhibitors were observed. In conclusion, rFIXFc was safe and efficacious, with prolonged dosing intervals and low consumption, when used perioperatively in haemophilia B. Surgery did not appear to alter rFIXFc pharmacokinetics.
A Trust Region Method for Nonlinear Programming Based on Primal Interior-Point Techniques

This paper describes a new trust region method for solving large-scale optimization problems with nonlinear equality and inequality constraints. The new algorithm employs interior-point techniques from linear programming, adapting them for more general nonlinear problems. A software implementation based entirely on sparse matrix methods is described. The software handles infeasible start points, identifies the active set of constraints at a solution, and can use second derivative information to solve problems. Numerical results are reported for large and small problems, and a comparison is made with other large-scale optimization codes.
Adaptively Preconditioned GMRES Algorithms

The restarted GMRES algorithm proposed by Saad and Schultz [SIAM J. Sci. Statist. Comput. , 7 (1986), pp. 856--869] is one of the most popular iterative methods for the solution of large linear systems of equations Ax=b with a nonsymmetric and sparse matrix. This algorithm is particularly attractive when a good preconditioner is available. The present paper describes two new methods for determining preconditioners from spectral information gathered by the Arnoldi process during iterations by the restarted GMRES algorithm. These methods seek to determine an invariant subspace of the matrix A associated with eigenvalues close to the origin and to move these eigenvalues so that a higher rate of convergence of the iterative methods is achieved.
Serum level of triglycerides is a potent risk factor comparable to LDL cholesterol for coronary heart disease in Japanese patients with type 2 diabetes: subanalysis of the Japan Diabetes Complications Study (JDCS).

CONTEXT Risk factors for cardiovascular complications in Japanese patients with diabetes have not been fully elucidated. OBJECTIVE Our objective was to determine incidence of and risk factors for coronary heart disease (CHD) and stroke in Japanese diabetic patients. DESIGN AND SETTINGS We conducted a prospective study at 59 hospitals throughout Japan. PATIENTS Patients included 940 men and 831 women with type 2 diabetes (mean age, 58.2 yr) without a history of cardiovascular complications who were followed for a median of 7.86 yr. INTERVENTION This was an observational study. MAIN OUTCOME MEASURES Incidence of CHD and stroke was evaluated. RESULTS Incidences of CHD and stroke per 1000 person-years were 9.59 and 7.45, respectively, whereas those of myocardial and brain infarctions were 3.84 and 6.29, respectively. Multivariate Cox analysis revealed that the serum log-transformed triglyceride level was a potent and independent predictor of CHD [hazard ratio (HR) = 1.54; 95% confidence interval (CI) = 1.22-1.94 per 1 sd increase), comparable to low-density lipoprotein (LDL) cholesterol (HR = 1.49; 95% CI = 1.25-1.78 per 1 sd increase). Triglycerides and LDL cholesterol linearly and continuously increased CHD risk, and subjects in the top third for both had markedly high risks of CHD, and their effects were possibly additive. However, serum triglycerides worked independently of blood pressure levels. Systolic blood pressure was the only significant predictor for stroke except for age (HR = 1.31; 95% CI = 1.04-1.65, per 1 sd increase). CONCLUSIONS In Japanese patients with type 2 diabetes, the serum triglyceride level was a leading predictor of CHD, comparable to LDL cholesterol. Because the serum triglyceride level is not a leading predictor of CHD in diabetic subjects in Western countries, ethnic group-specific strategies for prevention of diabetic macroangiopathy may be indicated.
Factors predicting survival in peripheral T‐cell lymphoma in the USA: a population‐based analysis of 8802 patients in the modern era

Current prognostic models for peripheral T‐cell lymphoma (PTCL) have multiple limitations, and questions exist regarding applicability to current patients. We utilized the Surveillance Epidemiology and End Results (SEER)‐18 database to evaluate factors affecting overall survival (OS) of PTCL in the modern era and identified 8802 patients between 2000–2010. Most subtypes of PTCL increased in incidence during the study period. In univariate analyses, age >55 years, black race, advanced stage, absence of extra‐nodal disease, omission of radiation therapy (RT) and high‐risk histology each predicted inferior OS (P < 0·0001). Multivariate analysis (MVA) demonstrated that hepatosplenic, enteropathy‐associated and extra‐nodal Natural Killer/T cell histologies, each had hazard ratios >1·5 (P ≤ 0·0001) for death. Further, age ≥55 years, black race and advanced stage maintained their significance in the MVA (P < 0·0001 each). Based on the significant factors, a prognostic model was constructed and subsequently validated in an independent cohort. The new model incorporated age, stage, histology and race, with an OS ranging from 9 months (highest risk group) to 120 months (lowest risk group). In summary, this is the largest study of PTCL patients in the modern era that provides risk stratification utilizing a new prognostic model that can be incorporated into future prospective clinical trials.
Cybernetics, or Control and Communication in the Animal and the Machine.

This is an extremely thought-provoking book, by the professor of mathematics of the Masachusetts Institute of Technology. The subject matter ranges from mathematical calculators to the nerves and brain of the human body. It is the outcome of a monthly series of discussion meetings, the participants of which were mostly young scientists at the Harvard Medical School who gathered for dinner about a round table in Vanderbilt Hall. At each meeting, one of the group or an invited guest would read a paper on some scientific topic, generally one in which methods of methodology were the first consideration. General discussion followed, and the meetings were apparently not for those who were unable to stand frank criticism. The author, whose field is mathematics, was therefore exposed to experts in many different fields of biology and medicine. He soon became aware that there were common grounds and that the problems of one
On the Approximate Cyclic Reduction Preconditioner

We present a preconditioning method for the iterative solution of large sparse systems of equations. The preconditioner is based on ideas both from ILU preconditioning and from multigrid. The resulting preconditioning technique requires the matrix only. A multilevel structure is obtained by using maximal independent sets for graph coarsening. A Schur complement approximation is constructed using a sequence of point-Gaussian elimination steps. The resulting preconditioner has a transparent modular structure similar to the algorithmic structure of a multigrid V-cycle.
Maintenance lenalidomide in combination with 5‐azacitidine as post‐remission therapy for acute myeloid leukaemia

In this Phase 1b study, the safety and tolerability of maintenance therapy, comprising lenalidomide (0–25 mg, days 5–25) in combination with azacitidine (50–75 mg/m2, days 1–5) every 28 d, was explored in 40 patients with acute myeloid leukaemia (AML) in complete remission after chemotherapy. Eligibility included AML in first complete remission (CR1) with adverse risk karyotype (n = 8), fms‐related tyrosine kinase 3‐internal tandem duplication (FLT3‐ITD) (n = 5), age ≥60 years (n = 31) or AML in second remission (CR2) (n = 14). Dose‐limiting toxicity was not reached. Common toxicities were haematological, infection, injection pain, constipation, fatigue and diarrhoea. In CR1, median relapse‐free (RFS) and overall survival (OS) was 12 and 20 months, respectively. In CR2, median RFS was 11 months, with median OS not yet reached. Among 29 patients with intermediate cytogenetic risk, RFS was 50% at 24 months. There were five patients with concomitant FLT3‐ITD and nucleophosmin (NPM1) mutation; none have relapsed and all are still alive after 17–39 months. Maintenance lenalidomide/azacitidine augmented the function of cytotoxic T lymphocytes, particularly in patients with NPM1 mutation. The lenalidomide/azacitidine maintenance combination was effective in suppressing residual DNA (cytosine‐5‐)‐methyltransferase 3 alpha (DNMT3A)‐positive disease, resulting in sustained remission in patients with concurrent NPM1 mutation. Azacitidine/lenalidomide as maintenance therapy for high‐risk AML warrants further exploration.
Long‐term outcome of patients with acquired chronic pure red cell aplasia (PRCA) following immunosuppressive therapy: a final report of the nationwide cohort study in 2004/2006 by the Japan PRCA collaborative study group

Immunosuppressive therapy has been employed as the initial treatment for acquired chronic pure red cell aplasia (PRCA), such as idiopathic, thymoma‐associated, or large granular lymphocyte (LGL) leukaemia‐associated PRCA, which is thought to be immune‐mediated. To explore the overall long‐term outcome following immunosuppression and to identify the risk factors for death in these disorders, we conducted nationwide surveys in Japan 2004 and 2006, and identified a total of 185 patients with acquired chronic PRCA, including 72 idiopathic, 41 thymoma‐associated and 14 LGL leukaemia‐associated cases of PRCA for whom data was available. The present study evaluated 127 patients with these three subsets of PRCA. The median overall survival has not yet been reached in idiopathic PRCA. The estimated median overall survival times in patients with thymoma‐associated and LGL leukaemia‐associated PRCA were 142·1 and 147·8 months, respectively. Twenty‐two deaths were reported, and the response to induction therapy and relapse of anaemia were found to be associated with death. The major causes of death were infection in seven patients and organ failure in another seven patients. The results suggest that maintenance therapy and the management of infectious complications are crucial for improving the prognosis of chronic PRCA.
Poor functional antibody responses are present in nearly all patients with chronic lymphocytic leukaemia, irrespective of total IgG concentration, and are associated with increased risk of infection

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Are soy foods protective against ischemic stroke

Ischemic stroke is one of the leading causes of mortality and morbidity in the world. A large number of studies have observed the beneficial effects of soy protein and soy polyunsaturated fat in lowering blood cholesterol, reducing blood pressure and improving cardiovascular health. This study aims to investigate the potential of a soy food diet in the prevention of ischemic stroke through evaluation of evidence from clinical trials, meta-analyses, experimental and epidemiological studies.