Miracle-dz/UniFAR-FTUs huggingface dataset:
UK consultant rheumatologists' access to biological agents and views on the BSR Biologics Register.

OBJECTIVES The British Society for Rheumatology Biologics Register (BSRBR) is a prospective cohort study to determine the efficacy and toxicity of biological agents in rheumatoid arthritis (RA) patients compared with RA controls. Entry of patients to the register is a condition of use of anti-tumour necrosis factor (anti-TNF) therapy in the UK, but little is known of clinicians' views of its usefulness. Data from the register suggest uneven provision of anti-TNF-alpha therapy. METHODS A questionnaire was sent on behalf of the BSRBR to all UK consultant rheumatologists concerning provision and use of anti-TNF-alpha therapy and their experience of working with the BSRBR. RESULTS Response rate was 49.5% representing 252 consultants. Fourty-six per cent had some limitation of access to anti-TNF-alpha drugs, usually a financial cap (70%), even for RA patients meeting National Institute for Health and Clinical Excellence (NICE) criteria. Sixty-seven per cent could prescribe for ankylosing spondylitis (AS) or psoriatic arthritis (PsA) in some circumstances but only 25 and 35%, respectively, could prescribe according to BSR guidance. More than 50% found the workload involved in submitting data to the registry at least difficult, but most had favourable impressions of the BSRBR and thought similar registries desirable or essential for PsA, AS and rituximab. CONCLUSIONS Access to anti-TNF therapy for patients with inflammatory arthritis is variable in the UK, even for RA where it is NICE-approved. Access is more limited for conditions where NICE has not yet issued guidance. The BSRBR generates a significant workload for rheumatology staff but is generally well-regarded.
Renal glomerular and tubular function in neonates with perinatal problems

Objective. To investigate perinatal risk factors that may be associated with impaired renal function during the first 2 weeks of life. Methods. The case notes of 150 neonates of gestational age (GA) 34–36 weeks and 494 of GA > 36 weeks were studied. Clinical risk factors were retrieved, along with indices of renal function: serum creatinine (SeCr), fractional excretion (FE) of sodium (FENa) and potassium (FEK), and the urinary calcium to creatinine ratio (UCa/UCr). Associations were identified by multiple and logistic regression analysis. Results. In infants with GA > 36 weeks, raised SeCr was related to perinatal stress, odds ratio (OR): 1.9, confidence interval (CI): 1.2–2.9, p < 0.05, and to duration of treatment with aminoglycosides (AGs) (t = 2.4, p < 0.01); FEK was associated with jaundice (t = −3.1, p < 0.01), and FENa with duration of AGs treatment (t = 2.6, p < 0.01). Full-term neonates with both hypoxic-ischemic encephalopathy (HIE) and AGs administration had an 80% increase in OR for impaired SeCr levels. In infants of GA 34–36 weeks, SeCr was related to perinatal stress (OR: 9, CI: 1.3–38, p < 0.05), FEK to jaundice (t = −2.1, p < 0.05), and FENa to duration of AGs administration (t = 2.2, p < 0.05) and antenatal steroid treatment (OR: 0.8, CI: 0.6–0.95, p < 0.05). Conclusion. In neonates, renal impairment, being multifactorial in origin, may be caused by the additive effect of different perinatal factors. The strong negative relationship observed between jaundice and K excretion merits further investigation.
Dietary epicatechin intake and 25-y risk of cardiovascular mortality: the Zutphen Elderly Study.

BACKGROUND Prospective cohort studies have shown that the consumption of cocoa and tea is associated with lower risk of cardiovascular diseases (CVDs), and cocoa and tea have been shown to improve CVD risk factors in randomized controlled trials. Cocoa and tea are major dietary sources of the flavan-3-ol epicatechin. OBJECTIVE We investigated the associations of dietary epicatechin intake with 25-y CVD mortality in elderly Dutch men. DESIGN We used data from the Zutphen Elderly Study, which was a prospective cohort study of 774 men aged 65-84 y in 1985. Epicatechin intake was estimated 4 times in 15 y with the use of the crosscheck dietary history method. Time-dependent Cox proportional hazards models were used to investigate repeated measures of epicatechin intake in relation to 25-y CVD mortality. RESULTS Mean intake of epicatechin was 15.2 ± 7.7 mg/d, and the major dietary sources were tea (51%), apples (28%), and cocoa (7%). During 25 y of follow-up, 329 men died from CVD, 148 died from coronary heart disease (CHD), and 72 men died from stroke. Risk of CHD mortality was 38% lower in men in the top tertile of epicatechin intake than in men in the bottom tertile of epicatechin intake (HR: 0.62; 95% CI: 0.39, 0.98). Epicatechin intake was also significantly associated with 46% lower risk of CVD mortality in men with prevalent CVD (HR: 0.54; 95% CI: 0.31, 0.96) but not in men who were free of CVD. CONCLUSIONS We show, for the first time to our knowledge, that epicatechin intake is inversely related to CHD mortality in elderly men and to CVD mortality in prevalent cases of CVD. More studies are needed before conclusions can be drawn.
Onco-Embryonic Antigens on Murine Normal Adult Cells 1

Normal adult C57BL/6J fibroblasts, cultured to saturation density and therefore in resting phase, were harvested by EDTA, treated with trypsin at various concentrations for different lengths of time and then tested for absorbing capacity of a C57BL/He anti-embryo serum, the residual cytotoxic activity being measured by a 51Cr release assay on a C57BL/He lymphosarcoma known to carry embryonic antigens. A weak proteolytic treatment (0.05 – 0.25 % trypsin for 5–10 min) uncovered structures which absorbed over 40 % activity of the anti-embryo serum. The treated fibroblasts partially retained the absorbing capacity for an antihistocompatibility serum. Higher doses or longer exposure to trypsin progressively inactivated the absorbing capacity of fibroblasts for both antisera. Trypsin treatment of fibrosarcoma cells, which when untreated completely absorbed the anti-embryo serum, decreased their absorbing capacity. Additionally, normal untreated fibroblasts in growing phase were found to absorb the anti-embryo serum.
Occult Hepatitis B in HIV-Infected Patients

Prevalence of hepatitis B virus (HBV) markers, including occult HBV, has not been described in diverse cohorts among HIV-infected patients. The objective of this study was to assess prevalence and significance of active and occult HBV infection in an HIV-positive US cohort. A random sample was taken from 2 prospective multicenter treatment intervention cohorts. The sample population (n = 240) was HIV-1 infected and highly active antiretroviral therapy–naive. Prevalence of HBV serologic markers and quantitative HBV DNA were determined. Serum alanine aminotransferase (ALT) levels were measured to evaluate correlates of hepatocyte injury. A total of 64.6% of subjects demonstrated reactivity for any marker of current or past HBV infection or prior vaccination. Chronic HBV infection characterized by hepatitis B surface antigen (HBsAg) reactivity was present in 7.1% while 15.8% exhibited HB anticore IgG only. Approximately 10% of the latter group was HBV DNA positive by a polymerase chain reaction–based assay. Only patients with a serologic pattern of HBsAg or HB anticore alone reactivity had HBV DNA. Occult HBV was observed in approximately 10% of HIV-infected patients with HB anticore IgG antibody in a geographically representative national cohort. Though viral titers and serum ALT levels were low, screening of this subset of HIV-infected patients may have implications in terms of antiretroviral therapy and risk of immune reconstitution–associated flares.
A case of del(13)(q22) with multiple major congenital anomalies, imperforate anus and penoscrotal transposition.

"13q-"syndrome is known to have widely variable manifestations, including retinoblastoma, mental & growth retardation, malformation of brain & heart, anal atresia, and anomalies of the face and limbs. Here we report a case of del(13)(q22) with multiple major congenital anomalies for the first time in Korea. The patient was born at 36(+4) weeks of pregnancy by caesarian section. Birth weight was 1490g. On examination the following features were noted: - imperforate anus, ambiguous genitalia (bifid scrotum, penoscrotal transposition, hypospadia), syndactyly of toes, absence of thumbs, abnormal facies (dolichocephaly, telecanthus, large low set ears, saddle nose, high arched palate, micrognathia). Neurocranial ultrasonography showed atrophy of the corpus callosum and multiple calcifications. He died at 14 days. Post-mortem autopsy findings showed cholestasis and fatty metamorphosis of liver, abnormal lobulation (Rt:2, Lt:1) and lymphangiectasis of the lung, VSD, ASD, PDA of heart, and acute tubular necrosis of kidney. Cytogenetic studies was confirmed to 46,XY,del(13) (q22) by Giemsa banded chromosomes from peripheral blood lymphocytes.
Market power and trading strategies on the electricity market: a market design view

In this paper, we examine auction-based electricity markets from the viewpoint of a power company in order to evaluate the market design. Optimal trading strategies under uncertainty are developed by abolishing the widespread assumption that a single company has no influence on the market price. The resulting trading strategies explain the high prices and the high volatility observed in real electricity auction markets and show to what extent power companies can manipulate the market price. From these trading strategies, we derive critical points in market design and formulate necessary and sufficient conditions that characterize a competitive electricity auction market. Unfortunately, these conditions are far from being realizable in practice, from which follows that electricity auction markets cannot be competitive
RY10-4 Inhibits the Proliferation of Human Hepatocellular Cancer HepG2 Cells by Inducing Apoptosis In Vitro and In Vivo

This study aimed to investigate the anti-tumor activity of RY10-4, a small molecular that was designed and synthesized based on the structure of protoapigenone. A previous screening study showed that RY10-4 possessed anti-proliferative effects against HepG2 human hepatocellular carcinoma cells. However, the full range of RY10-4 anti-cancer effects on liver tumors and the underlying mechanisms have not been identified. Herein, employing flow cytometry, and Western blot analysis, we demonstrate that RY10-4 can induce cell cycle arrest, intracellular reactive oxygen species (ROS) production and apoptosis in HepG2 cells. In HepG2 cell xenograft tumor model, RY10-4 significantly inhibited the growth of tumors and induced apoptosis in tumor cells, with little side effects. Moreover, RY10-4 caused the suppression of STAT3 activation, which may be involved the apoptosis induction. In addition, RY10-4 inhibited the proliferation of Hep3B and HuH-7 human hepatocellular carcinoma cells in a concentration-dependent manner. Taken together, our results suggest that RY10-4 has a great potential to develop as chemotherapeutic agent for liver cancer.
Development of a novel AIDS vaccine: the HIV-1 transactivator of transcription protein vaccine

Introduction: Classical approaches aimed at targeting the HIV-1 envelope as well as other structural viral proteins have largely failed. The HIV-1 transactivator of transcription (Tat) is a key HIV virulence factor, which plays pivotal roles in virus gene expression, replication, transmission and disease progression. Notably, anti-Tat Abs are uncommon in natural infection and, when present, correlate with the asymptomatic state and lead to lower or no disease progression. Hence, targeting Tat represents a pathogenesis-driven intervention. Areas covered: Here, we review the rationale and the translational development of a therapeutic vaccine targeting the Tat protein. Preclinical and Phase I studies, Phase II trials with Tat in anti-Tat Ab-negative, virologically suppressed highly active antiretroviral therapy-treated subjects in Italy and South Africa were conducted. The results indicate that Tat-induced immune responses are necessary to restore immune homeostasis, to block the replenishment and to reduce the size of the viral reservoir. Additionally, they may help in establishing key parameters for highly active antiretroviral therapy intensification and a functional cure. Expert opinion: We propose the therapeutic setting as the most feasible to speed up the testing and comparison of preventative vaccine candidates, as the distinction lies in the use of the vaccine in uninfected versus infected subjects and not in the vaccine formulation.
Phase I study of paclitaxel in patients with recurrent malignant glioma: a North American Brain Tumor Consortium report.

PURPOSE To determine the maximum-tolerated dose (MTD) of paclitaxel administered as a 3-hour infusion in patients with recurrent malignant glioma. PATIENTS AND METHODS Patients were stratified by starting dose of paclitaxel and concurrent anticonvulsant (AC) use and were treated in cohorts of three patients. The starting dose was 240 mg/m2 administered intravenously with escalations of 30 mg/m2 until the MTD was established. Pharmacokinetic data were obtained for each patient for the first infusion. Tumor response was assessed at 6-week intervals and treatment was continued until documented tumor progression, unacceptable toxicity, or a total of 12 paclitaxel infusions. RESULTS From April 1995 to December 1996, 34 patients were treated; 27 patients in the AC group and seven patients in the non-AC group. The MTD for patients who received ACs was established at 360 mg/m2 and the dose-limiting toxicity (DLT) was central neurotoxicity, characterized as transient encephalopathy and seizures. In contrast, the MTD for patients who did not receive ACs was 240 mg/m2, and myelosuppression, gastrointestinal toxicity, and fatigue were the DLTs. Pharmacokinetic data confirmed that the plasma drug levels and clearance rates were similar for patients in both groups at the respective dose levels that produced DLTs. CONCLUSION The pharmacokinetics of paclitaxel are altered by ACs, and significantly larger doses of the drug can be administered to patients with brain tumors on AC therapy. The toxicity profile is different for patients on AC therapy treated at these higher doses. A phase II study has been initiated that uses a dose of 330 mg/m2 for patients on AC therapy and 210 mg/m2 for patients not on AC therapy.
Preoperative Staging and Tumor Resectability Assessment of Pancreatic Cancer: Prospective Study Comparing Endoscopic Ultrasonography, Helical Computed Tomography, Magnetic Resonance Imaging, and Angiography

OBJECTIVES:The objective of this study was to evaluate prospectively the efficacy of different strategies based on endoscopic ultrasonography (EUS), helical computed tomography (CT), magnetic resonance imaging (MRI), and angiography (A) in the staging and tumor resectability assessment of pancreatic cancer.METHODS:All consecutive patients with pancreatic carcinoma judged fit for laparotomy were studied by EUS, CT, MRI, and A. Results of each of the imaging techniques regarding primary tumor, locoregional extension, lymph-node involvement, vascular invasion, distant metastases, tumor TNM stage, and tumor resectability were compared with the surgical findings. Univariate, logistic regression, decision, and cost minimization analyses were performed.RESULTS:Sixty-two patients with pancreatic cancer were included. Helical CT had the highest accuracy in assessing extent of primary tumor (73%), locoregional extension (74%), vascular invasion (83%), distant metastases (88%), tumor TNM stage (46%), and tumor resectability (83%), whereas EUS had the highest accuracy in assessing tumor size (r = 0.85) and lymph node involvement (65%). The decision analysis demonstrated that the best strategy to assess tumor resectability was based on CT or EUS as initial test, followed by the alternative technique in those potentially resectable cases. Cost minimization analysis favored the sequential strategy in which EUS was used as a confirmatory technique in those patients in whom helical CT suggested resectability of the tumor.CONCLUSIONS:Helical CT and EUS are the most useful individual imaging techniques in the staging of pancreatic cancer. In those cases with potentially resectable tumors a sequential approach consisting of helical CT as an initial test and EUS as a confirmatory technique seems to be the most reliable and cost minimization strategy.
Drug Burden Index, Physical Function, and Adverse Outcomes in Older Hospitalized Patients

The Drug Burden Index (DBI) is associated with poorer physical function in stable, community‐dwelling, older people. The authors speculated that a higher DBI is associated with reduced physical function (Barthel Index, primary outcome) and predicts adverse outcomes (length of stay, in‐hospital mortality, secondary outcomes) in frail, acutely ill, older hospitalized patients. Clinical and demographic characteristics, Barthel Index, DBI, and full medication exposure were recorded on admission in 362 consecutive patients (84 ± 7 years old) admitted to 2 acute geriatric units between February 1, 2010, and June 30, 2010. A unit increase in DBI was associated with a 29% reduction in the odds of being in a higher Barthel Index quartile than a lower quartile (odds ratio, 0.71; 95% confidence interval, 0.55–0.91; P = .007). The Barthel Index components mostly affected were bathing (P < .001), grooming (P < .001), dressing (P = .001), bladder function (P < .001), transfers (P = .001), mobility (P < .001), and stairs (P < .001). A higher DBI independently predicted length of stay (hazard ratio, 1.23; 95% confidence interval, 1.06–1.42; P = .005) but not in‐hospital mortality (hazard ratio, 1.17; 95% confidence interval, 0.72–1.90; P = .52). Higher DBI scores on admission are independently associated with lower scores of the Barthel Index and predict length of stay among older hospitalized patients. The DBI may be useful in the acute setting to improve risk stratification.
Prevalence of diabetes mellitus and prediabetes in the adult Romanian population: PREDATORR study

The PREDATORR (PREvalence of DiAbeTes mellitus, prediabetes, overweight, Obesity, dyslipidemia, hyperuricemia and chronic kidney disease in Romania) study is the first national study analyzing the prevalence of diabetes mellitus (DM) and prediabetes, and their association with cardiometabolic, sociodemographic, and lifestyle risk factors in the Romanian population aged 20–79 years.
Immunology of Hematopoietic Stem Cell Transplant

Hematopoietic stem cell transplantation (HSCT) is a procedure in which infusion of hematopoietic stem cells is used to reestablish hematopoietic function in patients with damaged or defective bone marrow or immune systems. Early and late complications following allogeneic HSCT include acute and chronic graft-versus-host disease (GVHD), donor rejection, graft failure, relapse of primary malignancy, conditioning-related toxicity, immunodeficiency and infections. Immunology has a central role in allogeneic hematopoietic cell transplantation. Any appreciation of the immunological mechanism involved in engraftment, GVHD, the development of tolerance, immune reconstitution, and the control of malignancy requires some understanding of the immunologic basis for immune reactions provoked by grafting tissue from one individual to another. In the future it should be possible to learn what gene(s) must be activated and which must be repressed to force stem cells into division without maturation; to engineer a mechanism into the cells that stops proliferation and sets the stage for amplification; to search if there could be a universal donor cell line, neatly packaged and stabilized in sealed vials and distributed by the pharmaceutical industry; to modify the transplanted cells in such a way that they have a proliferative advantage over those of the host and to deliver the lethal blow against the neoplasm, perhaps the cells that are infused will be engineered in such a way as to be able to distinguish between normal host cells and tumor.
Negligible pharmacokinetic interaction between oral DA‐8159, a new erectogenic, and amlodipine in rats

A pharmacokinetic interaction between oral DA‐8159 and amlodipine was evaluated in male Sprague–Dawley rats. In rats pretreated with troleandomycin (a main inhibitor of CYP3A1/2 in rats), the AUC0−6 h of amlodipine was significantly greater than the controls (34.5±6.01 compared with 28.0±4.70 µg min/ml), indicating that amlodipine is metabolized via CYP3A1/2 in rats. It was reported that the metabolism of DA‐8159 and the formation of DA‐8164 (a metabolite of DA‐8159) were mainly mediated via CYP3A1/2 in rats, and amlodipine significantly inhibited the CYP3A2 in rats. Therefore, a pharmacokinetic interaction between the two drugs could be expected. However, after oral administration of DA‐8159 at a dose of 30 mg/kg with or without oral amlodipine at a dose of 5 mg/kg to rats, the pharmacokinetic parameters of DA‐8159 and DA‐8164 were not significantly different between the two groups of rats. Similar results were also obtained from amlodipine between with and without DA‐8159. The above data indicated that the pharmacokinetic interaction between oral DA‐8159 and amlodipine was almost negligible in rats. Copyright © 2006 John Wiley & Sons, Ltd.
Markers of bone remodeling in the elderly subject: Effects of vitamin D insufficiency and its correction

The elderly subject is prone to both vitamin D insufficiency and calcium insufficiency due to a low calcium intake and calcium malabsorption. These two alterations may lead to secondary hyperparathyroidism, and thus to increased bone loss. We investigated 72 elderly subjects (16 men and 56 women) with vitamin D insufficiency and 25 healthy elderly women with normal vitamin D status, with respect to their indices of calcium metabolism and of bone remodeling: serum total alkaline phosphatases (AP), bone AP (BAP), osteocalcin (BGP), tartrate‐resistant acid phosphatase (TRAP), urine hydroxyproline (HYP), and the 3‐OH‐pyridinium derivatives pyridinoline (PYD) and deoxypyridinoline (DPD), which are new markers of bone resorption. We then studied the modifications of these markers in the patients with vitamin D insufficiency at 3 months and 6 months after onset of a daily vitamin D and calcium supplementation. When compared with elderly subjects with normal vitamin D status, patients with vitamin D insufficiency had increased intact parathyroid hormone (iPTH) levels (60.1 ± 10.2 vs 30.2 ± 4.5, p < 0.001) and a high bone turnover as reflected by increased values of most serum and urine markers of bone remodeling. PYD and DPD levels were significantly correlated with all indices of bone turnover, unlike HYP, which showed no correlation with bone formation markers (AP, BAP, and BGP). A daily supplement of 800 IU vitamin D3 and 1 g of elemental calcium increased 25(OH)D levels and induced a dramatic decrease of iPTH levels; at 3 and 6 months, the mean iPTH level decreased by 50% (p < 0.0001), reaching the mean value of healthy vitamin D sufficient elderly women. All markers of bone turnover, except TRAP, decreased significantly at 3 and 6 months. The PYD/DPD ratio increased significantly at 3 and 6 months. The decrease of bone markers was more marked in patients with more severe hyperparathyroidism, the greatest variations being obtained with BAP (45%, p = 0.006) and DPD (43%, p = 0.036) levels. Most markers of bone remodeling are increased in elderly subjects with vitamin D insufficiency and vary with its correction. However, BAP and DPD are the most sensitive indicators of increased bone turnover due to secondary hyperparathyroidism.