Miracle-dz/UniFAR-FTUs huggingface dataset:
Improved efficacy of basiliximab over antilymphocyte globulin induction therapy in paediatric renal transplantation.

BACKGROUND Basiliximab is a chimeric human/mouse monoclonal antibody directed against the alpha chain of the IL-2 receptor, CD25, which has been reported as successfully reducing rejection in adult renal transplant recipients. Reported clinical experience of basiliximab in paediatric renal transplantation is limited. METHODS Using two intravenous doses on day 0 (pre-operatively) and day 4 with prednisolone and cyclosporin A (dual) maintenance immunosuppression in 42 children undergoing renal transplantation in our unit (SIM group), we have compared patient and graft outcome, rejection rates in the first 6 months, renal function and the incidence of Cytomegalovirus (CMV) infection with 42 consecutive children who previously received antilymphocyte globulin immunoprophylaxis with prednisolone, cyclosporin A and azathioprine (triple) maintenance immunosuppression (ALG group). The two groups were similar, including HLA mismatching, apart from age and size at transplantation (SIM=10.3+/-5.4 years vs ALG=12.4+/-4.2 years, P<0.05). RESULTS One patient in the SIM group died from food inhalation with a functioning kidney and one patient in the ALG group from Pneumocystis pneumonia and post-transplant lymphoproliferative disorders with a rejecting graft. Both 1- and 2-year actuarial graft survivals were 93% for the SIM group and 86% for the ALG group (NS). Three grafts were lost in the SIM group-none from rejection (thrombosis 2, death 1)-and seven in the ALG group-three from rejection. Occurrence of biopsy documented rejection in the first 6 months after transplantation was 0.15+/-0.22 for the SIM group and 0.35+/-0.51 episodes per pt-month at risk for ALG treatment (P<0.04). Early rejection within 30 post-operative days occurred in only four SIM patients, three of whom had undergone retransplantation. Forty-seven per cent of rejection episodes occurred between days 30 and 44 in SIM treated patients. Switching to tacrolimus was similar in both groups; 24% of the SIM groups were prescribed triple therapy. Estimated glomerular filtration rate was 46.0 and 46.2 ml/min for SIM and ALG groups, respectively, six months after transplantation. Ten per cent of SIM and 19% of ALG treated patients developed clinically significant CMV infection (NS) but none of 16 (R(+)) SIM children had CMV infection compared with 8 out of 15 (R(+)) ALG patients (P<0.01). CONCLUSIONS Basiliximab immunoprophylaxis and dual therapy reduces rejection episodes in the first six months and maintains graft survival and function after paediatric renal transplantation. Seventy-six per cent of children receiving basiliximab immunoprophylaxis were successfully maintained on long-term dual immunosuppression. This immunosuppressive protocol reduces CMV disease in CMV(+) recipients compared with ALG induction and triple therapy.
The anterior cardiac plexus: an intrinsic neurosecretory site within the stomatogastric nervous system of the crab Cancer productus

SUMMARY The stomatogastric nervous system (STNS) of decapod crustaceans is modulated by both locally released and circulating substances. In some species, including chelate lobsters and freshwater crayfish, the release zones for hormones are located both intrinsically to and at some distance from the STNS. In other crustaceans, including Brachyuran crabs, the existence of extrinsic sites is well documented. Little, however, is known about the presence of intrinsic neuroendocrine structures in these animals. Putative intrinsic sites have been identified within the STNS of several crab species, though ultrastructural confirmation that these structures are in fact neuroendocrine in nature remains lacking. Using a combination of anatomical techniques, we demonstrate the existence of a pair of neurosecretory sites within the STNS of the crab Cancer productus. These structures, which we have named the anterior cardiac plexi (ACPs), are located on the anterior cardiac nerves (acns), which overlie the cardiac sac region of the foregut. Each ACP starts several hundred μm from the origin of the acn and extends distally for up to several mm. Transmission electron microscopy done on these structures shows that nerve terminals are present in the peripheral portion of each acn, just below a well defined epineurium. These terminals contain dense-core and, occasionally, electron-lucent vesicles. In many terminals, morphological correlates of hormone secretion are evident. Immunocytochemistry shows that the ACPs are immunopositive for FLRFamide-related peptide. All FLRFamide labeling in the ACPs originates from four axons, which descend to these sites through the superior oesophageal and stomatogastric nerves. Moreover, these FLRFamide-immunopositive axons are the sole source of innervation to the ACPs. Collectively, our results suggest that the STNS of C. productus is not only a potential target site for circulating hormones, but also serves as a neuroendocrine release center itself.
Flexibility of Neural Stem Cells

Embryonic cortical neural stem cells are self-renewing progenitors that can differentiate into neurons and glia. We generated neurospheres from the developing cerebral cortex using a mouse genetic model that allows for lineage selection and found that the self-renewing neural stem cells are restricted to Sox2 expressing cells. Under normal conditions, embryonic cortical neurospheres are heterogeneous with regard to Sox2 expression and contain astrocytes, neural stem cells, and neural progenitor cells sufficiently plastic to give rise to neural crest cells when transplanted into the hindbrain of E1.5 chick and E8 mouse embryos. However, when neurospheres are maintained under lineage selection, such that all cells express Sox2, neural stem cells maintain their Pax6+ cortical radial glia identity and exhibit a more restricted fate in vitro and after transplantation. These data demonstrate that Sox2 preserves the cortical identity and regulates the plasticity of self-renewing Pax6+ radial glia cells.
Radiologic visualization of neck vessels in healthy men

BECAUSE OF THE DEVELOPMENT of new technics for visualizing the arterial supply to the brlriii and the increasing interest in surgery for the removal of obstructive lesions demonstrated by such technics, we have felt that determining the true significance of such abnormalities was imperative. In order to do this, it seemed essential to obtain :ideqn;ite radiologic visualization of the neck vessels in a group of completely healthy persons, specifically, those who had never exhibited the signs and symptoms of cerelxovuscular insufficiency. We wanted to see whetlrer there was a direct causal relationship hetwwi occlusive and obstructive lesions of the ireck vessels and the manifestation of neurologic signs and symptoms. A p u p of inmates at the Kansas State Penitentiary in Lansing, Kansas, volunteered 3s subjects for the performance of transbrachial percutaneous arteriography for this purpose.
Reactive Oxygen Metabolites are Closely Associated With the Diagnosis and Prognosis of Coronary Artery Disease

Background Reactive oxygen species (ROS) are associated with development of coronary artery disease (CAD). However, there's no useful biomarker of ROS in CAD. Methods and Results We recruited 395 consecutive CAD patients who were performed coronary angiography (262 male and 133 female, age 70.2±10), and we measured serum derivatives of reactive oxidative metabolites (DROM) were measured. Two hundred twenty‐seven non‐CAD patients were also enrolled. We performed follow‐up study in these 395 CAD patients and case‐control study after risk factor and 1:1 pair matching (both, n=163). As subgroup analysis, DROM were also measured at the aortic root and the coronary sinus in 59 CAD patients. DROM were significantly higher in CAD patients (n=163, median [inter‐quartile range, IQR]=338 [302 to 386]) than in risk factor‐matched non‐CAD patients (n=163, 311 [282 to 352.5], effect size=0.33, P<0.001). During a mean follow‐up period of 20 months of 395 CAD patients, 83 cardiovascular events were recorded. Kaplan‐Meier analysis showed a higher probability of cardiovascular events in the high‐DROM group (>346 U.CARR) than in the low‐DROM group (≤346 U.CARR) (P=0.001 [log‐rank test]). Multivariate Cox hazard analysis identified ln‐DROM as an independent predictor for cardiovascular events (hazard ratio: 10.8, 95% confidence interval: 2.76 to 42.4, P=0.001). The transcardiac gradient of DROM was significantly higher in CAD patients than in non‐CAD patients (−2.0 [−9.0 to 9.0] versus 8 [−8.0 to 28.3], effect size=0.21, P=0.04), indicating that DROM production in coronary circulation is associated with development of CAD. Conclusion DROM are increased in CAD patients and associated with future cardiovascular events. DROM might provide clinical benefits for risk stratification of CAD. Clinical Trial Registration URL: http://www.umin. ac.jp/ctr/. Unique identifier: UMIN000012990.
Melatonin Efficacy in Obese Leptin-Deficient Mice Heart

Cardiomyocytes are particularly sensitive to oxidative damage due to the link between mitochondria and sarcoplasmic reticulum necessary for calcium flux and contraction. Melatonin, important indoleamine secreted by the pineal gland during darkness, also has important cardioprotective properties. We designed the present study to define morphological and ultrastructural changes in cardiomyocytes and mainly in mitochondria of an animal model of obesity (ob/ob mice), when treated orally or not with melatonin at 100 mg/kg/day for 8 weeks (from 5 up to 13 week of life). We observed that ob/ob mice mitochondria in sub-sarcolemmal and inter-myofibrillar compartments are often devoid of cristae with an abnormally large size, which are called mega-mitochondria. Moreover, in ob/ob mice the hypertrophic cardiomyocytes expressed high level of 4hydroxy-2-nonenal (4HNE), a marker of lipid peroxidation but scarce degree of mitofusin2, indicative of mitochondrial sufferance. Melatonin oral supplementation in ob/ob mice restores mitochondrial cristae, enhances mitofusin2 expression and minimizes 4HNE and p62/SQSTM1, an index of aberrant autophagic flux. At pericardial fat level, adipose tissue depot strictly associated with myocardium infarction, melatonin reduces adipocyte hypertrophy and inversely regulates 4HNE and adiponectin expressions. In summary, melatonin might represent a safe dietary adjuvant to hamper cardiac mitochondria remodeling and the hypoxic status that occur in pre-diabetic obese mice at 13 weeks of life.
Multiple human papillomavirus infections and type competition in men.

BACKGROUND There is little information on multiple human papillomavirus (HPV) infections and the potential for type competition in men, yet competition may impact the type-specific efficacy of HPV vaccination. METHODS Among 2702 uncircumcised men in Kisumu, Kenya, who were seronegative for human immunodeficiency virus, the observed numbers of HPV types detected were compared with the expected number, which was simulated under the assumption of independent infections. To assess the potential for HPV type competition, adjusted odds ratios for pairwise combinations of prevalent HPV type infections were estimated using semi-Bayesian methods. RESULTS Half of all men were HPV positive, of whom 57% had multiple HPV types. We observed men without HPV infection and with ≥4 HPV types more often than expected if infections were independent. No negative associations between individual HPV types were observed. HPV types 31, 39, 56, 58, and 59 were positively associated with both carcinogenic vaccine types HPV-16 and HPV-18 (2-sided P value <.05). CONCLUSIONS Men who were HPV infected were likely to test positive for >1 HPV type. Cross-sectional associations between individual HPV types were positive and did not appear to be type-specific. Thus, we did not identify HPV types that are candidates for potential HPV type competition in men.
Global Tumor RNA Expression in Early Establishment of Experimental Tumor Growth and Related Angiogenesis following Cox-Inhibition Evaluated by Microarray Analysis

Altered expression of COX-2 and overproduction of prostaglandins, particularly prostaglandin E2, are common in malignant tumors. Consequently, non-steroidal anti-inflammatory drugs (NSAIDs) attenuate tumor net growth, tumor related cachexia, improve appetite and prolong survival. We have also reported that COX-inhibition (indomethacin) interfered with early onset of tumor endothelial cell growth, tumor cell proliferation and apoptosis. It is however still unclear whether such effects are restricted to metabolic alterations closely related to eicosanoid pathways and corresponding regulators, or whether a whole variety of gene products are involved both up- and downstream effects of eicosanoids. Therefore, present experiments were performed by the use of an in vivo, intravital chamber technique, where micro-tumor growth and related angiogenesis were analyzed by microarray to evaluate for changes in global RNA expression caused by indomethacin treatment. Indomethacin up-regulated 351 and down-regulated 1852 genes significantly (p < 0.01); 1066 of these genes had unknown biological function. Genes with altered expression occurred on all chromosomes. Our results demonstrate that indomethacin altered expression of a large number of genes distributed among a variety of processes in the carcinogenic progression involving angiogenesis, apoptosis, cell-cycling, cell adhesion, inflammation as well as fatty acid metabolism and proteolysis. It remains a challenge to distinguish primary key alterations from secondary adaptive changes in transcription of genes altered by cyclooxygenase inhibition.
Scalable Fast Rate-Distortion Optimization for H.264/AVC

The latest H.264/AVC video coding standard aims at significantly improving compression performance compared to all existing video coding standards. In order to achieve this, variable block-size inter- and intra-coding, with block sizes as large as and as small as, is used to enable very precise depiction of motion and texture details. The Lagrangian rate-distortion optimization (RDO) can be employed to select the best coding mode. However, exhaustively searching through all coding modes is computationally expensive. This paper proposes a scalable fast RDO algorithm to effectively choose the best coding mode without exhaustively searching through all the coding modes. The statistical properties of MBs are analyzed to determine the order of coding modes in the mode decision priority queue such that the most probable mode will be checked first, followed by the second most probable mode, and so forth. The process will be terminated as soon as the computed rate-distortion (RD) cost is below a threshold which is content adaptive and is also dependent on the RD cost of the previous MBs. By adjusting the threshold we can choose a good tradeoff between timesaving and peak signal-to-noise (PSNR) ratio. Experimental results show that the proposed fast RDO algorithm can drastically reduce the encoding time up to 50% with negligible loss of coding efficiency.
Thymidine kinase not required for antiviral activity of acyclovir against mouse cytomegalovirus

Previous studies of herpesvirus infections have indicated that a virus-specified thymidine kinase is required for the initial phosphorylation of acyclovir [acycloguanosine or 9-(2-hydroxyethoxymethyl)guanine] in the formation of acycloguanosine triphosphate. The latter compound accumulates in infected cells and competitively inhibits the viral DNA polymerase. We found that mouse cytomegalovirus, which does not express a thymidine kinase, was sensitive to the antiviral effects of acyclovir at a 50% inhibitory dose of approximately 0.23 microM. Acyclovir was equally effective against mouse cytomegalovirus in normal 3T3 cells and in 3T3 cells deficient in cellular thymidine kinase. Furthermore, the activity of acyclovir could not be reversed by excess thymidine, which easily reversed the antiviral activity of acyclovir against herpes simplex virus. Using a high-pressure liquid chromatography technique that easily detected acycloguanosine triphosphate in cells infected with herpes simplex virus, we could not detect acycloguanosine triphosphate in mouse cytomegalovirus-infected cells. These experiments demonstrated that the activity of acyclovir against mouse cytomegalovirus is not dependent on a thymidine phosphorylation pathway. Additional experiments are underway to determine whether acycloguanosine triphosphate is produced by another pathway in concentrations sufficient to inhibit mouse cytomegalovirus DNA polymerase.
Survival outcome and prognostic factors of neoadjuvant treatment followed by resection for borderline resectable pancreatic cancer

Purpose Neoadjuvant treatment may provide improved survival outcomes for patients with borderline resectable pancreatic cancer (BRPC). The purpose of this study is to evaluate the clinical outcomes of neoadjuvant treatment and to identify prognostic factors. Methods Forty patients who met the National Comprehensive Cancer Network definition of BRPC and received neoadjuvant treatment followed by surgery between 2007 and 2015 were evaluated. Prospectively collected clinicopathological outcomes were analyzed retrospectively. Results The mean age was 61.7 years and the male-to-female ratio was 1.8:1. Twenty-six, 3, and 11 patients received gemcitabine-based chemotherapy, 5-fluorouracil, and FOLFIRINOX, respectively. The 2-year survival rate (2YSR) was 36.6% and the median overall survival (OS) was 20 months. Of the 40 patients, 34 patients underwent resection and the 2YSR was 41.2% while the 2YSR of patients who did not undergo resection was 16.7% (P = 0.011). The 2YSR was significantly higher in patients who had partial response compared to stable disease (60.6% vs. 24.3%, P = 0.038), in patients who did than did not show a CA 19-9 response after neoadjuvant treatment (40.5% vs. 0%, P = 0.039) and in patients who did than did not receive radiotherapy (50.8% vs. 25.3%, P = 0.036). Five patients had local recurrence and 17 patients had systemic recurrence with a median disease specific survival of 15 months. Conclusion Neoadjuvant treatment followed by resection is effective for BRPC. Pancreatectomy and neoadjuvant treatment response may affect survival. Effective systemic therapy is needed to improve long-term survival since systemic metastasis accounts for a high proportion of recurrence.
Genetic variation at the FADS1-FADS2 gene locus influences delta-5 desaturase activity and LC-PUFA proportions after fish oil supplement[S]

Delta-5 and delta-6 desaturases (D5D and D6D) are key enzymes in endogenous synthesis of long-chain PUFAs. In this sample of healthy subjects (n = 310), genotypes of single nucleotide polymorphisms (SNPs) rs174537, rs174561, and rs3834458 in the FADS1-FADS2 gene cluster were strongly associated with proportions of LC-PUFAs and desaturase activities estimated in plasma and erythrocytes. Minor allele carriage associated with decreased activities of D5D (FADS1) (5.84 × 10−19 ≤ P ≤ 4.5 × 10−18) and D6D (FADS2) (6.05 × 10−8 ≤ P ≤ 4.20 × 10−7) was accompanied by increased substrate and decreased product proportions (0.05 ≤ P ≤ 2.49 × 10−16). The significance of haplotype association with D5D activity (P = 2.19 × 10−17) was comparable to that of single SNPs, but haplotype association with D6D activity (P = 3.39 × 10−28) was much stronger. In a randomized controlled dietary intervention, increasing eicosapentaenoic acid (EPA, 20:5n-3) and docosahexaenoic acid (DHA, 22:6n-3) intake significantly increased D5D (P = 4.0 × 10−9) and decreased D6D activity (P = 9.16 × 10−6) after doses of 0.45, 0.9, and 1.8 g/day for six months. Interaction of rs174537 genotype with treatment was a determinant of D5D activity estimated in plasma (P = 0.05). In conclusion, different sites at the FADS1-FADS2 locus appear to influence D5D and D6D activity, and rs174537 genotype interacts with dietary EPA+DHA to modulate D5D.
Background subtraction in technetium-99m-MAG3 renography.

UNLABELLED Correction represents a potential source of error in estimating split renal function and camera-based clearances. The purpose of this study was to determine which of five background options and four time intervals was associated with the least error for 99mTc-mercaptoacetyltriglycine (MAG3). METHODS Fifteen single-kidney patients were imaged supine after 111-370 MBq (3-10 mCi) 99mTc-MAG3 injection. A phantom kidney was drawn on the 2-3-min images, approximately equal in size to the solitary kidney and used for all time intervals. Counts in the phantom and native kidneys were calculated using manual inferior and lateral regions of interest (ROIs), automated elliptical and perirenal background ROIs and no background correction at various time intervals (1-2, 1-2.5, 1.5-2.5 and 2-3 min) postinjection. With optimal background correction, counts and the relative function in the phantom kidney should be zero. The error was measuring by estimating both the relative function and absolute function expressed as the percent injected dose in the phantom kidney. RESULTS The percent injected dose in the phantom kidney as well as the error in measuring relative function were significantly greater than zero for the inferior background correction and the no background correction options at all time intervals, p < 0.05. The percent dose in the kidney and the error associated with the lateral, elliptical and perirenal ROIs were not significantly different from zero. CONCLUSION Regardless of time interval, the greatest error was associated with no background correction. The inferior ROI consistently underestimated the background correction and probably should not be used for 99mTc-MAG3. There was no significant difference between errors generated using the lateral and automated ROIs, although automated ROIs are probably more reproducible for sequential studies.
The Effects of Repeated Opioid Administration on Locomotor Activity: I. Opposing Actions of μ and κ Receptors

Repeated administration of many addictive drugs leads to a progressive increase in their locomotor effects. This increase in locomotor activity often develops concomitantly with increases in their positive-reinforcing effects, which are believed to contribute to the etiology of substance use disorders. The purpose of this study was to examine changes in sensitivity to the locomotor effects of opioids after their repeated administration and to determine the role of μ and κ receptors in mediating these effects. Separate groups of rats were treated with opioid receptor agonists and antagonists every other day for 10 days, and changes in locomotor activity were measured. Repeated administration of the μ agonists, morphine and buprenorphine, produced a progressive increase in locomotor activity during the treatment period, and this effect was blocked by coadministration of the opioid antagonist naltrexone. The κ agonist spiradoline decreased locomotor activity when administered alone and blocked the progressive increase in locomotor activity produced by morphine. The ability of spiradoline to block morphine-induced increases in locomotor activity was itself blocked by pretreatment with the κ antagonist nor-binaltorphimine. Repeated administration of high doses, but not low or moderate doses, of the mixed μ/κ agonists butorphanol, nalbuphine, and nalorphine produced a progressive increase in locomotor activity during the treatment period. Doses of butorphanol, nalbuphine, and nalorphine that failed to produce a progressive increase in locomotor activity when administered alone did so when subjects were pretreated with nor-binaltorphimine. These findings suggest that μ and κ receptors have functionally opposing effects on opioid-mediated locomotor activity and sensitization-related processes.