Miracle-dz/UniFAR-FTUs huggingface dataset:
Pediatric Organ Transplantation and Risk of Premalignant and Malignant Tumors in Sweden

Increased cancer risks are well documented in adult organ transplant recipients. However, the spectrum of malignancies and risk in the pediatric organ transplant population are less well described. We identified all solid organ transplanted patients aged <18 in Sweden between 1970–2007 (n = 536) in the National Patient Register and linked to the Cancer Register. Nationwide rates were used to calculate standardized incidence rate ratios and 95% CI estimating the association between transplant and cancer during maximum 36 years of follow‐up. Nearly 7% of pediatric solid organ transplant recipients developed a premalignant or malignant tumor during follow‐up. Transplantation was associated with an increased risk of any cancer (n = 24, SIR = 12.5, 95% CI: 8.0–18.6): non‐Hodgkin lymphoma (NHL) (n = 13, SIR = 127, 95% CI: 68–217), renal cell (n = 3, SIR = 105, 95% CI: 22–307), vulva/vagina (n = 3, SIR = 665, 95% CI: 137–1934) and nonmelanoma skin cancers (n = 2, SIR = 64.7, 95% CI: 7.8–233.8). NHL typically appeared during childhood, while other tumors were diagnosed during adulthood. Apart from short‐term attention toward the potential occurrence of NHL, our results suggest cancer surveillance into adulthood with special attention to skin, kidneys and the female genitalia.
Negative Elongation Factor-Mediated Suppression of RNA Polymerase II Elongation of Kaposi's Sarcoma-Associated Herpesvirus Lytic Gene Expression

ABSTRACT Genome-wide chromatin immunoprecipitation assays indicate that the promoter-proximal pausing of RNA polymerase II (RNAPII) is an important postinitiation step for gene regulation. During latent infection, the majority of Kaposi's sarcoma-associated herpesvirus (KSHV) genes is silenced via repressive histone marks on their promoters. Despite the absence of their expression during latency, however, several lytic promoters are enriched with activating histone marks, suggesting that mechanisms other than heterochromatin-mediated suppression contribute to preventing lytic gene expression. Here, we show that the RNAPII-mediated transcription of the KSHV OriLytL, K5, K6, and K7 (OriLytL-K7) lytic genes is paused at the elongation step during latency. Specifically, the RNAPII-mediated transcription is stalled by the host's negative elongation factor (NELF) at the promoter regions of OriLytL-K7 lytic genes during latency, leading to the hyperphosphorylation of the serine 5 residue and the hypophosphorylation of the serine 2 of the C-terminal domain of the RNAPII large subunit, a hallmark of stalled RNAPII. Consequently, depletion of NELF expression induced transition of stalled RNAPII into a productive transcription elongation at the promoter-proximal regions of OriLytL-K7 lytic genes, leading to their RTA-independent expression. Using an RTA-deficient recombinant KSHV, we also showed that expression of the K5, K6, and K7 lytic genes was highly inducible upon external stimuli compared to other lytic genes that lack RNAPII on their promoters during latency. These results indicate that the transcription elongation of KSHV OriLytL-K7 lytic genes is inhibited by NELF during latency, but can also be promptly reactivated in an RTA-independent manner upon external stimuli.
Molecular Epidemiology of Human Coronavirus OC43 Reveals Evolution of Different Genotypes over Time and Recent Emergence of a Novel Genotype due to Natural Recombination

ABSTRACT Although human coronavirus OC43-OC43 (HCoV-OC43) is the coronavirus most commonly associated with human infections, little is known about its molecular epidemiology and evolution. We conducted a molecular epidemiology study to investigate different genotypes and potential recombination in HCoV-OC43. Twenty-nine HCoV-OC43 strains from nasopharyngeal aspirates, collected from 2004 to 2011, were subjected to RNA-dependent RNA polymerase (RdRp), spike, and nucleocapsid gene analysis. Phylogenetic analysis showed at least three distinct clusters of HCoV-OC43, although 10 unusual strains displayed incongruent phylogenetic positions between RdRp and spike genes. This suggested the presence of four HCoV-OC43 genotypes (A to D), with genotype D most likely arising from recombination. The complete genome sequencing of two genotype C and D strains and bootscan analysis showed recombination events between genotypes B and C in the generation of genotype D. Of the 29 strains, none belonged to the more ancient genotype A, 5 from 2004 belonged to genotype B, 15 from 2004 to 2006 belonged to genotype C, and 1 from 2004 and all 8 from 2008 to 2011 belonged to the recombinant genotype D. Molecular clock analysis using spike and nucleocapsid genes dated the most recent common ancestor of all genotypes to the 1950s, genotype B and C to the 1980s, genotype B to the 1990s, and genotype C to the late 1990s to early 2000s, while the recombinant genotype D strains were detected as early as 2004. This represents the first study to describe natural recombination in HCoV-OC43 and the evolution of different genotypes over time, leading to the emergence of novel genotype D, which is associated with pneumonia in our elderly population.
Hopf bifurcation and the existence and stability of closed orbits in three-sector models of optimal endogenous growth

Abstract The present paper constructs a family of three-sector models of optimal endogenous growth, and conducts exact bifurcation analysis. In so doing, original six-dimensional equilibrium dynamics is decomposed into five-dimensional stationary autonomous dynamics and one-dimensional endogenously growing component. It is shown that the stationary dynamics thus decomposed undergoes supercritical Hopf bifurcation. It is inferred from the convex structure of our model that the dimension of a stable manifold of each closed orbit thus bifurcated in this five-dimensional dynamics should be two.
Homology modeling and docking studies of FabH (β-ketoacyl-ACP synthase III) enzyme involved in type II fatty acid biosynthesis of Chlorella variabilis: a potential algal feedstock for biofuel production

The concept of using microalgae as an alternative renewable source of biofuel has gained much importance in recent years. However, its commercial feasibility is still an area of concern for researchers. Unraveling the fatty acid metabolic pathway and understanding structural features of various key enzymes regulating the process will provide valuable insights to target microalgae for augmented oil content. FabH (β-ketoacyl-acyl carrier protein synthase; KAS III) is a condensing enzyme catalyzing the initial elongation step of type II fatty acid biosynthetic process and acyl carrier protein (ACP) facilitates the shuttling of the fatty acyl intermediates to the active site of the respective enzymes in the pathway. In the present study, a reliable three-dimensional structure of FabH from Chlorella variabilis, an oleaginous green microalga was modeled and subsequently the key residues involved in substrate binding were determined by employing protein–protein docking and molecular dynamics (MD) simulation protocols. The FabH-ACP complex having the lowest docking energy score showed the binding of ACP to the electropositive FabH surface with strong hydrogen bond interactions. The MD simulation results indicated that the substrate-complexed FabH adopted a more stable conformation than the free enzyme. Further, the FabH structure retained its stability throughout the simulation although noticeable displacements were observed in the loop regions. Molecular simulation studies suggested the importance of crucial hydrogen bonding of the conserved Arg91 of FabH with Glu53 and Asp56 of ACP for exhibiting high affinity between the enzyme and substrate. The molecular modeling results are consistent with available experimental results on the flexibility of FabH and the present study provides first in silico insights into the structural and dynamical aspect of catalytic mechanism of FabH, which could be used for further site-specific mutagenic experiments to develop engineered high oil-yielding microalgal strains for biofuel production.
New Insights into Muscle Fiber Types in the Pig

The accurate classification of skeletal muscle fiber types according to myosin heavy chain (MyHC) polymorphism remains a difficult task in the pig. Combined myofibrillar ATPase and metabolic enzyme histochemistry, in situ hybridization, and immunocytochemistry were performed on serial transverse sections of pig longissimus (L) and rhomboideus (R) muscles at 100 kg body weight to give a new insight into muscle fiber typing in the pig. Several monoclonal antibodies (MAbs) either specific for a single MyHC (I, IIa, or IIb) or of multiple MyHCs (IIa + IIx or I + IIx + IIb) were used. No monospecific IIx antibody was available for the pig. All three adult Type II isoforms were expressed in the white L muscle, whereas no IIb was observed in the red R muscle, which was confirmed using RNase protection analysis. In most fibers, the distribution of the transcripts closely matched that of the corresponding proteins. When observed, co-expression of MyHCs mostly occured for IIx and IIb in L muscle, and was more common at the protein (11.5%) than at the mRNA (2.2%) level. A minor proportion of myofibers showed a mismatch between MyHC mRNA and protein. According to the type grouping distribution of myofibers encountered in pig muscle, MyHC isoform expression followed the rank order of I→Iia→Iix→IIb from the center to the periphery of the islets, concomitantly with a decrease in oxidative metabolism and an increase in fiber size. The developmental origin and functional significance of the type grouping distribution are discussed.
18beta-glycyrrhetinic acid and glabridin prevent oxidative DNA fragmentation in UVB-irradiated human keratinocyte cultures.

BACKGROUND UVB radiation is the major etiological factor in the pathogenesis of skin aging and cancer development. New approaches to prevent and reverse UVB damage are needed to reduce sunlight-induced skin cancer. This study aimed to investigate a possible protective activity of liquorice root extracts glycyrrhizin (GL), 18β-glycyrrhetinic acid (18β-GA) and glabridin (GLB) against UVB radiation damage in human keratinocyte cultures. MATERIALS AND METHODS The MTT test was performed to assess cell viability. DNA damage was evaluated by comet assay, whereas generation of intracellular reactive oxygen species (ROS) was measured by fluorescent 2'7'-dichlorodihydrofluorescein diacetate assay. In addition, the activation of p53, regulation of BCL-2 and PARP cleavage were analyzed by Western blot analysis. RESULTS The treatment of human keratinocytes with 18β-GA and GLB prevented direct and indirect DNA damage avoiding apoptosis activation. CONCLUSION 18β-glycyrrhetinic acid and glabridin are potent antioxidants that prevent oxidative DNA fragmentation and the activation of apoptosis-associated proteins in human keratinocytes.
A probability random scheme of distributed routing algorithm for MANETS

Since the mobile hosts in a MANET keep moving, topological changes take place frequently in the network. This causes routing information kept by the nodes to get outdated easily. These problems become more complex in wireless networks, where bandwidth is limited. This paper proposes a probability random routing algorithm as a solution to this problem. The proposed algorithm, the probability random routing scheme (PRS), has a route discovery feature that when a source needs to find a routing path to a destination, it does not flood the network with control packets, which is an approach widely used in most of the ad hoc routing algorithms. Instead, the source randomly selects one of its neighbors to send out a route request packet. The operations in the algorithm are designed to generate a small number of control packets. The question that how much the successful rate is in finding a path without flooding has been studied in this paper. Our studies show that the successful rate in finding a path with only one attempt can be as high as 90%. Through simulations, we study the performance of the network using the proposed PRS routing algorithm, and compare with the well known on-demand routing protocol, dynamic source routing (DSR) and zone routing protocol (ZRP). Our PRS is simple and can be easily implemented while produces better performance
Differential Regulation of Endosomal GPCR/β-Arrestin Complexes and Trafficking by MAPK*

Background: Regulation between GPCRs and β-arrestins in endosomes has never been reported. Results: A novel ERK regulatory site in β-arrestin-2 controls the binding to GPCRs in endosomes, and receptor trafficking and signaling. Conclusion: Differential MAPK-dependent regulation of endosomal complexes exists among β-arrestin subtypes and species. Significance: Such divergent mode of regulation may help understanding the physiological role of the endosomal GPCR/β-arrestins signaling axis. β-Arrestins are signaling adaptors that bind to agonist-occupied G protein-coupled receptors (GPCRs) and target them for endocytosis; however, the mechanisms regulating receptor/β-arrestin complexes and trafficking in endosomes, remain ill defined. Here we show, in live cells, differential dynamic regulation of endosomal bradykinin B2 receptor (B2R) complexes with either β-arrestin-1 or -2. We find a novel role for MAPK in the B2R/β-arrestin-2 complex formation, receptor trafficking and signaling mediated by an ERK1/2 regulatory motif in the hinge domain of the rat β-arrestin-2 (PET178P), but not rat β-arrestin-1 (PER177P). While the ERK1/2 regulatory motif is conserved between rat and mouse β-arrestin-2, it is surprisingly not conserved in human β-arrestin-2 (PEK178P). However, mutation of lysine 178 to threonine is sufficient to confer MAPK sensitivity to the human β-arrestin-2. Furthermore, substitution for a phosphomimetic residue in both the rat and the human β-arrestin-2 (T/K178D) significantly stabilizes B2R/β-arrestin complexes in endosomes, delays receptor recycling to the plasma membrane and maintains intracellular MAPK signaling. Similarly, the endosomal trafficking of β2-adrenergic, angiotensin II type 1 and vasopressin V2 receptors was altered by the β-arrestin-2 T178D mutant. Our findings unveil a novel subtype specific mode of MAPK-dependent regulation of β-arrestins in intracellular trafficking and signaling of GPCRs, and suggest differential endosomal receptor/β-arrestin-2 signaling roles among species.
Automatic classification of glaucomatous images using wavelet and moment feature

Automation in retinal medical field is highly adopted as quick and precise diagnosis. Computational decision support is easy and affordable system for early diagnosis of glaucoma to prevent the vision loss. In the proposed methodology, glaucoma detection using wavelet and geometric moment features of image texture are presented. Three wavelet filters Daubechies (db3), Symlets (sym3) and Biorthogonal (bior3.3, bior3.5, bior3.7) are used for image decomposition and higher order moments are used for feature computation. The z-score normalization is applied on features before classification. Three classifiers viz. support vector machine (SVM), k-nearest neighbor (KNN) and Error Back-Propagation Training Algorithm (EBPTA) are employed for classification and respective accuracies are calculated. Standard data base RIM-ONE r2 is used for comparison of existing and proposed method. Proposed algorithm provides better accuracy and less computational time than existing algorithm using wavelet and moment features.
Effect of intravenous taurine on endotoxin-induced acute lung injury in sheep.

OBJECTIVE To find out if pretreatment with taurine would reduce the severity of endotoxin-induced acute lung injury in a large animal model. DESIGN Randomised controlled study under licence from the Department of Health. SETTING Department of Surgical Research, Ireland. ANIMALS 15 male Suffolk sheep. INTERVENTIONS Vascular catheters were placed in the femoral artery and vein and a Swan-Ganz catheter in the external jugular vein under general anaesthetic. Animals were randomized into three groups: control with measurements taken at baseline and half hourly up to 90 minutes; endotoxin, given Escherichia coli endotoxin intravenously after baseline measurements and taurine given 300 mg/kg 1 hour before endotoxin was given. MAIN OUTCOME MEASURES Mean systemic arterial pressure, mean pulmonary arterial pressure, arterial oxygen tension (PO2), pulmonary myeloperoxidase activity, and neutrophil respiratory burst activity. RESULTS Endotoxin induced a severe lung injury characterised by a decrease in mean systemic blood pressure and an increase in pulmonary artery pressure, hypoxia, and an increase in pulmonary myeloperoxidase activity. Pretreatment with intravenous taurine significantly reduced these haemodynamic changes. It reduced pulmonary myeloperoxidase activity and peripheral neutropenia and increased neutrophil respiratory burst activity. CONCLUSIONS This data suggest that taurine may have a therapeutic role in preventing the lung injury seen in endotoxaemia.
Nature or nurture in low back pain? Results of a systematic review of studies based on twin samples

Twin studies are becoming popular to investigate risk factors for low back pain (LBP) because they consider the genetic factor and allow for more precise estimates of risks. We aimed to identify and summarize the results of studies based on twin samples investigating risk factors for LBP. The MEDLINE, CINAHL, LILACS, Web of Science and EMBASE databases were searched. Prospective and cross‐sectional observational studies of LBP involving twins were included. The exposure factors could be genetics (heritability) or environmental such as smoking, alcohol consumption, body mass index and medical history. Pooling was attempted using an inverse variance weighting and fixed effects model. Twenty‐seven studies were included. Estimates of heritability effects ranged from 21% to 67%. The genetic component was higher for more chronic and disabling LBP than acute and less disabling LBP. Smoking was significantly associated with LBP [pooled odds ratio (OR) = 3.0; 95% confidence interval (CI) 2.8–3.3] with a longitudinal and a cross‐sectional study also identifying a dose–response relationship in people with chronic LBP. Obesity was associated with LBP (pooled OR = 1.9; 95% CI 1.6–2.2) with a cross‐sectional study identifying a dose–response relationship. No association between alcohol consumption and LBP was identified. Co‐morbidities such as asthma, diabetes and osteoarthritis were associated with LBP (pooled OR ranging from 1.6 to 4.2). The contribution of genetics to LBP appears to be dependent on the severity of the condition. Twin studies could be better used to explore possible causation paths between lifestyle factors, co‐morbidities and LBP.
Effect of intra‐operative pressure support vs pressure controlled ventilation on oxygenation and lung function in moderately obese adults*

Obesity impairs peri‐operative lung function. To evaluate the impact of pressure support ventilation vs pressure controlled ventilation in moderately obese adults upon early postoperative lung function, we randomly assigned 68 moderately obese patients (body mass index 25–35 kg.m−2) undergoing minor surgery to receive intra‐operative ventilation either with pressure support or pressure controlled ventilation. We performed intra‐operative blood gas analysis and measured pulse oximetry saturation, spirometry values at pre‐operative assessment (baseline) and at 10 min, 30 min, 2 h and 24 h after extubation. The intra‐operative oxygenation index (arterial partial pressure of oxygen/fraction of inspired oxygen) in the pressure support ventilation group was significantly improved over time (p < 0.0001). Postoperatively, the pressure support ventilation group also had better lung function and oxygenation values than did the pressure controlled ventilation group (p < 0.005). We conclude that pressure support ventilation better maintains lung function than pressure controlled ventilation in moderately overweight patients scheduled for minor surgery.
The Safety and Efficacy of Extended Thromboprophylaxis With Fondaparinux After Major Orthopedic Surgery of the Lower Limb With or Without a Neuraxial or Deep Peripheral Nerve Catheter: The EXPERT Study

BACKGROUND:The benefit-risk ratio of extended fondaparinux therapy has not been assessed in patients undergoing major lower limb joint arthroplasty. Few data on the concomitant use of fondaparinux and continuous neuraxial or deep peripheral nerve blockade are available. We performed a prospective intervention study in patients undergoing major orthopedic surgery primarily designed to assess the efficacy of fondaparinux when drug administration was withheld for 48 h to permit removal of a neuraxial or deep peripheral nerve catheter. The safety and efficacy of extended fondaparinux therapy for the prevention of venous thromboembolism were also evaluated. METHODS:Patients received a daily subcutaneous injection of 2.5 mg fondaparinux for 3 to 5 wk postoperatively. In patients with a neuraxial or deep peripheral nerve catheter, the catheter was removed 36 h after the last fondaparinux dose. The next fondaparinux dose was administered 12 h after catheter removal. The primary end points were symptomatic venous thromboembolism and major bleeding up to 4–6 wk after surgery. RESULTS:We recruited 5704 patients. A neuraxial or deep peripheral nerve catheter was inserted in 1553 (27%) patients and 78 (1.4%) patients, respectively. The rate of venous thromboembolism was 1.0% (54 of 5387). There was no difference between patients without (1.1%) or with (0.8%) a catheter (the upper limit of the 95% confidence interval of the odds ratio, 1.49, being below the predetermined noninferiority margin of 1.75). The incidence of major bleeding was 0.8% (42 of 5382). No neuraxial or perineural hematoma was reported. CONCLUSIONS:Once-daily subcutaneous injection of 2.5 mg fondaparinux given for 3 to 5 wk was effective and safe for prevention of venous thromboembolism after major orthopedic surgery. Temporary discontinuation of fondaparinux for 48 h permitted safe removal of a neuraxial or deep peripheral nerve catheter without decreasing thromboprophylatic efficacy.
Long-Term Survival of Women With Epithelial Ovarian Cancer Detected by Ultrasonographic Screening

OBJECTIVE: To estimate the effect of ultrasonographic screening on stage at detection and long-term disease-specific survival of women with epithelial ovarian cancer. METHODS: Eligibility included all asymptomatic women aged 50 years and older and women aged 25 years and older with a documented family history of ovarian cancer. From 1987 to 2011, 37,293 women received annual ultrasonographic screening. Women with abnormal screens underwent tumor morphology indexing, serum biomarker analysis, and surgery. RESULTS: Forty-seven invasive epithelial ovarian cancers and 15 epithelial ovarian tumors of low malignant potential were detected. No women with low malignant potential tumors experienced recurrent disease. Stage distribution for invasive epithelial cancers was: stage I, 22 (47%); stage II, 11 (23%); stage III, 14 (30%), and stage IV, 0 (0%). Follow-up varied from 2 months to 20.1 years (mean, 5.8 years). The 5-year survival rate for invasive epithelial ovarian cancers detected by screening was: stage I, 95%±4.8%; stage II, 77.1%±14.5%; and stage III, 76.2%±12.1%. The 5-year survival rate for all women with invasive epithelial ovarian cancer detected by screening as well as interval cancers was 74.8%±6.6% compared with 53.7%±2.3% for unscreened women with ovarian cancer from the same institution treated by the same surgical and chemotherapeutic protocols (P<.001). CONCLUSION: Annual ultrasonographic screening of asymptomatic women achieved increased detection of early-stage ovarian cancer cases and an increase in 5-year disease-specific survival rate for women with ovarian cancer. LEVEL OF EVIDENCE: II