Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic and bioenvironmental factors associated with warfarin response in Colombian patients.

Introduction. Warfarin is an anticoagulant that is difficult to administer because of its narrow therapeutic margin and the numerous factors that influence patient response. Objective. Demographic, clinical and genetic variables were characterized to establish the appropriate maintenance dosages of warfarin. Materials and methods. The Colombian patients consisted of 145 adults of both sexes. They were in stable anticoagulation status with international normalized ratio between 2 and 3 for at least two months, and without changes in the warfarin commercial preparation or in the dosage. After signing the informed consent, the following data was recorded for each volunteer: age, gender, weight, height, smoker status, co-morbidity, co-medication, International Normalized Ratio (INR), warfarin dose, and commercial brand. Each patient was typed for genes CYP2C9, VKORC1, CYP4F2 and PROC; for 59 patients, the serum levels of warfarin were quantified. The genotyping and the blood quantification were performed by mini-sequencing and HPLC methods, respectively. Results. Age, co-medication with enzymatic inhibitors (amiodarone, sertraline, fluoxetine) or inducers (phenytoin, carbamazepine), and the alleles rs1799853 (*2) and rs1057910 (*3) of the CYP2C9 gene, as well as rs9923231 of the VKORC1 gene were associated with warfarin dose required to achieve anticoagulation with INR of 2-3. These variables were included in a multiple linear regression model for predicting the optimum dose/week of warfarin. This resulted in an algorithm that explained 47.4% of the variability in the dose responses. Conclusion: Clinical and pharmacogenetic variables provided a basis for improving the safety and effective dosage of warfarin; however, the use of a pharmacogenetic algorithm will require patient data obtained during clinical trials.
Clinical Factors Associated with Sodium Removal in Peritoneal Dialysis Patients

A cross-sectional study was conducted in 156 clinically-stable peritoneal dialysis patients to identify the factors associated with sodium removal. Serum biochemistry, peritoneal function (modified peritoneal equilibration test [PET]) and the adequacy of dialysis were analysed in relation to sodium removal using multivariate linear regression. Factors significantly affecting peritoneal sodium removal included infusion volume and ultrafiltration volume per 24 h, sodium dip in the first hour of PET and sodium difference between serum and fresh dialysate. Factors significantly affecting total sodium removal included ultrafiltration and urine volume per 24 h, sodium dip in the first hour of PET and sodium difference between serum and fresh dialysate. With traditional dialysate, adequate fluid removal is required to ensure sufficient sodium removal, but a low-sodium dialysate may prevent sodium retention. Sodium removal should be included in evaluation of the adequacy of dialysis.
An unusual cause of multiple organ dysfunction syndrome in the pediatric intensive care unit: Hemophagocytic lymphohistiocytosis

Objective: To report our experience in children with primary or secondary hemophagocytic lymphohistiocytosis (HLH) presented with multiple organ dysfunction syndrome (MODS) in pediatric intensive care unit (PICU). Design: The records of patients with a diagnosis of HLH and MODS between January 2005 and January 2008 were reviewed. The patients' characteristics, treatment modalities, and outcomes were assessed. Setting: PICU of Ege University Hospital. Patients/Subjects: Twelve children who were hospitalized in the PICU met the diagnostic criteria for HLH, and presented with MODS were entered into the study. Results: The median age of the patients was 3 years (range, 2 months–15.5 years). Six patients had a history of parental consanguinity and two had an affected sibling. Five of the patients were classified as primary HLH. All of the patients had hepatosplenomegaly, elevated ferritin levels, hypofibrinogenemia, anemia, thrombocytopenia, and hemophagocytosis in bone marrow examination at presentation. The median Pediatric Logistic Organ Dysfunction score of the patients at onset was 51 (range, 12–62). Four patients had six, four had five, two had four, and the remaining two had three organ dysfunctions. Organ dysfunction, other than hematologic dysfunction which was present in all patients, was most commonly seen in hepatic (n = 11, 91.7%), respiratory (n = 11, 91.7%), and cardiovascular systems (n = 10, 83.3%). Although nine patients showed neurologic dysfunction including convulsion and coma, renal failure was detected in five patients. Eleven patients were supported with mechanical ventilation and four patients required hemodialysis. Eight patients were treated according to the HLH 2004 treatment protocol, consisting of cyclosporine A, etoposide, and dexamethasone. The remaining four patients received only intravenous immunoglobulin and supportive treatment. Seven of the patients died. Conclusion: HLH is a frequently lethal disease and with a clinical presentation similar to severe sepsis, MODS, disseminated intravascular coagulation, or septic shock, which are frequent diagnoses in the PICU. In the PICU, HLH should be considered in the case of prolonged fever, splenomegaly, cytopenia, and MODS. It is important for pediatricians and particularly pediatric intensivists to know the diagnostic criteria and possible clinical presentations of HLH so treatment is initiated promptly.
Performance Feedback and Firm Risk Taking: The Moderating Effects of CEO and Outside Director Stock Options

We contribute to the behavioral theory of the firm and the behavioral agency model by developing a theoretical framework that predicts the differential interaction effects of performance feedback and values of stock option grants of multiple agents on firm risk taking. We explain how chief executive officers (CEOs) versus outside directors awarded with stock option grants perceive negative or positive deviations from prior performance. We argue that in a negative attainment discrepancy context, high values of option grants will increase the risk aversion of CEOs who already bear excessive employment and compensation risks, resulting in less risk taking; however, it will enhance the risk-taking propensity of influential outside directors who increase monitoring and support for risky projects because their risk preferences are better aligned with those of shareholders. In a positive attainment discrepancy context, high values of option grants will amplify risk aversion in both CEOs and outside directors who perceive risky strategies as potential threats to anticipated incentive values associated with a gain domain, thereby reducing risk-taking activities. Analysis of panel data from 1992 to 2006 on the research and development spending of U.S. manufacturing firms based on Arellano–Bond dynamic panel regression reveals findings largely consistent with our predictions.
Knowledge, attitudes and barriers regarding vaccination against hepatitis A and B in patients with chronic hepatitis C virus infection: a survey of family medicine and internal medicine physicians in the United States

Background: Although vaccination against hepatitis A virus (HAV) and hepatitis B virus (HBV) is recommended for all patients with chronic hepatitis C virus (HCV) infection, physician vaccination practices are suboptimal. Since training for family medicine (FM) and internal medicine (IM) physicians differ, we hypothesised that there are differences in knowledge, attitudes and barriers regarding vaccination against HAV and HBV in patients with chronic HCV between these two groups.
Effect of myo-inositol and melatonin versus myo-inositol, in a randomized controlled trial, for improving in vitro fertilization of patients with polycystic ovarian syndrome

Abstract Polycystic ovarian syndrome (PCOS) induces anovulation in women of reproductive age, and is one of the pathological factors involved in the failure of in vitro fertilization (IVF). Indeed, PCOS women are characterized by poor quality oocytes. Therefore, a treatment for enhancing oocyte quality becomes crucial for these patients. Myo-Inositol and melatonin proved to be efficient predictors for positive IVF outcomes, correlating with high oocyte quality. We tested the synergistic effect of myo-inositol and melatonin in IVF protocols with PCOS patients in a randomized, controlled, double-blind trial. Five-hundred twenty-six PCOS women were divided into three groups: Controls (only folic acid: 400 mcg), Group A (Inofolic® plus, a daily dose of myo-inositol: 4000 mg, folic acid: 400 mcg, and melatonin: 3 mg), and Group B (Inofolic®, a daily dose of myo-inositol: 4000 mg, and folic acid: 400 mcg). The main outcome measures were oocyte and embryo quality, clinical pregnancy and implantation rates. The treatment lasted from the first day of the cycle until 14 days after embryo transfer. Myo-inositol and melatonin have shown to enhance, synergistically, oocyte and embryo quality. In consideration of the beneficial effect observed in our trial and on the bases of previous studies, we decided to integrate routinely MI and M supplementation in the IVF protocols. The same treatment should be taken carefully in consideration in all procedures of this kind.
Incorporation of primary patient‐derived glycoproteins into authentic infectious hepatitis C virus particles

The Japanese fulminant hepatitis‐1 (JFH1)‐based hepatitis C virus (HCV) infection system has permitted analysis of the complete viral replication cycle in vitro. However, lack of robust infection systems for primary, patient‐derived isolates limits systematic functional studies of viral intrahost variation and vaccine development. Therefore, we aimed at developing cell culture models for incorporation of primary patient‐derived glycoproteins into infectious HCV particles for in‐depth mechanistic studies of envelope gene function. To this end, we first constructed a packaging cell line expressing core, p7, and NS2 based on the highly infectious Jc1 genotype (GT) 2a chimeric genome. We show that this packaging cell line can be transfected with HCV replicons encoding cognate Jc1‐derived glycoprotein genes for production of single‐round infectious particles by way of trans‐complementation. Testing replicons expressing representative envelope protein genes from all major HCV genotypes, we observed that virus production occurred in a genotype‐ and isolate‐dependent fashion. Importantly, primary GT 2 patient‐derived glycoproteins were efficiently incorporated into infectious particles. Moreover, replacement of J6 (GT 2a) core, p7, and NS2 with GT 1a‐derived H77 proteins allowed production of infectious HCV particles with GT 1 patient‐derived glycoproteins. Notably, adaptive mutations known to enhance virus production from GT 1a‐2a chimeric genomes further increased virus release. Finally, virus particles with primary patient‐derived E1‐E2 proteins possessed biophysical properties comparable to Jc1 HCVcc particles, used CD81 for cell entry, were associated with ApoE and could be neutralized by immune sera. Conclusion: This work describes cell culture systems for production of infectious HCV particles with primary envelope protein genes from GT 1 and GT 2‐infected patients, thus opening up new opportunities to dissect envelope gene function in an individualized fashion. (Hepatology 2014;60:508–520)
Inflammatory monocytes require type I interferon receptor signaling to activate NK cells via IL-18 during a mucosal viral infection

The requirement of type I interferon (IFN) for natural killer (NK) cell activation in response to viral infection is known, but the underlying mechanism remains unclear. Here, we demonstrate that type I IFN signaling in inflammatory monocytes, but not in dendritic cells (DCs) or NK cells, is essential for NK cell function in response to a mucosal herpes simplex virus type 2 (HSV-2) infection. Mice deficient in type I IFN signaling, Ifnar−/− and Irf9−/− mice, had significantly lower levels of inflammatory monocytes, were deficient in IL-18 production, and lacked NK cell–derived IFN-&ggr;. Depletion of inflammatory monocytes, but not DCs or other myeloid cells, resulted in lower levels of IL-18 and a complete abrogation of NK cell function in HSV-2 infection. Moreover, this resulted in higher susceptibility to HSV-2 infection. Although Il18−/− mice had normal levels of inflammatory monocytes, their NK cells were unresponsive to HSV-2 challenge. This study highlights the importance of type I IFN signaling in inflammatory monocytes and the induction of the early innate antiviral response.
Hemodynamic effects of the somatostatin analog lanreotide in humans: Placebo‐controlled, cross‐over dose‐ranging echo‐doppler study

Because of their vasoactive effects, somatostatin and its analogs are increasingly used in the management of complications of chronic liver diseases such as variceal bleeding. Postprandial hyperemia augments splanchnic blood flow, subsequently increasing portal pressure. The aim of this study was to explore effects of the somatostatin analog, lanreotide, on food‐stimulated hemodynamic parameters in healthy human subjects. A dose‐response curve was constructed in eight healthy male subjects in a placebo‐controlled cross‐over study. On 4 different days, either 0 (placebo), 50, 100, or 200 μg/h of lanreotide was infused intravenously in random order, starting at 45 minutes for 7 hours. On each day, a liquid test meal (Ensure plus, 1.5 kcal/mL) was perfused intraduodenally at a rate of 3 mL/min over 7 hours after a 45‐minute basal period. Diastolic arterial pressure (dBP), heart rate (HR), superior mesenteric arterial (SMA) average flow velocity (SMA‐V), SMA pulsatility index (SMA‐PI), portal venous volume flow (PV‐F), and renal artery (RA) resistance index (RA‐RI) were measured on regular intervals (flows using Echo‐Doppler technology). Lanreotide at all doses abolished food‐stimulated splanchnic hyperemia both in the SMA and PV over 7 hours. The fall in dBP and increase in HR after food perfusion were blunted under lanreotide. Food as well as lanreotide did not modify RA‐RI. In summary: 1) lanreotide inhibits food‐induced splanchnic hyperemia in normal subjects; 2) in parallel, systemic hemodynamic alterations to food stimulation are abolished with lanreotide; and 3) renal vascular resistance is unchanged. Because of its persistent splanchnic vasoconstrictive effect, lanreotide should be tested in patients with portal hypertension.
Thirty-Day, All-cause Readmissions for Elderly Patients Who Have an Injury-related Inpatient Stay

Background:Policymakers are exploring ways to reduce readmission rates. Much attention has been given to readmissions for conditions such as heart failure, acute myocardial infarction, and pneumonia, but little attention has been given to readmissions of patients with injury-related index admissions. Methods:This analysis is a retrospective cohort study of elderly persons who are admitted to a community hospital for a principal diagnosis of injury. We use 2006 Healthcare Cost and Utilization Project State Inpatient Databases and State Emergency Department Databases from 11 States. With logistic regression we identify factors associated with a 30-day, all-cause inpatient readmission. Factors include: patient characteristics, injury characteristics, clinical experiences during the hospital stay, and hospital characteristics. Results:About 1 in 7 elderly patients with an injury-related admission were readmitted in 30 days (13.7%). We found that severe injuries had higher predicted readmission rates. Patients receiving transfusions, experiencing a Patient Safety Indicator event, and with infections had higher readmission rates. Patients discharged to nursing homes or home health care had higher readmission rates compared with patients discharged to the community. Conclusions:This study expands evidence for the influence of injury characteristics on readmission rates. It also provides evidence about hospital experiences that affect readmissions. These findings suggest that a focus on preventing complications during the hospital stay may help reduce hospital-specific readmissions for patients with injury-related conditions. It also suggests that a strategy to reduce readmission rates should not only focus on hospitals but also nursing homes and home health care.
Apomorphine and Alzheimer Aβ: Roles for regulated α cleavage, autophagy, and antioxidation?

In this issue, Himeno and colleagues1 describe a new, exciting – and potentially therapeutically important – regulatory event in the life cycle of the Alzheimer's amyloid precursor protein (APP) and the fragments of APP generated by proteolytic processing. At the outset, before diving deeply into the cell biology of APP and Aβ metabolism, it should be noted that, if confirmed, the effect identified by Himeno et al 1 would constitute an important addition to the experimental Aβ–lowering armamentarium currently being martialed against the cerebral amyloidosis of Alzheimer's disease (AD). About half of the over 65 population has measurable cerebral accumulation of fibrillar Aβ as defined by PET scans employing Pittsburgh compound B (PiB) as tracer2. By extension, at the time of diagnosis, patients with clinically apparent mild cognitive impairment (MCI) or early AD are bound to have a substantial cerebral burden of both fibrillar (detectable on PiB scan) and oligomeric Aβ (undetectable on PiB scan). All current experimental therapies are more effective as prophylaxis than as treatment3,4,5. The potential breakthrough from Himeno et al is the suggestion that something as simple and drug-like as apomorphine – through some pathway that is not immediately obvious – can activate clearance of Aβ from the brain. Because of this potential clinical implication, it is important to try to make sense of the new data in light of the current conventional wisdom about APP metabolism.
An FPGA implementation architecture for decoding of polar codes

Polar codes are a class of codes versatile enough to achieve the Shannon bound in a large array of source and channel coding problems. For that reason it is important to have efficient implementation architectures for polar codes in hardware. Motivated by this fact we propose a belief propagation (BP) decoder architecture for an increasingly popular hardware platform; Field Programmable Gate Array (FPGA). The proposed architecture supports any code rate and is quite flexible in terms of hardware complexity and throughput. The architecture can also be extended to support multiple block lengths without increasing the hardware complexity a lot. Moreover various schedulers can be adapted into the proposed architecture so that list decoding techniques can be used with a single block. Finally the proposed architecture is compared with a convolutional turbo code (CTC) decoder for WiMAX taken from a Xilinx Product Specification and seen that polar codes are superior to CTC codes both in hardware complexity and throughput.
Temporal Regularization of the PN Equations

In this paper, we introduce a regularization of the $P_N$ equations for one-dimensional, slab geometries. These equations are used to describe particle transport through a material medium. Our regularization is based on a temporal splitting of fast and slow dynamics in the $P_N$ system. It uses ideas first introduced in [S. Jin, SIAM J. Sci. Comput. , 21 (1999), pp. 441–454] for $2\times2$ systems to address systems of arbitrary size and with spatially varying media. The regularization captures the proper diffusion limit in diffusive regimes but behaves like the original $P_N$ system in streaming regimes. It also allows for larger times steps in diffusive regimes, when the original $P_N$ system is stiff. In particular, for simulations in which the computational mesh does not resolve the particle mean free path, the regularization admits a simple scheme with no stability restrictions on the time step.
Credit risk with infinite dimensional Lévy processes

The forward rate curve is assumed to follow a stochastic differential equation w.r. t. a Levy process with infinite dimensions. Conditions under which the market is free of arbitrage are provided for both the interest rate case and for the case of credit risk with ratings. A simulation shows that typical movements of the yield curve are well captured by the model.
APPRECIATING THE USER'S PERSPECTIVE: LISTENING TO THE “METHADONIANS”

Researchers have long neglected the user's perspective and experiences in assessing drug effects and drug use. With increased interest in Canada directed at prescribing heroin in place of methadone, researchers took the relatively unique approach of gathering data and information from methadone users to determine their views and experiences with methadone programs and alternative treatment choices. The results of that research portrayed very interesting and useful notions of users regarding methadone maintenance and the prescribing of heroin.
Cell cycle regulation of pEg3, a new Xenopus protein kinase of the KIN1/PAR-1/MARK family.

We report the characterization of pEg3, a Xenopus protein kinase related to members of the KIN1/PAR-1/MARK family. The founding members of this newly emerging kinase family were shown to be involved in the establishment of cell polarity and both microtubule dynamic and cytoskeleton organization. Sequence analyses suggest that pEg3 and related protein kinases in human, mouse, and Caenorhabditis elegans might constitute a distinct group in this family. pEg3 is encoded by a maternal mRNA, polyadenylated in unfertilized eggs and specifically deadenylated in embryos. In addition to an increase in expression, we have shown that pEg3 is phosphorylated during oocyte maturation. Phosphorylation of pEg3 is cell cycle dependent during Xenopus early embryogenesis and in synchronized cultured XL2 cells. In embryos, the kinase activity of pEg3 is correlated to its phosphorylation state and is maximum during mitosis. Using Xenopus egg extracts we demonstrated that phosphorylation occurs at least in the noncatalytic domain of the kinase, suggesting that this domain might be important for pEg3 function.
Inhibition of hepatitis B virus DNA polymerase by 3′‐fluorothymidine triphosphate and other modified nucleoside triphosphate analogs

The 3′‐fluoromodified nucleotide analogs 3′‐fluorothymidine triphosphate (FdTTP), 2′,3′‐dideoxy‐3′‐fluoro‐5‐chlorouridine triphosphate (F‐5CldUTP), 2′,3′‐dideoxy‐3′‐fluoro‐5‐ethyluridine triphosphate (F‐5EtdUTP), 2′,3′‐dideoxy‐3′‐fluorouridine triphosphate (FdUTP), and 2′,3′‐dideoxy‐3′‐fluoro‐5‐fluorouridine triphosphate (F‐5FdUTP) as well as 2′,3′‐dideoxythymidine triphosphate (ddTTP), 2′,3′‐didehydro‐2′,3′‐dideoxythymidine triphosphate (ddeTTP), 3′‐chlorothymidine triphosphate (CldTTP), and 3′‐rhodanothymidine triphosphate (SCNdTTP) were tested for their ability to inhibit hepatitis B virus (HBV)‐associated DNA polymerase activity in vitro. The ID50 values of the most potent inhibitors were 0.15 μM for FdTTP, 0.2 μM for ddeTTP, 0.45 μM for ddTTP, and 0.8 μM for F‐5CldUTP. SCNdTTP, CldTTP, and F‐5EtdUTP were less efficient (ID50 = 3–5 μM), and FdUTP and F‐5FdUTP were the least efficient inhibitors (ID50 = 25 μM) of the enzyme activity. Kinetic analysis revealed a competitive type of inhibition for FdTTP and ddeTTP. The Ki values were estimated to be 0.04 μM and 0.08 μM, respectively, compared with a Km value for dTTP of about 0.18 μM.
Equalization Methods for NLIN Mitigation

We investigate the potential of adaptive equalization techniques to mitigate inter-channel nonlinear interference noise (NLIN). We derive a lower bound on the mutual information of a system using adaptive equalization, showing that the channel estimation error determines the equalizer's performance. We develop an adaptive equalization scheme which uses the statistics of the NLIN to obtain optimal detection, based on Kalman filtering and maximum likelihood sequence estimation (MLSE). This scheme outperforms commonly used equalizers and significantly increases performance.