Miracle-dz/UniFAR-FTUs huggingface dataset:
Fifth mutation in human immunodeficiency virus type 1 reverse transcriptase contributes to the development of high-level resistance to zidovudine.

It is recognized that high-level resistance to 3'-azido-3'-deoxythymidine (AZT, zidovudine, or Retrovir) is conferred by the presence of four mutations in the human immunodeficiency virus (HIV) reverse transcriptase [RT; deoxynucleoside-triphosphate:DNA deoxynucleotidyltransferase (RNA-directed), EC 2.7. 7.49] coding sequence. However, a number of clinical isolates have been observed that exhibit high-level resistance but contain only three of the four identified mutations (Asn-67, Arg-70, and Tyr-215). Construction of a molecular clone with this genotype gave rise to only a partially resistant virus, raising the possibility that an additional mutation existed in some clinical isolates. Using an HIV marker rescue system, we have mapped and identified a fifth mutation conferring resistance to zidovudine, namely, methionine to leucine at codon 41 of HIV RT. An infectious molecular clone containing this mutation together with three previously identified mutations in the RT coding sequence yielded highly resistant HIV after transfection of T cells. Direct detection of the fifth mutation in DNA samples from cocultured peripheral blood lymphocytes by the PCR revealed that it occurred relatively early in the development of zidovudine resistance. However, this mutation was only detected after the appearance of the codon 215 change in the RT coding sequence. Identification of this mutation in addition to the other known mutations conferring resistance enables rapid and direct correlation between an RT genotype and sensitivity of the virus.
Development of a pediatric end-stage liver disease score to predict poor outcome in children awaiting liver transplantation1

Background. A pediatric end-stage liver disease (PELD) score for children with chronic liver disease using easily obtainable, objective, verifiable parameters, would be useful to prioritize children awaiting liver transplantation. Methods. Data from the Studies of Pediatric Liver Transplantation (SPLIT), a consortium of 29 U.S. and Canadian centers, were used to develop the PELD score. Two pretransplantation endpoints were evaluated: (1) death, n=884; and (2) death or moving to the intensive care unit (ICU), n=779. The analyses were restricted to children with chronic liver disease who were listed for a first transplant. Preliminary analyses of 17 possible factors yielded 6 parameters of interest: age <1 year, total bilirubin, international normalized ratio (INR), albumin, growth failure (height or weight Z score <−2), and calculated glomerular filtration rate. In a univariate Cox regression analysis, age, bilirubin, INR, and albumin were significant (P <0.01) predictors of both endpoints; glomerular filtration rate was not significant for either endpoint; and growth failure was significant for death/ICU but not death alone. In the multivariate analyses, age, bilirubin, and INR were significant for the death endpoint; and bilirubin, INR, growth failure, and albumin were significant for the death/ICU endpoint. From these results, three PELD models were evaluated to predict both outcomes at 3 and 6 months: PELD 1 (age, bilirubin, INR); PELD 2 (bilirubin, INR, albumin, growth failure); and PELD 3 (bilirubin, INR, albumin, growth failure, and age). The area under the receiver operating characteristic curve (AUC ROC) was used to compare models. For PELD 3, the most inclusive model, the AUC ROC at 3 months was 0.92 for death and 0.82 for “death–moved to ICU. ” A comparison of the AUC ROCs for the other models and for the model of end-stage liver disease ([MELD], the adult end-stage liver disease severity score model), none of which performed better than PELD 3, are presented. Conclusion. A model using five objective parameters can accurately predict death or death–moved to ICU in children awaiting liver transplantation.
Naturally acquired immunity to sexual stage P. falciparum parasites

SUMMARY Gametocytes are the specialized form of Plasmodium parasites that are responsible for human-to-mosquito transmission of malaria. Transmission of gametocytes is highly effective, but represents a biomass bottleneck for the parasite that has stimulated interest in strategies targeting the transmission stages separately from those responsible for clinical disease. Studying targets of naturally acquired immunity against transmission-stage parasites may reveal opportunities for novel transmission reducing interventions, particularly the development of a transmission blocking vaccine (TBV). In this review, we summarize the current knowledge on immunity against the transmission stages of Plasmodium. This includes immune responses against epitopes on the gametocyte-infected erythrocyte surface during gametocyte development, as well as epitopes present upon gametocyte activation in the mosquito midgut. We present an analysis of historical data on transmission reducing immunity (TRI), as analysed in mosquito feeding assays, and its correlation with natural recognition of sexual stage specific proteins Pfs48/45 and Pfs230. Although high antibody titres towards either one of these proteins is associated with TRI, the presence of additional, novel targets is anticipated. In conclusion, the identification of novel gametocyte-specific targets of naturally acquired immunity against different gametocyte stages could aid in the development of potential TBV targets and ultimately an effective transmission blocking approach.
IPv6-Based Dynamic Quality of Service Control Strategy for Wireless Network

On the basis of the architecture for fast handover of hierarchical IPv6, a coordinated call admission control mechanism was presented, providing an end-to-end RSVP context transfer for real-time applications to overcome t he weakness of the context transfer protocol which cannot meet the need of end-to-end QoS mechanisms because the contexts were only transferred between the previous and new access routers. The mechanism decreased the delay caused by re-initiate QoS signaling from scratch to reestablish QoS forwarding process, and minimized the handover service disruption. The signaling overhead and handover latencies could be reduced by adopting t he fast handover for hierarchical IPv6 architecture. The approach was compared with the re-initiating RSVP signaling to reestablish QoS states using network simulator ns2. The numerical results showed that the scheme has the less latency and packet loss than that of the re-initiating approach.
More data on major depression as an antecedent risk factor for first onset of chronic back pain

Background. Few epidemiological studies have examined the temporal relationship between chronic pain and depression using longitudinal data. In the present study, we examined major depression as both an antecedent risk factor and consequence of chronic back pain (CBP) in the general population. Method. Data on 9909 pain-free individuals 15 years and older with no history of back problems were drawn from cycle 1 of the National Population Health Survey and followed up 24 months later. Major depression was assessed using a structured diagnostic interview. Results. At cycle 2, the rate of new cases of CBP in persons who were depressed at cycle 1 was 3·6% compared to 1·1% in non-depressed persons. Compared to pain-free individuals, new cases of CBP were more likely to perceive their health status as poor or fair at cycle 1, were less likely to be working, reported more chronic health problems, and sustained a back or neck injury in the preceding 12 months. After controlling for other factors, pain-free individuals diagnosed as major depressed at cycle 1 were almost three times more likely (OR 2·9, 95% CI 1·2–7·0) to develop CBP at cycle 2. Conclusions. Consistent with other longitudinal studies major depression increases the risk of developing future chronic pain. The causal mechanism linking these conditions is unknown however depression may represent a modifiable risk factor in the development of CBP.
Body Composition Modeling: Application to Exploration of the Resting Energy Expenditure Fat‐free Mass Relationship

Abstract: There are now many published methods for predicting resting energy expenditure (REE) from measured body mass and composition. Although these published reports extend back almost a century, new related studies appear on a regular basis. It remains unclear what the similarities and differences are between these many methods and what, if any, advantages the newly introduced REE prediction models offer. These issues led us to develop an organizational system for REE prediction methods with the ultimate aim of clarifying prevailing ambiguities in the field. Our classification scheme is founded on the mathematical function type (descriptive and mechanistic) and body composition level (whole body → molecular) used in REE prediction model development. The model is applied in an exploration of the well‐established empirical relationship between REE and fat‐free body mass (FFM). The developed relationships indicate that REE vs. FFM is a curvilinear relationship in mammals as a whole, that the relationship can be described as a linear function in humans, and that the simple linear regression line coefficients can be reconstructed from established tissue‐system level component relationships. Our classification system, the first founded on a conceptual basis, highlights similarities and differences between the many diverse REE body composition prediction methods, provides a framework for teaching REE‐body composition relationships to students, and suggests important future research opportunities.
Video games as a tool to train visual skills.

PURPOSE Adult brain plasticity, although possible, is often difficult to elicit. Training regimens in adults can produce specific improvements on the trained task without leading to general enhancements that would improve quality of life. This paper considers the case of playing action video games as a way to induce widespread enhancement in vision. CONCLUSIONS We review the range of visual skills altered by action video game playing as well as the game components important in promoting visual plasticity. Further, we discuss what these results might mean in terms of rehabilitation for different patient populations.
Performance Analysis of Massive Spatial Modulation MIMO in High-Speed Railway

For high-speed railway (HSR), an essential characteristic of the propagation channels is the specific spatial-temporal correlation caused by a dominant strong line-of-sight (LOS) component. Multiple-antenna gain is therefore far from being achieved due to this strong channel correlation. However, it is interesting to note that if the resulted intercarrier interference (ICI) is elaborately controlled, high mobility may decrease the channel correlation. Spatial modulation (SM) is one of the promising multiple-antenna technologies for wireless communication systems, which needs only the activation of one transmit antenna to convey information bits implicitly through the index of the active transmit antenna, in addition to conveying information bits through modulation symbols during transmission. In SM, ICI is avoided, which therefore helps in the implementation of the idea of decreasing channel correlation by increasing the velocity in an HSR scenario. In this paper, the performance of massive SM multiple-input multiple-output (MIMO) over a spatial-temporal correlated Rician fading channel is investigated under an HSR scenario. The impacts of velocity, Rician factor K, and signal-to-noise ratio (SNR) are discussed. In addition, the correlation factor and the correlation comparison function are defined as metrics of channel correlation. We theoretically find out that higher velocity makes the impact of temporal correlation more dominant, which weakens the influence of spatial correlation. In other words, spatial correlation can be weakened by high mobility. Our theoretical analysis and simulations further demonstrate that, with an appropriate scheme, massive SM MIMO outperforms Vertical Bell Laboratories Layered Space-Time (VBLAST), except at a lower SNR region with high velocity (usually more than 360 km/h). Consequently, massive SM MIMO is a promising solution within an appropriate range of velocity for HSR wireless communication systems.
Variability of IgE reactivity profiles among European mite allergic patients

Background House dust mites (HDM) Dermatophagoides pteronyssinus are a frequent indoor allergen source. Our aim was to determine the frequencies of IgE reactivity to purified HDM allergen molecules in mite allergic patients from different parts of Europe in order to establish an allergen panel for diagnosis of HDM allergy.
Small dense LDL-cholesterol relative to LDL-cholesterol is a strong independent determinant of hypoadiponectinemia in metabolic syndrome.

BACKGROUND Small dense low-density lipoprotein (sd-LDL) is an atherogenic lipoprotein closely associated with an increased risk of cardiovascular diseases. However, a precise analysis of the actual amount of sd-LDL-cholesterol (sd-LDL-C) in patients with metabolic syndrome (MS) has not been performed. METHODS AND RESULTS Among 214 patients enrolled in the present study, 101 patients (47%) met the Japanese MS criteria. The serum levels of sd-LDL-C determined with a dual detection HPLC system were higher in MS than non-MS patients, while total cholesterol and low-density lipoprotein-cholesterol (LDL-C) were similar between MS and non-MS patients. Compared with the sd-LDL-C and LDL-C level, the ratio sd-LDL-C/LDL-C was more closely correlated with various parameters associated with MS. A multivariate regression analysis revealed that the ratio sd-LDL-C/LDL-C is the strongest independent determinant of hypoadiponectinemia. Furthermore, weight reduction therapy through diet and exercise rapidly decreased LDL-C but slowly decreased sd-LDL-C. At 12 months after the therapy, weight reduction led to a significant decrease in the ratio sd-LDL-C/LDL-C in tandem with increasing adiponectin levels. CONCLUSIONS These findings demonstrate that the ratio sd-LDL-C/LDL-C is tightly connected with hypoadiponectinemia and provides a useful clinical indicator for MS. The results also suggest that the elevation of this ratio can be modulated by long-term lifestyle changes.
Failure of Cilostazol in the Prevention of Ventricular Fibrillation in a Patient with Brugada Syndrome

The ECG appearance in Brugada syndrome is caused by failure of the dome of the action potential to develop. Increased activity of the I(to) current in epicardial cells generates a transmural gradient with repolarization dispersion between the epicardium and the endocardium in the right ventricular wall, thus favoring the development of VF by a phase 2 reentry mechanism. The efficacy of cilostazol for the management of these arrhythmias has been reported. This drug is a phosphodiesterase inhibitor with positive chronotropic properties, thus blocking outward potassium currents I(to) in the myocardial tissue. We present a patient with Brugada syndrome with an implantable cardioverter defibrillator (ICD), who suffered multiple ICD discharges due to VF during therapy with this drug.
The Yale Observation Scale Score and the Risk of Serious Bacterial Infections in Febrile Infants

In our large prospective cohort of febrile infants, neither the YOS score nor unstructured clinician suspicion reliably identified infants with serious bacterial infections. OBJECTIVES: To assess the performance of the Yale Observation Scale (YOS) score and unstructured clinician suspicion to identify febrile infants ≤60 days of age with and without serious bacterial infections (SBIs). METHODS: We performed a planned secondary analysis of a prospective cohort of non–critically ill, febrile, full-term infants ≤60 days of age presenting to 1 of 26 participating emergency departments in the Pediatric Emergency Care Applied Research Network. We defined SBIs as urinary tract infections, bacteremia, or bacterial meningitis, with the latter 2 considered invasive bacterial infections. Emergency department clinicians applied the YOS (range: 6–30; normal score: ≤10) and estimated the risk of SBI using unstructured clinician suspicion (<1%, 1%–5%, 6%–10%, 11%–50%, or >50%). RESULTS: Of the 4591 eligible infants, 444 (9.7%) had SBIs and 97 (2.1%) had invasive bacterial infections. Of the 4058 infants with YOS scores of ≤10, 388 (9.6%) had SBIs (sensitivity: 51/439 [11.6%]; 95% confidence interval [CI]: 8.8%–15.0%; negative predictive value: 3670/4058 [90.4%]; 95% CI: 89.5%–91.3%) and 72 (1.8%) had invasive bacterial infections (sensitivity 23/95 [24.2%], 95% CI: 16.0%–34.1%; negative predictive value: 3983/4055 [98.2%], 95% CI: 97.8%–98.6%). Of the infants with clinician suspicion of <1%, 106 had SBIs (6.4%) and 16 (1.0%) had invasive bacterial infections. CONCLUSIONS: In this large prospective cohort of febrile infants ≤60 days of age, neither the YOS score nor unstructured clinician suspicion reliably identified those with invasive bacterial infections. More accurate clinical and laboratory predictors are needed to risk stratify febrile infants.
Expression of the voltage‐ and Ca2+‐dependent BK potassium channel subunits BKβ1 and BKβ4 in rodent astrocytes

Large‐conductance Ca2+‐activated (BK) potassium channels are centrally involved in neurovascular coupling, immunity, and neural transmission. The ability to be synergistically activated by membrane depolarization, different ligands and intracellular Ca2+ links intracellular signaling and membrane excitability. The diverse physiological functions of BK channels crucially depend on regulatory β subunits. Although first studies characterized the neuronal distribution of BKβ subunits in the rodent brain, it is largely unknown which β subunit proteins are expressed in astrocytes and thus mediate these regulatory effects. We therefore analyzed the expression of BKβ subunits in rat and mouse brain and glial cell cultures. A monospecific polyclonal antibody against the BKβ4 channel subunit was raised, affinity‐purified and extensively characterized. BKβ4 and to a lesser degree BKβ1 transcripts and protein were detected in several astrocytic populations and cultured cells. Particularly strong BKβ4 immunostaining was detected in astrocytic progenitors derived from the subventricular zone. The overlapping expression of BKα and BKβ4 in astrocytes implies a functional relationship and suggests that BKβ4 is an important accessory β subunit for astrocytic BK channels. In addition, BKβ4 might exert effects independent of the α subunit as functional heterologous co‐expression of Nav1.6 and BKβ4 resulted in reduced Nav1.6 sodium currents. Thus, BKβ4 expression in astrocytes likely participates in regulating astrocytic voltage gradients and maintaining K+ homeostasis, hence enabling astrocytes to fulfill their complex regulatory influence on proper brain function. © 2011 Wiley‐Liss, Inc.
Zebrafish exposure to environmentally relevant concentration of depleted uranium impairs progeny development at the molecular and histological levels

Uranium is an actinide naturally found in the environment. Anthropogenic activities lead to the release of increasing amounts of uranium and depleted uranium (DU) in the environment, posing potential risks to aquatic organisms due to radiological and chemical toxicity of this radionucleide. Although environmental contaminations with high levels of uranium have already been observed, chronic exposures of non-human species to levels close to the environmental quality standards remain scarcely characterized. The present study focused on the identification of the molecular pathways impacted by a chronic exposure of zebrafish to 20 μg/L of DU during 10 days. The transcriptomic effects were evaluated by the use of the mRNAseq analysis in three organs of adult zebrafish, the brain the testis and the ovaries, and two developmental stages of the adult fish progeny, two-cells embryo and four-days larvae. The results highlight generic effects on the cell adhesion process, but also specific transcriptomic responses depending on the organ or the developmental stage investigated. The analysis of the transgenerational effects of DU-exposure on the four-day zebrafish larvae demonstrate an induction of genes involved in oxidative response (cat, mpx, sod1 and sod2), a decrease of expression of the two hatching enzymes (he1a and he1b), the deregulation of the expression of gene coding for the ATPase complex and the induction of cellular stress. Electron microscopy analysis of skeletal muscles on the four-days larvae highlights significant histological impacts on the ultrastructure of both the mitochondria and the myofibres. In addition, the comparison with the transcriptomic data obtained for the acetylcholine esterase mutant reveals the induction of protein-chaperons in the skeletal muscles of the progeny of fish chronically exposed to DU, pointing towards long lasting effects of this chemical in the muscles. The results presented in this study support the hypothesis that a chronic parental exposure to an environmentally relevant concentration of DU could impair the progeny development with significant effects observed both at the molecular level and on the histological ultrastructure of organs. This study provides a comprehensive transcriptomic dataset useful for ecotoxicological studies on other fish species at the molecular level. It also provides a key DU responsive gene, egr1, which may be a candidate biomarker for monitoring aquatic pollution by heavy metals.
Time-Domain Modeling of Low-Frequency Noise in Deep-Submicrometer MOSFET

1/f noise and random telegraph signal (RTS) noise are increasingly dominant sources of low-frequency noise as the MOSFET enters the nanoscale regime. In this study, 1/f noise and RTS noise in the n-channel MOSFET are modelled in the time domain for efficient implementation in transient circuit simulation. A technique based on sum-of-sinusoids models 1/f noise while a Monte Carlo based technique is used to generate RTS noise. Low-frequency noise generated using these models exhibits the correct form of noise characteristics as predicted by theory, with noise parameters from standard 0.35-mum and 35-nm CMOS technology. Implementation of the time-domain model in SPICE shows the utility of the noisy MOSFET model in simulating the effect of low-frequency noise on the operation of deep-submicrometer analog integrated circuits.
The Effect of Metformin as an Adjunct Therapy in Adolescents with Type 1 Diabetes.

INTRODUCTION The strict control of blood glucose levels in adolescents with Type 1 Diabetes Mellitus (T1DM) is accompanied with a considerable long term decrease in microvasular and macrovascular complications. AIM This study was conducted to investigate the effect of metformin as an adjunct therapy in adolescents with poorly controlled Type 1 diabetes. MATERIALS AND METHODS It was a quasi-experimental (an uncontrolled before and after) study. The study population consisted of the patients aged over 10 years with T1DM. Metformin tablet was added to patient's insulin therapy for 12 months. Haemoglobin A1c protein was measured in the beginning of the study and repeated with three months intervals till the end of it. Insulin dosage, Body Mass Index (BMI), serum lipid, creatinine and lactate level were measured twice; in the beginning of the study and at the end of it (after 12 months). Data was analysed by SPSS (version 18) software. Paired- t-test, Wilcoxon signed ranks test and Repeated Measure ANOVA were used to examine the study's hypothesis. A p-value <0.05 was considered as significant. RESULTS Twenty nine patients were included in the study. HbA1c level and insulin dosage was significantly reduced (p<0.001) after one month of metformin as an adjunct therapy. Serum lipid was decreased (p=0.7). Weight (p<0.001) and BMI (p=0.007) were increased. CONCLUSION Adjunctive metformin therapy reduced HbA1c value and the insulin dosage received in adolescents with T1DM.