Miracle-dz/UniFAR-FTUs huggingface dataset:
Challenges and Priorities in the Management of HIV/HBV and HIV/HCV Coinfection in Resource-Limited Settings

Abstract Liver disease due to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is now emerging as an increasing cause of morbidity and mortality in human immunodeficiency virus- (HIV-) infected persons in resource-limited settings (RLS). Existing management guidelines have generally focused on care in tertiary level facilities in developed countries. Less than half of low-income countries have guidance, and in those that do, there are important omissions or disparities in recommendations. There are multiple challenges to delivery of effective hepatitis care in RLS, but the most important remains the limited access to antiviral drugs and diagnostic tests. In 2010, the World Health Assembly adopted a resolution calling for a comprehensive approach for the prevention, control, and management of viral hepatitis. We describe activities at the World Health Organization (WHO) in three key areas: the establishment of a global hepatitis Program and interim strategy; steps toward the development of global guidance on management of coinfection for RLS; and the WHO prequalification program of HBV and HCV diagnostic assays. We highlight key research gaps and the importance of applying the lessons learned from the public health scale-up of ART to hepatitis care.
Left ventricular apical ballooning due to severe physical stress in patients admitted to the medical ICU.

PURPOSES We sought to assess the frequency and clinical implications of left ventricular apical ballooning (LVAB) in patients who had been admitted to the medical ICU for noncardiac physical illnesses. METHODS Ninety-two consecutive patients who were admitted to the medical ICU from March to May 2003 were prospectively enrolled. Patients underwent echocardiography on the day of ICU admission, and on the third and seventh days in the hospital. LVAB was defined as symmetric severe hypokinesia or akinesia of the left ventricular wall, except for the basal part of the left ventricle, with a < 50% ejection fraction. RESULTS Of the 92 patients, 65 (71%) were men, and they had a mean (+/- SD) age of 63 +/- 11 years. LVAB was observed in 26 patients (28%), with a mean lowest ejection fraction of 33 +/- 8% (range, 19 to 46%). Compared with the 66 patients (72%) without LVAB, those with LVAB had a higher frequency of sepsis (62% vs 14%, respectively; p < 0.001), a higher prevalence of hypotension on ICU admission, more frequent use of inotropic agents, and a higher frequency of cardiomegaly and pulmonary edema (p < 0.005 for each). Sepsis was the only variable associated with the development of LVAB (odds ratio, 9.2; 95% confidence interval, 2.4 to 35.8; p < 0.001). The development of Q-wave or ST-segment displacement was associated with LVAB, but the sensitivities were 12% and 19%, respectively. Serum creatine kinase level was elevated in 12 of 26 patients (46%) with LVAB. The normalization of this condition occurred in 20 of 26 patients (77%) a mean duration of 7.4 +/- 5.6 days later (range, 2 to 25 days). The mean 2-month survival rate was lower in patients with LVAB than in those without (71 +/- 6% vs 52 +/- 10%, respectively; p = 0.047). CONCLUSION LVAB develops in a considerable number of patients who are admitted to the medical ICU, and echocardiography is useful in detecting this phenomenon.
The effect of experience and socio-economic status on web searching performance: a South African perspective

The digital divide can be described in terms of two dimensions: access and usage. Many statistics exist to prove the existence of the gap with regard to access to information and communication technology, and specifically the Internet, in South Africa. In this study, the focus was on users' aptitude in searching for information on the World Wide Web once access had been obtained. It was found that experience of 20 browser sessions is not adequate to ensure that learners from lower socio-economic communities improve in their ability to obtain the correct information during web searches but learners from higher socio-economic communities may, depending on the level of difficulty of the task and the phase of search, benefit from this amount of experience. Web experience has no effect on users' efficiency in terms of the number of mouse clicks made although socio-economic status (SES) is a significant predictor of efficiency for users with no or limited experience. Although low-SES users make fewer clicks en route to an answer as they gain experience, it does not necessarily mean that they perform better in obtaining the correct information.
A model for the cooperative free energy transduction and kinetics of ATP hydrolysis by F1-ATPase

Although the binding change mechanism of rotary catalysis by which F1-ATPase hydrolyzes ATP has been supported by equilibrium, kinetic, and structural observations, many questions concerning the function remain unanswered. Because of the importance of this enzyme, the search for a full understanding of its mechanism is a key problem in structural biology. Making use of the results of free energy simulations and experimental binding constant measurements, a model is developed for the free energy change during the hydrolysis cycle. This model makes possible the development of a kinetic scheme for ATP hydrolysis by F1-ATPase, in which the rate constants are associated with specific configurations of the β subunits. An essential new element is that the strong binding site for ADP,Pi is shown to be the βDP site, in contrast to the strong binding site for ATP, which is βTP. This result provides a rationale for the rotation of the γ subunit, which induces the cooperativity required for a tri-site binding change mechanism. The model explains a series of experimental data, including the ATP concentration dependence of the rate of hydrolysis and catalytic site occupation for both the Escherichia coli F1-ATPase (EcF1) and Thermophilic Bacillus PS3 F1-ATPase (TF1), which have different behavior.
Cost-Effectiveness of Automated Telephone Self-Management Support With Nurse Care Management Among Patients With Diabetes

PURPOSE This study evaluated the cost-effectiveness of an automated telephone self-management support with nurse care management (ATSM) intervention for patients with type 2 diabetes, which was tested among patients receiving primary care in publicly funded (safety net) clinics, focusing on non-English speakers. METHODS We performed cost analyses in the context of a randomized trial among primary care patients comparing the effects of ATSM (n = 112) and usual care (n = 114) on diabetes-related outcomes in 4 San Francisco safety net clinics. ATSM uses interactive phone technology to provide surveillance, patient education, and one-on-one counseling, and was implemented in 3 languages for a 9-month period. Cost utility was examined using quality-adjusted life-years (QALYs) derived from changes in scores on the 12-Item Short Form Health Survey. We also examined cost-effectiveness for costs associated with a 10% increase in the proportion of patients meeting diabetes-specific public health goals for increasing exercise, as recommended by Healthy People 2010 and the American Diabetes Association. RESULTS The annual cost of the ATSM intervention per QALY gained, relative to usual care, was $65,167 for start-up and ongoing implementation costs combined, and $32,333 for ongoing implementation costs alone. In sensitivity analyses, costs per QALY ranged from $29,402 to $72,407. The per-patient cost to achieve a 10% increase in the proportion of intervention patients meeting American Diabetes Association exercise guidelines was estimated to be $558 when all costs were considered and $277 when only ongoing costs were considered. CONCLUSIONS The ATSM intervention for diverse patients with diabetes had a cost utility for functional outcomes similar to that of many other accepted interventions targeted at diabetes prevention and treatment, and achieved public health physical activity objectives at modest costs. Because a considerable proportion of costs were fixed, cost-utility and cost-effectiveness estimates would likely be substantially improved in a scaled-up ATSM program.
Marriage-Related Policies in an Estimated Life-Cycle Model of Households' Labor Supply and Savings for Two Cohorts

In the U.S., both taxes and old age Social Security benefits explicitly depend on one's marital status. We study the effects of eliminating these marriage-related provisions on the labor supply and savings of two different cohorts. To do so, we estimate a rich life-cycle model of couples and singles using the Method of Simulated Moments (MSM) on the 1945 and 1955 birth-year cohorts. Our model matches well the life cycle profiles of labor market participation, hours, and savings for married and single people and generates plausible elasticities of labor supply. We find that these marriage-related provisions reduce the participation of married women over their life cycle, the participation of married men after age 55, and the savings of couples. These effects are large for both the 1945 and 1955 cohorts, even though the latter had much higher labor market participation of married women to start with.
A Stochastic Geometry Model for Multi-Hop Highway Vehicular Communication

Carrier sense multiple access (CSMA) protocol is standardized for vehicular communication to ensure a distributed and efficient communication between vehicles. However, several vehicular applications require efficient multi-hop information dissemination. This paper exploits stochastic geometry to develop a tractable and accurate modeling framework to characterize the multi-hop transmissions for vehicular networks in a multilane highway setup. In particular, we study the tradeoffs between per-hop packet forward progress, per-hop transmission success probability, and spatial frequency reuse (SFR) efficiency imposed by different packet forwarding schemes, namely, most forward with fixed radius (MFR), the nearest with forward progress (NFP), and the random with forward progress (RFP). We also define a new performance metric, denoted as the aggregate packet progress (APP), which is a dimensionless quantity that captures the aforementioned tradeoffs. To this end, the developed model reveals the interplay between the spectrum sensing threshold (ρth) of the CSMA protocol and the packet forwarding scheme. Our results show that, contrary to ALOHA networks, which always favor NFP, MFR may achieve the highest APP in CSMA networks if ρth is properly chosen.
Purification of uroporphyrinogen decarboxylase from human erythrocytes. Immunochemical evidence for a single protein with decarboxylase activity in human erythrocytes and liver.

Uroporphyrinogen decarboxylase (EC 4.1.1.37) has been purified 4419-fold to a specific activity of 58.3 nmol of coproporphyrinogen III formed/min per mg of protein (with pentacarboxyporphyrinogen III as substrate) from human erythrocytes by adsorption to DEAE-cellulose, (NH4)2SO4 fractionation, gel filtration, phenyl-Sepharose chromatography and polyacrylamide-gel electrophoresis. Progressive loss of activity towards uroporphyrinogens I and III occurred during purification. Experiments employing immunoprecipitation, immunoelectrophoresis and titration with solid-phase antibody indicated that all the uroporphyrinogen decarboxylase activity of human erythrocytes resides in one protein, and that the substrate specificity of this protein had changed during purification. The purified enzyme had a minimum mol.wt. of 39 500 on sodium dodecyl sulphate/polyacrylamide-gel electrophoresis. Gel filtration gave a mol.wt. of 58 000 for the native enzyme. Isoelectric focusing showed a single band with a pI of 4.60. Reaction with N-ethylmaleimide abolished both catalytic activity and immunoreactivity. Incubation with substrates or porphyrins prevented inactivation by N-ethylmaleimide. An antiserum raised against purified erythrocyte enzyme precipitated more than 90% of the uroporphyrinogen decarboxylase activity from human liver. Quantitative immunoprecipitation and crossed immunoelectrophoresis showed that the erythrocyte and liver enzymes are very similar but not identical. The differences observed may reflect secondary modification of enzyme structure by proteolysis or oxidation of thiol groups, rather than a difference in primary structure.
Costimulation of superantigen-activated T lymphocytes by autologous dendritic cells is dependent on B7.

Highly purified populations of dendritic cells (DCs) can be isolated from various tissues such as skin and blood. These sites are likely to encounter secreted toxins of bacteria such as superantigens. In vivo, DCs express the cell surface molecule B7, a counterreceptor for CD28 which provides costimulation to resting T cells. Highly purified preparations of DCs obtained from the epidermis and dermis of normal skin as well as blood were used to study the role of B7 in superantigen presentation to autologous T cells, as well as in alloantigen responses. We compared these results to those obtained with nondendritic antigen presenting cells (APCs) such as mononuclear cells derived from the Ficoll-Hypaque interface (PBMCs). All DC populations strongly express B7, and in a purely autologous system staphylococcal enterotoxin B (SEB)-mediated T cell proliferation was inhibited by 55-85% using a soluble chimeric fusion protein (i.e., CTLA4Ig), a potent inhibitor of CD28:B7 interaction. In contrast, while T cells also proliferated vigorously when stimulated by SEB in the presence of autologous PBMC (which only weakly express B7), costimulation was not inhibited by CTLA4Ig. In allogeneic responses, DCs were also more potent stimulators compared to PBMC, but both types of APC:T cell reactions were almost completely inhibited by CTLA4Ig (> 90%). For both SEB-mediated reactions and alloantigen reactions, the relative importance of LFA-1 and HLA-DR was similar between DCs and PBMCs. The data indicate that these DCs express B7, which can function in the SEB-driven response of autologous T cells, as well as in allogeneic T cell reactions. Overall, when comparing the relative costimulatory capabilities of different types of APCs, it appears the relatively low level of B7 expressed by PBMC functioned effectively in allogeneic reactions, whereas only the higher levels of B7 expressed by these DC populations functioned in SEB-mediated T cell responses.
Induction of Efficient Energy Dissipation in the Isolated Light-harvesting Complex of Photosystem II in the Absence of Protein Aggregation*

Under excess illumination, the Photosystem II light-harvesting antenna of higher plants has the ability to switch into an efficient photoprotective mode, allowing safe dissipation of excitation energy into heat. In this study, we show induction of the energy dissipation state, monitored by chlorophyll fluorescence quenching, in the isolated major light-harvesting complex (LHCII) incorporated into a solid gel system. Removal of detergent caused strong fluorescence quenching, which was totally reversible. Singlet-singlet annihilation and gel electrophoresis experiments suggested that the quenched complexes were in the trimeric not aggregated state. Both the formation and recovery of this quenching state were inhibited by a cross-linker, implying involvement of conformational changes. Absorption and CD measurements performed on the samples in the quenched state revealed specific alterations in the spectral bands assigned to the red forms of chlorophyll a, neoxanthin, and lutein 1 molecules. The majority of these alterations were similar to those observed during LHCII aggregation. This suggests that not the aggregation process as such but rather an intrinsic conformational transition in the complex is responsible for establishment of quenching. 77 K fluorescence measurements showed red-shifted chlorophyll a fluorescence in the 690-705 nm region, previously observed in aggregated LHCII. The fact that all spectral changes associated with the dissipative mode observed in the gel were different from those of the partially denatured complex strongly argues against the involvement of protein denaturation in the observed quenching. The implications of these findings for proposed mechanisms of energy dissipation in the Photosystem II antenna are discussed.
Pharmacokinetics of vancomycin in neonates admitted to the neonatology unit at the Jordan University Hospital.

BACKGROUND Vancomycin is used in neonatal intensive care units to treat nosocomial infections caused by methicillin-resistant Staphylococcus aureus (MRSA) or coagulase-negative staphylococci. Current dosing regimens are not adequate, producing trough concentrations below the target range. PATIENTS AND METHODS 151 neonates who received vancomycin and had vancomycin peak and trough concentration measurements as part of regular therapeutic drug monitoring were utilized. The patients were divided into three groups according to gestational age; less than 28 weeks, 28 to less than 34 weeks and 34 weeks to term. Neonates were given vancomycin doses as per guidelines. The pharmacokinetic parameters, elimination rate constant (K), elimination half-life (t1/2), volume of distribution (VD) and clearance (CL), were calculated. RESULTS Peak vancomycin concentrations ranged from 9.4 to 52.8 mg/l, while troughs ranged from 0.0 to 16.6 mg/l. One third of the trough concentrations were below 5 mg/l and are thus, subtherapeutic. There were no statistically significant differences between the three groups in regard to elimination rate constant and half-life. However, there was a statistically significant difference in volume of distribution between the three groups (p < 0.05), and in clearance between the first group and the other two (p < 0.05), using Kruskal-Wallis statistical test. CONCLUSIONS The empirical dosing method used was inadequate in one third of patients. Individualization of vancomycin dosing in the neonatal critical care unit at The Jordan University Hospital seems necessary.
Reduced cortical gray matter in narcolepsy: Preliminary findings with voxel-based morphometry

There is a selective loss of hypocretin/orexin-containing hypothalamic neurons in patients with narcolepsy. The authors compared MRI-derived gray matter maps of 12 patients with narcolepsy with matched controls using voxel-based morphometry to ascertain whether there are other structural brain abnormalities. Patients with narcolepsy showed bilateral cortical gray matter reductions predominantly in inferior temporal and inferior frontal brain regions. Relative global gray matter loss was independent of disease duration or medication history. No significant subcortical gray matter alterations were noted.
A Highly Conserved Neutralizing Epitope on Group 2 Influenza A Viruses

An antibody against a conserved epitope broadly neutralizes group 2 influenza viruses. Current flu vaccines provide only limited coverage against seasonal strains of influenza viruses. The identification of VH1-69 antibodies that broadly neutralize almost all influenza A group 1 viruses constituted a breakthrough in the influenza field. Here, we report the isolation and characterization of a human monoclonal antibody CR8020 with broad neutralizing activity against most group 2 viruses, including H3N2 and H7N7, which cause severe human infection. The crystal structure of Fab CR8020 with the 1968 pandemic H3 hemagglutinin (HA) reveals a highly conserved epitope in the HA stalk distinct from the epitope recognized by the VH1-69 group 1 antibodies. Thus, a cocktail of two antibodies may be sufficient to neutralize most influenza A subtypes and, hence, enable development of a universal flu vaccine and broad-spectrum antibody therapies.
Comparison of renal disease severity and outcome in patients with primary antiphospholipid syndrome, antiphospholipid syndrome secondary to systemic lupus erythematosus (SLE) and SLE alone.

OBJECTIVE To ascertain the clinical presentation, histopathology and outcome of renal involvement in patients with primary antiphospholipid syndrome (PAPS), antiphospholipid syndrome secondary to systemic lupus erythematosus (SAPS) and systemic lupus erythematosus alone. METHOD A retrospective analysis was undertaken of 20 patients with PAPS, 25 patients with SAPS and 275 patients with systemic lupus erythematosus to ascertain the frequency and pattern of renal involvement. RESULTS Renal involvement was found most frequently in patients with SAPS, in whom it occurred in 68% of patients. Renal disease was equally common in patients with PAPS and systemic lupus erythematosus alone where it was seen in 30% of patients. Patients with systemic lupus erythematosus most frequently presented with nephrotic syndrome due to glomerulonephritis, whereas those with PAPS and SAPS were more likely to present with hypertension and reduced glomerular filtration rate. No patients with PAPS developed end-stage renal failure compared with 5.9% of patients with SAPS and 16.9% of patients with systemic lupus erythematosus alone; 23.5% of patients with SAPS died compared with 15.7% of patients with systemic lupus erythematosus alone and no patients with PAPS. CONCLUSION Renal involvement is a major feature of both PAPS and SAPS, where renal thrombosis frequently leads to reduced glomerular filtration rate and hypertension. One-third of patients with systemic lupus erythematosus alone develop glomerulonephritis leading to renal disease which most commonly presents with nephrotic syndrome. Patients with PAPS were less likely to develop end-stage renal failure or die during the follow-up period.
Trends in Relative Earnings and Marital Dissolution: Are Wives Who Outearn Their Husbands Still More Likely to Divorce?

As women's labor-force participation and earnings have grown, so has the likelihood that wives outearn their husbands. A common concern is that these couples may be at heightened risk of divorce. Yet with the rise of egalitarian marriage, wives’ relative earnings may be more weakly associated with divorce than in the past. We examine trends in the association between wives’ relative earnings and marital dissolution using data from the 1968–2009 Panel Study of Income Dynamics. We find that wives’ relative earnings were positively associated with the risk of divorce among couples married in the late 1960s and 1970s, and that this was especially true for wives who outearned their husbands, but this was no longer the case for couples married in the 1990s. Change was concentrated among middle-earning husbands and those without college degrees, a finding consistent with the economic squeeze of the middle class over this period.
A subclass of polyomavirus middle tumor antigen binds to DNA cellulose

We examined the binding of polyomavirus large (L-T)-, middle (M-T)-, and small-tumor antigens to DNA cellulose. At pH 6.0, the majority of L-T bound to calf thymus DNA cellulose, while little or no small tumor antigen was retained under these conditions. Unexpectedly, a small but reproducible proportion of M-T bound to both native and denatured DNA cellulose. M-T encoded by polyomavirus mutant dl 8, which expressed shortened L-T and M-T, bound to DNA, indicating that the deleted sequences are not required for DNA binding. Also, M-T from transformed BMT-1 rat cells, which synthesize exclusively this polyomavirus tumor antigen, bound to DNA, indicating that its binding is not due to association with other polyomavirus-encoded proteins. Using the DNA fragment immunoassay, we found that, under conditions in which L-T bound specifically to DNA fragments containing viral regulatory sequences, no viral DNA fragments were bound by M-T. The existence of distinct subpopulations of M-T that differ in their DNA-binding properties was indicated by rebinding experiments in which M-T that had bound to DNA cellulose rebound very efficiently, while that which had not been originally retained by DNA cellulose rebound poorly. Furthermore, the M-T-pp60 c-src complex did not bind to DNA cellulose. These data suggest that polyomavirus M-T is heterogeneous, consisting of populations of molecules that differ in their interactions with DNA cellulose.