Miracle-dz/UniFAR-FTUs huggingface dataset:
Rapid Production of Neutralizing Antibody Leads to Transient Hepadnavirus Infection

ABSTRACT Hepatitis B virus (HBV) frequently causes transient infections in adults but chronic infections in infants. The basis of these age-related outcomes is not known. Infection of ducks with duck hepatitis B virus (DHBV) displays a similar dependence of outcome on the age of the host at the time of infection. In this study we compared the infection of ducks at 3 days and 3 weeks of age. We found that the efficiency of infection of hepatocytes by virus in the inoculum was similar between the two age groups but that spread of the infection throughout the liver was severely inhibited in the 3-week-old-old ducks, while a rapid spread of the infection was observed in 3-day-old ducklings. Inhibition of virus spread was accompanied by the appearance in the serum of virus neutralizing activity, as assayed by blocking of infection of primary hepatocyte cultures. Neutralizing activity appeared as early as 1 or 2 days postinfection and increased during the next 2 weeks. Depletion of immunoglobulins from serum eliminated the neutralizing activity. The specific depletion of IgM indicated that IgM appeared as the dominant fraction of neutralizing antibody in the first 2 days postinfection, but declined from day 3 on while IgG antibody rose. We conclude that excess neutralizing antibody arising rapidly in birds inoculated at 3 weeks of age but not in newly hatched ducks prevented secondary cycles of infection, resulting in a limited infection in the liver and contributing to the eventual transient outcome of the infection.
Effectiveness of two intracanal dressings in adult Portuguese patients: a qPCR and anaerobic culture assessment.

AIM To quantify bacterial equivalents before and after chemomechanical preparation using 3% sodium hypochlorite (NaOCl) and intracanal dressing with calcium hydroxide paste (Ca(OH)2 ) or 2% Chlorhexidine digluconate gel (CHX) in necrotic pulps associated or not with apical periodontitis and to further compare this quantification with counts of anaerobic microorganisms. METHODOLOGY Prospective clinical trial in 69 single-rooted adult teeth (strict inclusion criteria); CHX group: 34; Ca(OH)2 group: 35. Bacteria samples were taken at baseline (S1), after chemomechanical preparation (S2) and after 14 days of intracanal dressing (S3). Bacterial equivalents were assessed by broad-range real-time polymerase chain reaction (qPCR), and live viable bacteria measured with conventional anaerobic culture (CFU/mL). Descriptive/inferential analysis was performed with spss vs. 20.0 (α = 0.05) using the Kruskal-Wallis, Mann-Whitney and chi-squared tests and Spearman's correlation coefficients. RESULTS Both groups showed a significant decrease between S1 and S2 (Mann-Whitney U-test; P < 0.001) both in qPCR and in culture. In the Ca(OH)2 -group, no variation was observed between S2 and S3 by qPCR and culture. In contrast, the CHX group showed a significant increase from S2 to S3 by both techniques. The two groups were only significantly different in S3 (Mann-Whitney U-test; P ≤ 0.001), with a worse performance in the CHX group. Again, these results were congruent by both approaches. Data from both approaches correlate reasonably (rS < 0.5). CONCLUSIONS Infected root canals contained a high bacterial load, and the chemomechanical root canal preparation reduced bacterial equivalents by 99.1% and anaerobic counts by 98.5%. Intracanal dressings were not efficient at reducing bacterial load, but the 14-day intracanal dressing with Ca(OH)2 performed significantly better than CHX, particularly in cases with apical periodontitis.
Adalimumab in the treatment of plaque-type psoriasis and psoriatic arthritis

Introduction: Psoriasis and psoriatic arthritis (PsA) are chronic immune-mediated diseases, and TNF-α (tumor necrosis factor) is a pro-inflammatory cytokine that plays a critical role in the pathogenesis of these conditions. Adalimumab is an anti-TNF-α drug widely used for the treatment of both psoriasis and PsA. Controlled clinical trials demonstrated that adalimumab is characterized by a high degree of clinical response. The aim of this review is to report the safety, efficacy, and recent findings in the treatment of psoriasis and PsA with adalimumab. Areas covered: This article reviews the results of Phase II, III, controlled, and observational clinical studies on adalimumab in the treatment of psoriasis and PsA. A systematic search was conducted using the Pubmed Medline database for primary articles. Expert opinion: Treatment of psoriasis and PsA represents a therapeutic challenge for dermatologists and rheumatologists. The efficacy, tolerability, and safety profiles suggest adalimumab as a suitable anti-psoriatic drug in the long-term treatment of psoriasis and PsA. Management of long-term treatment, loss of efficacy, and comorbidities has been described.
MIF intersubunit disulfide mutant antagonist supports activation of CD74 by endogenous MIF trimer at physiologic concentrations

Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine. In addition to its known receptor-mediated biological activities, MIF possesses a catalytic site of unknown function between subunits of a homotrimer. Each subunit contributes three β-strands to adjacent subunits to form a core seven-stranded β-sheet for each monomer. MIF monomers, dimers, or trimers have been reported, but the active form that binds and activates the MIF receptor (CD74) is still a matter of debate. A cysteine mutant (N110C) that covalently locks MIF into a trimer by forming a disulfide with Cys-80 of an adjacent subunit is used to study this issue. Partial catalytic activity and receptor binding to CD74 are retained by N110C (locked trimer), but there is no cellular signaling. Wild-type MIF-induced cellular signaling, in vivo lung neutrophil accumulation, and alveolar permeability are inhibited with a fivefold excess of N110C. NMR and size-exclusion chromatography with light scattering reveal that N110C can form a higher-order oligomer in equilibrium with a single locked trimer. The X-ray structure confirms a local conformational change that disrupts the subunit interface and results in global changes responsible for the oligomeric form. The structure also confirms these changes are consistent for the partial catalytic and receptor binding activities. The absence of any potential monomer and the retention of partial catalytic and receptor binding activities despite changes in conformation (and dynamics) in the mutant support an endogenous MIF trimer that binds and activates CD74 at nanomolar concentrations. This conclusion has implications for therapeutic development.
Chemical Composition of Hexane Extract of Citrus aurantifolia and Anti-Mycobacterium tuberculosis Activity of Some of Its Constituents

The main aim of this study was to isolate and characterize the active compounds from the hexane extract of the fruit peels of Citrus aurantiifolia, which showed activity against one sensitive and three monoresistant (isoniazid, streptomycin or ethambutol) strains of Mycobacterium tuberculosis H37Rv. The active extract was fractionated by column chromatography, yielding the following major compounds: 5-geranyloxypsoralen (1); 5-geranyloxy-7-methoxycoumarin (2); 5,7-dimethoxycoumarin (3); 5-methoxypsoralen (4); and 5,8-dimethoxypsoralen (5). The structures of these compounds were elucidated by 1D and 2D NMR spectroscopy. In addition, GC-MS analysis of the hexane extract allowed the identification of 44 volatile compounds, being 5,7-dimethoxycoumarin (15.79%), 3-methyl-1,2-cyclopentanedione (8.27%), 1-methoxy-ciclohexene (8.0%), corylone (6.93%), palmitic acid (6.89%), 5,8-dimethoxypsoralen (6.08%), α-terpineol (5.97%), and umbelliferone (4.36%), the major constituents. Four isolated coumarins and 16 commercial compounds identified by GC-MS were tested against M. tuberculosis H37Rv and three multidrug-resistant M. tuberculosis strains using the Microplate Alamar Blue Assay. The constituents that showed activity against all strains were 5 (MICs = 25–50 μg/mL), 1 (MICs = 50–100 μg/mL), palmitic acid (MICs = 25–50 μg/mL), linoleic acid (MICs = 50–100 μg/mL), oleic acid (MICs = 100 μg/mL), 4-hexen-3-one (MICs = 50–100 μg/mL), and citral (MICs = 50–100 μg/mL). Compound 5 and palmitic acid were the most active ones. The antimycobacterial activity of the hexane extract of C. aurantifolia could be attributed to these compounds.
[Reducing ambiguity: semantic statistical studies of "normal" probands, neurotic patients, borderline patients and schizophrenic patients].

The present study tries to answer three questions: 1. ) Do patients with neurotic disorders differ from normals by a stronger tendency to avoid or reduce ambiguity? 2. ) Does the tendency to avoid or reduce ambiguity increase with increasing ambiguity of the stimulus? 3. ) Does the avoidance or reduction of ambiguity increase with affects of anxiety and hostility? In order to answer these questions, Ertel's dogmatism-dictionary was applied to the answers of 30 normals, 30 patients with neurotic disorders, 30 borderline-patients, 25 acute and 25 chronic schizophrenics in the Holtzman Inkblot Technique (HIT). According to the results, (1) patients with neurotic disorders do not differ from normals by a stronger tendency to avoid or reduce ambiguity. 2. ) The tendency to avoid or reduce ambiguity increases with measures of increasing stimulus ambiguity of the HIT cards in all diagnostic groups studied with the exception of chronic schizophrenics. As far as response ambiguity (variability of interpretation) is concerned, only in chronic schizophrenics the tendency to avoid or reduce ambiguity decreases with increasing response ambiguity. 3. ) The avoidance or reduction of ambiguity increases with affects of anxiety and/or aggression assessed by HIT-measures in all diagnostic groups studied with the exception of normals and chronic schizophrenics. In both normals and chronic schizophrenics, the reduction of ambiguity decreases significantly with increasing anxiety, in chronic schizophrenics the reduction of ambiguity decreases significantly with an increase of low levels of aggression.
Charges, hydrogen bonds, and correlated motions in the 1 A resolution refined structure of the mating pheromone Er-1 from Euplotes raikovi.

A detailed description is given of the structure of the small protein mating pheromone Er-1 at atomic resolution. Emphasis is placed on the locations of charges and hydrogen bonds. The model includes all the protein atoms, anisotropic displacement parameters, four disordered side chains, 22 water molecules, a disordered ethanol, and "riding" hydrogen atoms. Analysis of the model revealed that this dense crystal is perfused by hydrogen-bonding networks of solvent and protein atoms. The termini of helices are capped by hydrogen bonding to solvent and protein atoms, and to symmetry-related molecules. An examination of the valencies and charges of the hydrogen-bonding groups suggests that three of the "water" molecules capping the C termini of two helices, and one other, may instead be NH4 ions. Water molecules mediate all but one of the interhelical hydrogen bonds, and many of the lattice interactions. Regions of the molecule where the atomic vibrations deviate from isotropy are identified. There is almost no overall libration of the molecule allowed by the packing, but the side-chains vibrate relative to the backbone. Four side-chains display alternate conformations. Indirect evidence is presented that the switches between their conformations are correlated and driven by protonation of acidic side-chains. These structural features are discussed in the context of function and stability. Equipped with the analysis of the model, we review the course and results of the refinement of the model against 1 A X-ray diffraction data to a crystallographic R-factor of 12.92%.
Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial.

IMPORTANCE Secretory phospholipase A2 (sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95% CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95% CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01130246.
On blind decision feedback equalization

Derived from the predictive structure of (non-blind) minimum mean square error decision feedback equalizer (MMSE-DFE), two new schemes, referred to as DFE(CMA, SF) and DFE(CMA, CMA), are investigated. The DFE(CMA, SF) design optimizes the forward filter using the constant modulus criterion applied to its output and obtains the feedback filter by the spectral factorization of the observation process. In contrast, the DFE(CMA, CMA) uses only the constant modulus criterion to design both the forward and feedback filters. At high SNR, both approaches offer asymptotic near optimal performance (in mean-square error). They are different in their implementation complexities and efficiencies. We also show that, at high SNR, the feedback filter in DFE(CMA, CMA) converges to the global minimum at a rate equal to that of a nonblind case. At low SNR, however, CMA updates of the feedback filter is affected by error propagation.
Human squamous cell carcinoma lines express oncofetal 44‐kd polypeptide defined by monoclonal antibody to mouse fetus

Most primary human carcinomas uniformly express an oncofetal epitope which has not been demonstrated previously in established human carcinoma cell lines. We successfully derived several low‐passage cell lines of human squamous cell carcinoma (SCC) from head and neck tumors using an in vitro adaptation procedure, characterized these lines, and examined them for expression of a 44‐kilodalton (kD) polypeptide (PP) oncofetal antigen (OFA) at the cell surface. Newly established and in vitro‐passaged SCC cells retained characteristic microvilli, numerous desmosomes and tonofilaments, abundant rough endoplasmic reticulum, osmophilic keratohyaline granules, and other features of the primary SCC cells. These new cell lines and two long‐term, established SCC lines (FaDu and Detroit 562) displayed OFA at the cell surface, as determined by flow cytometry using monoclonal antibody (MoAb) 115. While the FaDu and Detroit 562 lines exhibited aneuploidy during flow cytometric analysis, the new, low‐passage SCC lines that we developed remained diploid as were the primary SCC cells from which they were derived. We propose that the expression of a 44‐kD OFA is a common feature of human SCC. This marker may prove useful in the detection and treatment of these tumors.
Communication in pediatric oncology: State of the field and research agenda

From the time of diagnosis through either survivorship or end of life, communication between healthcare providers and patients or parents can serve several core functions, including fostering healing relationships, exchanging information, responding to emotions, managing uncertainty, making decisions, and enabling patient/family self‐management. We systematically reviewed all studies that focused on communication between clinicians and patients or parents in pediatric oncology, categorizing studies based on which core functions of communication they addressed. After identifying gaps in the literature, we propose a research agenda to further the field.
Touch-level model (TLM): evolving KLM-GOMS for touchscreen and mobile devices

In the early days of personal computing, a model called "Goals, Operators, Methods, and Selection Rules" (GOMS) provided a method with which to quantify user interaction with a system. [2] Soon after, the Keystroke Level Model (KLM) allowed decomposition of complex tasks into atomic, benchmarked 'operators' that could generalize and estimate interactions on any keyboard interface. However, this the model is dated and unsuitable for today's modern devices. These touchscreen interfaces are now pervasive [4], but the HCI implications of this shift are not fully researched; an imperative exists for research in human-computer interaction to study these interfaces and the interactions of the people using them. [3] In this paper, we introduce new operators and other modifications to KLM-GOMS to accommodate modern touchscreen interfaces. We call these additions, together with updates to the existing KLM operators, the Touch Level Model (TLM). We propose that this model can be employed to model human task performance on a constrained-input touchscreen device and, with proper benchmarking, accurately predict actual user performance. Our goal is to provide a means for quantitative analysis of touchscreen interfaces for HCI research and to enable description of interactions with such interfaces in terms of these operators, thus predicting user performance with less need to create prototypes or perform user studies.
On Channel Reciprocity to Activate Uplink Channel Training for Downlink Wireless Transmission in Tactile Internet Applications

We determine, for the first time, the requirement on channel reciprocity to activate uplink channel training, instead of downlink channel training, to achieve a higher data rate for the downlink transmission from a multi-antenna base station to a single-antenna user. We first derive novel closed-form expressions for the lower bounds on the data rates achieved by the two channel training strategies by considering the impact of finite blocklength. The performance comparison result of these two strategies is determined by the amount of channel reciprocity that is utilized in the uplink channel training. We then derive an approximated expression for the minimum channel reciprocity that enables the uplink channel training to outperform the downlink channel training. Through numerical results, we demonstrate that this minimum channel reciprocity decreases as the blocklength decreases or the number of transmit antennas increases, which shows the necessity and benefits of activating the uplink channel training for short-packet communications with multiple transmit antennas. This work provides pivotal and unprecedented guidelines on choosing channel training strategies and channel reciprocity calibrations, offering valuable insights into latency reduction in the Tactile Internet applications.
Electrocutaneous Nerve Stimulation-II: Stimulus Waveform Selection

The large number of investigations involving the use of electrocutaneous nerve stimulation as a surrogate sensory channel, and for relíef of acute and chronic pain, have raised questions about the effect of the stimulus parameters on both nerve excitation and passive tissue heating. The short and long term influence of the stimulus parameters upon nerve stimulation has formerly been described on the basis of clinical studies. The approach taken here was to examine the effects of stimulus parameters using models. For myelinated nerve the Frankenhaeuser-Huxley model of Xenopus Laevis was used. The influence of the stimulus parameters on tissue heating was evaluated by the use of a passive model described in the literature. Consideration of electrolytic effects led to the selection of a stimulus with zero net charge flow. The desire for a stimulus that was independent of skin resistance resulted in the investigation of biphasic current waveforms.
Feature—Taking Stock of Catch Shares: Lessons from the Past and Directions for the Future

With the widespread implementation of catch shares (i.e., rights-based fisheries management) at the end of the twentieth century, economists have begun to examine empirical evidence about their performance. Yet despite documented positive outcomes and predicted gains from wider adoption of this approach, catch shares face persistent political opposition and criticism in the noneconomics literature. The debate surrounding catch shares focuses on equity, industry consolidation, nonlocal ownership of quotas, employment, and other impacts on fishing communities, but the evidence on both sides has been largely anecdotal. To inform this debate, it is important for economists and other researchers to produce rigorous analyses that quantify the effects of catch shares on employment, the distribution of economic value in the harvest and processing sectors, and other indicators of community well-being. We assess catch shares to identify research needs and guide policymakers. Using examples from the experiences of the United States and Argentina with rights-based fisheries, we demonstrate that a key challenge for researchers and policymakers is accounting for multiple species, globalization of seafood markets, and climate change. We urge policymakers to consider these forces and their impacts, along with available empirical evidence, when evaluating fisheries management options that balance efficiency and equity goals.
Sensitivity and accuracy analysis in scanning microwave microscopy

The introduction of scanning microwave microscopy (SMM) tools have pioneered many applications, notably including mapping and quantitative measurement of the electrical properties of materials and devices at micro and nano scale. The ability to measure accurately and in a sensitive manner high impedance nanoscale devices is mainly related to the strategy used to match the AFM probe close to the 50 Ω impedance of the vector network analyzer (VNA). Different measurement configurations of a homemade interferometric matching network inserted between the AFM probe and the VNA are studied. Measurement sensitivity and accuracy related to nanoscale metal oxide semiconductor (MOS) structures are discussed.