Miracle-dz/UniFAR-FTUs huggingface dataset:
Medication adherence in patients with apparent resistant hypertension: findings from the SYMPATHY trial

AIMS Hypertension is only controlled in approximately 35% of the patients, which could be partially due to nonadherence. Recently, bioanalytical assessment of adherence to blood pressure (BP) lowering drugs has gaining interest. Our aim was to explore possible determinants of nonadherence in treatment resistant hypertension, assessed by objective screening for antihypertensive agents in serum. The secondary aim was to study the effect of adherence on the change in BP. METHODS This project was a substudy of SYMPATHY; an open-label randomized-controlled trial to assess the effect of renal denervation on BP 6 months after treatment compared to usual care in patients with resistant hypertension. Stored serum samples were screened for antihypertensive agents to assess adherence at baseline and 6 months after intervention, using liquid chromatography-tandem mass spectrometry. Office and 24-h BP were measured on the same day as blood was sampled. Patients and physicians were unaware of adherence measurements. RESULTS Ninety-eight baseline and 83 6-month samples were available for analysis. Sixty-eight percent [95% confidence interval (CI) 59-78%] of the patients was nonadherent (n = 67). For every onw pill more prescribed, 0.785 [95%CI 0.529-0.891] prescribed pill was less detected in blood. A decrease of one pill in adherence between baseline and 6 months was associated with a significant rise in office systolic BP of 4 (95%CI 0.230-8.932) mmHg. CONCLUSION Objective measurement of BP lowering drugs in serum, as a tool to assess adherence, showed that nonadherence was very common in patients with apparent resistant hypertension. Furthermore, the assessment results were related to (changes in) blood pressure. Our findings provide direct and objective methodology to help the physician to understand and to improve the condition of apparent resistant hypertension.
Finite-sample corrected generalized estimating equation of population average treatment effects in stepped wedge cluster randomized trials

Stepped wedge designs are increasingly commonplace and advantageous for cluster randomized trials when it is both unethical to assign placebo, and it is logistically difficult to allocate an intervention simultaneously to many clusters. We study marginal mean models fit with generalized estimating equations for assessing treatment effectiveness in stepped wedge cluster randomized trials. This approach has advantages over the more commonly used mixed models that (1) the population-average parameters have an important interpretation for public health applications and (2) they avoid untestable assumptions on latent variable distributions and avoid parametric assumptions about error distributions, therefore, providing more robust evidence on treatment effects. However, cluster randomized trials typically have a small number of clusters, rendering the standard generalized estimating equation sandwich variance estimator biased and highly variable and hence yielding incorrect inferences. We study the usual asymptotic generalized estimating equation inferences (i.e., using sandwich variance estimators and asymptotic normality) and four small-sample corrections to generalized estimating equation for stepped wedge cluster randomized trials and for parallel cluster randomized trials as a comparison. We show by simulation that the small-sample corrections provide improvement, with one correction appearing to provide at least nominal coverage even with only 10 clusters per group. These results demonstrate the viability of the marginal mean approach for both stepped wedge and parallel cluster randomized trials. We also study the comparative performance of the corrected methods for stepped wedge and parallel designs, and describe how the methods can accommodate interval censoring of individual failure times and incorporate semiparametric efficient estimators.
Factors associated with romantic relationship formation difficulties in women with breast cancer

Many un‐partnered women report difficulty in forming romantic relationships after breast cancer, characterized by high dating‐related anxiety and low perceived interpersonal competence. This study examined the relationship between poor body image (appearance investment and body dissatisfaction) and self‐compassion, and women's ability to form romantic relationships post‐breast cancer.
Porphyromonas gingivalis Outer Membrane Vesicles Induce Selective Tumor Necrosis Factor Tolerance in a Toll-Like Receptor 4- and mTOR-Dependent Manner

ABSTRACT Porphyromonas gingivalis is an important member of the anaerobic oral flora. Its presence fosters growth of periodontal biofilm and development of periodontitis. In this study, we demonstrated that lipophilic outer membrane vesicles (OMV) shed from P. gingivalis promote monocyte unresponsiveness to live P. gingivalis but retain reactivity to stimulation with bacterial DNA isolated from P. gingivalis or AIM2 ligand poly(dA·dT). OMV-mediated tolerance of P. gingivalis is characterized by selective abrogation of tumor necrosis factor (TNF). Neutralization of interleukin-10 (IL-10) during OMV challenge partially restores monocyte responsiveness to P. gingivalis; full reactivity to P. gingivalis can be restored by inhibition of mTOR signaling, which we previously identified as the major signaling pathway promoting Toll-like receptor 2 and Toll-like receptor 4 (TLR2/4)-mediated tolerance in monocytes. However, despite previous reports emphasizing a central role of TLR2 in innate immune recognition of P. gingivalis, our current findings highlight a selective role of TLR4 in the promotion of OMV-mediated TNF tolerance: only blockade of TLR4—and not of TLR2—restores responsiveness to P. gingivalis. Of further note, OMV-mediated tolerance is preserved in the presence of cytochalasin B and chloroquine, indicating that triggering of surface TLR4 is sufficient for this effect. Taking the results together, we propose that P. gingivalis OMV contribute to local immune evasion of P. gingivalis by hampering the host response.
Boron Toxicity Reduces Water Transport from Root to Shoot in Arabidopsis Plants. Evidence for a Reduced Transpiration Rate and Expression of Major PIP Aquaporin Genes

Toxic boron (B) concentrations cause impairments in several plant metabolic and physiological processes. Recently we reported that B toxicity led to a decrease in the transpiration rate of Arabidopsis plants in an ABA-dependent process within 24 h, which could indicate the occurrence of an adjustment of whole-plant water relations in response to this stress. Since plasma membrane intrinsic protein (PIP) aquaporins are key components influencing the water balance of plants because of their involvement in root water uptake and tissue hydraulic conductance, the aim of the present work was to study the effects of B toxicity on these important parameters affecting plant water status over a longer period of time. For this purpose, transpiration rate, water transport to the shoot and transcript levels of genes encoding four major PIP aquaporins were measured in Arabidopsis plants treated or not with a toxic B concentration. Our results indicate that, during the first 24 h of B toxicity, increased shoot ABA content would play a key role in reducing stomatal conductance, transpiration rate and, consequently, the water transport to the shoot. These physiological responses to B toxicity were maintained for up to 48 h of B toxicity despite shoot ABA content returning to control levels. In addition, B toxicity also caused the down-regulation of several genes encoding root and shoot aquaporins, which could reduce the cell to cell movement of water in plant tissues and, consequently, the water flux to shoot. All these changes in the water balance of plants under B toxicity could be a mechanism to prevent excess B accumulation in plant tissues.
Potential Economic Benefits of Paid Sick Leave in Reducing Absenteeism Related to the Spread of Influenza-Like Illness

Objective: Most U.S. employers are not required to provide paid sick leave (PSL), and there is limited information on the economic return of providing PSL. We estimated potential benefits to employers of PSL in reducing absenteeism related to the spread of influenza-like illness (ILI). Methods: We used nationally representative data and a negative binomial random effects model to estimate the impact of PSL in reducing overall absence due to illness or injury. We used published data to compute the share of ILI from the total days of absence, ILI transmission rates at workplaces, wages, and other parameters. Results: Providing PSL could have saved employers $0.63 to $1.88 billion in reduced ILI-related absenteeism costs per year during 2007 to 2014 in 2016 dollars. Conclusion: These findings might help employers consider PSL as an investment rather than as a cost without any return.
Local context effects during emotional item directed forgetting in younger and older adults

ABSTRACT This paper explored the differential sensitivity young and older adults exhibit to the local context of items entering memory. We examined trial-to-trial performance during an item directed forgetting task for positive, negative, and neutral (or baseline) words each cued as either to-be-remembered (TBR) or to-be-forgotten (TBF). This allowed us to focus on how variations in emotional valence (independent of arousal) and instruction (TBR vs. TBF) of the previous item (trial n-1) impacted memory for the current item (trial n) during encoding. Different from research showing impairing effects of emotional arousal, both age groups showed a memorial boost for stimuli when preceded by items high in positive or negative valence relative to those preceded by neutral items. This advantage was particularly prominent for neutral trial n items that followed emotional items suggesting that, regardless of age, neutral memories may be strengthened by a local context that is high in valence. A trending age difference also emerged with older adults showing greater sensitivity when encoding instructions changed between trial n-1 and n. Results are discussed in light of age-related theories of cognitive and emotional processing, highlighting the need to consider the dynamic, moment-to-moment fluctuations of these systems.
Complexity of non-monotonic logics

Over the past few decades, non-monotonic reasoning has developed to be one of the most important topics in computational logic and artificial intelligence. Different ways to introduce non-monotonic aspects to classical logic have been considered, e.g., extension with default rules, extension with modal belief operators, or modification of the semantics. In this survey we consider a logical formalism from each of the above possibilities, namely Reiter's default logic, Moore's autoepistemic logic and McCarthy's circumscription. Additionally, we consider abduction, where one is not interested in inferences from a given knowledge base but in computing possible explanations for an observation with respect to a given knowledge base. Complexity results for different reasoning tasks for propositional variants of these logics have been studied already in the nineties. In recent years, however, a renewed interest in complexity issues can be observed. One current focal approach is to consider parameterized problems and identify reasonable parameters that allow for FPT algorithms. In another approach, the emphasis lies on identifying fragments, i.e., restriction of the logical language, that allow more efficient algorithms for the most important reasoning tasks. In this survey we focus on this second aspect. We describe complexity results for fragments of logical languages obtained by either restricting the allowed set of operators (e.g., forbidding negations one might consider only monotone formulae) or by considering only formulae in conjunctive normal form but with generalized clause types. The algorithmic problems we consider are suitable variants of satisfiability and implication in each of the logics, but also counting problems, where one is not only interested in the existence of certain objects (e.g., models of a formula) but asks for their number.
Methodological Guidelines for Accurate Detection of Viruses in Wild Plant Species

ABSTRACT Ecological understanding of disease risk, emergence, and dynamics and of the efficacy of control strategies relies heavily on efficient tools for microorganism identification and characterization. Misdetection, such as the misclassification of infected hosts as healthy, can strongly bias estimates of disease prevalence and lead to inaccurate conclusions. In natural plant ecosystems, interest in assessing microbial dynamics is increasing exponentially, but guidelines for detection of microorganisms in wild plants remain limited, particularly so for plant viruses. To address this gap, we explored issues and solutions associated with virus detection by serological and molecular methods in noncrop plant species as applied to the globally important Barley yellow dwarf virus PAV (Luteoviridae), which infects wild native plants as well as crops. With enzyme-linked immunosorbent assays (ELISA), we demonstrate how virus detection in a perennial wild plant species may be much greater in stems than in leaves, although leaves are most commonly sampled, and may also vary among tillers within an individual, thereby highlighting the importance of designing effective sampling strategies. With reverse transcription-PCR (RT-PCR), we demonstrate how inhibitors in tissues of perennial wild hosts can suppress virus detection but can be overcome with methods and products that improve isolation and amplification of nucleic acids. These examples demonstrate the paramount importance of testing and validating survey designs and virus detection methods for noncrop plant communities to ensure accurate ecological surveys and reliable assumptions about virus dynamics in wild hosts.
Position-Indexed Formulations for Kidney Exchange

A kidney exchange is an organized barter market where patients in need of a kidney swap willing but incompatible donors. Determining an optimal set of exchanges is theoretically and empirically hard. Traditionally, exchanges took place in cycles, with each participating patient-donor pair both giving and receiving a kidney. The recent introduction of chains, where a donor without a paired patient triggers a sequence of donations without requiring a kidney in return, increased the efficacy of fielded kidney exchanges---while also dramatically raising the empirical computational hardness of clearing the market in practice. While chains can be quite long, unbounded-length chains are not desirable: planned donations can fail before transplant for a variety of reasons, and the failure of a single donation causes the rest of that chain to fail, so parallel shorter chains are better in practice. In this paper, we address the tractable clearing of kidney exchanges with short cycles and chains that are long but bounded. This corresponds to the practice at most modern fielded kidney exchanges. We introduce three new integer programming formulations, two of which are compact. Furthermore, one of these models has a linear programming relaxation that is exactly as tight as the previous tightest formulation (which was not compact) for instances in which each donor has a paired patient. On real data from the UNOS nationwide exchange in the United States and the NLDKSS nationwide exchange in the United Kingdom, as well as on generated realistic large-scale data, we show that our new models are competitive with all existing solvers---in many cases outperforming all other solvers by orders of magnitude. Finally, we note that our position-indexed chain-edge formulation can be modified in a straightforward way to take post-match edge failure into account, under the restriction that edges have equal probabilities of failure. Post-match edge failure is a primary source of inefficiency in presently-fielded kidney exchanges. We show how to implement such failure-aware matching in our model, and also extend the state-of-the-art general branch-and-price-based non-compact formulation for the failure-aware problem to run its pricing problem in polynomial time.
Terahertz spectroscopy of biomolecules

Terahertz (THz) electromagnetic wave belonging to the frequency band from 0.1 to 10 THz (pundits narrow this range to 0.3-3 THz) has emerged as a powerful tool for investigating biomolecular systems. Since the energy level of THz wave largely coincides with that of the biomolecular low-frequency motions including vibration, rotation and translation of the molecular skeleton and that of the weak intermolecular interactions including hydrogen-bond and van der Waals etc., THz spectroscopy as a molecular detection technology has its unique advantages over some other existing ones. In the last several years, our group has focused on THz spectroscopy detection and spectral imaging of biomolecules, especially on the development of a THz near-field microscopy equipment for imaging of cells and even biomacromolecules. On the theoretical front, we have calculated and analyzed the characteristic spectra of polypeptides and investigated the effects of conformation and size of biomolecules on their THz spectra. Experimentally, microfluidic channels for THz spectroscopy tests were fabricated and the THz spectra of -DNA were investigated. A scattering-type scanning near-field terahertz microscopy based on the atomic force microscopy and the THz spectrometer was built and initial results about the modulation of the THz near-filed signals were presented.
Prognostic factors of methotrexate-associated lymphoproliferative disorders associated with rheumatoid arthritis and plausible application of biological agents

Abstract Objectives: To determine prognostic factors of methotrexate-associated lymphoproliferative disorder (MTX-LPD) and evaluate the efficacy and safety of biological therapy in rheumatoid arthritis (RA) complicated with MTX-LPD. Methods: Thirty RA patients who developed MTX-LPD were investigated in this study. We compared the clinical and laboratory parameters of patients who achieved regression of LPD by MTX withdrawal with those who required chemotherapy and evaluated the clinical course of RA after LPD development. Results: Twenty-three patients (76.7%) achieved regression of LPD by MTX withdrawal. Chemotherapy-free patients had a tendency of shorter RA duration (13.1 vs. 22.0 years, p = 0.108) and higher doses of MTX at LPD diagnosis (8.0 vs. 5.3 mg/w, p = 0.067) than patients who required chemotherapy. A significantly higher positive rate of peripheral blood Epstein–Barr virus (EBV)-DNA was observed in the chemotherapy-free group (9/9 vs. 0/3, p = 0.0002). Of 15 patients that received biological agents after LPD development, 14 patients (93.3%) demonstrated an improved disease activity of RA and persistent remission of LPD, whereas only one patient experienced relapse of LPD during tocilizumab therapy. Conclusions: Peripheral blood EBV-DNA positivity is a potential prognostic marker of better outcome in MTX-LPD. Biological agents could be an option for the treatment of RA patients with MTX-LPD.
Morning surge in blood pressure using a random‐effects multiple‐component cosinor model

Blood pressure (BP) fluctuates throughout the day. The pattern it follows represents one of the most important circadian rhythms in the human body. For example, morning BP surge has been suggested as a potential risk factor for cardiovascular events occurring in the morning, but the accurate quantification of this phenomenon remains a challenge. Here, we outline a novel method to quantify morning surge. We demonstrate how the most commonly used method to model 24‐hour BP, the single cosinor approach, can be extended to a multiple‐component cosinor random‐effects model. We outline how this model can be used to obtain a measure of morning BP surge by obtaining derivatives of the model fit. The model is compared with a functional principal component analysis that determines the main components of variability in the data. Data from the Mitchelstown Study, a population‐based study of Irish adults (n = 2047), were used where a subsample (1207) underwent 24‐hour ambulatory blood pressure monitoring. We demonstrate that our 2‐component model provided a significant improvement in fit compared with a single model and a similar fit to a more complex model captured by b‐splines using functional principal component analysis. The estimate of the average maximum slope was 2.857 mmHg/30 min (bootstrap estimates; 95% CI: 2.855‐2.858 mmHg/30 min). Simulation results allowed us to quantify the between‐individual SD in maximum slopes, which was 1.02 mmHg/30 min. By obtaining derivatives we have demonstrated a novel approach to quantify morning BP surge and its variation between individuals. This is the first demonstration of cosinor approach to obtain a measure of morning surge.
Fucosyltransferase Induction during Influenza Virus Infection Is Required for the Generation of Functional Memory CD4+ T Cells

T cells mediating influenza viral control are instructed in lymphoid and nonlymphoid tissues to differentiate into memory T cells that confer protective immunity. The mechanisms by which influenza virus–specific memory CD4+ T cells arise have been attributed to changes in transcription factors, cytokines and cytokine receptors, and metabolic programming. The molecules involved in these biosynthetic pathways, including proteins and lipids, are modified to varying degrees of glycosylation, fucosylation, sialation, and sulfation, which can alter their function. It is currently unknown how the glycome enzymatic machinery regulates CD4+ T cell effector and memory differentiation. In a murine model of influenza virus infection, we found that fucosyltransferase enzymatic activity was induced in effector and memory CD4+ T cells. Using CD4+ T cells deficient in the Fut4/7 enzymes that are expressed only in hematopoietic cells, we found decreased frequencies of effector cells with reduced expression of T-bet and NKG2A/C/E in the lungs during primary infection. Furthermore, Fut4/7−/− effector CD4+ T cells had reduced survival with no difference in proliferation or capacity for effector function. Although Fut4/7−/− CD4+ T cells seeded the memory pool after primary infection, they failed to form tissue-resident cells, were dysfunctional, and were unable to re-expand after secondary infection. Our findings highlight an important regulatory axis mediated by cell-intrinsic fucosyltransferase activity in CD4+ T cell effectors that ensure the development of functional memory CD4+ T cells.