In-person versus virtual administration of the American College of Rheumatology gold standard cognitive battery in systemic lupus erythematosus: Are they interchangeable?

OBJECTIVE: During the COVID-19 pandemic, many research studies were adapted, including our longitudinal study examining cognitive impairment (CI) in systemic lupus erythematosus (SLE). Cognitive testing was switched from in-person to virtual. This analysis aimed to determine if the administration method (in-person vs. virtual) of the ACR-neuropsychological battery (ACR-NB) affected participant cognitive performance and classification. METHODS: Data from our multi-visit, SLE CI study included demographic, clinical, and psychiatric characteristics, and the modified ACR-NB. Three analyses were undertaken for cognitive performance: (1) all visits, (2) non-CI group visits only and (3) intra-individual comparisons. A retrospective preferences questionnaire was given to participants who completed the ACR-NB both in-person and virtually. RESULTS: We analysed 328 SLE participants who had 801 visits (696 in-person and 105 virtual). Demographic, clinical, and psychiatric characteristics were comparable except for ethnicity, anxiety and disease-related damage. Across all three comparisons, six tests were consistently statistically significantly different. CI classification changed in 11/71 (15%) participants. 45% of participants preferred the virtual administration method and 33% preferred in-person. CONCLUSIONS: Of the 19 tests in the ACR-NB, we identified one or more problems with eight (42%) tests when moving from in-person to virtual administration. As the use of virtual cognitive testing will likely increase, these issues need to be addressed - potentially by validating a virtual version of the ACR-NB. Until then, caution must be taken when directly comparing virtual to in-person test results. If future studies use a mixed administration approach, this should be accounted for during analysis.

Spatiotemporal behaviors of the ridership of a public transportation system during an epidemic outbreak: case of MERS in Seoul.

During May and June 2015, an outbreak of the Middle East respiratory syndrome (MERS) occurred in Korea, which raised the fear of contagion throughout society and suppressed the use of public transportation systems. Exploring daily ridership data of the Seoul bus transportation system, along with the number of infected patients and search volume in web portals, we observe that ridership decreased abruptly while attention was heavily focused online. Then this temporal reduction recovered exponentially with a characteristic time of 3 weeks when newly confirmed cases began to decrease. We also find with the data of ranked keywords of web portals that areas with severely reduced ridership tended to cluster and spatiotemporal variations of such clusters were highly associated with general hospitals where MERS patients were treated. On the other hand, the spatial reduction in ridership relaxed algebraically with the distance from a general hospital while the outbreak was severe. We further probe the influence of the epidemic outbreak in the framework of linear response theory, which relates the responses to the epidemic outbreak ("perturbation") with correlations in the absence of the perturbation. Indeed, the spatial correlation function of the ridership changes is observed to follow a power law, sharing the same exponent as the spatial relaxation of the response function. This new theoretical approach offers a useful tool for understanding responses of public transportation system to epidemic or accidental disasters.

Autoantibodies in SLE: prediction and the p value matrix.

Autoantibodies (AA) and antinuclear antibodies (ANA) serve as key diagnostic and classification criteria for systemic lupus erythematosus (SLE). More than 200 different AA have been reported in SLE, although only a handful (<20) are considered "mainstream" because they are widely and routinely used in diagnostic, research and clinical medicine. Although the vast majority of AA have been relegated to the diminished status of "orphan" AA, some serve as predictors of SLE because they first appear in very early or subclinical SLE. Some AA are pathogenic, whereas others are thought to protect against or ameliorate disease progression and, hence, taken together can be used as predictive biomarkers of prognosis. Although studies have shown that specific AA are detected in the preclinical phase of SLE and are biomarkers of increased risk of developing the disease, AA are currently not widely used to predict very early SLE in individuals who have low pretest probability of disease. With the advent of multianalyte arrays with analytic algorithms, emerging evidence indicates that when certain combinations of biomarkers, such as the interferon signature and stem cell factor accompany AA and ANA, the predictive power for SLE is markedly increased.

Dynamics of analyst forecasts and emergence of complexity: Role of information disparity.

We report complex phenomena arising among financial analysts, who gather information and generate investment advice, and elucidate them with the help of a theoretical model. Understanding how analysts form their forecasts is important in better understanding the financial market. Carrying out big-data analysis of the analyst forecast data from I/B/E/S for nearly thirty years, we find skew distributions as evidence for emergence of complexity, and show how information asymmetry or disparity affects financial analysts' forming their forecasts. Here regulations, information dissemination throughout a fiscal year, and interactions among financial analysts are regarded as the proxy for a lower level of information disparity. It is found that financial analysts with better access to information display contrasting behaviors: a few analysts become bolder and issue forecasts independent of other forecasts while the majority of analysts issue more accurate forecasts and flock to each other. Main body of our sample of optimistic forecasts fits a log-normal distribution, with the tail displaying a power law. Based on the Yule process, we propose a model for the dynamics of issuing forecasts, incorporating interactions between analysts. Explaining nicely empirical data on analyst forecasts, this provides an appealing instance of understanding social phenomena in the perspective of complex systems.

The prevalence and determinants of anti-DFS70 autoantibodies in an international inception cohort of systemic lupus erythematosus patients.

Autoantibodies to dense fine speckles 70 (DFS70) are purported to rule out the diagnosis of SLE when they occur in the absence of other SLE-related autoantibodies. This study is the first to report the prevalence of anti-DFS70 in an early, multinational inception SLE cohort and examine demographic, clinical, and autoantibody associations. Patients were enrolled in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort within 15 months of diagnosis. The association between anti-DFS70 and multiple parameters in 1137 patients was assessed using univariate and multivariate logistic regression. The frequency of anti-DFS70 was 7.1% (95% CI: 5.7-8.8%), while only 1.1% (95% CI: 0.6-1.9%) were monospecific for anti-DFS70. In multivariate analysis, patients with musculoskeletal activity (Odds Ratio (OR) 1.24 [95% CI: 1.10, 1.41]) or with anti-ß2 glycoprotein 1 (OR 2.17 [95% CI: 1.22, 3.87]) were more likely and patients with anti-dsDNA (OR 0.53 [95% CI: 0.31, 0.92]) or anti-SSB/La (OR 0.25 [95% CI: 0.08, 0.81]) were less likely to have anti-DFS70. In this study, the prevalence of anti-DFS70 was higher than the range previously published for adult SLE (7.1 versus 0-2.8%) and was associated with musculoskeletal activity and anti-ß2 glycoprotein 1 autoantibodies. However, 'monospecific' anti-DFS70 autoantibodies were rare (1.1%) and therefore may be helpful to discriminate between ANA-positive healthy individuals and SLE.

Cirmtuzumab inhibits Wnt5a-induced Rac1 activation in chronic lymphocytic leukemia treated with ibrutinib.

Signaling via the B cell receptor (BCR) plays an important role in the pathogenesis and progression of chronic lymphocytic leukemia (CLL). This is underscored by the clinical effectiveness of ibrutinib, an inhibitor of Bruton's tyrosine kinase (BTK) that can block BCR-signaling. However, ibrutinib cannot induce complete responses (CR) or durable remissions without continued therapy, suggesting alternative pathways also contribute to CLL growth/survival that are independent of BCR-signaling. ROR1 is a receptor for Wnt5a, which can promote activation of Rac1 to enhance CLL-cell proliferation and survival. In this study, we found that CLL cells of patients treated with ibrutinib had activated Rac1. Moreover, Wnt5a could induce Rac1 activation and enhance proliferation of CLL cells treated with ibrutinib at concentrations that were effective in completely inhibiting BTK and BCR-signaling. Wnt5a-induced Rac1 activation could be blocked by cirmtuzumab (UC-961), an anti-ROR1 mAb. We found that treatment with cirmtuzumab and ibrutinib was significantly more effective than treatment with either agent alone in clearing leukemia cells in vivo. This study indicates that cirmtuzumab may enhance the activity of ibrutinib in the treatment of patients with CLL or other ROR1+ B-cell malignancies.

How complexity emerges in urban systems: Theory of urban morphology.

Human beings develop the land and transform land use patterns, constructing artificial structures. Among them, the city is a representative system and its morphology has attracted much attention. While most existing studies have been devoted to individual dynamics and focused on the proximity of specific areas of a city, we here pay attention to the city as a complex system, where interactions between individuals give rise to emergent properties. Specifically, analyzing the big data on every building in Seoul City, we specify the relevant interactions among constituents and probe the emergence of complex land use patterns. In particular, based on the empirical observations, we illustrate that interactions between land uses are frustrated, which serves as a basic postulate of the theory of urban morphology. We examine this conjecture with the help of a layered Ising-type model and disclose that the actual land use pattern emerges at the criticality of the system in the presence of heterogeneously distributed fields. It is also remarked that our model, allowing quantitative predictions, can easily be applied to other cities around the world.

Preventing the development of SLE: identifying risk factors and proposing pathways for clinical care.

Although challenging, developing evidence-based approaches to an early and accurate diagnosis of systemic lupus erythematosus is a key approach to preventing disease and lupus-associated morbidity and mortality. Advances in our understanding of preclinical and incomplete lupus erythematosus have enabled the identification of risk factors that may predict disease and the development of potential strategies aimed at primary prevention. Emerging data support the notion that there is a temporal disease progression from initial asymptomatic autoimmunity (preclinical lupus) through early clinical features of the disease (incomplete lupus erythematosus) to finally becoming fully classifiable systemic lupus erythematosus (complete lupus erythematosus). Here, we review the demographic, clinical, biomarker as well as genetic and environmental features that are reported to increase the risk of disease progression. Based on these risk factors, we propose a clinical care pathway for patients with early disease. We envisage that such a pathway, through early identification of disease, may improve patient outcomes, while reducing health care costs.

Ofatumumab and high-dose methylprednisolone for the treatment of patients with relapsed or refractory chronic lymphocytic leukemia.

Ofatumumab is a humanized anti-CD20 monoclonal antibody that has been approved by the FDA for the treatment of patients with chronic lymphocytic leukemia. We conducted a phase II single-arm study at a single center. Patients received ofatumumab (300 mg then 1000 mg weekly for 12 weeks) and methylprednisolone (1000 mg/m(2) for 3 days of each 28-day cycle). Twenty-one patients enrolled, including 29% with unfavorable cytogenetics (del17p or del11q). Ninety percent of patients received the full course without dose reductions or delays. The overall response rate was 81% (17/21) with 5% complete response, 10% nodular partial response, 67% partial response, 14% stable disease and 5% progressive disease. After a median follow-up of 31 months, the median progression-free survival was 9.9 months and the median time to next treatment was 12.1 months. The median overall survival has not yet been reached. The combination of high-dose methylprednisolone and ofatumumab is an effective and tolerable treatment regimen. This regimen may be useful for patients who are unable to tolerate more aggressive therapies, or have not responded to other treatments.

Generalized hydromechanical model for stomatal responses to hydraulic perturbations.

Stomata respond in a common pattern to various hydraulic perturbations on any part of the 'soil-plant-air' system: initial transient 'wrong-way' responses and final stationary 'right-way' responses. In order to describe this pattern on the basis of statistical physics, we propose a simple model where turgor pressure of a cell is taken to be a power function of its volume, and obtain results in qualitative agreement with experimental data for responses to a variety of hydraulic perturbations: Firstly, stationary stomatal conductance as a function of the vapor pressure deficit divides into three regimes characterized by sensitivities of the stomatal conductance and the transpiration rate with respect to vapor pressure deficit; secondly, for every hydraulic perturbation, the initial transient 'wrong-way' responses always appear; thirdly, on condition that water is supplied insufficiently, stomatal oscillations are often observed; finally, stomatal responses following leaf excision exhibit, after the initial transient wrong-way responses, slow relaxation to stomatal closing. In particular, comparison of areoles having different numbers of stomata demonstrates that areoles with small numbers of stomata tend to provoke lack of water in the soil as well as in the plant. In addition, our model also describes well dependence of the stomatal conductance on temperature. It may be extended further to describe stomatal responses to other environmental factors such as carbon dioxide, light, and temperature.

A model for the receptive field of retinal ganglion cells.

Most retina ganglion cells have center-surround receptive fields, where the center may be either ON or OFF while the surround is the opposite. We clarify the functional roles of the receptive field structure, on the basis of the modern theory of natural data processing. It is suggested that the retina shares the principal mechanism and performance of image processing with a video codec in computers, where the antagonism in spatial or temporal receptive fields originates from the orthogonality condition between linear filters for optimal coding of visual signals. We also reveal what visual information is multiplexed across the discharges of an ensemble of ganglion cells. Our theory makes it possible to predict the cross-correlations between ganglion cell spikes, which are optimized for LGN cells to respond accurately and quickly to their receptive fields.

Information exchange dynamics of the two-dimensional XY model.

Information exchange dynamics of the two-dimensional XY model is studied by means of the entropic sampling algorithm. Combining the analytic and numerical results, we obtain the entropy in the whole range of the energy at various system sizes. The time evolution of the order parameter and of the number of vortices is explored, and the corresponding relaxation times are found to grow algebraically with the system size. Such absence of characteristic time scales in the thermodynamic limit manifests the emergent criticality of the exchanging process of information with the environment. The mechanism of information exchange in the XY model is discussed in terms of the dynamic exponents, in comparison with the Ising model.

A multicenter, phase II trial of everolimus in locally advanced or metastatic thyroid cancer of all histologic subtypes.

BACKGROUND: This phase II study investigated the efficacy and safety of everolimus, an inhibitor of mammalian target of rapamycin (mTOR), in locally advanced or metastatic thyroid cancer. PATIENTS AND METHODS: Patients with thyroid cancer of any histology that was resistant or not appropriate for (131)I received everolimus 10 mg daily orally until unacceptable toxicity or disease progression. The primary end point was disease control rate [partial response (PR) + stable response ≥12 weeks]. Secondary end points included response rates, clinical benefit (PD + durable stable disease (SD)], progression-free survival (PFS), overall survival, duration of response, and safety. RESULTS: Thirty-eight of 40 enrolled patients were evaluable for efficacy. The disease control rate was 81% and two (5%) patients achieved objective response; their duration of response was 21+ and 24+ weeks. Stable disease (SD) and progressive disease was reported in 76% and 17% of patients, respectively. Seventeen (45%) patients showed durable SD (≥24 weeks) and clinical benefit was reported in 19 (50%) patients. Median PFS was 47 weeks [95% confidence interval (CI) 14.9-78.5]. Calcitonin, CEA, and thyroglobulin concentrations were ≥50% lower than baseline in three (30%) and four (44%) patients with medullary thyroid cancer and five (33%) patients with PTC, respectively. The most common treatment-related adverse events were mucositis (84%), anorexia (44%), and aspartate transaminase/alanine transaminase elevation (26%). CONCLUSIONS: Everolimus had a limited activity with low response rate in locally advanced or metastatic thyroid cancer. Reasonable clinical benefit rate and safety profile may warrant further investigation. CLINICALTRIALSGOV NUMBER: NCT01164176.

Identification and characterization of the pyrokinin/pheromone biosynthesis activating neuropeptide family of G protein-coupled receptors from Ostrinia nubilalis.

Insects have two closely related G protein-coupled receptors belonging to the pyrokinin/pheromone biosynthesis activating neuropeptide (pyrokinin/PBAN) family, one with the ligand PBAN or pyrokinin-2 and another with diapause hormone or pyrokinin-1 as a ligand. A related receptor is activated by products of the capa gene, periviscerokinins. Here we characterized the PBAN receptor and the diapause hormone receptor from the European corn borer, Ostrinia nubilalis. We also identified a partial sequence for the periviscerokinin receptor. Quantitative PCR of mRNA for all three receptors indicated differential expression in various life stages and tissues. All three splice variants of the PBAN receptor were identified with all variants found in pheromone gland tissue. Immunohistochemistry of V5 tags of expressed receptors indicated that all three variants and the diapause hormone receptor were expressed at similar levels in Spodoptera frugiperda 9 (Sf9) cells. However, the A- and B-variants were not active in our functional assay, which confirms studies from other moths. Functional expression of the C-variant indicated that it is has a 44 nM half effective concentration for activation by PBAN. The diapause hormone receptor was activated by diapause hormone with a 150 nM half effective concentration.

Modification of the gravity model and application to the metropolitan Seoul subway system.

The Metropolitan Seoul Subway system is examined through the use of the gravity model. Exponents describing the power-law dependence on the time distance between stations are obtained, which reveals a universality for subway lines of the same topology. In the short (time) distance regime the number of passengers between stations does not grow with the decrease in the distance, thus deviating from the power-law behavior. It is found that such reduction in passengers is well described by the Hill function. Further, temporal fluctuations in the passenger flow data, fitted to the gravity model modified by the Hill function, are analyzed to reveal the Yule-type nature inherent in the structure of Seoul.

Spontaneous organization of the cortical structure through endogenous neural firing and gap junction transmission.

We explore the effects of gap junctions, direct neural transmission between adjacent cells, on activity-dependent network formation. It is found that endogenous neural activities and weak firing correlations via gap junctions can regulate elaborately both the topographic structure in vertical connections and the radial structure in horizontal connections. Provided that pre-establishment of the lateral connection structure is required for the postnatal cortical map organization and genetic factors cannot perform such detailed regulation of synaptic connections, neural interactions via gap junctions could play an indispensable role in the brain development.

Weibull-type limiting distribution for replicative systems.

The Weibull function is widely used to describe skew distributions observed in nature. However, the origin of this ubiquity is not always obvious to explain. In the present paper, we consider the well-known Galton-Watson branching process describing simple replicative systems. The shape of the resulting distribution, about which little has been known, is found essentially indistinguishable from the Weibull form in a wide range of the branching parameter; this can be seen from the exact series expansion for the cumulative distribution, which takes a universal form. We also find that the branching process can be mapped into a process of aggregation of clusters. In the branching and aggregation process, the number of events considered for branching and aggregation grows cumulatively in time, whereas, for the binomial distribution, an independent event occurs at each time with a given success probability.

Vitamin D effects on pregnancy and the placenta.

Vitamin D is a pleiotropic secosteroid hormone important for health and disease prevention. The actions of vitamin D are mediated by the vitamin D receptor that binds the active form of vitamin D [1,25(OH)(2)D] to induce both transcriptional and non-genomic responses. Vitamin D has well known classical functions in calcium uptake and bone metabolism, but more recent work highlights the importance of the nonclassical actions of vitamin D in a variety of cell types. These actions include modulation of the innate and adaptive immune systems and regulation of cell proliferation. Adequate vitamin D intake is essential for maternal and fetal health during pregnancy, and epidemiological data indicate that many pregnant women have sub-optimal vitamin D levels. Notably, vitamin D deficiency correlates with preeclampsia, gestational diabetes mellitus, and bacterial vaginosis, and an increased risk for C-section delivery. Recent work emphasizes the importance of nonclassical roles of vitamin D in pregnancy and the placenta. The placenta produces and responds to vitamin D where vitamin D functions as a modulator of implantation, cytokine production and the immune response to infection. We describe vitamin D metabolism and the cellular responses to vitamin D, and then summarize the role of vitamin D in placental trophoblast, pregnancy and the fetus.

Comment on "Dynamical phase transition of a one-dimensional transport process including death".

Motivated by the mycologic situation, Dorosz and collaborators considered a modification of the totally asymmetric exclusion process, including the probabilities of injection and of death. In the case of the backward-ordered sequential dynamics with the death probability larger than the critical value, the average particle density in the stationary state was erroneously reported to equal the injection probability. Correcting the error, we find that the average density is given by the death probability rather than the injection probability.

Blind oral endotracheal intubation of rats using a ventilator to verify correct placement.

Endotracheal intubation in rats is challenging due to difficulties visualizing the epiglottis and vocal cords. No visualization of these structures results in repeated intubation attempts which can cause trauma to the oral cavity and/or oesophagus, and death of the animal due to respiratory failure. Here, we describe a simple blind oral tracheal intubation technique in the rat that decreases the frequency of repeated intubations using an intubation device that comprises a 16 G intravenous catheter and a modified 18 G epidural needle, and a rodent ventilator. The epidural needle is bent in such a way that it curves in conformity with the rat's oral airway in order to direct the catheter into the larynx, and the rodent ventilator is used to verify its correct placement. The first attempt success rate of endotracheal intubation using the blind oral tracheal intubation technique with a rodent ventilator was greater than the first attempt success rate using the blind oral tracheal intubation technique without using a rodent ventilator. Although this method is a simple modification of a previously described method of blind oral endotracheal intubation, our method is easy to learn, inexpensive and does not require specialized equipment.