Intervertebral disc degeneration (IVDD) is one of the leading causes of low back pain and one of the most common health problems in the world. The nucleotide-binding oligomerization domain-like ...receptor family pyrin domain-containing-3 (NLRP3) inflammasome, as a pattern recognition receptor, has been shown to be associated with the pathological processes of many diseases in recent years. With the exploration of the mechanism of IVDD, recent studies have shown that activation of the NLRP3 inflammasome is associated with intervertebral disc (IVD) inflammation, pyroptosis, extracellular matrix degradation and apoptosis of IVD cells. In this review, we summarize the structural characteristics of NLRP3 inflammasome and the activation signalling mechanisms. We also describe the role of the NLRP3 inflammasome in the pathological process of IVDD and the application of the targeting the NLRP3 inflammasome in IVDD treatment.
Purpose
To review the pathophysiology, diagnosis and management of postpartum thyroid dysfunction, and related management of thyroid disorders during lactation.
Methods
We reviewed the literature on ...postpartum thyroid dysfunction and management of thyroid disorders during lactation.
Results
The postpartum period is characterized by a rebound from the immunotolerance induced by pregnancy. Routine thyroid function screening is not recommended for asymptomatic women in the postpartum period. Testing thyroid function should be considered at 6–12-week postpartum for high-risk populations, including women with a previous episode of postpartum thyroiditis, Graves’ disease, or those with Hashimoto’s thyroiditis on thyroid hormone replacement, known thyroid peroxidase antibody positivity, type 1 diabetes mellitus, other nonthyroidal autoimmune disease, or chronic hepatitis C. A serum TSH should also be checked in the setting of postpartum depression or difficulty lactating. If patients have thyrotoxicosis, new-onset or recurrent Graves’ disease must be differentiated from postpartum thyroiditis, because the management differs. Periodic thyroid function testing is recommended following recovery from postpartum thyroiditis due to high lifetime risk of developing permanent hypothyroidism. Levothyroxine, and the lowest effective dose of antithyroid drugs, (propylthiouracil, methimazole, and carbimazole) can be safely used in lactating women. The use of radiopharmaceutical scanning is avoided during lactation and radioactive iodine treatment is contraindicated.
Conclusions
Diagnosing postpartum thyroid dysfunction is challenging, because symptoms may be subtle. A team approach involving primary care providers, endocrinologists, and obstetricians is essential for transitioning thyroid care from the gestational to the postpartum setting.
Machine learning is increasingly recognized as a promising technology in the biological, biomedical, and behavioral sciences. There can be no argument that this technique is incredibly successful in ...image recognition with immediate applications in diagnostics including electrophysiology, radiology, or pathology, where we have access to massive amounts of annotated data. However, machine learning often performs poorly in prognosis, especially when dealing with sparse data. This is a field where classical physics-based simulation seems to remain irreplaceable. In this review, we identify areas in the biomedical sciences where machine learning and multiscale modeling can mutually benefit from one another: Machine learning can integrate physics-based knowledge in the form of governing equations, boundary conditions, or constraints to manage ill-posted problems and robustly handle sparse and noisy data; multiscale modeling can integrate machine learning to create surrogate models, identify system dynamics and parameters, analyze sensitivities, and quantify uncertainty to bridge the scales and understand the emergence of function. With a view towards applications in the life sciences, we discuss the state of the art of combining machine learning and multiscale modeling, identify applications and opportunities, raise open questions, and address potential challenges and limitations. We anticipate that it will stimulate discussion within the community of computational mechanics and reach out to other disciplines including mathematics, statistics, computer science, artificial intelligence, biomedicine, systems biology, and precision medicine to join forces towards creating robust and efficient models for biological systems.
Renin–angiotensin–aldosterone system inhibitors (RAASi) are associated with improved survival outcomes in patients receiving immune checkpoint inhibitors (ICIs), but the data on the response to ...treatment and tumour-based endpoints across different tumour types are unknown.
We carried out a retrospective study at two tertiary referral centres in Taiwan. All adult patients treated with ICIs between January 2015 and December 2021 were included. The primary outcome was overall survival and the secondary outcomes were progression-free survival (PFS) and clinical benefit rates.
In total, 734 patients were enrolled in our study, of which 171 were RAASi users and 563 were non-users. Compared with non-users, RAASi users had a longer median overall survival 26.8 (interquartile range 11.3–not reached) versus 15.2 (interquartile range 5.1–58.4) months, P < 0.001 and PFS 12.2 (interquartile range 3.9–34.5) versus 5.0 (interquartile range 2.2–15.2) months, P < 0.001. In univariate Cox proportional hazard analyses, the use of RAASi was associated with a 40% reduction in the risk of mortality hazard ratio 0.58 (95% confidence interval 0.44–0.76), P < 0.001 and disease progression hazard ratio 0.62 (95% confidence interval 0.50–0.77), P < 0.001. The association remained significant after adjusting for underlying comorbidities and cancer therapy in multivariate Cox analyses. A similar trend was observed for PFS. Furthermore, RAASi users experienced a greater clinical benefit rate than non-users (69% versus 57%, P = 0.006). Importantly, the use of RAASi before ICI initiation was not associated with improved overall survival and PFS. RAASi were not associated with an increased risk of adverse events.
The use of RAASi is associated with improved survival outcomes, treatment response and tumour-based endpoints in patients undergoing immunotherapy.
•RAASi were associated with improved clinical outcomes across a broad range of cancer patients receiving ICI.•Subgroup analysis showed that ARB were associated with improved clinical outcomes in patients undergoing immunotherapy.•The use of RAASi before immune checkpoint blockade was not associated with improved survival.•RAASi were not associated with increased risk of adverse events among cancer patients receiving ICI.
We develop a hierarchical entropy (HE) method to quantify the complexity of a time series based on hierarchical decomposition and entropy analysis. The proposed method is applied to the Gaussian ...white noise and the
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noise. We prove that the difference frequency components of the Gaussian white noise with the same scale factor have the same value of entropies, and the values decline as the scale factor increases. We also apply the HE method to the
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noise and verify numerically that a higher frequency component of a
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random vector is approximately equal to a Gaussian random vector. The theoretical results are confirmed by numerical results. Moreover, we show that the HE method is an efficient method to analyze heartbeat signals by applying it to the cardiac interbeat interval time series of healthy young and elderly subjects, congestive heart failure (CHF) subjects and atrial fibrillation (AF) subjects.
Utilization of synchrophasor measurements for wide-area monitoring applications enables system operators to acquire real-time grid information. However, intentional injections of false synchrophasor ...measurements can potentially lead to inappropriate control actions, jeopardizing the security, and reliability of power transmission networks. To resolve this issue, a multisensor track-level fusion-based model prediction (TFMP) has been proposed. It has been demonstrated on a mature wide-area monitoring application, which detect electromechanical oscillations. In this paper, to extract the initial correlation information about attacked oscillation parameters, Kalman-like particle filter (KLPF)-based smoother has been used at each monitoring node. To reduce its computational burden, the KLPF-based smoother is diagonalized into subsystems. The scheme is further supported by the characteristics of moving horizon estimates for handling continuous load fluctuations and perturbations caused by data injections in power grids. Performance evaluations are conducted using different data-injection scenarios in the IEEE New England 39 Bus system. Results show the proposed TFMP accurately extracted oscillatory parameters from the contaminated measurements in the presence of multiple system disturbances and random data injections.
Diminished control of standing balance, traditionally indicated by greater postural sway magnitude and speed, is associated with falls in older adults. Tai Chi (TC) is a multisystem intervention that ...reduces fall risk, yet its impact on sway measures vary considerably. We hypothesized that TC improves the integrated function of multiple control systems influencing balance, quantifiable by the multi-scale "complexity" of postural sway fluctuations.
To evaluate both traditional and complexity-based measures of sway to characterize the short- and potential long-term effects of TC training on postural control and the relationships between sway measures and physical function in healthy older adults.
A cross-sectional comparison of standing postural sway in healthy TC-naïve and TC-expert (24.5±12 yrs experience) adults. TC-naïve participants then completed a 6-month, two-arm, wait-list randomized clinical trial of TC training. Postural sway was assessed before and after the training during standing on a force-plate with eyes-open (EO) and eyes-closed (EC). Anterior-posterior (AP) and medio-lateral (ML) sway speed, magnitude, and complexity (quantified by multiscale entropy) were calculated. Single-legged standing time and Timed-Up-and-Go tests characterized physical function.
At baseline, compared to TC-naïve adults (n = 60, age 64.5±7.5 yrs), TC-experts (n = 27, age 62.8±7.5 yrs) exhibited greater complexity of sway in the AP EC (P = 0.023), ML EO (P<0.001), and ML EC (P<0.001) conditions. Traditional measures of sway speed and magnitude were not significantly lower among TC-experts. Intention-to-treat analyses indicated no significant effects of short-term TC training; however, increases in AP EC and ML EC complexity amongst those randomized to TC were positively correlated with practice hours (P = 0.044, P = 0.018). Long- and short-term TC training were positively associated with physical function.
Multiscale entropy offers a complementary approach to traditional COP measures for characterizing sway during quiet standing, and may be more sensitive to the effects of TC in healthy adults.
ClinicalTrials.gov NCT01340365.
Monitoring critical infrastructures is highly dependent on the accuracy of the installed sensors and the robustness of estimation algorithms. Data-injection attacks can degrade the operational ...reliability and security of any cyber-physical infrastructures. An attacker can compromise the integrity of the monitoring algorithms by hijacking a subset of sensor measurements and sending manipulated readings. Such approach can result in wide-area blackouts in power grids. This paper considers several cases of severe data-injections with high probabilities of information loss. To achieve an accurate supervision, a Bayesian-based approximated filter (BAF) has been proposed at each monitoring node using a distributed architecture. To maintain a reduced communication overhead and time complexity, upper and lower bound methods have been developed. The performance of the proposed technique has been demonstrated in a mature synchrophasor application known as the oscillation detection. Two test cases have been generated to examine the immunity of the proposed estimation scheme in New Zealand and Oman power grids. The tests were conducted in the presence of harsh data-injection attacks and multiple system disturbances. Results show the proposed BAF method can accurately extract the oscillatory parameters from the contaminated measurements.
There has been considerable interest in quantifying the complexity of physiologic time series, such as heart rate. However, traditional algorithms indicate higher complexity for certain pathologic ...processes associated with random outputs than for healthy dynamics exhibiting long-range correlations. This paradox may be due to the fact that conventional algorithms fail to account for the multiple time scales inherent in healthy physiologic dynamics. We introduce a method to calculate multiscale entropy (MSE) for complex time series. We find that MSE robustly separates healthy and pathologic groups and consistently yields higher values for simulated long-range correlated noise compared to uncorrelated noise.
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