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Advances in upstream production of biologics–particularly intensified fed‐batch processes beyond 10% cell solids–have severely strained harvest operations, especially depth filtration. Bioreactors containing high amounts of cell debris (more than 40% particles <10 µm in diameter) are increasingly common and drive the need for more robust depth filtration processes, while accelerated timelines emphasize the need for predictive tools to accelerate development. Both needs are constrained by the current limited mechanistic understanding of the harvest filter‐feedstream system. Historically, process development relied on screening scale‐down depth filter devices and conditions to define throughput before fouling, indicated by increasing differential pressure and/or particle breakthrough (measured via turbidity). This approach is straightforward, but resource‐intensive, and its results are inherently limited by the variability of the feedstream. Semi‐empirical models have been developed from first principles to describe various mechanisms of filter fouling, that is, pore constriction, pore blocking, and/or surface deposit. Fitting these models to experimental data can assist in identifying the dominant fouling mechanism. Still, this approach sees limited application to guide process development, as it is descriptive, not predictive. To address this gap, we developed a hybrid modeling approach. Leveraging historical bench scale filtration process data, we built a partial least squares regression model to predict particle breakthrough from filter and feedstream attributes, and leveraged the model to demonstrate prediction of filter performance a priori. The fouling models are used to interpret and provide physical meaning to these computational models. This hybrid approach–combining the mechanistic insights of fouling models and the predictive capability of computational models–was used to establish a robust platform strategy for depth filtration of Chinese hamster ovary cell cultures. As new data continues to teach the computational models, in silico tools will become an essential part of harvest process development by enabling prospective experimental design, reducing total experimental load, and accelerating development under strict timelines. [ABSTRACT FROM AUTHOR]

In this paper, the predefined-time control problem with prescribed performance is investigated for bilateral teleoperation systems with a single master and multiple slaves. The difficulty lies in the realization of predefined time stability and synchronization control of single-master and multi-slave manipulators. A prescribed performance function is introduced and an improved error conversion mechanism for matrix transformation is designed to ensure that joint displacement tracking error is constrained. A novel coordination position error transformation is defined such that the positional synchronization of the single-master-multiple-slave manipulators is achieved. Based on graph theory and Lyapunov stability theorem, a novel adaptive neural control approach is developed with predefined time interval via the backstepping technique, such that the convergence time can be predefined by users specification, the tracking error can be limited within a prescribed bound and in the meantime can converge to zero within predefined time interval. Simulation results are provided to prove the effectiveness of the presented scheme. [ABSTRACT FROM AUTHOR]

Being composed of blood cells and plasma, the blood flow has different rheological properties from common fluids. The viscoelastic properties of blood not only affect the flow characteristics of blood but also influence the shape of bleeding. In order to achieve the bleeding simulation with physical viscoelastic, we consider the effect of the aggregation behavior of red blood cells on the bleeding process. The elastic force caused by viscoelastic fluid elasticity is incorporated into the standard Navier–Stokes momentum equation, and an improved momentum equation that characterizes the rheological characteristics of viscoelastic blood is constructed. The effect of introducing elastic force on the particles motion is analyzed from the microscopic particle perspective by designing a two-dimensional particle system. The results of bleeding simulation show that the improved method eliminates the discontinuous boundary due to blood gushing out of the wound and forms irregular bleeding shapes in the bleeding process. In addition, the viscoelastic bleeding simulation exhibits a similar bleeding effect without distortion when the number of particles decreases, which further proves the reliability of proposed method. [ABSTRACT FROM AUTHOR]

The event-based finite-time H ∞ filtering problem for networked systems is concerned. A novel hybrid attack model is introduced considering denial-of-service and deception attacks in the communication channel between sampler and filter with an aperiodic form. In order to increase the effectiveness of data transmission in network communication channel and enable the filtering system against attack, an adaptive event–triggered mechanism is proposed. Sufficient condition for ensuring exponential mean-square finite-time boundedness of the filtering error system with an expected H ∞ disturbance attenuation index is obtained. The design of the filter and the adaptive event–triggered mechanism is derived. A practical example is given to demonstrate the effectiveness of the proposed filtering scheme in an active suspension system. [ABSTRACT FROM AUTHOR]

In this article, the tracking control problem is addressed for uncertain nonlinear systems with actuator saturation and unmeasurable unmodeled dynamics. Being different from the existing performance function control results, to constraint the output tracking error within a predefined boundary in finite time, an improved performance function, that is, finite‐time performance function, is introduced. The design difficulties of asymmetric input saturation and unmodeled dynamics are solved simultaneously for the first time by applying a smooth non‐affine function and a measurable dynamic signal. Furthermore, an adaptive fuzzy control scheme is established via command filtering, which not only guarantees the semi‐global boundedness of all the controlled system signals but also makes the output tracking error that can be restrained by the described performance bound within a finite‐time interval. At last, an effective example is supplied to validate the availability of the presented theoretical finding. [ABSTRACT FROM AUTHOR]

In this paper, the quantisation synchronisation control problem of bilateral teleoperation systems with communication delays is investigated. The inaccurate modelling problem including the system uncertainties and the unknown disturbances are compensated by using the radial basis function networks (RBFN). By introducing the hysteretic quantiser, the control signals are quantised to a set of discrete values to ease the accuracy requirement for actual physical systems and the requirement for communication rate. The position synchronisation of joint variables between the master and slave manipulators is achieved by using the designed control signals and adaptive parameters. Simulation results verify that the synchronisation tracking errors gradually converge to a small neighbourhood around zero. [ABSTRACT FROM AUTHOR]

The current thyroid ultrasound relies heavily on the experience and skills of the sonographer and the expertise of the radiologist, and the process is physically and cognitively exhausting. In this paper, we report a fully autonomous robotic ultrasound system, which is able to scan thyroid regions without human assistance and identify malignant nod- ules. In this system, human skeleton point recognition, reinforcement learning, and force feedback are used to deal with the difficulties in locating thyroid targets. The orientation of the ultrasound probe is adjusted dynamically via Bayesian optimization. Experimental results on human participants demonstrated that this system can perform high-quality ultrasound scans, close to manual scans obtained by clinicians. Additionally, it has the potential to detect thyroid nodules and provide data on nodule characteristics for American College of Radiology Thyroid Imaging Reporting and Data System (ACR TI-RADS) calculation. Current thyroid ultrasounds rely heavily on the experience and skills of the sonographer and of the radiologist, and the process is physically and cognitively exhausting. Here, the authors show a fully autonomous robotic ultrasound system, which is able to scan thyroid regions without human assistance and identify malignant nodules. [ABSTRACT FROM AUTHOR]

In this paper, an adaptive fault‐tolerant fixed‐time control problem is considered via command‐filter technique for stochastic nonlinear systems with sensor fault and actuator hysteresis. With the application of command‐filtering technique, a novel command‐filter compensate mechanism is designed, which implies that the improved control scheme not only eliminates "the explosion of complexity" but also realizes the compensate signal is bounded within fixed‐time interval. The unavailability of state variables caused by sensor fault is solved by applying parameter separation and regrouping approach. Meanwhile, an adaptive auxiliary signal is designed to cope with the backlash‐like hysteresis phenomenon, which can avoid singularity, reduce chattering, and facilitate controller design. Combining backstepping technique and Lyapunov stability theorem, an adaptive fault‐tolerant control approach is developed, which can guarantee all closed‐loop signals remain semi‐globally practical fixed‐time stable (SGPFS) in probability. The validity of the proposed strategy is illustrated by simulation examples. [ABSTRACT FROM AUTHOR]

In this research, the issue of decentralised adaptive neural finite-time prescribed performance control is discussed for nonstrict-feedback large-scale nonlinear interconnected systems subject to dead zones input and unknown control direction. The obstacle of 'explosion of complex' occurred in conventional backstepping design can be surmounted by adopting the command filter technique and nonlinearities are approximated by introducing an adaptive neural control approach. To handle the obstacles due to unknown directions and unknown interconnections, Nussbaum-type functions and two smooth functions are used and designed. Meanwhile, error compensation signals are introduced to deal with the problem associated with the dynamic surface method. To constraint the output tracking error within a predefined boundary in finite time, an improved performance function, i.e. finite-time performance function is introduced. Different from existing control results, the developed control methodology does not require any information on the boundedness of dead-zone parameters. It is further proved that the constructed controller not only assures the semi-global boundedness of all the controlled system signals, but also makes the output tracking errors reach within a predefined small set. Finally, both numerical and practical examples are supplied to further validate the effectiveness of the presented theoretic result. [ABSTRACT FROM AUTHOR]

There is a lack of studies that concurrently differentiate the effect of the holiday season from the weekend effect on mortality risk in patients with acute myocardial infarction (AMI). We evaluated the mortality risk among patients admitted with AMI who underwent percutaneous coronary intervention, using data from the Taiwan National Health Insurance Research Database. Adult AMI patients admitted during January and February between 2013 and 2020 were enrolled and classified into the holiday season (using the Chinese New Year holiday seasons as an indicator) (n = 1729), weekend (n = 4725), and weekday (n = 14,583) groups according to the first day of admission. A multivariable logistic regression model was used to assess the risk. With the weekday group or the weekend group as the reference, the holiday season group did not have increased risks of in-hospital mortality (adjusted odds ratio [aOR] 1.15; 95% confidence intervals [CI] 0.93–1.42 or aOR 1.23; 95% CI 0.96–1.56) and 7-day mortality (aOR 1.20; 95% CI 0.90–1.58 or aOR 1.24; 95% CI 0.90–1.70). Stratified and subgroup analyses showed similar trends. We conclude that holiday season-initiated admissions were not associated with higher mortality risks in AMI admission cases than weekday or weekend admissions. [ABSTRACT FROM AUTHOR]

To address model-based event-triggered fixed-time consensus of nonlinear multi-agent systems with both fixed topology and switching topologies, a novel model-based event-triggered protocol is presented. In the proposed protocol, agents in multi-agent systems update controllers by utilizing estimated state values in the triggered intervals. And for reducing the burdens of bandwidth further, the model-based event-triggered protocol is extended to self-triggered protocol which does not need continuous communication in triggered intervals. It is proven that Zeno behavior is excluded. Our main contributions are giving a novel distributed model-based event-triggered protocol for fixed-time consensus and extending it into a self-triggered protocol. Finally, a couple of simulation examples are provided to verify the effectiveness of the proposed protocols. [ABSTRACT FROM AUTHOR]

The article discusses the challenges in diagnosing and treating myocarditis, which is inflammation of the heart muscle. Myocarditis can have various causes and presentations, making it difficult to diagnose and predict outcomes. To address this, the European Society of Cardiology launched a registry to study the performance of diagnostic criteria, the spectrum of causes, and treatment outcomes. The registry found that lymphocytic myocarditis was the most common pathological finding, and viral infections were present in a significant number of cases. The study also identified predictors of adverse outcomes, such as low left ventricular ejection fraction and the initiation of immunosuppressive treatment. The article highlights the need for further research to address gaps in knowledge and improve diagnosis and treatment. [Extracted from the article]

Recurrent neural networks (RNNs) are excellent solvers for time-variant linear matrix–vector inequality (TVLMVI). However, it is difficult for traditional RNNs to track the theoretical solution of TVLMVI under non-ideal conditions [e.g., noisy environment]. Therefore, by introducing a novel nonlinear activation function (NNAF) and time-variant-gain, a new super-predefined-time convergence and noise-tolerant RNN (SPCNT-RNN) is proposed to acquire an online solution to TVLMVI in noisy environment. The difference between SPCNT-RNN and traditional fixed-parameter RNNs (FP-RNNs) is that the error function equation of SPCNT-RNN has NNAF and time-variant-gain coefficient. Due to this difference, the SPCNT-RNN can achieve super-predefined-time convergence in both noise-free and noisy environments, which is superior to that of existing RNNs. The stability, super-predefined-time convergence, and robustness of SPCNT-RNN are theoretically demonstrated. Moreover, the simulation results between various existing RNNs and SPCNT-RNN verify the feasibility, validity, robustness and rapid convergence effect of the proposed SPCNT-RNN. [ABSTRACT FROM AUTHOR]

An event-based dynamic output feedback control (DOFC) strategy for unmanned marine vehicle (UMV) systems is considered in this work. Whole UMV systems are composed of a UMV closed-loop system, a land-based control unit and the communication network. To increase the effectiveness of data transmission in the network channel and better enable the control unit against an attack, an adaptive event-triggered mechanism (AETM) is applied. Moreover, a quantizer is installed between the sampler and the control unit. The quantizer further reduces the communication burden. The occurrence of an aperiodic denial-of-service (DoS) attack is considered in the channel from the control unit to the UMV system. A sufficient criterion for ensuring the global exponential stability of a system with an expected H ∞ disturbance attenuation index is obtained. The co-design of the dynamic output feedback controller and the AETM is derived. The effectiveness of the proposed approach is verified in the given illustrative simulation. The simulation results indicate that the reduction percentages of the yaw angle amplitudes and yaw velocity accumulative error of the UMV system with the control strategy proposed in this paper are 43.2% and 45.9%, respectively, which are a 0.3% and 5.8% improvement in both metrics compared to the previously published work. [ABSTRACT FROM AUTHOR]

Aims: Sodium‐glucose cotransporter‐2 inhibitors (SGLT‐2i) have off‐target effects on haemoconcentration and anti‐inflammation. The impact of SGLT‐2i on the risk of venous thromboembolism (VTE) in patients with diabetes mellitus (DM) remains unclear. This study aimed to evaluate the risk of newly diagnosed VTE in patients with DM using SGLT‐2i in comparison to dipeptidyl peptidase‐4 inhibitors (DPP‐4i) or glucagon‐like peptide‐1 receptor agonists (GLP‐1RA). Materials and Methods: In this nationwide retrospective cohort study, we used data from Taiwan's National Health Insurance Research Database. Patients with diabetes aged 20 years or older who received SGLT‐2i, DPP‐4i, or GLP‐1RA between 1 May 2016, and 31 December 2020, were included. The risks of VTE in SGLT‐2i users were compared with those of DPP‐4i and GLP‐1RA users. A Cox regression model with stabilised inverse probability of treatment weighting was used to calculate hazard ratio (HR) for VTE risk. Additionally, a meta‐analysis of relevant articles published before 23 May 2023, was conducted. Results: Data from 136,530 SGLT‐2i, 598,280 DPP‐4i, and 5760 GLP‐1RA users were analysed. SGLT‐2i use was associated with a lower risk of VTE than DPP‐4i (HR, 0.70; 95% CI, 0.59–0.84; p < 0·001), but not with GLP‐1RA (HR, 1.39; 95% CI, 0.32–5.94; p = 0.66). Our meta‐analysis further supported these findings (SGLT‐2i vs. DPP‐4i: HR, 0.71; 95% CI, 0.62–0.82; p < 0·001; SGLT‐2i vs. GLP‐1RA: HR, 0.91; 95% CI, 0.73–1.15; p = 0.43), suggesting the robustness of our retrospective analysis. Conclusions: In patients with DM, SGLT‐2i was associated with a lower risk of VTE compared to DPP‐4i, but not GLP‐1RA. [ABSTRACT FROM AUTHOR]

The variable-order fractional (VOF) chaotic systems offer a promising solution for applications in secure communication due to their unique properties. This paper addresses the synchronisation problem in secure communication for these systems, which have uncertainties and external disturbances with unknown bounds. According to the variable-order fractional type Mittag-Leffler stability theorem, a fractional-order derivative is applied to a sliding surface, and suitable adaptive laws are devised to address uncertainties and disturbances. A variable-order fractional control strategy and a new criterion are developed to ensure the synchronisation error systems achieve asymptotic stability in finite time, for which the upper limit can be obtained. Simulation outcomes demonstrate the efficacy of the proposed synchronisation strategy in secure communication scenarios. [ABSTRACT FROM AUTHOR]

Sleep-disordered breathing (SDB) is a prevalent disorder characterized by recurrent episodic upper airway obstruction. Using data from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), we apply principal component analysis (PCA) to seven SDB-related measures. We estimate the associations of the top two SDB PCs with serum levels of 617 metabolites, in both single-metabolite analysis, and a joint penalized regression analysis. The discovery analysis includes 3299 individuals, with validation in a separate dataset of 1522 individuals. Five metabolite associations with SDB PCs are discovered and replicated. SDB PC1, characterized by frequent respiratory events common in older and male adults, is associated with pregnanolone and progesterone-related sulfated metabolites. SDB PC2, characterized by short respiratory event length and self-reported restless sleep, enriched in young adults, is associated with sphingomyelins. Metabolite risk scores (MRSs), representing metabolite signatures associated with the two SDB PCs, are associated with 6-year incident hypertension and diabetes. These MRSs have the potential to serve as biomarkers for SDB, guiding risk stratification and treatment decisions.Sleep-disordered breathing (SDB) is a prevalent disorder linked to higher cardiovascular disease risk. Here, the authors show that summary scores reflecting SDB metabolite signatures are associated with increased risks for incident hypertension and diabetes, potentially useful in guiding risk stratification. [ABSTRACT FROM AUTHOR]

In this article, under the circumstance of dead zones input and unknown control direction, the adaptive practical fixed‐time control strategy is presented for a general class of multi‐input and multi‐output (MIMO) nonlinear systems. The inherent explosion of computational complexity difficulty is eliminated by adopting a command filter technique and the universal approximation properties of radial basis function neural networks (RBFNNs) are applied to model the unknown nonlinear functions. The difficulties of the dynamic surface method and unknown directions can be handled by invoking error compensation mechanism and Nussbaum‐type functions, respectively. The uniqueness of the presented control scheme is that the tracking system can achieve the fixed‐time stability without relying on the boundedness of dead‐zone parameters. The fixed‐time convergence of the output tracking error and the semiglobally fixed‐time stable of closed‐loop system are assured via the developed adaptive fixed‐time command filtered controller. Finally, a practical example is supplied to further validate the availability of the presented theoretic result. [ABSTRACT FROM AUTHOR]

The problem of exponential stability for time‐delay systems with flexible delayed impulse control is investigated. Unlike the conventional Razumikhin‐type inequality, variable parameter δ(t)$$ \delta (t) $$ based on the flexible impulsive gain is introduced. Sufficient conditions for exponential stability are developed for a class of time‐delay systems, for which the size of delay is not limited by impulsive intervals. A flexible impulse control scheme is developed by utilizing the flexible impulsive gain and time‐varying delays. When the system is disturbed by the impulse interferences, both the impulse gain and impulse delay can be adjusted accordingly to make the system exponential stable. The effectiveness of the present results is illustrated by two numerical examples and an application. [ABSTRACT FROM AUTHOR]

This article addresses the tracking control problem of uncertain fractional-order nonlinear systems in the presence of input quantization and external disturbance. An adaptive backstepping scheme is proposed by combining with radial basis function (RBF) neural networks (NNs), fractional-order disturbance observer (FODO), and backstepping method. The RBF NNs are used to approximate the unknown nonlinearities of fractional-order systems. The FODO is designed to compensate for disturbance and uncertain parameters. The hysteresis quantizer is used to avoid chattering that possibly appears in actual application. The stability of the proposed controller is proved by fractional-order Lyapunov method. In addition, all the signals in the closed-loop system are bounded. The effectiveness of the proposed method is confirmed by the simulation results. [ABSTRACT FROM AUTHOR]

This paper addresses the output tracking problem of adaptive fixed-time fault-tolerant control for a class of nonlinear systems. In particular, we focus on two types of actuator faults: lock-in-place and loss of effectiveness. Specifically, a robust adaptive fault-tolerant controller is designed to compensate for the effect of actuator faults. By applying the classical backstepping design algorithm and fixed-time control theory, an adaptive fixed-time controller is developed, ensuring that the tracking error converges into a small neighbourhood around the origin within a fixed time where the convergence time is independent of initial conditions. Theoretical analysis and simulation outcomes prove that the closed-loop system is fixed-time stable and all signals are bounded by choosing the parameters appropriately. The effectiveness and feasibility of the presented control scheme are verified through the simulation results. [ABSTRACT FROM AUTHOR]

Solving matrix equation with noise interference is a challenging problem in mathematical and engineering applications. Unlike the traditional recurrent neural network, a novel varying-parameter periodic rhythm neural network (VP-PRNN) is proposed and used to solve the time-varying matrix equation in finite energy noise environment online. Particularly, VP-PRNN can enable the state solution to converge to the theoretical solution rapidly and robustly, which is also proved by theoretical analysis. Four kinds of noise are used to test the system, which proves the effectiveness of VP-PRNN. Compared with the zeroing neural network and circadian rhythms learning network with fixed parameters, VP-PRNN with variable parameters shows superior convergence performance in the disturbance of finite energy noise. [ABSTRACT FROM AUTHOR]

This study investigates an adaptive fixed-time tracking problem of nonlinear interconnected high-order systems with unknown control direction and stochastic disturbances. Under the framework of adaptive feedback, the backstepping method and fuzzy logic system are utilized to handle the stochastic disturbances and the packaged unknown nonlinearities. By utilizing the Nussbaum gain technique, an adaptive fixed-time controller is proposed to overcome the difficulties associated with unknown control directions. Distinguishing from the most existing results, a modified fixed-time control scheme is presented to deal with the positive odd integer terms from the interconnected high-order system with the help of adding a power integrator method. The designed control strategy guarantees that the tracking error converges within a fixed settling time and all signals of the closed-loop system are fixed-time stable. Simulation results validate the designed control approach. [ABSTRACT FROM AUTHOR]

During the course of biopharmaceutical production, heterologous protein expression in Chinese hamster ovary (CHO) cells imposes a high proteostatic burden that requires cellular adaptation. To mitigate such burden, cells utilize the unfolded protein response (UPR), which increases endoplasmic reticulum (ER) capacity to accommodate elevated rates of protein synthesis and folding. In this study, we show that during production the UPR regulates growth factor signaling to modulate growth and protein synthesis. Specifically, the protein kinase R‐like ER kinase (PERK) branch of the UPR is responsible for transcriptional down‐regulation of platelet‐derived growth factor receptor alpha (PDGFRa) and attenuation of the IRE1‐alpha (IRE1a) branch of the UPR. PERK knockout (KO) cell lines displayed reduced growth and viability due to higher rates of apoptosis despite having stabilized PDGFRa levels. Knocking out PERK in an apoptosis impaired (Bax/Bak double KO) antibody‐expressing cell line prevented apoptotic cell death and revealed that apoptosis was likely triggered by increased ER stress and reactive oxygen species levels in the PERK KO hosts. Our findings suggest that attenuation of IRE1a and PDGFRa signaling by the PERK branch of the UPR reduces ER protein folding capacity and hence specific productivity of CHO cells in order to mitigate UPR and prevent apoptotic cell death. Last, Bax/Bak/PERK triple KO CHO cell lines displayed 2–3 folds higher specific productivity and titer (up to 8 g/L), suggesting that modulation of PERK signaling during production processes can greatly improve specific productivity in CHO cells. [ABSTRACT FROM AUTHOR]

Background: Outcomes of diabetes screening in contemporary, multi-ethnic populations are unknown. We examined the association of prior outpatient diabetes screening with the risks of cardiovascular events and mortality in Ontario, Canada. Methods: We conducted a population-based cohort study using administrative databases among adults aged ≥ 20 years with incident diabetes diagnosed during 2014–2016. The exposure was outpatient diabetes screening performed within 3 years prior to diabetes diagnosis. The co-primary outcomes were (1) a composite of all-cause mortality and hospitalization for myocardial infarction, stroke, coronary revascularization, and (2) all-cause mortality (followed up until 2018). We calculated standardized rates of each outcome and conducted cause-specific hazard modelling to determine the adjusted hazard ratio (HR) of the outcomes, adjusting for prespecified confounders and accounting for the competing risk of death. Results: We included 178,753 Ontarians with incident diabetes (70.2% previously screened). Individuals receiving prior screening were older (58.3 versus 53.4 years) and more likely to be women (49.6% versus 40.0%) than previously unscreened individuals. Individuals receiving prior screening had relatively lower standardized event rates than those without prior screening across all outcomes (composite: 12.8 versus 18.1, mortality: 8.2 versus 11.1 per 1000 patient-years). After multivariable adjustment, prior screening was associated with 34% and 32% lower risks of the composite (HR 0.66, 0.63–0.69) and mortality (0.68, 0.64–0.72) outcomes. Among those receiving prior screening, a result in the prediabetes range was associated with lower risks of the composite (0.82, 0.77–0.88) and mortality (0.71, 0.66–0.78) outcomes than a result in the normoglycemic range. Conclusions: Previously screened individuals with diabetes had lower risks of cardiovascular events and mortality versus previously unscreened individuals. Better risk assessment tools are needed to support wider and more appropriate uptake of diabetes screening, especially among young adults. [ABSTRACT FROM AUTHOR]

Objectives: A watch and wait strategy with the goal of organ preservation is an emerging treatment paradigm for rectal cancer following neoadjuvant treatment. However, the selection of appropriate patients remains a challenge. Most previous efforts to measure the accuracy of MRI in assessing rectal cancer response used a small number of radiologists and did not report variability among them. Methods: Twelve radiologists from 8 institutions assessed baseline and restaging MRI scans of 39 patients. The participating radiologists were asked to assess MRI features and to categorize the overall response as complete or incomplete. The reference standard was pathological complete response or a sustained clinical response for > 2 years. Results: We measured the accuracy and described the interobserver variability of interpretation of rectal cancer response between radiologists at different medical centers. Overall accuracy was 64%, with a sensitivity of 65% for detecting complete response and specificity of 63% for detecting residual tumor. Interpretation of the overall response was more accurate than the interpretation of any individual feature. Variability of interpretation was dependent on the patient and imaging feature investigated. In general, variability and accuracy were inversely correlated. Conclusions: MRI-based evaluation of response at restaging is insufficiently accurate and has substantial variability of interpretation. Although some patients' response to neoadjuvant treatment on MRI may be easily recognizable, as seen by high accuracy and low variability, that is not the case for most patients. Key Points: • The overall accuracy of MRI-based response assessment is low and radiologists differed in their interpretation of key imaging features. • Some patients' scans were interpreted with high accuracy and low variability, suggesting that these patients' pattern of response is easier to interpret. • The most accurate assessments were those of the overall response, which took into consideration both T2W and DWI sequences and the assessment of both the primary tumor and the lymph nodes. [ABSTRACT FROM AUTHOR]

In this paper, an adaptive fixed-time output feedback formation control problem is investigated for nonlinear multi-agent systems with a nonstrict-feedback structure. In the controller design procedure, the neural network state observer is designed to estimate the unmeasurable state variables. Dynamic surface control (DSC) technique is applied to avoid the repeated differentiation for the virtual control signals. The dynamic surface compensation signals can realise the practical fixed-time bounded. Utilising the classified discussion method, the difficulty of controller design caused by the existence of observer error term is addressed. The technique of transformation of the index set is employed to cope with the related variables of the neighbour states, which simplifies the controller design. Under the presented control mechanism, all closed-loop signals remain bound for a fixed period of time, the formation control performance target between all followers and leader can be achieved. And the formation errors and state observers errors are both bounded such that can converge to a little domain around zero. Simulation results are provided to test the availability of the presented strategy. [ABSTRACT FROM AUTHOR]

In this article, the finite-time adaptive fuzzy output-feedback control strategy is presented for a class of multi-input and multi-output (MIMO) nonlinear systems with multiple actuator constraints and unmeasured states. Fuzzy logic systems and a fuzzy adaptive state observer are adopted to estimate the nonlinear uncertainties and the unmeasured states, respectively. The inherent 'explosion of complexity' problem is eliminated by adopting command filter technology and the corresponding error compensation mechanism is exploited to alleviate the influence of the errors generated by command filters. It is further proved that all the signals can be fast finite-time bounded in the closed-loop systems based on the Lyapunov stability theory. Besides, the observer and tracking errors can reach a small region around the origin in fast finite time. Finally, the practicability of the presented theoretic result can be demonstrated through the numerical and practical examples. [ABSTRACT FROM AUTHOR]

Keywords: andrology; guidelines; testosterone EN andrology guidelines testosterone 398 400 3 09/12/23 20231001 NES 231001 The function of the hypothalamic-pituitary-testicular (HPT) axis during all epochs of life is to regulate androgenization and maintain fertility through repeated incremental and decremental feedforward (stimulatory) and feedback (inhibitory) signaling among its neural and hormonal components.[1] Male hypogonadism is the clinical syndrome that results from failure to secrete sufficient testosterone (T) and/or produce spermatozoa of adequate quality or quantity due to the culmination of single, sequential or simultaneous pathophysiological abnormalities in the HPT axis.[[2], [4]] This definition is simple to apply when the cause of HPT axis failure is obvious (" I organic hypogonadism i ", e.g. due to pituitary tumor causing secondary hypogonadism or due to Klinefelter syndrome causing primary hypogonadism); however, many chronic illnesses can dysregulate the HPT axis, decrease T and impair fertility (" I functional hypogonadism i "). Testosterone therapy in men with hypogonadism: an endocrine society clinical practice guideline. European Academy of Andrology (EAA) guidelines on investigation, treatment and monitoring of functional hypogonadism in males: endorsing organization: European Society of Endocrinology. [Extracted from the article]

In this article, the problem of adaptive fixed‐time tracking control is addressed for non‐triangular structural stochastic switching nonlinear systems. Fuzzy logic systems are used to compensate for unknown nonlinearities, and in the meantime, to avoid the algebraic loop problem, which exists in traditional backstepping controller design processes for non‐triangular structural nonlinear systems. The unknown control gain problem is addressed by the construction of proper Lyapunov function candidates. By employing Lyapunov stability theorem, all the closed‐loop signals can be ensured to be semi‐globally practical fixed‐time stable, the output signal can track the desired signal, and the tracking error can converge to a small zone around the origin. The effectiveness of the developed control approach is verified through simulation results. [ABSTRACT FROM AUTHOR]

A novel wearable upper arm tactile display device, which can simultaneously provide three types of tactile stimuli (i.e., squeezing, stretching, and vibration) is presented. The squeezing and stretching stimulation of the skin is generated by two motors simultaneously driving the nylon belt in the opposite and the same direction, respectively. In addition, four evenly spaced vibration motors are fixed around the user's arm by an elastic nylon band. There is also a unique structural design for assembling the control module and actuator, powered by two lithium batteries, making it portable and wearable. Psychophysical experiments are conducted to investigate the effect of interference on the perception of squeezing and stretching stimulation by this device. Results show that (1) different tactile stimuli actually interfere with the user's perception compared to the case where only one stimulus is applied to the user; (2) the squeezing has a considerable impact on the stretch just noticeable difference (JND) values when both stimuli are exerted on the user, and when the squeezing is strong, while the impact of stretch on the squeezing JND values is negligible. [ABSTRACT FROM AUTHOR]

This paper considers the problem of leader-following consensus and fault detection for a class of multi-agent systems with Lipschitz nonlinear dynamics. To reduce the amount of redundant information and avoid checking triggering conditions continually, this paper proposes an efficient network framework with a double periodic event-triggered mechanism. Based on the proposed framework, an improved fault detection observer and a consensus controller are designed. Then, the original problem is converted into a set of stability problems with constraints. According to Lyapunov–Krasovskii theorem and the free-weighting matrix technique, sufficient conditions for solving these stability problems are derived in the form of bilinear matrix inequalities (BMIs). Further, to eliminate the nonlinear terms of BMI and obtain optimal performance, two iterative algorithms based on linear matrix inequalities (LMIs) are developed. Two simulation examples are provided to verify the practicality and validity of the theoretical results. [ABSTRACT FROM AUTHOR]

A class of heterogeneous second-order multi-agent consensus problems is studied, in which an event-triggered method is used to improve the feasibility of the control protocol. The sliding mode control method is used to achieve the robustness of the system. A special type of general radial basis function neural network is applied to estimate the uncertainties. The event-triggered mechanism is introduced to reduce the update frequency of the controller and the communication frequency among the agents. Zeno behavior is avoided by ensuring a lower bound between two adjacent trigger instants. Finally, the simulation results are provided to demonstrate that the time evolution of consensus errors eventually approaches zero. The consensus of multi-agent systems is achieved. [ABSTRACT FROM AUTHOR]

In this paper, the tracking control problem of flexible joint robotic manipulator (FJRM) system subjected to system uncertainties and time-varying external disturbances (TVED) is addressed. A new disturbance observer-based neural network integral sliding mode controller with output constraints (DNISMCOC) that comprises the merits of neural networks, disturbance observer and integral sliding mode is proposed. Considering that the radial basis function neural network (RBFNN) has a fast learning convergence speed and great approximation ability, two matrices of RBFNN are utilized to estimate the parameter matrices of the dynamic model of FJRM. In view of the estimation errors of RBFNNs and TVED in the system, a disturbance observer is introduced to estimate the lump uncertainties which consist of them. Integral sliding mode is introduced for eliminating steady errors further. For ensuring security in some high-accuracy using occasions, a barrier lyapunov functions (BLF) is adopted to achieve output constraints of FJRM. To validate the effectiveness of the proposed control scheme, numerical simulations on 2-link FJRM are conducted. According to the comparisons among DNISMCOC and other state-of-the-art controllers, the superiorities of DNISMCOC in several aspects are proved. [ABSTRACT FROM AUTHOR]

Aims: Guidelines for the management of heart failure (HF) are evolving, and increasing emphasis is placed on patient‐centred care. As part of the REWOLUTION HF (REal WOrLd EdUcaTION in HF) programme, we conducted two international surveys aimed at assessing healthcare professionals' (HCPs) educational needs and patients' perspectives on the care of HF. Methods and results: Anonymous online questionnaires co‐developed by HF experts and patients assessed HCPs' educational needs (520 respondents, mostly cardiologists, in 67 countries) and patients' perceptions on HF impact and management (98 respondents in 18 countries). Among HCPs, 62.7% prioritized rapid initiation of all guideline‐mandated medications over up‐titration of some medications, and 87.7% always or frequently discussed treatment goals with patients. There was good agreement between HCPs and patients on key treatment goals, except for a greater emphasis on reducing hospitalizations among HCPs. The most frequently cited barriers to the provision of guideline‐recommended pharmacological therapy were treatment side effects/intolerance, complex treatment regimens, low blood pressure, cost/reimbursement issues, and low estimated glomerular filtration rate. Most patients (81.6%) reported no difficulties taking medications as prescribed, although 21.4% felt they were taking too many pills. Patients wanted more information about HF and its consequences, prognosis, and treatments (70.4%, 74.5% and 76.6%, respectively). Cardiologists were the preferred source of information about HF, followed by general practitioners and HF nurses. Conclusions: These surveys provide valuable insights into HCPs' needs about personalized care for patients with HF, as well as patients' perceptions, expectations and preferences. These findings will be helpful to develop patient‐centred, needs‐driven quality improvement programmes. [ABSTRACT FROM AUTHOR]

Primary sclerosing cholangitis (PSC) is a progressive liver disease for which there is no effective therapy. Hepatocytes and cholangiocytes from a PSC patient were cocultured with mesenchymal stem cells (MSCs) to assess in vitro change. A single patient with progressive PSC was treated with 150 million MSCs via direct injection into the common bile duct. Coculture of MSCs with cholangiocytes and hepatocytes showed in vitro improvement. Local delivery of MSCs into a single patient with progressive PSC was safe. Radiographic and endoscopic evaluation showed stable distribution of multifocal structuring in the early postoperative period. MSCs may be effective for the treatment of PSC. [ABSTRACT FROM AUTHOR]

Background: Heart failure (HF) is a critical complication in elderly patients with atrial fibrillation (AF) and diabetes mellitus (DM). Recent preclinical studies suggested that non-vitamin K antagonist oral anticoagulants (NOACs) can potentially suppress the progression of cardiac fibrosis and ischemic cardiomyopathy. Whether different oral anticoagulants influence the risk of HF in older adults with AF and DM is unknown. This study aimed to evaluate the risk of HF in elderly patients with AF and DM who were administered NOACs or warfarin. Methods: A nationwide retrospective cohort study was conducted based on claims data from the entire Taiwanese population. Target trial emulation design was applied to strengthen causal inference using observational data. Patients aged ≥ 65 years with AF and DM on NOAC or warfarin treatment between 2012 and 2019 were included and followed up until 2020. The primary outcome was newly diagnosed HF. Propensity score-based fine stratification weightings were used to balance patient characteristics between NOAC and warfarin groups. Hazard ratios (HRs) were estimated using Cox proportional hazard models. Results: The study included a total of 24,835 individuals (19,710 NOAC and 5,125 warfarin users). Patients taking NOACs had a significantly lower risk of HF than those taking warfarin (HR = 0.80, 95% CI 0.74–0.86, p < 0.001). Subgroup analyses for individual NOACs suggested that dabigatran (HR = 0.86, 95% CI 0.80–0.93, p < 0.001), rivaroxaban (HR = 0.80, 95% CI 0.74–0.86, p < 0.001), apixaban (HR = 0.78, 95% CI 0.68–0.90, p < 0.001), and edoxaban (HR = 0.72, 95% CI 0.60–0.86, p < 0.001) were associated with lower risks of HF than warfarin. The findings were consistent regardless of age and sex subgroups and were more prominent in those with high medication possession ratios. Several sensitivity analyses further supported the robustness of our findings. Conclusions: This nationwide cohort study demonstrated that elderly patients with AF and DM taking NOACs had a lower risk of incident HF than those taking warfarin. Our findings suggested that NOACs may be the preferred oral anticoagulant treatment when considering the prevention of heart failure in this vulnerable population. Future research is warranted to elucidate causation and investigate the underlying mechanisms. [ABSTRACT FROM AUTHOR]

Players-based emotion recognition can help the understanding game players’ emotional states, contributing to the improvement of the game's quality and value. This article develops a hybrid neural network learning framework called convolutional smooth feedback fuzzy network (CSFFN) to detect a player's emotional states in real-time during a gaming process based on electroencephalogram (EEG) signals. Specifically, CSFFN rationally combines a convolutional neural network (CNN), a fuzzy neural network (FNN), and a recurrent neural network (RNN). CNN not only captures spatial characteristics between EEG signals from different channels but also eliminates noise from EEG signals, improving the accuracy and anti-noise performance in game emotion recognition. FNN extracts the membership degree of a player's different emotional states, further improving the emotion recognition accuracy. Since a player's current emotional state is influenced by the previous emotional states during the game process, RNN is employed to capture the temporal characteristics of EEG signals, better improving the emotion recognition accuracy. Experimental results show that CSFFN has higher recognition accuracy and noise resistance in identifying four emotional states (happiness, sadness, superiority, and anger) compared to support vector machine (SVM) with different kernels, linear discrimination analysis (LDA), AlexNet, and VGG16 methods. [ABSTRACT FROM AUTHOR]

Sleep serves important biological functions, and influences health and longevity through endocrine and metabolic related systems. Sleep debt, circadian misalignment and sleep disruption from obstructive sleep apnea is widespread in modern society and accumulates with life because recovery sleep is not completely restorative. Accumulated disordered sleep throughout life impacts the ageing process and the development of age-related diseases. When epidemiological and interventional studies are considered collectively, sleep loss and lower sleep duration are associated with lower morning, afternoon and 24-h testosterone; as well as higher afternoon, but not morning or 24-h cortisol. These reciprocal changes imbalances anabolic-catabolic signaling because testosterone and cortisol are respectively the main anabolic and catabolic signals in man. Fixing testosterone-cortisol balance by means of a novel dual-hormone clamp mitigates the induction of insulin resistance by sleep restriction and provided the first proof-of-concept that the metabolic harm from sleep loss can be ameliorated by approaches that do not require sleeping more. Obstructive sleep apnea is associated with lower testosterone, even after controlling for age and obesity whereas the conclusion that continuous positive airway pressure therapy has no effect on testosterone is premature because available studies are underpowered and better-quality studies suggest otherwise. High dose testosterone therapy induces OSA, but more physiological dosing may not; and this effect may be transient or may dissipate with longer term therapy. Studies investigating the origin of the diurnal testosterone rhythm, the effect of circadian misalignment on testosterone-cortisol balance, and methods to mitigate metabolic harm, are required. [ABSTRACT FROM AUTHOR]

Context Night-shift work causes circadian misalignment, predicts the development of metabolic diseases, and complicates the interpretation of hormone measurements. Objective To investigate endogenous circadian rhythms, dissociated from behavioral and environmental confounds, in adrenal and gonadal steroids after simulated shift work. Methods Fourteen healthy adults (ages 25.8 ± 3.2 years) were randomized to 3 days of night or day (control) shift work followed by a constant routine protocol designed to experimentally unveil rhythms driven endogenously by the central circadian pacemaker. Blood was sampled every 3 hours for 24 hours during the constant routine to concurrently obtain 16 Δ4 steroid profiles by mass spectrometry. Cosinor analyses of these profiles provided mesor (mean abundance), amplitude (oscillation magnitude), and acrophase (peak timing). Results Night-shift work marginally increased cortisol by 1 μg/dL (P = 0.039), and inactive/weak derivatives cortisone (P = 0.003) and 18-hydroxycortisol (P < 0.001), but did not alter the mesor of potent androgens testosterone and 11-ketotestosterone. Adrenal-derived steroids, including 11-ketotestosterone (P < 0.01), showed robust circadian rhythmicity after either day- or night-shift work. In contrast, testosterone and progesterone showed no circadian pattern after both shift work conditions. Night-shift work did not alter the amplitude or acrophase of any of the steroid profiles. Conclusion Experimental circadian misalignment had minimal effects on steroidogenesis. Adrenal steroids, but not gonadal hormones, showed endogenous circadian regulation robust to prior shift schedule. This dichotomy may predispose night-shift workers to metabolic ill health. Furthermore, adrenal steroids, including cortisol and the main adrenal androgen 11-ketostosterone, should always be evaluated during the biological morning whereas assessment of gonadal steroids, particularly testosterone, is dependent on the shift-work schedule. [ABSTRACT FROM AUTHOR]

In this article, the problem of fuzzy adaptive fixed-time control is addressed for nonstrict-feedback nonlinear systems with input saturation and dead zone. The universal approximation properties of fuzzy logic systems are employed to model the unknown nonlinear functions. A command filter-based fixed-time adaptive fuzzy control strategy is presented based on the backstepping framework and fixed-time control theory. The command filter technique is presented to address the "computational explosion" problem inherent in the backstepping scheme, and an error compensation mechanism is adopted to reduce the errors arising from command filters. Meanwhile, the non-smooth input saturation and dead zone nonlinearities are approximated using a non-affine smooth function, and they are transformed into an affine form based on the mean-value theorem. The fixed-time convergence of the tracking error and the boundedness of the closed-loop signals are proved using the fixed-time stability theory. Finally, simulation was performed to demonstrate the effectiveness of the presented method. [ABSTRACT FROM AUTHOR]

Several infections can predispose to certain malignancies in different body parts. These infections include viral, bacterial, and fungal pathogens. Imaging plays a vital role in the diagnosis, staging, and management of these neoplastic conditions. Furthermore, it can help in differentiating infection-related non-neoplastic processes that can mimic malignancies. Both radiologists and clinicians should be familiar with these conditions. This review discusses the epidemiology, pathogenesis, and imaging features of infection-related tumors. [ABSTRACT FROM AUTHOR]

Existing visual-based fatigue detection methods usually monitor drivers’ fatigue by capturing their facial features, including eyelid movements, yawn frequency and head pose. However, these approaches typically do not take drivers’ biological signals into consideration. An accurate model for fatigue detection requires combining both facial behavior and biological data. This paper proposes a novel non-intrusive method for driver multimodal fusion fatigue detection by extracting eyelid features and heart rate signals from the RGB video. The multimodal feature fusion method could significantly increase the accuracy of fatigue detection. Specifically, we established two fatigue detection models based on heart rate and the PERCLOS value respectively with one-dimensional Convolutional Neural Network (1D CNN), where the PERCLOS refers to the percentage of eyelid closure over the pupil. Finally, the outputs of the two models are weighted to achieve the multimodal fusion fatigue detection. Simulation results show that our method yield better performance than traditional methods. [ABSTRACT FROM AUTHOR]

Objective: Heart failure (HF) often develops in patients with diabetes and is recognized for its role in increased cardiovascular morbidity and mortality in this population. Most existing models predict risk in patients with prevalent rather than incident diabetes and fail to account for sex differences in HF risk factors. We derived sex-specific models in Ontario, Canada to predict HF at diabetes onset and externally validated these models in the U.K.Research Design and Methods: Retrospective cohort study using international population-based data. Our derivation cohort comprised all Ontario residents aged ≥18 years who were diagnosed with diabetes between 2009 and 2018. Our validation cohort comprised U.K. patients aged ≥35 years who were diagnosed with diabetes between 2007 and 2017. Primary outcome was incident HF. Sex-stratified multivariable Fine and Gray subdistribution hazard models were constructed, with death as a competing event.Results: A total of 348,027 Ontarians (45% women) and 54,483 U.K. residents (45% women) were included. At 1, 5, and 9 years, respectively, in the external validation cohort, the C-statistics were 0.81 (95% CI 0.79-0.84), 0.79 (0.77-0.80), and 0.78 (0.76-0.79) for the female-specific model; and 0.78 (0.75-0.80), 0.77 (0.76-0.79), and 0.77 (0.75-0.79) for the male-specific model. The models were well-calibrated. Age, rurality, hypertension duration, hemoglobin, HbA1c, and cardiovascular diseases were common predictors in both sexes. Additionally, mood disorder and alcoholism (heavy drinker) were female-specific predictors, while income and liver disease were male-specific predictors.Conclusions: Our findings highlight the importance of developing sex-specific models and represent an important step toward personalized lifestyle and pharmacologic prevention of future HF development. [ABSTRACT FROM AUTHOR]

The National Heart, Lung, and Blood Institute (NHLBI) convened a workshop of international experts to discuss new research opportunities for the prevention, detection, and intervention of myocarditis in May 2021. These experts reviewed the current state of science and identified key gaps and opportunities in basic, diagnostic, translational, and therapeutic frontiers to guide future research in myocarditis. In addition to addressing community-acquired myocarditis, the workshop also focused on emerging causes of myocarditis including immune checkpoint inhibitors and SARS-CoV-2 related myocardial injuries and considered the use of systems biology and artificial intelligence methodologies to define workflows to identify novel mechanisms of disease and new therapeutic targets. A new priority is the investigation of the relationship between social determinants of health (SDoH), including race and economic status, and inflammatory response and outcomes in myocarditis. The result is a proposal for the reclassification of myocarditis that integrates the latest knowledge of immunological pathogenesis to refine estimates of prognosis and target pathway-specific treatments. [ABSTRACT FROM AUTHOR]

Summary: A new fault‐tolerant approach to input saturation and sensor faults is presented for flexible‐joint robotic stochastic nonlinear systems with finite‐time convergence performance. More precisely, a new command filter is designed and embedded into the backstepping framework, which greatly reduces the amount of calculation. By using the estimation ability of fuzzy logic system and less adjustable parameters, the problems of sensor faults and unknown functions are solved, which facilitates the design of controllers. A smooth function and mean‐value theorem are used to deal with the difficulty associated with system signals. A novel simpler controller is developed to ensure that the trajectory tracking error converges to a sufficiently small neighborhood around the origin within finite time, while there are random noises. Finally, the effectiveness of the presented scheme is verified by simulation results. [ABSTRACT FROM AUTHOR]

This paper solves the finite-time tracking problem of a class of high-order nonlinear systems under event-triggered input. Unlike existing event-triggered frameworks based on signal transmission channels from the sensor to the controller or from the controller to the actuator, these developed trigger mechanisms only compare the difference between the signal to be transmitted and the holding signal. By introducing internal trigger conditions and external trigger conditions, a novel error-to-actuator based event-triggered framework is proposed. It further considers the response of the trigger mechanism to system control performance such that the tracking performance of the system can be guaranteed while reducing the number of signal transmissions. In addition, filter-based techniques (such as the dynamic surface control method), for the first time, are utilised to eliminate some strong constraints that exist in the literature for most high-order nonlinear systems. The effectiveness of the proposed approach is evaluated on simulation examples including comparative studies and a practical example. [ABSTRACT FROM AUTHOR]