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Heart failure (HF) imposes a major global health care burden on society and suffering on the individual. About 50% of HF patients have preserved ejection fraction (HFpEF). More intricate and comprehensive measurement-focused imaging of multiple strain components may aid in the diagnosis and elucidation of this disease. Here, we describe the development of a semi-automated hyperelastic warping method for rapid comprehensive assessment of biventricular circumferential, longitudinal, and radial strains that is physiological meaningful and reproducible. We recruited and performed cardiac magnetic resonance (CMR) imaging on 30 subjects [10 HFpEF, 10 HF with reduced ejection fraction patients (HFrEF) and 10 healthy controls]. In each subject, a three-dimensional heart model including left ventricle (LV), right ventricle (RV), and septum was reconstructed from CMR images. The hyperelastic warping method was used to reference the segmented model with the target images and biventricular circumferential, longitudinal, and radial strain–time curves were obtained. The peak systolic strains are then measured and analyzed in this study. Intra- and inter-observer reproducibility of the biventricular peak systolic strains was excellent with all ICCs > 0.92. LV peak systolic circumferential, longitudinal, and radial strain, respectively, exhibited a progressive decrease in magnitude from healthy control→HFpEF→HFrEF: control (-15.5 ± 1.90, -15.6 ± 2.06, 41.4 ± 12.2%); HFpEF (-9.37 ± 3.23, -11.3 ± 1.76, 22.8 ± 13.1%); HFrEF (-4.75 ± 2.74, -7.55 ± 1.75, 10.8 ± 4.61%). A similar progressive decrease in magnitude was observed for RV peak systolic circumferential, longitudinal and radial strain: control (-9.91 ± 2.25, -14.5 ± 2.63, 26.8 ± 7.16%); HFpEF (-7.38 ± 3.17, -12.0 ± 2.45, 21.5 ± 10.0%); HFrEF (-5.92 ± 3.13, -8.63 ± 2.79, 15.2 ± 6.33%). Furthermore, septum peak systolic circumferential, longitudinal, and radial strain magnitude decreased gradually from healthy control to HFrEF: control (-7.11 ± 1.81, 16.3 ± 3.23, 18.5 ± 8.64%); HFpEF (-6.11 ± 3.98, -13.4 ± 3.02, 12.5 ± 6.38%); HFrEF (-1.42 ± 1.36, -8.99 ± 2.96, 3.35 ± 2.95%). The ROC analysis indicated LV peak systolic circumferential strain to be the most sensitive marker for differentiating HFpEF from healthy controls. Our results suggest that the hyperelastic warping method with the CMR-derived strains may reveal subtle impairment in HF biventricular mechanics, in particular despite a “normal” ventricular ejection fraction in HFpEF.

In order to improve the utilization efficiency of converting low-flow current energy into electric energy for Reynolds number 10,000 ≤ Re ≤ 40,000, this paper proposes a vortex-induced vibration power generation system based on a side-by-side double blunt body. In this system, the side-by-side double blunt body structure is used in the current energy capture part to enhance the collection of low-flow current energy; the permanent magnet linear motor is used in the electric energy conversion part to improve the efficiency of electric energy conversion; and a laboratory device is constructed for testing. The effects of the blunt body structure parameters and the center spacing ratio on the energy harvesting performance of the system are qualitatively explained by constructing a simulation model. Compared with the single blunt body energy capture structure, the side-by-side double blunt body structure increases the vibration amplitude by 1.04 times and the lift by 1.14 times at the center spacing S/D = 2.4. Meanwhile, energy harvesting can be realized at a lower flow velocity, increasing the vortex-induced vibration’s energy capture range. Finally, the power generation system was experimentally verified in the laboratory, and the results showed that the vibration amplitude of the double blunt body structure was increased by 1.12 times compared to the single blunt body. The maximum output power of the generator is 10.55 W when the water velocity is 0.7 m/s. The energy conversion efficiency of the power generation system can reach a maximum of 52.93%, which is 12.33% higher than that of a single blunt body structure, which proves that the system has a higher power conversion efficiency than that of a conventional single conversion system.

Abstract Purpose To study the effect of exosomes derived from the induced pluripotent stem cells (iPSCs) in the neuroinflammatory response of microglia caused by lipopolysaccharide (LPS) and reveal the potential underlying mechanism. Methods A permanent microglia cell line HMO6 was activated by LPS. The features of exosomes were analyzed by nano flow cytometry, Western blot and transmission electron microscope. The RNA‐seq was used to analyze the difference of noncoding RNA profiles between iPSC‐Exos and HMO6 derived exosomes and proved that long no‐coding RNA (lncRNA‐0949) was highly expressed in the iPSC‐Exos. Activated HMO6 cells were cocultured with iPSC‐Exos in which lncRNA‐0949 was overexpressed, knocked down or normally expressed. Quantitative real‐time polymerase chain reaction (RT‐qPCR), Enzyme‐Linked Immunosorbent Assay and Western blot assay were adopted to analyze RNA and protein expression of inflammatory factors in HMO6 cells. Results The oxidative stress and inflammatory response of microglia were significantly attenuated with the iPSC derived exosomes treatment. LncRNA‐0949 was effectively delivered into the HMO6 cells through the iPSC‐Exos, which largely alleviated the production of malondialdehyde, IL‐6, IL‐1β and TNF‐α in HMO6 cells. Overexpression of lncRNA‐0949 could enhance the anti‐inflammatory effect of the iPSC‐Exos, and knock‐down of lncRNA‐0949 impaired this availability. Conclusion According to our results, lncRNA‐0949 enriched exosomes from iPSC could potentially be used as a therapeutic strategy to prevent/treat neuroinflammatory diseases.

Background: Mitochondrial myopathy is a group of diseases caused by abnormal mitochondrial structure or function. The mitochondrial myopathy impacts muscles of the whole body and exhibits variable symptoms. Respiratory muscle deficits deteriorate pulmonary function in patients with severe pneumonia. Case presentation: We report the case of a male patient with severe pneumonia-induced respiratory failure. He was abnormally dependent invasive ventilator-assisted ventilation after his condition had improved. Then we found abnormal ventilator waveform and a decline in muscle strength of him. Mitochondrial myopathy was ultimately confirmed by muscle pathological biopsy and body fluid genetic testing. Vitamin B complex, coenzyme Q10, Neprinol AFD, l-arginine, and MITO-TONIC were used to improve mitochondrial function and muscle metabolism. After treatment, discomfort associated with chest tightness, fatigue, cough, and sputum disappeared, and the patient was discharged. Conclusion: This case presented an uncommon cause of difficult weaning and extubation—acute onset of mitochondrial myopathy. Muscle biopsy and genetic testing of body fluid are essential for diagnosing mitochondrial myopathy. The A3243G mutation in the MT-TL1 gene of mitochondrial DNA contributes to pathogenesis of this case.

Pulmonary arterial hypertension (PAH) causes an increase in the mechanical loading imposed on the right ventricle (RV) that results in progressive changes to its mechanics and function. Here, we quantify the mechanical changes associated with PAH by assimilating clinical data consisting of reconstructed three-dimensional geometry, pressure, and volume waveforms, as well as regional strains measured in patients with PAH (n = 12) and controls (n = 6) within a computational modeling framework of the ventricles. Modeling parameters reflecting regional passive stiffness and load-independent contractility as indexed by the tissue active tension were optimized so that simulation results matched the measurements. The optimized parameters were compared with clinical metrics to find usable indicators associated with the underlying mechanical changes. Peak contractility of the RV free wall (RVFW) γRVFW,max was found to be strongly correlated and had an inverse relationship with the RV and left ventricle (LV) end-diastolic volume ratio (i.e., RVEDV/LVEDV) (RVEDV/LVEDV)+ 0.44, R2 = 0.77). Correlation with RV ejection fraction (R2 = 0.50) and end-diastolic volume index (R2 = 0.40) were comparatively weaker. Patients with with RVEDV/LVEDV > 1.5 had 25% lower γRVFW,max (P < 0.05) than that of the control. On average, RVFW passive stiffness progressively increased with the degree of remodeling as indexed by RVEDV/LVEDV. These results suggest a mechanical basis of using RVEDV/LVEDV as a clinical index for delineating disease severity and estimating RVFW contractility in patients with PAH. NEW & NOTEWORTHY This article presents patient-specific data assimilation of a patient cohort and physical description of clinical observations. [ABSTRACT FROM AUTHOR]

Abstract Synchrotron Radiation Computed Tomography (SRCT) allows a better detection of fatigue cracks in metals than laboratory CT due to the existence of phase contrast. However the presence in reconstructed images of fringes at the edges of objects generated by Fresnel diffraction makes it difficult to identify and analyze the cracks quantitatively. Simulations of phase contrast synchrotron tomography images containing cracks with different sizes and shapes are obtained by using GATE software. Analyzing the simulation results, firstly, we confirmed that the bright parts with strong contrast in SRCT image are streak artifacts; secondly, we found that the gray scale values within the cracks in SRCT images are related to the crack size; these simulation results are used to analyse SRCT images of internal fatigue cracks in a cast Al alloy, providing a clearer visualisation of damage.

Patient-specific biventricular computational models associated with a normal subject and a pulmonary arterial hypertension (PAH) patient were developed to investigate the disease effects on ventricular mechanics. These models were developed using geometry reconstructed from magnetic resonance (MR) images, and constitutive descriptors of passive and active mechanics in cardiac tissues. Model parameter values associated with ventricular mechanical properties and myofiber architecture were obtained by fitting the models with measured pressure-volume loops and circumferential strain calculated from MR images using a hyperelastic warping method. Results show that the peak right ventricle (RV) pressure was substantially higher in the PAH patient (65mmHg versus 20mmHg), who also has a significantly reduced ejection fraction (EF) in both ventricles (left ventricle (LV): 39% versus 66% and RV: 18% versus 64%). Peak systolic circumferential strain was comparatively lower in both the left ventricle (LV) and RV free wall (RVFW) of the PAH patient (LV: -6.8% versus -13.2% and RVFW: -2.1% versus -9.4%). Passive stiffness, contractility, and myofiber stress in the PAH patient were all found to be substantially increased in both ventricles, whereas septum wall in the PAH patient possessed a smaller curvature than that in the LV free wall. Simulations using the PAH model revealed an approximately linear relationship between the septum curvature and the transseptal pressure gradient at both early-diastole and end-systole. These findings suggest that PAH can induce LV remodeling, and septum curvature measurements may be useful in quantifying transseptal pressure gradient in PAH patients. [ABSTRACT FROM AUTHOR]

With the coming of intelligent vehicles and vehicular communication, Intelligent Transportation Systems (ITS) of connected vehicles are emerging and now evolving to Cooperative-ITS (C-ITS), as service platforms for smart cities. Considering new service properties, the autonomous cooperation of such vehicles has exhibited novel QoS features that imply new requirements: guaranteeing the traffic efficiency of any emergent vehicle while trying to promote the throughput at an intersection. So, after analyzing the classic reservation-based cooperation mechanisms, new QoS-oriented cooperation methods and policies are studied in this work. Concretely, several models of related traffic objects we have proposed are firstly introduced briefly. Then, the scheduling policies of vehicles approaching an intersection have been presented, including three existing policies (FAFP-SV, FAFP-SQ, and HQEP-SV) and five new polices (FAFP-SQ-SV, FAFP-MQ, HWFP-SQ, HWFP-SQ-SV, HWFP-MQ). These policies combine two major factors: vehicular priority for scheduling and concurrency in traffics. The first one includes the vehicular arrival-time, priority mapped to QoS, and the weight of reserved vehicles on a lane etc. In addition, the second refers to schedule a platoon rather than single vehicle each time, or platoons on different lanes instead of one platoon on only one lane. All these policies have been implemented, and further, verified within the parameter-configurable traffic simulator QoS-CITS (v2.1) we designed and developed with C#. Abundant experiments have been conducted with configured typical traffic scenes, and experimental results show that HWFP-SQ-SV and HWFP-MQ can guarantee both the QoS of emergent vehicles and traffic throughput better than other six policies.

Microtubule-associated protein 2 (MAP2) and Tau are abundant neuronal microtubule-associated proteins. Both proteins have highly homologous carboxyl-terminal sequences that function as microtubule-binding domains. Whereas Tau is widely accepted as a pathoetiological factor in human tauopathies, including Alzheimer's disease (AD), it is not known whether there is a relationship between MAP2 and tauopathy. To better understand the pathological roles of MAP2 and Tau, we compared their behaviors in transgenic Caenorhabditis elegans in which MAP2 or Tau was expressed pan-neuronally. Both MAP2 and Tau elicited severe neuronal dysfunction and neuritic abnormalities, despite the absence of detergent-insoluble aggregates in worm neurons. Biochemical analysis revealed that the expressed MAP2 or Tau in worms was highly phosphorylated and did not bind to microtubules. Newly raised antibodies to MAP2 that effectively distinguished between the highly homologous carboxyl-terminal sequences of MAP2 and Tau showed that MAP2 was not involved in the growth process of neurofibrillary tangles in the AD brain. These results indicate that Tau and MAP2 have different fates in the inclusion formation and raise the possibility that MAP2 plays a significant role in neurotoxicity in the AD brain despite the absence of MAP2-aggregates.

Background: Regulatory applications for cell therapy face more objections compared to conventional small molecule or biological drugs, leading to delays in market approval and clinical adoption. Increased regulatory objections frequently relate to issues regarding preclinical evidence, such as experimental design of animal studies, selection of animal models, endpoints, and determination of mechanism of action. Synthesis and clarification of the preclinical evidence necessary to demonstrate treatment efficacy and advance into early-phase clinical trials is needed to help researchers avoid regulatory objections., Methods: We conducted a scoping review in which we searched repositories of the International Council for Harmonisation and all national member organizations (N = 38) for documents related to preclinical studies of cell therapies. Active guidance documents related to cell therapy were included, with no restrictions based on the year or language of publication. Data extraction was conducted in duplicate with conflicts resolved through consensus discussion., Results: From 1215 identified documents, a total of 182 were included and analyzed, with 71% originating from ten major regulatory agencies. The most prevalent preclinical item addressed was the mechanism of action (n = 161, 88% of documents), underscoring its importance in bridging preclinical findings to clinical application. Most documents (n = 140, 77%) emphasized the importance of using clinically relevant preclinical models, though specific recommendations on models of disease were less common (n = 81, 45%). Selection of clinically relevant intervention parameters (n = 136, 75%) and outcome measures (n = 121, 66%) were also frequently recommended, but selection of relevant comparator groups appeared less frequently (n = 35, 19%). Furthermore, robust study design elements such as randomization and blinding were less frequently recommended, appearing in 31% of documents (n = 57). Comparison with clinical trial guidance revealed a significant gap in the rigor of study design recommendations for preclinical research., Conclusions: Regulatory guidance for preclinical efficacy studies often recommends a strong emphasis on the clinical relevance of animal models, intervention parameters, outcomes, and mechanism of action. Incorporating these recommendations into early preclinical studies should improve the acceptability of preclinical evidence for approval by the relevant national regulators and can be used as a guide to ensure that all evidence that regulators say they expect is efficiently assembled into new clinical trial applications., (© 2024. The Author(s).)

Background: An estimated 30% of veterans live with chronic pain, compared to 20% of Canadians in the general population. Veterans face health care challenges upon release from the military, increasing difficulties in obtaining chronic pain care., Aims: We explored experiences of Canadian Armed Forces veterans living with chronic pain, their transition from military to civilian care, perceived barriers and facilitators to chronic pain care, and impacts of their pain on the domains of well-being., Methods: We conducted a qualitative descriptive study using semistructured interviews. We used a deductive/inductive approach to derive themes and concepts from interview transcripts., Results: Thirty-five veterans living with chronic pain participated. Participants reported that pain affected their lives in numerous ways, including negatively impacting relationships and limiting activities of daily living and leisure. They identified barriers to care, including lack of access to family doctors or health care services, reluctance to ask for help, and challenges in obtaining coverage for services from Veterans Affairs Canada. Facilitators included support from other veterans and online resources. Chronic pain had bidirectional effects on domains of well-being., Conclusions: Experiences of pain varied among Canadian veterans, and military culture played a role in perceptions and management of pain. Barriers and facilitators to chronic pain care were highlighted from their time in the military into their transition to civilian care. Participants described the impact of chronic pain on their overall well-being. Determining whether these findings are relevant to a larger population of Canadian veterans will be important for future research and knowledge translation to improve chronic pain care for Canadian veterans., Competing Interests: Moizza Zia Ul Haq has not declared any conflicts of interest. Vahid Ashoorion has not declared any conflicts of interest. Cheng En Xi has not declared any conflicts of interest. Eileen Wang has not declared any conflicts of interest. Natasha Ross has not declared any conflicts of interest. Nandana Parakh has not declared any conflicts of interest. Jason W. Busse is supported, in part, by a CIHR Research Chair in the prevention and management of chronic pain. Andrea J. Darzi has not declared any conflicts of interest. Elizabeth Alvarez has not declared any conflicts of interest., (© 2024 The Author(s). Published with license by Taylor & Francis Group, LLC.)