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This study presents a quad-band stub-incorporated split octagonal ring antenna specifically designed for wireless applications that rely on satellite communication. The antenna is fabricated on an FR4 substrate with dimensions of 26×21×1.6 mm³ and its performance is simulated using the CST EM Studio software. The device operates in the frequency range from 2.15 GHz to 6.35 GHz, using stub integration and gap modification to achieve resonant bands. The antenna has resonant frequencies of 2.23 GHz, 3.28 GHz, 4.77 GHz, and 5.89 GHz, with corresponding bandwidths of 153 MHz, 9011 MHz, 7692 MHz, and 6813 MHz, respectively. The parametric analysis optimizes the values of the design parameters, while the experimental validation shows the consistency between the measured and simulated results. The antenna is characterized by a small size, a consistent radiation pattern and a wide range of applications including ISM, WIFI, WLAN, WIMAX, 5G, and C-Band Satellite. The device is capable of operating in two frequency bands and consistently maintains a gain of over 1 dBi across its resonating range.

Abstract Background Human mitochondrial DNA mutations are associated with common to rare mitochondrial disorders, which are multisystemic with complex clinical pathologies. The pathologies of these diseases are poorly understood and have no FDA-approved treatments leading to symptom management. Leigh syndrome (LS) is a pediatric mitochondrial disorder that affects the central nervous system during early development and causes death in infancy. Since there are no adequate models for understanding the rapid fatality associated with LS, human-induced pluripotent stem cell (hiPSC) technology has been recognized as a useful approach to generate patient-specific stem cells for disease modeling and understanding the origins of the phenotype. Methods hiPSCs were generated from control BJ and four disease fibroblast lines using a cocktail of non-modified reprogramming and immune evasion mRNAs and microRNAs. Expression of hiPSC-associated intracellular and cell surface markers was identified by immunofluorescence and flow cytometry. Karyotyping of hiPSCs was performed with cytogenetic analysis. Sanger and next-generation sequencing were used to detect and quantify the mutation in all hiPSCs. The mitochondrial respiration ability and glycolytic function were measured by the Seahorse Bioscience XFe96 extracellular flux analyzer. Results Reprogrammed hiPSCs expressed pluripotent stem cell markers including transcription factors POU5F1, NANOG and SOX2 and cell surface markers SSEA4, TRA-1-60 and TRA-1-81 at the protein level. Sanger sequencing analysis confirmed the presence of mutations in all reprogrammed hiPSCs. Next-generation sequencing demonstrated the variable presence of mutant mtDNA in reprogrammed hiPSCs. Cytogenetic analyses confirmed the presence of normal karyotype in all reprogrammed hiPSCs. Patient-derived hiPSCs demonstrated decreased maximal mitochondrial respiration, while mitochondrial ATP production was not significantly different between the control and disease hiPSCs. In line with low maximal respiration, the spare respiratory capacity was lower in all the disease hiPSCs. The hiPSCs also demonstrated neural and cardiac differentiation potential. Conclusion Overall, the hiPSCs exhibited variable mitochondrial dysfunction that may alter their differentiation potential and provide key insights into clinically relevant developmental perturbations.

IntroductionParavalvular leak (PVL) is a severe complication of transcatheter aortic valve replacement (TAVR) that can lead to poor outcomes. TAVR-in-TAVR is a promising treatment for PVL; however, reports on its safety or efficacy are limited. In this study, we aimed to investigate the clinical outcomes of TAVR-in-TAVR using balloon-expandable prostheses for PVLs after TAVR.MethodsWe retrospectively analyzed data from patients who underwent TAVR-in-TAVR using balloon-expandable Sapien prostheses for PVL after an initial TAVR at our institution. The procedural success, in-hospital complications, all-cause mortality, and echocardiographic data for up to 2 years post-surgery were evaluated.ResultsIn total, 31 patients with a mean age of 81.1 ± 7.9 years and mean Society of Thoracic Surgeons score of 8.8 ± 5.4% were identified. The procedural success rate of TAVR-in-TAVR was 96.8% (30/31). No in-hospital deaths, cardiac tamponade, or conversion to sternotomy occurred. Re-intervention was performed in only one patient (3.2%) during hospitalization. The all-cause mortality rates at 30 days and 2 years were 0% and 16.1%, respectively. A significant reduction in the PVL rate was observed at 30 days compared with that at baseline (p

IntroductionImmersive virtual reality (VR) based laboratory demonstrations have been gaining traction in STEM education as they can provide virtual hands-on experience. VR can also facilitate experiential and visual learning and enhanced retention. However, several optimizations of the implementation, in-depth analyses of advantages and trade-offs of the technology, and assessment of receptivity of modern techniques in STEM education are required to ensure better utilization of VR-based labs.MethodsIn this study, we developed VR-based demonstrations for a biomolecular engineering laboratory and assessed their effectiveness using surveys containing free responses and 5-point Likert scale-based questions. Insta360 Pro2 camera and Meta Quest 2 headsets were used in combination with an in-person lab. A cohort of 53 students watched the experimental demonstration on VR headsets in the lab after a brief lab overview in person and then performed the experiments in the lab.ResultsOnly 28.29% of students reported experiencing some form of discomfort after using the advanced VR equipment as opposed to 63.63% of students from the previous cohort. About 40% of the students reported that VR eliminated or reduced auditory and visual distractions from the environment, the length of the videos was appropriate, and they received enough information to understand the tasks.DiscussionThe traditional lab method was found to be more suitable for explaining background information and lab concepts while the VR was found to be suitable for demonstrating lab procedures and tasks. Analyzing open-ended questions revealed several factors and recommendations to overcome the potential challenges and pitfalls of integrating VR with traditional modes of learning. This study provides key insights to help optimize the implementation of immersive VR to effectively supplement in-person learning experiences.

Abstract We present a multi-stage neural network approach for 3D reconstruction of coronary artery trees from uncalibrated 2D X-ray angiography images. This method uses several binarized images from different angles to reconstruct a 3D coronary tree without any knowledge of image acquisition parameters. The method consists of a single backbone network and separate stages for vessel centerline and radius reconstruction. The output is an analytical matrix representation of the coronary tree suitable for downstream applications such as hemodynamic modeling of local vessel narrowing (i.e., stenosis). The network was trained using a dataset of synthetic coronary trees from a vessel generator informed by both clinical image data and literature values on coronary anatomy. Our multi-stage network achieved sub-pixel accuracy in reconstructing vessel radius (RMSE = 0.16 ± 0.07 mm) and stenosis radius (MAE = 0.27 ± 0.18 mm), the most important feature used to inform diagnostic decisions. The network also led to 52% and 38% reduction in vessel centerline reconstruction errors compared to a single-stage network and projective geometry-based methods, respectively. Our method demonstrated robustness to overcome challenges such as vessel foreshortening or overlap in the input images. This work is an important step towards automated analysis of anatomic and functional disease severity in the coronary arteries.

Abstract Mesenchymal stem/stromal cells (MSCs) have been carefully examined to have tremendous potential in regenerative medicine. With their immunomodulatory and regenerative properties, MSCs have numerous applications within the clinical sector. MSCs have the properties of multilineage differentiation, paracrine signaling, and can be isolated from various tissues, which makes them a key candidate for applications in numerous organ systems. To accentuate the importance of MSC therapy for a range of clinical indications, this review highlights MSC-specific studies on the musculoskeletal, nervous, cardiovascular, and immune systems where most trials are reported. Furthermore, an updated list of the different types of MSCs used in clinical trials, as well as the key characteristics of each type of MSCs are included. Many of the studies mentioned revolve around the properties of MSC, such as exosome usage and MSC co-cultures with other cell types. It is worth noting that MSC clinical usage is not limited to these four systems, and MSCs continue to be tested to repair, regenerate, or modulate other diseased or injured organ systems. This review provides an updated compilation of MSCs in clinical trials that paves the way for improvement in the field of MSC therapy.

Abstract Background Recent advancements in additive manufacturing have made 3D design a desirable skill in combating the historically slow development of biomedical products. Due to the broad applicability of additive manufacturing to biomedical engineering, 3D design and 3D printing are attractive educational tools for biomedical engineering students. However, due to the multidisciplinary nature of biomedical engineering, finding a suitable spot in the curriculum to teach students basic and application-based skills for 3D manufacturing is difficult. Furthermore, prior training in fundamental 3D design skills may be needed to support the use of application-based supplementary content. Results We designed a SolidWorks Simulations toolkit to complement a sophomore (2nd-year)-level Biomechanics course and distributed this assignment to students with and without prior training in 3D design delivered in an introductory biomedical engineering course. Using short videos, example-based problem solving, and step-by-step tutorials, students completed this as an extra-credit assignment and completed a survey gauging student opinion on SolidWorks and 3D design, confidence in each target skill, and the effectiveness of assignment delivery. The compilation of survey responses suggests that the assignment effectively increased positive responses in student opinion on interest in and likeliness to use SolidWorks in both groups. However, confidence in the target assignment skills was higher in the trained group and fewer problems occurred in operating SolidWorks for trained students. Further, analyzing the distribution of student grades with respect to survey responses suggests that responses had no relationship with initial class grade. Conclusion These data collectively indicate that prior training provided to the students had a positive impact on the effectiveness of the assignment although increases in student opinion on the utility of 3D design were observed in both trained and untrained students. Our work has generated and identified a useful educational supplement to enrich existing biomedical engineering course materials with practical skills.

IntroductionTranscatheter aortic valve intervention (TAVR) has emerged as a promising alternative to surgical aortic valve replacement for patients with severe aortic stenosis. However, leaflet thrombosis has raised concerns about the long-term durability and outcomes of TAVR. This study aims to provide an overview of the mechanisms, prevention strategies, and treatment options for leaflet thrombosis in TAVR.Clinical evidenceLeaflet thrombosis refers to the formation of blood clots on bioprosthetic valve leaflets, leading to impaired leaflet mobility, early valve degeneration and dysfunction, and potential clinical implications. While the mechanisms underlying thrombus formation on valve leaflets are not fully understood, several factors, such as altered blood flow patterns within valve neosinuses, prothrombotic surfaces, and patient-related causes, have been implicated. Two distinct entities have been identified, namely, hypoattenuated leaflet thickening and restricted leaflet motion. Their occurrence appears dynamic over time and is related to the valve type. Imaging, including transesophageal echocardiography and multidetector computed tomography, plays a crucial role in the diagnosis and follow-up of leaflet thrombosis.Prevention and treatment optionsPreventing leaflet thrombosis requires a comprehensive and tailored approach involving identifying high-risk patients, close monitoring, and antithrombotic therapy. Antithrombotic therapy with dual antiplatelet agents or anticoagulation is commonly employed in TAVR patients, although the optimal regimen is yet to be defined. Novel antithrombotic agents, such as direct oral anticoagulants, are being investigated for their efficacy and safety in preventing leaflet thrombosis. When leaflet thrombosis is detected, treatment options include intensified antithrombotic therapy, valve-in-valve intervention, or balloon valvuloplasty. The long-term outcomes and impact of leaflet thrombosis on valve durability and patient prognosis are areas of ongoing research.SummaryLeaflet thrombosis in TAVR is a considerable complication affecting valve function and patient outcomes. Understanding the mechanisms underlying thrombus formation and implementing appropriate prevention strategies are essential for mitigating this risk. Treatment options aim to restore leaflet mobility and optimize valve performance. Further research is needed to establish standardized protocols for antithrombotic therapy, identify high-risk patient populations, and determine the long-term consequences of leaflet thrombosis on TAVR outcomes.

Abstract Background The Covid-19 pandemic caused a sudden shift towards remote learning, moving classes to online formats. Not exempt from this switch, laboratory courses traditionally taught in-person were also moved to remote methods, costing students the opportunity to learn these skills hands-on. In order for instructors to provide course materials effectively and engagingly, non-traditional methods should be explored. Virtual reality (VR) has become more accessible in recent years. VR simulations have been used for many years as educational tools in high-risk settings such as flight or medical simulations. Immersive VR videos implemented in a remote laboratory course could provide the students with an engaging and suitable learning experience. To test the effectiveness of VR videos as a tool for remote education, VR videos of the laboratory component of a Biomolecular Engineering course were provided to students. A survey was distributed for students to self-report their experience with the videos. The survey contained quantitative and qualitative ratings of VR as an educational tool. Results The survey showed that students (~ 89% strongly agree or agree) believed the videos provided the opportunity to work at their own pace and were an appropriate length. While ~ 74% of students said that the videos provided enough information to understand the tasks, a small percentage felt that the videos improved their retention (~ 16%) and understanding (~ 9%) of the course material. About 28% of the students responded positively when asked about how VR videos improved their engagement with the material. ~ 30% reported confidence in applying the skills learned in the videos in the future and ~ 43% believe the VR videos were an acceptable alternative to in-person labs. Two-thirds of students reported feeling some form of discomfort while viewing the VR videos and 54% reported not using the headset for the videos and using the 3D video feature instead. Conclusions As many students reported the videos containing appropriate information, the content of the videos was not an issue. A combination of improved camera quality with motion stability, more comfortable headsets, and a reduction in editing issues could greatly improve the quality and effectiveness of VR videos.

ObjectiveDesign a predictive risk model for minimizing iliofemoral vascular complications (IVC) in a contemporary era of transfemoral-transcatheter aortic valve replacement (TF-TAVR).BackgroundIVC remains a common complication of TF-TAVR despite the technological improvement in the new-generation transcatheter systems (NGTS) and enclosed poor outcomes and quality of life. Currently, there is no accepted tool to assess the IVC risk for calcified and tortuous vessels.MethodsWe reconstructed CT images of 516 propensity-matched TF-TAVR patients using the NGTS to design a predictive anatomical model for IVC and validated it on a new cohort of 609 patients. Age, sex, peripheral artery disease, valve size, and type were used to balance the matched cohort.ResultsIVC occurred in 214 (7.2%) patients. Sheath size (p = 0.02), the sum of angles (SOA) (p 100, in predicting IVC (C-stat 0.936, 95% CI 0.911–0.959, p 1.00 in a tree model increased the overall accuracy to 97.7%. In the validation cohort, the model predicted 89.5% of the IVC cases with an overall 89.5% sensitivity, 98.9% specificity, and 94.2% accuracy (C-stat 0.842, 95% CI 0.904–0.980, p

Background There are limited data on repeat mitral transcatheter edge‐to‐edge repair for recurrent significant mitral regurgitation (MR). Methods and Results We conducted a single‐center, retrospective analysis of consecutive patients referred to a second mitral transcatheter edge‐to‐edge repair after a technically successful first procedure. Clinical, laboratory, and echocardiographic measures were assessed up to 1 year after the intervention. The composite of all‐cause death or heart failure (HF) hospitalizations constituted the primary outcome. A total of 52 patients (median age, 81 [interquartile range, 76–87] years, 29 [55.8%] men, 26 [50.0%] with functional MR) met the inclusion criteria. MR recurrences were mostly related to progression of the underlying cardiac pathology. All procedures were technically successful. At 1 year, most patients with available records (n=24; 96.0%) experienced improvement in MR severity or New York Heart Association functional class that was statistically significant but numerically modest. Fourteen (26.9%) patients died or were hospitalized due to HF. These were higher‐risk cases with predominantly functional MR who mostly underwent an urgent procedure and exhibited more severe HF indices before the intervention, as well as an attenuated 1‐month clinical and echocardiographic response. Overall, 1‐year course was comparable to that experienced by patients who underwent only a first transcatheter edge‐to‐edge repair at our institution (n=902). Tricuspid regurgitation of greater than moderate grade was the only baseline parameter to independently predict the primary outcome. Conclusions Repeat mitral transcatheter edge‐to‐edge repair is feasible, safe, and clinically effective, especially in non‐functional MR patients without concomitant significant tricuspid regurgitation.

The discharge of wastewater into the ecosystem has an impact on fish and human health, therefore the toxins needs to be removed. It is sustainable to remove pollutants from wastewater by utilizing biochar made from lignocellulosic biomass (LCB) that has undergone thermal degradation. Because of it's large surface area, hollow structure, the oxygen groupings, and relatively low cost, bio Char is now known as a change rival in catalytic processes. Biochar was used in conjunction with a number of cutting-edge, creative technologies to treat wastewater efficiently. Details collected soil sampling, such as facts about the toxins current, the nature of the soil, its surrounding circumstances, and the efficacy of various rehabilitation methods, can be used to training machine learning methods. Through data analysis, machine learning models are able to spot relationships and trends which human beings might miss, which improves the accuracy of projections regarding the results of soil cleanup. The review paper outlines the challenges facing biochar-based enzymes using immediate and new technologies, along with emphasizes the application of algorithmic learning in pollution removal. Limitations and likelihoods for additional investigation are examined.

The challenging situations of growing energy consumption, waste collection and destruction of the surroundings had been made greater apparent by means of the explosive rise of the global population and commercial interest. Modern techniques based on the 5R principle (Recycle, Reduce, Reuse, Recover, and Repaired) are critical to efficaciously addressing these problems. One promising way to turn non-recyclable waste into beneficial power assets is waste-to-power (WtE) the conversion method. This work presents a comprehensive evaluation of various WtE technologies, consisting of pyrolysis, gasoline production, anaerobic digestion, and combustion, highlighting their ability to reduce waste associated troubles. Furthermore, as supplementary techniques for sustainable waste control methods, it seems at the combination of progressed waste control (IWM), higher landfill mining, and sustainable substances control (SSM). The impact on the environment of waste-to-power changes are evaluated through a radical evaluation of current research and technology advancements, emphasizing decreases in landfill utilization, GHG emissions, and the promoting of renewable energy resources. The consequences highlight the essential role that WtE generation performs in accomplishing power efficiency improvements, cleaner production, and the development of the round financial structure. Ultimately, the article makes suggestions for future studies initiatives and coverage recommendations intended to optimize the economic and environmental gains from WtE deployments.

The study paper investigates the rapidly evolving field of sustainable design and the increasing acceptance of biodegradable materials in the method of developing products. This research explores the movement towards environmentally conscious designs in light of increased environmental concerns and increasing customer demand for goods that are sustainable. This study addresses a range of biodegradable materials, examining their corresponding characteristics and investigating their integration into product design in various industries. This research discusses some of the challenges encountered in the purchase, production, and promotion of biodegradable products, all the while assuring their practicality and physical appeal. Also, the article examines the environmental consequences linked to these materials, drawing comparisons with traditional non-biodegradable alternatives. This study utilizes a mixture of theoretical analysis and case studies to offer useful insight into efficient techniques for implementing materials that decompose into product design. The research places a strong focus on achieving an equilibrium between ecological responsibility, practicality, and appealing to consumers.

(1) Background Pharmacological treatment for psychiatric disorders has shown to only be effective in about one-third of patients, as it is associated with frequent treatment failure, often because of side effects, and a long process of trial-and-error pharmacotherapy until an effective and tolerable treatment is found. This notion emphasizes the urgency for a personalized medicine approach in psychiatry. (2) Methods This prospective patient- and rater-blinded, randomized, controlled study will investigate the effect of dose-adjustment of antidepressants escitalopram and sertraline or antipsychotics risperidone and aripiprazole according to the latest state-of-the-art international dosing recommendations for CYP2C19 and CYP2D6 metabolizer status in patients with mood, anxiety, and psychotic disorders. A total sample of N = 2500 will be recruited at nine sites in seven countries (expected drop-out rate of 30%). Patients will be randomized to a pharmacogenetic group or a dosing-as-usual group and treated over a 24-week period with four study visits. The primary outcome is personal recovery using the Recovery Assessment Scale as assessed by the patient (RAS-DS), with secondary outcomes including clinical effects (response or symptomatic remission), side effects, general well-being, digital phenotyping, and psychosocial functioning. (3) Conclusions This is, to our knowledge, the first international, multi-center, non-industry-sponsored randomized controlled trial (RCT) that may provide insights into the effectiveness and utility of implementing pharmacogenetic-guided treatment of psychiatric disorders, and as such, results will be incorporated in already available dosing guidelines.

Background: The optimal antithrombotic therapy after transcatheter aortic valve replacement (TAVR) is controversial. We performed a systematic review and meta-analysis of randomized controlled trials comparing high-intensity vs. low-intensity antithrombotic therapy after TAVR in the absence of an established indication for anticoagulation. Methods: The primary efficacy and safety endpoints were a composite of death or thromboembolic events and Valve Academic Research Consortium 2–defined significant bleeding, respectively. All analyses were by intention to treat. Risk ratios (RRs) were calculated using the inverse variance random-effects model. Results: Four studies comprising 3358 patients (mean age 81 years, mean Society of Thoracic Surgery score 3.3%) were identified. Two studies compared anticoagulation vs. antiplatelet therapy after TAVR; the other 2 trials compared dual-antiplatelet therapy vs. mono-antiplatelet therapy after TAVR. The incidence of death or thromboembolic events (RR 0.66 [95% confidence interval (CI) 0.55-0.80], p < 0.0001, I2 = 0%), death (RR 0.68 [95% CI 0.51-0.92], I2 = 11%, p = 0.01), and Valve Academic Research Consortium 2–defined major bleeding (RR 0.69 [95% CI 0.48 - 1.00], p = 0.003, I2 = 44%) was significantly lower in patients on low-intensity antithrombotic therapy than in those on high-intensity antithrombotic therapy. Conclusions: In an elderly patient population undergoing TAVR, routine initiation of a high-intensity antithrombotic therapy in the absence of a clinical indication for anticoagulation was associated with increased risk of death or thromboembolic complications, increased risk of death, and increased risk of significant bleeding. Routine initiation of an anticoagulation therapy or dual-antiplatelet therapy after TAVR in the absence of an established indication for anticoagulation may not be advisable.

BackgroundThere are scarce data regarding the post-mitral transcatheter edge-to-edger repair (TEER) course in different racial groups.ObjectiveTo assess the impact of race on outcomes following TEER for mitral regurgitation (MR).MethodsThis is a single-center, retrospective analysis of consecutive TEER procedures performed during 2013–2020. The primary outcome was the composite of all-cause mortality or heart failure (HF) hospitalizations along the first postprocedural year. Secondary outcomes included individual components of the primary outcome, New York Heart Association (NYHA) class, MR grade, and left ventricular mass index (LVMi).ResultsOut of 964 cases, 751 (77.9%), 88 (9.1%), 68 (7.1%), and 57 (5.9%) were whites, blacks, Asians, and Hispanics, respectively. At baseline, non-whites and blacks were younger and more likely be female, based in lower socioeconomic areas, not fully insured, diagnosed with functional MR, and affected by biventricular dysfunction. Intra-procedurally, more devices were implanted in blacks. At 1-year, non-whites (vs. whites) and blacks (vs. non-blacks or whites) experienced higher cumulative incidence of the primary outcome (32.9% vs. 22.5%, p = 0.002 and 38.6% vs. 23.4% or 22.5%, p = 0.002 or p = 0.001, respectively), which were accounted for by hospitalizations in the functional MR sub-cohort (n = 494). NYHA class improved less among blacks with functional MR. MR severity and LVMi equally regressed in all groups. White race (HR 0.62, 95% CI 0.39–0.99, p = 0.047) and black race (HR 2.07, 95% CI 1.28–3.35, p = 0.003) were independently associated with the primary outcome in functional MR patients only.ConclusionMitral TEER patients of different racial backgrounds exhibit major differences in baseline characteristics. Among those with functional MR, non-whites and blacks also experience a less favorable 1-year clinical outcome.

Primary congenital glaucoma (PCG) is characterised by increased intraocular pressure, and variants in ANGPT1, or SVEP1 have been identified as risk alleles. Here, the authors show that deletion of these genes induces glaucoma in mice, and that activation of ANGPT1-TEK signaling ameliorates disease progression in mouse models.

Abstract Coronary Artery Disease (CAD) is commonly diagnosed using X-ray angiography, in which images are taken as radio-opaque dye is flushed through the coronary vessels to visualize the severity of vessel narrowing, or stenosis. Cardiologists typically use visual estimation to approximate the percent diameter reduction of the stenosis, and this directs therapies like stent placement. A fully automatic method to segment the vessels would eliminate potential subjectivity and provide a quantitative and systematic measurement of diameter reduction. Here, we have designed a convolutional neural network, AngioNet, for vessel segmentation in X-ray angiography images. The main innovation in this network is the introduction of an Angiographic Processing Network (APN) which significantly improves segmentation performance on multiple network backbones, with the best performance using Deeplabv3+ (Dice score 0.864, pixel accuracy 0.983, sensitivity 0.918, specificity 0.987). The purpose of the APN is to create an end-to-end pipeline for image pre-processing and segmentation, learning the best possible pre-processing filters to improve segmentation. We have also demonstrated the interchangeability of our network in measuring vessel diameter with Quantitative Coronary Angiography. Our results indicate that AngioNet is a powerful tool for automatic angiographic vessel segmentation that could facilitate systematic anatomical assessment of coronary stenosis in the clinical workflow.

BackgroundThere is growing evidence of the safety of same-day discharge for low-risk conscious sedated TAVR patients. However, the evidence supporting the safety of early discharge following GA-TAVR with routine transesophageal echocardiography (TEE) is limited.AimsTo assess the safety of early discharge following transcatheter aortic valve replacement (TAVR) using General Anesthesia (GA-TAVR) and identify predictors for patient selection.Materials and methodsWe used data from 2,447 TEE-guided GA-TAVR patients performed at Cedars-Sinai between 2016 and 2021. Patients were categorized into three groups based on the discharge time from admission: 24 h, 24–48 h, and >48 h. Predictors for 30-day outcomes (cumulative adverse events and death) were validated on a matched cohort of 24 h vs. >24 h using the bootstrap model.ResultsThe >48 h group had significantly worse baseline cardiovascular profile, higher surgical risk, low functional status, and higher procedural complications than the 24 h and the 24–48 h groups. The rate of 30-day outcomes was significantly lower in the 24 h than the >48 h but did not differ from the 24–48 h (11.3 vs. 15.5 vs. 11.7%, p = 0.003 and p = 0.71, respectively). Independent poor prognostic factors of 30-day outcomes had a high STS risk of ≥8 (OR 1.90, 95% CI 1.30–2.77, E-value = 3.2, P < 0.001), low left ventricle ejection fraction of

ObjectiveTo assess the incidence of new adverse coronary events (NACE) following transcatheter aortic valve replacement (TAVR) and valve-in-valve TAVR (ViV-TAVR).BackgroundViV-TAVR is an accepted treatment for degenerative prostheses among patients with high surgical-risk. TAVR studies have suggested an increased risk of coronary artery obstruction and flow stasis causing thrombus formation. Whether contemporary ViV-TAVR is associated with higher rate of coronary events compared to TAVR is unknown.MethodsWe used data from 1,224 TAVR patients between 2016 and 2021. We propensity-matched patients following ViV-TAVR and TAVR by significant predictors to overcome confounders in patients' baseline characteristics and procedural factors.ResultsThe matched population included 129 patients in each group. In line with prior reports, there was a higher in-hospital coronary artery obstruction rate with ViV-TAVR (3.1 vs. 1.6%; p = 0.23). Despite this, 2-year cumulative NACE rates were similar between groups (4.7 vs. 6.2%, respectively, p = 0.79), with no difference between its components: myocardial infarction (MI) (p = 0.210), unplanned coronary catheterization (p = 0.477), or coronary artery bypass grafting (CABG) (p = 0.998). Moreover, hypoattenuated leaflets thickening (HALT) at 30-day CT was observed in nearly a quarter of the patients with no difference between groups (23.9 vs. 23.1%, HR 1.02, 95% CI 0.50–1.28, p = 0.872). The progression rate of the coronary artery calcium score (CACS), assessed in a third of patients, was similar between groups (p log-rank = 0.468, 95% CI 0.12–1.24). Low coronary artery height was an unfavorable predictor for in-hospital coronary obstruction and 2-year NACE rate (HR 1.20 and HR 1.25, p = 0.001 and p < 0.0001, respectively).ConclusionAt 2-year follow-up, ViV-TAVR was not associated with a higher rate of myocardial infarction, unplanned catheterization, coronary artery bypass grafting, or hypoattenuated leaflet thickening.

BackgroundIn people with cognitive impairment, loss of social interactions has a major impact on well-being. Therefore, patients would benefit from early detection of symptoms of social withdrawal. Current measurement techniques such as questionnaires are subjective and rely on recall, in contradiction to smartphone apps, which measure social behavior passively and objectively. ObjectiveThis study uses the remote monitoring smartphone app Behapp to assess social behavior, and aims to investigate (1) the association between social behavior, demographic characteristics, and neuropsychiatric symptoms in cognitively normal (CN) older adults, and (2) if social behavior is altered in cognitively impaired (CI) participants. In addition, we explored in a subset of individuals the association between Behapp outcomes and neuropsychiatric symptoms. MethodsCN, subjective cognitive decline (SCD), and CI older adults installed the Behapp app on their own Android smartphone for 7 to 42 days. CI participants had a clinical diagnosis of mild cognitive impairment (MCI) or Alzheimer-type dementia. The app continuously measured communication events, app use and location. Neuropsychiatric Inventory (NPI) total scores were available for 20 SCD and 22 CI participants. Linear models were used to assess group differences on Behapp outcomes and to assess the association of Behapp outcomes with the NPI. ResultsWe included CN (n=209), SCD (n=55) and CI (n=22) participants. Older cognitively normal participants called less frequently and made less use of apps (P

Background Controversy exists over whether sex has significant interaction with revascularization strategy for unprotected left main coronary artery disease. Higher mortality has been reported among women treated with percutaneous coronary intervention compared with coronary artery bypass grafting. Methods and Results The DELTA (Drug‐Eluting Stents for Left Main Coronary Artery Disease) and DELTA‐2 registries are international, multicentric registries evaluating the outcomes of subjects undergoing coronary revascularization for unprotected left main coronary artery disease. The primary outcome was a composite of death, myocardial infarction, or cerebrovascular accidents. The population consisted of 6253 patients, including 1689 (27%) women. Women were older and more likely to have diabetes and chronic kidney disease than men (P

Human mesenchymal stromal cells (hMSCs) are multipotent cells that have been proposed for cell therapies due to their immunosuppressive capacity that can be enhanced in the presence of interferon-gamma (IFN-γ). In this study, multilayers of heparin (HEP) and collagen (COL) (HEP/COL) were used as a bioactive surface to enhance the immunomodulatory activity of hMSCs using soluble IFN-γ. Multilayers were formed, via layer-by-layer assembly, varying the final layer between COL and HEP and supplemented with IFN-γ in the culture medium. We evaluated the viability, adhesion, real-time growth, differentiation, and immunomodulatory activity of hMSCs on (HEP/COL) multilayers. HMSCs viability, adhesion, and growth were superior when cultured on (HEP/COL) multilayers compared to tissue culture plastic. We also confirmed that hMSCs osteogenic and adipogenic differentiation remained unaffected when cultured in (HEP/COL) multilayers in the presence of IFN-γ. We measured the immunomodulatory activity of hMSCs by measuring the level of indoleamine 2,3-dioxygenase (IDO) expression. IDO expression was higher on (HEP/COL) multilayers treated with IFN-γ. Lastly, we evaluated the suppression of peripheral blood mononuclear cell (PBMC) proliferation when co-cultured with hMSCs on (HEP/COL) multilayers with IFN-γ. hMSCs cultured in (HEP/COL) multilayers in the presence of soluble IFN-γ have a greater capacity to suppress PBMC proliferation. Altogether, (HEP/COL) multilayers with IFN-γ in culture medium provides a potent means of enhancing and sustaining immunomodulatory activity to control hMSCs immunomodulation.

Mitochondria are dynamic organelles with wide range of morphologies contributing to regulating different signaling pathways and several cellular functions. Leigh syndrome (LS) is a classic pediatric mitochondrial disorder characterized by complex and variable clinical pathologies, and primarily affects the nervous system during early development. It is important to understand the differences between mitochondrial morphologies in healthy and diseased states so that focused therapies can target the disease during its early stages. In this study, we performed a comprehensive analysis of mitochondrial dynamics in five patient-derived human induced pluripotent stem cells (hiPSCs) containing different mutations associated with LS. Our results suggest that subtle alterations in mitochondrial morphologies are specific to the mtDNA variant. Three out of the five LS-hiPSCs exhibited characteristics consistent with fused mitochondria. To our knowledge, this is the first comprehensive study that quantifies mitochondrial dynamics in hiPSCs specific to mitochondrial disorders. In addition, we observed an overall decrease in mitochondrial membrane potential in all five LS-hiPSCs. A more thorough analysis of the correlations between mitochondrial dynamics, membrane potential dysfunction caused by mutations in the mtDNA in hiPSCs and differentiated derivatives will aid in identifying unique morphological signatures of various mitochondrial disorders during early stages of embryonic development.

Background Most cell therapy trials failed to show an improvement in global left ventricular (LV) function measures after myocardial infarction (MI). Myocardial segments are heterogeneously impacted by MI. Global LV function indices are not able to detect the small treatment effects on segmental myocardial function which may have prognostic implications for cardiac events. We aimed to test the efficacy of allogeneic cardiosphere-derived cells (CDCs) for improving regional myocardial function and contractility.Methods In this exploratory analysis of a randomised clinical trial, 142 patients with post-MI with LVEF

Background: Digital technologies have the potential to provide objective and precise tools to detect depression-related symptoms. Deployment of digital technologies in clinical research can enable collection of large volumes of clinically relevant data that may not be captured using conventional psychometric questionnaires and patient-reported outcomes. Rigorous methodology studies to develop novel digital endpoints in depression are warranted.Objective: We conducted an exploratory, cross-sectional study to evaluate several digital technologies in subjects with major depressive disorder (MDD) and persistent depressive disorder (PDD), and healthy controls. The study aimed at assessing utility and accuracy of the digital technologies as potential diagnostic tools for unipolar depression, as well as correlating digital biomarkers to clinically validated psychometric questionnaires in depression.Methods: A cross-sectional, non-interventional study of 20 participants with unipolar depression (MDD and PDD/dysthymia) and 20 healthy controls was conducted at the Centre for Human Drug Research (CHDR), the Netherlands. Eligible participants attended three in-clinic visits (days 1, 7, and 14), at which they underwent a series of assessments, including conventional clinical psychometric questionnaires and digital technologies. Between the visits, there was at-home collection of data through mobile applications. In all, seven digital technologies were evaluated in this study. Three technologies were administered via mobile applications: an interactive tool for the self-assessment of mood, and a cognitive test; a passive behavioral monitor to assess social interactions and global mobility; and a platform to perform voice recordings and obtain vocal biomarkers. Four technologies were evaluated in the clinic: a neuropsychological test battery; an eye motor tracking system; a standard high-density electroencephalogram (EEG)-based technology to analyze the brain network activity during cognitive testing; and a task quantifying bias in emotion perception.Results: Our data analysis was organized by technology – to better understand individual features of various technologies. In many cases, we obtained simple, parsimonious models that have reasonably high diagnostic accuracy and potential to predict standard clinical outcome in depression.Conclusion: This study generated many useful insights for future methodology studies of digital technologies and proof-of-concept clinical trials in depression and possibly other indications.

To present our 12-year experience using an endoscopic approach to manage bladder neck contracture (BNC) without adjunctive intralesional agents and compare it to published series not incorporating them, we retrospectively reviewed 123 patients treated for BNC from 2008 to 2020. All underwent 24 Fr balloon dilation followed by transurethral incision of BNC (TUIBNC) with deep incisions at 3 and 9 o’clock using a Collins knife without the use of intralesional injections. Success was defined as a patent bladder neck and 16 Fr cystoscope passage into the bladder two months later. Most with recurrent BNC underwent repeat TUIBNC. Success rates, demographics, and BNC characteristics were analyzed. The etiology of BNC in our cohort was most commonly radical prostatectomy with or without radiation (36/123, 29.3%, 40/123, 32.5%). Some had BNC treatment prior to referral (30/123, 24.4%). At 12-month follow-up, bladder neck patency was observed in 101/123 (82.1%) after one TUIBNC. An additional 15 patients (116/123, 94.3%) had success after two TUIBNCs. On univariate and multivariate analyses, ≥2 endoscopic treatments was the only factor associated with failure. TUIBNC via balloon dilation and deep bilateral incisions without the use of adjunctive intralesional injections has a high patency rate. History of two or more prior endoscopic procedures is associated with failure.

Background Gait speed is a reliable measure of physical function and frailty in patients with aortic stenosis undergoing transcatheter aortic valve replacement (TAVR). Slow gait speed pre‐TAVR predicts worse clinical outcomes post‐TAVR. The consequences of improved versus worsened physical function post‐TAVR are unknown. Methods and Results The REPRISE III (Repositionable Percutaneous Replacement of Stenotic Aortic Valve Through Implantation of Lotus Valve System–Randomized Clinical Evaluation) trial randomized high/extreme risk patients to receive a mechanically‐expanded or self‐expanding transcatheter heart valve. Of 874 patients who underwent TAVR, 576 with complete data at baseline and 1 year were included in this analysis. Slow gait speed in the 5‐m walk test was defined as

Background As transcatheter aortic valve replacement (TAVR) is expected to progress into younger patient populations, valve‐in‐TAVR (ViTAVR) may become a frequent consideration. Data on ViTAVR, however, are limited. This study investigated the outcome of ViTAVR in comparison to valve in surgical aortic valve replacement (ViSAVR), because ViSAVR is an established procedure for higher‐risk patients requiring repeated aortic valve intervention. Methods and Results Clinical and procedural data of patients who underwent ViTAVR at 3 sites in the United States and Germany were retrospectively compared with data of patients who underwent ViSAVR at Cedars‐Sinai Medical Center, according to Valve Academic Research Consortium‐2 criteria. A total of 99 consecutive patients, 52.5% women, with a median Society of Thoracic Surgeons score of 7.2 were identified. Seventy‐four patients (74.7%) underwent ViSAVR, and 25 patients (25.3%) underwent ViTAVR. Balloon‐expandable devices were used in 72.7%. ViSAVR patients presented with smaller index devices (21.0 versus 26.0 mm median true internal diameter; P

Pancreatic ductal adenocarcinoma (PDAC) is a major cause of cancer-related death, with a 5-year survival of

Background As transcatheter aortic valve replacement expands to younger and/or lower risk patients, the long‐term consequences of permanent pacemaker implantation are a concern. Pacemaker dependency and impact have not been methodically assessed in transcatheter aortic valve replacement trials. We report the incidence and predictors of pacemaker implantation and pacemaker dependency after transcatheter aortic valve replacement with the Lotus valve. Methods and Results A total of 912 patients with high/extreme surgical risk and symptomatic aortic stenosis were randomized 2:1 (Lotus:CoreValve) in REPRISE III (The Repositionable Percutaneous Replacement of Stenotic Aortic Valve through Implantation of Lotus Valve System—Randomized Clinical Evaluation) trial. Systematic assessment of pacemaker dependency was pre‐specified in the trial design. Pacemaker implantation within 30 days was more frequent with Lotus than CoreValve. By multivariable analysis, predictors of pacemaker implantation included baseline right bundle branch block and depth of implantation; diabetes mellitus was also a predictor with Lotus. No association between new pacemaker implantation and clinical outcomes was found. Pacemaker dependency was dynamic (30 days: 43%; 1 year: 50%) and not consistent for individual patients over time. Predictors of pacemaker dependency at 30 days included baseline right bundle branch block, female sex, and depth of implantation. No differences in mortality or stroke were found between patients who were pacemaker dependent or not at 30 days. Rehospitalization was higher in patients who were not pacemaker dependent versus patients without a pacemaker or those who were dependent. Conclusions Pacemaker implantation was not associated with adverse clinical outcomes. Most patients with a new pacemaker at 30 days were not dependent at 1 year. Mortality and stroke were similar between patients with or without pacemaker dependency and patients without a pacemaker. Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier NCT02202434.

Cardiovascular diseases are the leading cause of death worldwide. A completely autologous treatment can be achieved by using elastogenic mesenchymal stem cell (MSC)-derived smooth muscle cells (SMC) at the affected tissue site of vascular diseases such as abdominal aortic aneurysms (AAA). Thus, our work focused on evaluating the efficacy of (a) the combination of various growth factors, (b) different time periods and (c) different MSC lines to determine the treatment combination that generated SMCs that exhibited the greatest elastogenicity among the tested groups using Western blotting and flow cytometry. Additionally, total RNA sequencing was used to confirm that post-differentiation cells were upregulating SMC-specific gene markers. Results indicated that MSCs cultured for four days in PDGF + TGFβ1 (PT)-infused differentiation medium showed significant increases in SMC markers and decreases in MSC markers compared to MSCs cultured without differentiation factors. RNA Seq analysis confirmed the presence of vascular smooth muscle formation in MSCs differentiated in PT medium over a seven-day period. Overall, our results indicated that origin, growth factor treatment and culture period played a major role in influencing MSC differentiation to SMCs.

Mitochondrial disorders represent a large group of severe genetic disorders mainly impacting organ systems with high energy requirements. Leigh syndrome (LS) is a classic example of a mitochondrial disorder resulting from pathogenic mutations that disrupt oxidative phosphorylation capacities. Currently, evidence-based therapy directed towards treating LS is sparse. Recently, the cell-permeant substrates responsible for regulating the electron transport chain have gained attention as therapeutic agents for mitochondrial diseases. We explored the therapeutic effects of introducing tricarboxylic acid cycle (TCA) intermediate substrate, succinate, as a cell-permeable prodrug NV118, to alleviate some of the mitochondrial dysfunction in LS. The results suggest that a 24-hour treatment with prodrug NV118 elicited an upregulation of glycolysis and mitochondrial membrane potential while inhibiting intracellular reactive oxygen species in LS cells. The results from this study suggest an important role for TCA intermediates for treating mitochondrial dysfunction in LS. We show, here, that NV118 could serve as a therapeutic agent for LS resulting from mutations in mtDNA in complex I and complex V dysfunctions.

The recent and exciting discovery of germline HOXB13 mutations in familial prostate cancer has brought HOX signaling to the forefront of prostate cancer research. An enhanced understanding of HOX signaling, and the co-factors regulating HOX protein specificity and transcriptional regulation, has the high potential to elucidate novel approaches to prevent, diagnose, stage, and treat prostate cancer. Toward our understanding of HOX biology in prostate development and prostate cancer, basic research in developmental model systems as well as other tumor sites provides a mechanistic framework to inform future studies in prostate biology. Here we describe our current understanding of HOX signaling in genitourinary development and cancer, current clinical data of HOXB13 mutations in multiple cancers including prostate cancer, and the role of HOX protein co-factors in development and cancer. These data highlight numerous gaps in our understanding of HOX function in the prostate, and present numerous potentially impactful mechanistic and clinical opportunities for future investigation.

Data is growing at an enormous rate in the present world. One of the finest and most popular technologies available for handling and processing that enormous amount of data is the Hadoop ecosystem. Enterprises are increasingly relying on Hadoop for storing their valuable data and processing it. However, Hadoop is still evolving. There is much vulnerability found in Hadoop, which can question the security of the sensitive information that enterprises are storing on it. In this paper, security issues associated with the framework have been identified. We have also tried to give a brief overview of the currently available solutions and what are their limitations. At the end a novel method is introduced, which can be used to eliminate the found vulnerabilities in the framework. In the modern era, information security has become a fundamental necessity for each and every individual. However, not everyone can afford the specialized distributions provided by different vendors to their Hadoop cluster. This paper presents a cost-effective technique that anyone can use with their Hadoop cluster to give it 3-D security.

Background: In India, an estimated 100-220 per million populations reach Chronic Kidney Disease (CKD) stage 5, but only 10% of them can afford to renal replacement therapy. Recent research has shown that there is increased mental health morbidity with attendant poor quality of life in this patient population. Very few studies have been done in this aspect in the Indian population. Aims: We aimed to study the psychiatric morbidity in hemodialysis patients, who were undergoing regular hemodialysis for CKD. The study was carried out at the Hemodialysis Unit of the Department of Nephrology, SRM Medical College Hospital, one of the largest centers in South India. Methodology: Study patients (n=100) were administered Mini Mental Status Examination, MINI - English version 5.0.0 for DSM IV, Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, Beck's Scale For Suicidal Ideation, Perceived social support scale and The Kidney Disease Quality Of Life (KD-QOL)SF 36 and the results were analyzed. Results: Seventy eight percent (78%) of patients suffer more than one psychiatric morbidity. Depression (74%) was the most common psychiatric morbidity followed by anxiety (59%). Elderly male patients living in nuclear family, undergoing hemodialysis had significant depression, anxiety and cognitive impairment. 83% reported poor quality of life while coping with regular hemodialysis. Conclusion: Our results show that psychiatric disorders are highly prevalent in hemodialysis patients, with attendant poor quality of life. An integrated approach between medical and mental health professionals will help improve the quality of life.

Objective: The purpose of our study was to determine whether there is a correlation between the lower limb rotational profile and tibial tuberosity-trochlea groove (TT-TG) distance. Design and patients: The computed tomography cross-sectional imaging on 50 patients’ lower limbs (100 limbs) was investigated at our institution. The TT-TG distance was measured along with rotational measurements including femoral version (FV), tibial torsion and knee joint rotation angle (KJRA). Patients were divided into two groups. Group 1 had a TT-TG ≥ 20 mm which was considered pathological and group 2 with a non-pathological TT-TG (≤19 mm). Rotational angles were compared between groups. Statistical analysis was performed using the t -test and Mann–Whitney U analysis. Results and conclusions: Our results demonstrated a statistically significant difference in the mean KJRA ( p = 0.026) between the pathological (mean = 10.6, standard deviation (SD) = 7.79°) and the non-pathological TT-TG groups (mean = 6.99, SD = 5.06°). A higher mean value for FV and tibial torsion was also demonstrated in patients with a pathological TT-TG (18.2 vs. 13.7, 32.8 vs. 30.9, p > 0.05, respectively). In conclusion, there was a statistically significant higher mean value for the KJRA in patients with a pathological TT-TG. Hence, a lateralized tibial tubercle as demonstrated by an increase in the TT-TG distance may be associated with a coexisting lower limb rotational malalignment.

Abstract Over the past two decades, the biological engineering research community has increased its efforts to promote ‘Convergence’. Many research endeavors have thus involved the synergy of multiple perspectives and approaches from originally distinct fields towards driving creative innovative solutions to address many grand challenges that face our society. Here, we introduce the JBE thematic series on emerging leaders in biological engineering. The aim of the series is to disseminate the latest developments in research that integrate the principles of biology and engineering methodologies to address grand challenges in human health and the health of the planet. This thematic series highlights exciting new areas and emerging leaders who are addressing many of these challenges.