Search

Abstract Existing risk prediction models for hospitalized heart failure patients are limited. We identified patients hospitalized with a diagnosis of heart failure between 7 May 2013 and 26 April 2022 from a large academic, quaternary care medical centre (training cohort). Demographics, medical comorbidities, vitals, and labs were collected and were used to construct random forest machine learning models to predict in‐hospital mortality. Models were compared with logistic regression, and to commonly used heart failure risk scores. The models were subsequently validated in patients hospitalized with a diagnosis of heart failure from a second academic, community medical centre (validation cohort). The entire cohort comprised 21 802 patients, of which 14 539 were in the training cohort and 7263 were in the validation cohort. The median age (25th–75th percentile) was 70 (58–82) for the entire cohort, 43.2% were female, and 6.7% experienced inpatient mortality. In the overall cohort, 7621 (35.0%) patients had heart failure with reduced ejection fraction (EF ≤ 40%), 1271 (5.8%) had heart failure with mildly reduced EF (EF 41–49%), and 12 910 (59.2%) had heart failure with preserved EF (EF ≥ 50%). Random forest models in the validation cohort demonstrated a c‐statistic (95% confidence interval) of 0.96 (0.95–0.97), sensitivity (SN) of 87.3%, and specificity (SP) of 90.6% for the prediction of in‐hospital mortality. Models for those with HFrEF demonstrated a c‐statistic of 0.96 (0.94–0.98), SN 88.2%, and SP 91.0%, and those for patients with HFpEF showed a c‐statistic of 0.95 (0.93–0.97), SN 87.4%, and SP 89.5% for predicting in‐hospital mortality. The random forest model significantly outperformed logistic regression (c‐statistic 0.87, SN 75.9%, and SP 86.9%), and current existing risk scores including the Acute Decompensated Heart Failure National Registry risk score (c‐statistic of 0.70, SN 69%, and SP 62%), and the Get With the Guidelines‐Heart Failure risk score (c‐statistic 0.69, SN 67%, and SP 63%); P

Abstract Patient‐derived xenografts (PDX) involve transplanting patient cells or tissues into immunodeficient mice, offering superior disease models compared with cell line xenografts and genetically engineered mice. In contrast to traditional cell‐line xenografts and genetically engineered mice, PDX models harbor the molecular and biologic features from the original patient tumor and are generationally stable. This high fidelity makes PDX models particularly suitable for preclinical and coclinical drug testing, therefore better predicting therapeutic efficacy. Although PDX models are becoming more useful, the several factors influencing their reliability and predictive power are not well understood. Several existing studies have looked into the possibility that PDX models could be important in enhancing our knowledge with regard to tumor genetics, biomarker discovery, and personalized medicine; however, a number of problems still need to be addressed, such as the high cost and time‐consuming processes involved, together with the variability in tumor take rates. This review addresses these gaps by detailing the methodologies to generate PDX models, their application in cancer research, and their advantages over other models. Further, it elaborates on how artificial intelligence and machine learning were incorporated into PDX studies to fast‐track therapeutic evaluation. This review is an overview of the progress that has been done so far in using PDX models for cancer research and shows their potential to be further improved in improving our understanding of oncogenesis.

Abstract Preeclampsia, a hypertensive disorder of pregnancy, poses significant risks to maternal and fetal health. Recent research highlights the potential of vertical circulating exosomes (VCEs) as biomarkers for early detection and monitoring of preeclampsia. Exosomes, small extracellular vesicles involved in intercellular communication, carry bioactive molecules that are messengers of the parental cell status (healthy or undergoing any pathological condition). In preeclampsia, alterations in the cargo of VCEssuch as proteins, lipids, and nucleic acids play the role of biomarkers in pathophysiology complications. These exosomal contents can provide insights into the underlying mechanisms, including endothelial dysfunction, immune response dysregulation, and placental abnormalities. Early identification of specific exosomal biomarkers may facilitate timely therapeutic interventions, improving outcomes for both mother and child. This article explores the emerging role of VCEs in preeclampsia, emphasizing their diagnostic and prognostic potential, and underscores the need for further research to validate these biomarkers and integrate them into clinical practice.

Abstract Exosomes are signalling molecules related to cell‐to‐cell communication. Based on sources (plants, stem cells, and immune cells derived exosomes) it offers promising therapeutic activity against cancer. Plant‐derived exosomes (PDEs) are natural extracellular vesicles (EVs) that are potent to provide organic precision nanomedicine to cancer therapeutics including targeted drug delivery. PDEs are gaining attention due to their safety and efficacy. There are plenty of different sources of PDEs in nature. This article explores various plants such as carrots, ginger, lemons, cabbages, blueberries, oranges, tomatoes, grapefruits, and tea leaves, which provide exosomes with distinct therapeutic properties, including anti‐inflammatory, antioxidant, and anticancer activities. PDEs exhibit significant potential in drug delivery. Ongoing research and clinical trials predict that PDEs will become effective, and affordable solutions for cancer treatment.

Abstract Pemphigoid, a rare autoimmune skin disease affecting the elderly, requires effective pharmacy management. This includes medication therapy, patient education, and counseling. Understanding pharmacokinetics and potential drug interactions are crucial for optimal treatment and minimizing adverse effects. In this case, the patient is a 65‐year‐old male who was diagnosed with pemphigoid 2 months ago. He is currently taking prednisone, an oral corticosteroid, to manage the symptoms. The pharmacist plays a crucial role in medication therapy by monitoring the patient's response to the medication and adjusting the dosage if necessary. Additionally, patient education is vital in ensuring that the patient understands the importance of adherence to the medication regimen and the potential side effects. The pharmacist can also provide counseling on lifestyle modifications and self‐care measures to alleviate symptoms and improve the quality of life. Overall, effective pharmacy management is essential for optimizing treatment outcomes and promoting patient well‐being in pemphigoid cases. The pharmacist's role in pemphigoid cases is crucial for effective medication management and patient education. They monitor the patient's response to treatment, make necessary adjustments, and empower them to take an active role in managing their condition. This approach ultimately improves the overall well‐being of patients with pemphigoid.

Abstract Electric Vehicles (EV) have the potential to completely transform the transportation industry, reduce carbon emissions significantly, and pave the road for significant climate progress. According to surveys, worries regarding range and charging accessibility are a significant barrier to EV customer adoption. The electricity grid will be significantly impacted by EV charging. A coordinated charging approach that facilitates EV charging while avoiding the power grid from overloading is required to manage EV charging. In this work, the EVs are classified based on their charging capacity. This classification includes car, truck, and bus. With this a charging discharging scheme has been established using Real Time Pricing for each hour for a 20‐min block. The Voltage Stability Index (VSI) for the system is calculated for the system and the strongest bus is identified for locating the EVs to charge/discharge. Augmenting this, in the present work, the power loss is analyzed when Distributed Generation (DG) units are installed after the EVs are located in the system for charging and discharging. The DG units are installed in each feeder, considering the VSI and Penetration Level (PL) and the power losses incurred due to the presence of EVs. The Monetary benefit of such an investment is analyzed for different topologies of IEEE‐33 and 69 bus systems and compared with the existing methods where DGs are installed before the EVs are located in the system for charging and discharging.

Molecular subtyping is essential to infer tumor aggressiveness and predict prognosis. In practice, tumor profiling requires in‐depth knowledge of bioinformatics tools involved in the processing and analysis of the generated data. Additionally, data incompatibility (e.g., microarray versus RNA sequencing data) and technical and uncharacterized biological variance between training and test data can pose challenges in classifying individual samples. In this article, we provide a roadmap for implementing bioinformatics frameworks for molecular profiling of human cancers in a clinical diagnostic setting. We describe a framework for integrating several methods for quality control, normalization, batch correction, classification and reporting, and develop a use case of the framework in breast cancer.

Abstract Objective To evaluate the readability, understandability, actionability, and accuracy of online resources covering vestibular migraine (VM). Study Design Cross‐sectional descriptive study design. Setting Digital collection of websites appearing on Google search. Methods Google searches were conducted to identify common online resources for VM. We examined readability using the Flesch Reading Ease (FRE) and Flesch‐Kincaid Grade Level scores, understandability and actionability using the Patient Education Materials Assessment Tool (PEMAT), and accuracy by comparing the website contents to the consensus definition of “probable vestibular migraine.” Results Eleven of the most popular websites were analyzed. Flesch‐Kincaid Grade Level averaged at a 13th‐grade level (range: 9th‐18th). FRE scores averaged 35.5 (range: 9.1‐54.4). No website had a readability grade level at the US Agency for Healthcare Research and Quality recommended 5th‐grade level or an equivalent FRE score of 90 or greater. Understandability scores varied ranging from 49% to 88% (mean 70%). Actionability scores varied more, ranging from 12% to 87% (mean 44%). There was substantial inter‐rater agreement for both PEMAT understandability scoring (mean κ = 0.76, SD = 0.08) and actionability scoring (mean κ = 0.65, SD = 0.08). Three sites included all 3 “probable vestibular migraine” diagnostic criteria as worded in the consensus statement. Conclusion The quality of online resources for VM is poor overall in terms of readability, actionability, and agreement with diagnostic criteria.

Abstract Meningioma is the most common benign primary brain tumour and does not usually metastasise. We report the case of a 69‐year‐old male patient with a history of meningioma who presented respiratory symptoms. He was found to have diffuse pleural metastasis from meningioma, which occurred 10 years after surgical management of recurrent meningioma. This case study provides insights into the clinical profile, workup and management of metastatic meningioma.

Abstract Soil bulk electrical conductivity (BEC) was evaluated alongside soil volumetric water content (VWC) and soil temperature measurements using the HydraProbe (model HydraProbe, Stevens Water Monitoring Systems, Inc.) (hereafter called HP) with accuracy range of BEC ≤ 0.3 S m−1, and the time domain reflectometry (TDR)‐315L Probe (model TDR‐315L, Acclima, Inc.) (hereafter called AP) suitable for BEC up to 0.6 S m−1, at 23 stations of the U.S. Climate Reference Network. Previous evaluations revealed inconsistent performance of both sensors in some clay soils using manufacturer‐recommended calibrations in converting dielectric permittivity measurements to VWC. Here, we found that hourly values of BEC reached 0.6 S m−1 in high clay content soils and exceeded 2 S m−1 in high saline soils, and these high values of BEC were associated with poor performance and failures of both HP and AP sensors. Large values of BEC occurred in predominantly saturated soils where VWC values reached about 0.5 m3 m−3 for saline soils and about 0.7 m3 m−3 for clay soils, while low magnitudes of BEC were associated with low soil water content and seldomly saturated soils. Low hourly BEC values of less than 0.1 S m−1 were observed in wide variety of soil types, where sensor performance was typically excellent. The most influential factor on BEC was high soil water content conditions. Although dielectric permittivity measurements in estimating the soil water content were sensitive to BEC as some high clay content and high salinity soils increased BEC, the impact of large BEC on dielectric permittivity measurements was smaller in the well‐drained top soil layers than in deep soil layers that remained near saturation. Soil temperature had only a small impact on BEC. With high clay content and high salinity, the specific area of clay minerals was also associated with the magnitude of BEC.

Abstract Cancers that can manifest in the oral cavity, nasal cavity, larynx, pharynx, sinuses, and other head and neck areas are collectively called “head and neck cancers” (HNC). HNC can be broadly classified into five types: salivary gland; oral and oropharyngeal; nasal cavity and paranasal sinus; nasopharyngeal, and laryngeal and hypopharyngeal cancers. HNC accounts for one million new diagnoses annually, making it the seventh most common form of the disease globally. Among all HNCs, 90% are head and neck squamous cell carcinoma (HNSCC) which is highly heterogenous, relapsing, and metastatic with poor survival. Despite the availability of new treatments, the five‐year survival rate for HNSCC patients has been reported to be approximately 50%. An early diagnosis may increase the disease management and outcomes, but it is challenging to detect smaller‐sized lesions and differentiate malignant and non‐malignant lesions with the available tools. Current circumstances demand an improvement in existing diagnostic strategies and the advent of novel diagnostic tools.

Abstract Vacuolar malic acid accumulation largely determines fruit acidity, a key trait for the taste and flavor of apple and other fleshy fruits. Aluminum‐activated malate transporter 9 (ALMT9/Ma1) underlies a major genetic locus, Ma, for fruit acidity in apple, but how the protein transports malate across the tonoplast is unclear. Here, it is shown that overexpression of the coding sequence of Ma1 (Ma1α) drastically decreases fruit acidity in “Royal Gala” apple, leading to uncovering alternative splicing underpins Ma1's function. Alternative splicing generates two isoforms: Ma1β is 68 amino acids shorter with much lower expression than the full‐length protein Ma1α. Ma1β does not transport malate itself but interacts with the functional Ma1α to form heterodimers, creating synergy with Ma1α for malate transport in a threshold manner (When Ma1β/Ma1α ≥ 1/8). Overexpression of Ma1α triggers feedback inhibition on the native Ma1 expression via transcription factor MYB73, decreasing the Ma1β level well below the threshold that leads to significant reductions in Ma1 function and malic acid accumulation in fruit. Overexpression of Ma1α and Ma1β or genomic Ma1 increases both isoforms proportionally and enhances fruit malic acid accumulation. These findings reveal an essential role of alternative splicing in ALMT9‐mediated malate transport underlying apple fruit acidity.

Abstract Diabetic ketoacidosis (DKA) is a life‐threatening acute complication of diabetes characterized by the accumulation of ketone bodies in the blood. Breath acetone, a ketone, directly correlates with blood ketones. Therefore, monitoring breath acetone can significantly enhance the safety and efficacy of diabetes care. In this work, the design and fabrication of an InP/Pt/chitosan nanowire array‐based chemiresistive acetone sensor is reported. By incorporation of chitosan as a surface‐functional layer and a Pt Schottky contact for efficient charge transfer processes and photovoltaic effect, self‐powered, highly selective acetone sensing is achieved. The sensor has exhibited an ultra‐wide acetone detection range from sub‐ppb to >100 000 ppm level at room temperature, covering those in the exhaled breath from healthy individuals (300–800 ppb) to people at high risk of DKA (>75 ppm). The nanowire sensor has also been successfully integrated into a handheld breath testing prototype, the Ketowhistle, which can successfully detect different ranges of acetone concentrations in simulated breath samples. The Ketowhistle demonstrates the immediate potential for non‐invasive ketone monitoring for people living with diabetes, in particular for DKA prevention.

Abstract High‐density polyethylene (HDPE) polymer is one of the largest contributors to plastic wastes causing detrimental effects on various sectors of society, and is not biodegradable in nature. In the first stage, river sand and a recycled HDPE as a binder were used to manufacture eco‐friendly plastic sand bricks with various sand(s):plastic(p) ratios: 60s:40p; 65s:35p; 70s:30p; 75s:25p; 80s:20p; 85s:15p. In the second stage, 1%, 5%, and 10% of Kaolin Clay was added to each ratio of sand:plastic, respectively. Three mechanical tests were conducted: compressive strength, impact, and short beam strength. First, the addition of 5% Kaolin Clay to 75s:25p ratio increased compressive strength significantly from 21.4 to 52.76 MPa. Second, the addition of 10% Kaolin Clay in the ratio of 75s:25p mixture increased the impact strength from 4.8 to 5 J. Finally, the addition of 5% Kaolin Clay in the ratio of 60s:40p mixture increased the short beam strength significantly from 1.84 to 2.27 MPa. SEM analysis showed a well‐compacted interface indicating effective bonding between the HDPE and river sand particles in the 75s:25p ratio. Hence, the results of this study present a potential for the use of recycled HDPE plastic to manufacture plastic sand bricks. Highlights Addition of Kaolin Clay improved the mechanical properties of the composite material.

Abstract The dose/exposure‐efficacy analyses are often conducted separately for oncology end points like best overall response, progression‐free survival (PFS) and overall survival (OS). Multistate models offer to bridge these dose‐end point relationships by describing transitions and transition times from enrollment to response, progression, and death, and evaluating transition‐specific dose effects. This study aims to apply the multistate pharmacometric modeling and simulation framework in a dose optimization setting of bintrafusp alfa, a fusion protein targeting TGF‐β and PD‐L1. A multistate model with six states (stable disease [SD], response, progression, unknown, dropout, and death) was developed to describe the totality of endpoints data (time to response, PFS, and OS) of 80 patients with non‐small cell lung cancer receiving 500 or 1200 mg of bintrafusp alfa. Besides dose, evaluated predictor of transitions include time, demographics, premedication, disease factors, individual clearance derived from a pharmacokinetic model, and tumor dynamic metrics observed or derived from tumor size model. We found that probabilities of progression and death upon progression decreased over time since enrollment. Patients with metastasis at baseline had a higher probability to progress than patients without metastasis had. Despite dose failed to be statistically significant for any individual transition, the combined effect quantified through a model with dose‐specific transition estimates was still informative. Simulations predicted a 69.2% probability of at least 1 month longer, and, 55.6% probability of at least 2‐months longer median OS from the 1200 mg compared to the 500 mg dose, supporting the selection of 1200 mg for future studies.

Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a sequela of a pulmonary embolus that occurs in approximately 1%−3% of patients. Pulmonary thromboendoarterectomy (PTE) can be a curative procedure, but balloon pulmonary angioplasty (BPA) has emerged as an option for poor surgical candidates. We used the National Inpatient Sample to query patients who underwent PTE or BPA between 2012 and 2019 with CTEPH. The primary outcome was a composite of in‐hospital mortality, myocardial infarction, stroke, tracheostomy, and prolonged mechanical ventilation. Outcomes were compared between low‐ and high‐volume centers, defined as 5 and 10 procedures per year for BPA and PTE, respectively. During our study period, 870 BPA and 2395 PTE were performed. There was a 328% relative increase in the number of PTE performed during the study period. Adverse events for BPA were rare. There was an increase in the primary composite outcome for low‐volume centers compared to high‐volume centers for PTE (24.4% vs. 12.1%, p = 0.003). Patients with hospitalizations for PTE in low‐volume centers were more likely to have prolonged mechanical ventilation (20.0%% vs. 7.2%, p

Abstract Lung transplantation remains an important therapeutic option for idiopathic pulmonary arterial hypertension (IPAH), yet short‐term survival is the poorest among the major diagnostic categories. We sought to develop a prediction model for 90‐day mortality using the United Network for Organ Sharing database for adults with IPAH transplanted between 2005 and 2021. Variables with a p value ≤ 0.1 on univariate testing were included in multivariable analysis to derive the best subset model. The cohort comprised 693 subjects, of whom 71 died (10.2%) within 90 days of transplant. Significant independent predictors of early mortality were: extracorporeal circulatory support and/or mechanical ventilation at transplant (OR: 3; CI: 1.4–5), pulmonary artery diastolic pressure (OR: 1.3 per 10 mmHg; CI: 1.07–1.56), forced expiratory volume in the first second percent predicted (OR: 0.8 per 10%; CI: 0.7–0.94), recipient total bilirubin >2 mg/dL (OR: 3; CI: 1.4–7.2) and ischemic time >6 h (OR: 1.7, CI: 1.01–2.86). The predictive model was able to distinguish 25% of the cohort with a mortality of ≥20% from 49% with a mortality of ≤5%. We conclude that recipient variables associated with increasing severity of pulmonary vascular disease, including pretransplant advanced life support, and prolonged ischemic time are important risk factors for 90‐day mortality after lung transplant for IPAH.

Key Clinical Message Spontaneous intracerebral hemorrhage commonly affects the brainstem. This report describes a 31‐year‐old male with hypertension who developed a pontine hemorrhage. The neurological deficits included left‐third nerve palsy, right‐sided weakness, and disabling tinnitus. Tinnitus is linked to central auditory pathway disruption. Magnetic resonance imaging revealed the hemorrhagic lesion and additional micro‐hemorrhages. The International Classification of Functioning, Disability, and Health (ICF) enhances rehabilitation by characterizing multifaceted stroke disability. The ICF profile revealed impairments in body structures/functions, limitations in activities/participation, and positive/negative environmental factors. ICF‐based goal‐setting informed interventions, including tinnitus retraining and physical/occupational therapy. Comprehensive ICF assessment is crucial for optimized, patient‐centered post‐stroke rehabilitation as it determines the extent of impact on functional level of the patient irrespective of disease severity.

Abstract The epithelial–mesenchymal transition (EMT) represents a pivotal frontier in oncology, playing a central role in the metastatic cascade of cancer—a leading global health challenge. This comprehensive review delves into the complexities of EMT, a process where cancer cells gain exceptional mobility, facilitating their invasion into distant organs and the establishment of secondary malignancies. We thoroughly examine the myriad of factors influencing EMT, encompassing transcription factors, signalling pathways, metabolic alterations, microRNAs, long non‐coding RNAs, epigenetic changes, exosomal interactions and the intricate dynamics of the tumour microenvironment. Particularly, the review emphasises the advanced stages of EMT, crucial for the development of highly aggressive cancer phenotypes. During this phase, cancer cells penetrate the vascular barrier and exploit the bloodstream to propagate life‐threatening metastases through the mesenchymal–epithelial transition. We also explore EMT's significant role in fostering tumour dormancy, senescence, the emergence of cancer stem cells and the formidable challenge of therapeutic resistance. Our review transcends a mere inventory of EMT‐inducing elements; it critically assesses the current state of EMT‐focused clinical trials, revealing both the hurdles and significant breakthroughs. Highlighting the potential of EMT research, we project its transformative impact on the future of cancer therapy. This exploration is aimed at paving the way towards an era of effectively managing this relentless disease, positioning EMT at the forefront of innovative cancer research strategies.

Abstract Co‐simulation is an approach where the simulation of both transmission and distribution system gets combined. This approach provides more accurate description of the results which can help the decision making of the operator. Due to increasing rate of decentralization, there is bidirectional energy flow. Thus, getting uninterrupted power supply even under any kind of stressed situation is possible with the help of renewable energy sources (RES), distributed generators (DG) and electric vehicles (EV) in the system. EVs can act as a source and load depending on the discharging or charging characteristics. The power in the EVs can be discharged during stressed hours to manage over loading of transmission lines by avoiding line limit violation. The IEEE 30 bus system is considered as transmission system in which IEEE 33 bus system and IEEE 69 bus system as Micro Grids (MGs) are being integrated at three different buses. Load flow analysis is performed for different cases using MATLAB software. The reduction of MVA flow in the transmission line is observed when it is managed using RES integrated in transmission system while DGs and EVs present within the microgrids.

Abstract On September 30 and October 1, 2021, the US Food and Drug Administration (FDA) and the Center for Research on Complex Generics cosponsored a live virtual workshop titled “Regulatory Utility of Mechanistic Modeling to Support Alternative Bioequivalence Approaches.” The overall aims of the workshop included (i) engaging the generic drug industry and other involved stakeholders regarding how mechanistic modeling and simulation can support their product development and regulatory submissions; (ii) sharing the current state of mechanistic modeling for bioequivalence (BE) assessment through case studies; (iii) establishing a consensus on best practices for using mechanistic modeling approaches, such as physiologically based pharmacokinetic modeling and computational fluid dynamics modeling, for BE assessment; and (iv) introducing the concept of a Model Master File to improve model sharing between model developers, industry, and the FDA. More than 1500 people registered for the workshop. Based on a postworkshop survey, the majority of participants reported that their fundamental scientific understanding of mechanistic models was enhanced, there was greater consensus on model validation and verification, and regulatory expectations for mechanistic modeling submitted in abbreviated new drug applications were clarified by the workshop.

Societal Impact Statement Restoring degraded tropical lands is important for biodiversity protection and human livelihoods. Newly planted tree seedlings are often challenged by drought brought about by climate change. Here, we explored how nitrogen sources used for plant growth affected the water use of tropical tree seedlings under water limitation. We found that the application of the amino acid arginine reduced water use in the studied seedlings under water limitation, compared with the conventional ammonium nitrate fertiliser. Alternative sources of nitrogen should be considered for tree seedling production in nurseries as this could enhance drought resilience traits and improve the survival of seedlings in restoration plantings. Summary Restoration via tree planting is impacted by climate change‐induced water scarcity. Nitrogen (N) supply modulates the morphology and physiology of plants and impacts water use. We compared the responses of rainforest tree seedlings Acacia mangium and Alphitonia petriei grown with inorganic N (Osmocote™, ammonium nitrate) or organic N (Argrow™, liquid arginine), hypothesising that organic N confers drought resilience by increasing water use efficiency (WUE). Seedlings were grown in a glasshouse for 12 weeks with organic or inorganic N in well‐watered conditions, and then half the seedlings were subjected to water limitation for a further 4 weeks. A. mangium grew equally well on all N sources, but water limitation reduced biomass production. In contrast, N sources but not water regimes influenced biomass production in A. petriei. Under water limitation, arginine‐supplied A. petriei had higher WUE and more depleted leaf δ13C than inorganic N‐supplied plants. Our results suggest that organic N in the form of arginine can regulate stomatal conductance in A. petriei to convey drought resilience in seedlings. The generality of these findings should be explored to evaluate if organic N is a feasible source for generating drought‐resilient seedlings for restoration plantings.

The hybrid composite plate is increasingly used in marine, robotic arm, and other applications. Edge crack is the greatest common fault in the structural systems during its working time. In this research, the successful fabrications of a hybrid composite of epoxy-based composites reinforced with bamboo and glass fibers have been done to examine the vibration characteristics under free vibration. First-order shear deformation theory is used to study the fundamental natural frequencies of asymmetrically hybrid composite beam with edge cracks for cantilever beam boundary conditions. Both numerical (FEM) using ABAQUS software and experimental investigations are done for the vibration analysis of unidirectional bamboo/glass fiber epoxy hybrid composite (BGHC) beam with edge cracks using fracture mechanics theory. It is observed that implications edge crack with different crack depth and various fiber weight ratio parameters have a major effect on vibration analysis. Also, it is clear that the natural frequencies of the hybrid composite are significantly affected due to the fiber weight ratio and crack depth of the hybrid composite materials. So, crack lengths are playing a vital role in the dynamic or vibration characteristics of the hybrid composite materials. The results of natural frequencies have been shown that they are decreased with an increase in crack depth and an increase in the bamboo fiber weight. Thus, BGHC-2 made from 30% bamboo and 10% glass fiber can be a viable candidate for applications that will produce good vibration properties. Generally, the first-third natural frequency of the hybrid composite beam decreases within the increase of bamboo fiber and decreases in glass fiber. The composite materials having 60% of epoxy with 20% bamboo and 20% glass fiber, and 60% of epoxy with 10% glass and 30% bamboo fibers, are observed with a gradual decrease in the values of natural frequencies with respect to increasing in crack depth. A fine agreement was accomplished between the simulation and experimental results. Therefore, the present approach can be used to identify cracks for mechanical health monitoring by linking the variation in natural frequencies of the hybrid composite beams.

This study focuses on the fabrication and analysis of the mechanical behaviour of unidirectional (UD) glass fibre-reinforced polymer (GFRP) facesheet and polyvinyl chloride (PVC) foam core sandwich structures fabricated by a vacuum-assisted resin infusion method (VARIM). These sandwich structures are commonly used in marine and wind turbine blade applications. To date, relatively little knowledge about the functional behaviour of UD GFRP compared to composites reinforced with bidirectional mats is available for day-to-day applications. The effects of the facesheet orientation, facesheet thickness, and core thickness on the mechanical behaviour of the specimens were examined. The UD fibres were oriented in cross-ply (0/90), angle-ply (+45/−45), and quasi-isotropic orientations. Various mechanical properties such as tensile, flexural, flatwise compression, and edgewise compression tests were examined. Characterization of the tensile properties of the facesheet showed that the cross-ply orientation had a higher strength than the angle-ply and quasi-isotropic orientations. The flexural load-carrying capacity of the cross-ply facesheet orientation was superior to the other orientations. The increase in the core thickness changed the flexural failure mode from face yield and core shear to core indentation. Flatwise compression (FWC) was tested to determine the core characteristics of the sandwich structure, and the peak loads of 4.90, 1.81, and 3.90 kN were obtained for 10-, 15-, and 20 mm core thicknesses, respectively. Edgewise compression (EWC) exhibited stable end crushing for thinner facesheet, whereas thicker facesheet showed core crushing and buckling. When the facesheet thickness was increased from 1.5 mm to 3 mm in the EWC, the buckling load increase ranged from 2.53% to 44.83% for core thicknesses 10-, 15-, and 20 mm, respectively.

Abstract Pulmonary vasodilator treatment can improve hemodynamics, right ventricular function, symptoms, and survival in pediatric pulmonary hypertension (PH). However, clinical trial data are lacking due to many constraints. One major limitation is the lack of relevant trial endpoints reflective of hemodynamics or functional status in patients in whom standard exercise testing is impractical, unreliable, or not reproducible. The Kids Mod PAH trial (Mono‐ vs. Duo Therapy for Pediatric Pulmonary Arterial Hypertension) is an ongoing multicenter, Phase III, randomized, open‐label, pragmatic trial to compare the safety and efficacy of first‐line combination therapy (sildenafil and bosentan) to first‐line monotherapy (sildenafil alone) in 100 pediatric patients with PH across North America. Investigators will measure participants’ physical activity with a research‐grade, wrist‐worn actigraphy device at multiple time points as an exploratory secondary outcome. Vector magnitude counts per minute and activity intensity will be compared between the treatment arms. By directly and noninvasively measuring physical activity in the ambulatory setting, we aim to identify a novel, simple, inexpensive, and highly reproducible approach for quantitative assessment of exercise tolerance in pediatric PH. These data will increase the field's understanding of the effect of pulmonary vasodilator treatment on daily activity – a quantitative measure of functional status and wellbeing in pediatric PH and a potential primary outcome for future clinical trials in children with cardiopulmonary disorders.

Background. COVID-19 belongs to the beta-corona cluster that spreads enormously via aerosols. Physiotherapists must be knowledgeable about the symptoms, mode of transmission, risk mitigation strategies, and practice guidelines for COVID-19. Objective. This study aimed to assess physiotherapists’ knowledge of COVID-19 guidelines, their attitude toward this new evolving field, and their practice routines in India’s COVID-19 ICUs. Methods. It was a cross-sectional study. A total of 600 questionnaires were distributed through e-mail and WhatsApp to physiotherapists using Google Forms between February 2022 and January 2023. The questionnaires consisted of demographics and 23 questions in three sections about the knowledge, attitude, and practice of physiotherapists working in the COVID-19 ICU. Data analysis was carried out using Jamovi. Results. A total of 136 responses were obtained from 18 states of India. Of 136 participants, 89 were female (65.4%) and 47 were male (34.6%). The highest level of qualification was BPT (n = 69 (50.7%)), followed by MPT (n = 62 (45.6%)) and Ph.D. (3 (3.7%)). The knowledge about COVID-19 guidelines is fair. Only 21.3% of the physiotherapists received training before being deployed in COVID-19 ICUs, and the CARP protocol was well known by only as few as 10.3%. The criteria advised for close monitoring of patients during treatment was aware by 29.4%. Most physiotherapists have a good attitude toward treating COVID-19 patients; 70.63% strongly agree that physiotherapy is vital in these patients despite the risk of self-exposure, and 64.7% agree that physiotherapy should be initiated during all phases of COVID-19. Physiotherapists follow good practices for COVID-19 patients in the ICU, which is as per the guideline recommendation. Conclusion. Physiotherapists working in COVID-19 ICUs have a fair knowledge of the existing physiotherapy guidelines for COVID-19, and they exhibit good attitudes and practice patterns.

Abstract Background The north and north‐eastern regions of India have among the highest incidence of gallbladder cancer (GBC) in the world. We report the clinicopathological charateristics and outcome of GBC patients in India. Methods Electronic medical records of patients diagnosed with GBC at Tata Medical Center, Kolkata between 2017 and 2019 were analyzed. Results There were 698 cases of confirmed GBC with a median age of 58 (IQR: 50–65) years and female:male ratio of 1.96. At presentation, 91% (496/544) had stage III/IV disease and 30% (189/640) had incidental GBC. The 2‐year overall survival (OS) was 100% (95% CI: 100–100); 61% (95% CI: 45–83); 30% (95% CI: 21–43); and 9% (95% CI: 6–13) for stages I–IV, respectively (p =

Abstract Background To evaluate the treatment cost and cost effectiveness of a risk‐stratified therapy to treat pediatric acute lymphoblastic leukemia (ALL) in India. Methods The cost of total treatment duration was calculated for a retrospective cohort of ALL children treated at a tertiary care facility. Children were risk stratified into standard (SR), intermediate (IR) and high (HR) for B‐cell precursor ALL, and T‐ALL. Cost of therapy was obtained from the hospital electronic billing systems and details of outpatient (OP) and inpatient (IP) from electronic medical records. Cost effectiveness was calculated in disability‐adjusted life years. Results One hundred and forty five patients, SR (50), IR (36), HR (39), and T‐ALL (20) were analyzed. Median cost of the entire treatment for SR, IR, HR, and T‐ALL was found to be $3900, $5500, $7400, and $8700, respectively, with chemotherapy contributing to 25%–35% of total cost. Out‐patient costs were significantly lower for SR (p

Abstract Pulmonary hypertension (PH) is a significant health problem that contributes to high morbidity and mortality in diverse cardiac, pulmonary, and systemic diseases in children. Evidence‐based advances in PH care have been challenged by a paucity of quality endpoints for assessing clinical course and the lack of robust clinical trial data to guide pharmacologic therapies in children. While the landmark adult AMBITION trial demonstrated the benefit of up‐front combination PH therapy with ambrisentan and tadalafil, it remains unknown whether upfront combination therapy leads to more rapid and sustained clinical benefits in children with various categories of PH. In this article, we describe the inception of the Kids Mod PAH Trial, a multicenter Phase III trial, to address whether upfront combination therapy (sildenafil and bosentan vs. sildenafil alone) improves PH outcomes in children, recognizing that marked differences between the etiology and therapeutic response between adults and children exist. The primary endpoint of this study is WHO functional class (FC) 12 months after initiation of study drug therapy. In addition to the primary outcome, secondary endpoints are being assessed, including a composite measure of time to clinical worsening, WHO FC at 24 months, echocardiographic assessment of PH and quantitative assessment of right ventricular function, 6‐min walk distance, and NT‐proBNP levels. Exploratory endpoints include selected biomarkers, actigraphy, and assessments of quality of life. This study is designed to pave the way for additional clinical trials by establishing a robust infrastructure through the development of a PPHNet Clinical Trials Network.

Abstract Surveying animal populations using drones (unoccupied aircraft systems [UAS]) provides numerous advantages; however, few best practices exist to survey animal communities with drones. Among myriad factors that can affect human identification and counts of animals from drone images, we focused on three factors typically controlled in the study design or by the drone pilot: flight altitude, camera angle, and time of day. Identifying interactions and patterns among these three variables represents an important first step to determining best survey practices. We used a drone to survey known numbers of eight animal decoy species, representing a range of body sizes and colors, at four ground sampling distance (GSD) values (0.35, 0.70, 1.06, and 1.41 cm/pixel) representing equivalent flight altitudes (15.2, 30.5, 45.7, and 61.0 m) at two camera angles (45° and 90°) and across a range of times of day (morning to late afternoon). Expert human observers identified and counted animals from drone images to determine how the three controllable factors affected accuracy and precision. Observer precision was high and unaffected by tested factors. However, results for observer accuracy revealed an interaction among all three controllable factors. Increasing flight altitude resulted in decreased accuracy in animal counts overall; however, accuracy was best at midday than during the morning and afternoon, when decoy and structure shadows were present or more pronounced. Surprisingly, the 45° camera enhanced accuracy more than the 90° camera, but only when animals were most difficult to identify and count, such as at higher flight altitudes or during the early morning and late afternoon. We provide recommendations for improving human accuracy in identifying and counting animals from drone images used in monitoring animal populations and communities. These results should be incorporated into drone survey design in addition to considering funding, logistical, and animal behavior constraints.

Abstract High cellular pigment levels in dense microalgal cultures contribute to excess light absorption. To improve photosynthetic yields in the marine microalga Picochlorum celeri, CAS9 gene editing was used to target the molecular chaperone cpSRP43. Depigmented strains (>50% lower chlorophyll) were generated, with proteomics showing attenuated levels of most light harvesting complex (LHC) proteins. Gene editing generated two types of cpSRP43 transformants with distinct lower pigment phenotypes: (i) a transformant (Δsrp43) with both cpSRP43 diploid alleles modified to encode non‐functional polypeptides and (ii) a transformant (STR30309) with a 3 nt in‐frame insertion in one allele at the CAS9 cut site (non‐functional second allele), leading to expression of a modified cpSRP43. STR30309 has more chlorophyll than Δsrp43 but substantially less than wild type. To further decrease light absorption by photosystem I in STR30309, CAS9 editing was used to stack in disruptions of both LHCA6 and LHCA7 to generate STR30843, which has higher (5–24%) productivities relative to wild type in solar‐simulating bioreactors. Maximal productivities required frequent partial harvests throughout the day. For STR30843, exemplary diel bioreactor yields of ~50 g m−2 day−1 were attained. Our results demonstrate diel productivity gains in P. celeri by lowering pigment levels.

Background The safety and efficacy of endovascular thrombectomy (EVT) in patients with acute ischemic stroke due to large vessel occlusion presenting beyond 24 hours from last known well (LKW) remains undetermined. Methods In this single center study, we identified patients with large vessel occlusion who were eligible for EVT based on noncontrast computed tomography (CT)/CT angiography (without CT perfusion or magnetic resonance imaging) using an Alberta Stroke Program Early CT Score of ≥5, National Institutes of Health Stroke Scale of ≥6, and presenting beyond 24 hours from LKW, between January 2018 and March 2022. During the study period, EVT service limitations meant patients eligible for EVT presenting outside service hours, routinely received best medical management (BMM). Functional and safety outcomes were compared between patients receiving EVT or BMM following multivariable adjustment for age, baseline stroke severity, Alberta Stroke Program Early CT Score, time from LKW, IV thrombolysis, and clot location. Results Among 35 patients presenting beyond 24 hours from LKW and eligible for EVT, 19 (54%) were treated with EVT and 16 (46%) with BMM. Alberta Stroke Program Early CT Score were similar across both groups (EVT: 7 [6.75–8] versus BMM: 7 [6–8]), but not the baseline National Institutes of Health Stroke Scale (EVT: 17 [11–19.5] versus BMM: 20 [9.75–26]). No significant difference was observed between the EVT and BMM groups in the symptomatic intracranial hemorrhage (5.3% versus 0%; P=0.28) or mortality (26.3% versus 37.5%; P=0.42) rates, respectively. The modified Rankin scale at 90 days (adjusted common odds ratio [OR], 1.94; [95% CI 0.42–8.87]; P=0.39) and functional independence rate, although numerically higher in the EVT group compared with the BMM group (modified Rankin scale≤2; 36.9% versus 18.8%; adjusted OR, 4.34; [95% CI 0.34–54.83]; P=0.25), were not significantly different. 94.7% of patients treated with EVT achieved successful reperfusion (modified thrombolysis in cerebral infarction 2b–3). Conclusion In routine clinical practice, EVT beyond 24 hours from LKW appears safe and feasible, when performed in patients with acute ischemic stroke who were deemed eligible for EVT by noncontrast CT /CT angiography alone. A large collaborative randomized trial assessing the efficacy of EVT beyond 24 hours is warranted. Our findings provide a basis for the sample size estimate for an adequately powered trial.

Abstract Exosome is nanosized tiny membrane‐bound vesicles and is a subpopulation of extracellular vesicles (EVs). In general, it participates in intercellular communication and acts as a messenger of several pathological complications. Exosome and cancer interlink is the most exciting domain of current cancer research. The internal molecular cargos (proteins, lipids, metabolites, miRNA, and DNA) of tumor derived exosomes (TEXs) are capable of transforming normal cells into tumor phenotypes. Exosome DNA is the less explored area of EVs research. It is involved in several events in cancer progression such as uncontrol cell growth, reprogramming of immune cells, metastasis, and therapeutic resistance. Exo‐DNA is also involved in epigenetic alteration, which promotes cancer. It has a great impact on cancer theranostics (biomarker and therapeutics) research. Exo‐DNA‐based cancer examination supports more detailed cancer research.

Key Clinical Message Identifying any potential comorbidity such as bulimia nervosa (BN) and ADHD in trichotillomania patients is essential for a thorough treatment plan. Combining a multidisciplinary approach was found to be feasible and effective in the treatment. Abstract Trichotillomania is frequently considered an isolated disorder; nevertheless, emerging evidence suggests that other psychiatric conditions, including obsessive‐compulsive disorder (OCD), eating disorders, and attention‐deficit/hyperactivity disorder (ADHD), are often found to coexist. Several studies showed that eating disorders, such as bulimia nervosa, were found in chronic hair‐pullers, while OCD was considered a factor in predicting the prevalence of eating disorders, as well as the severity of trichotillomania in the populations. While the relationship between trichotillomania and OCD has been quite well‐documented, the evidence of its association with bulimia nervosa and ADHD remains limited. Here, we report a case of trichotillomania with comorbid bulimia nervosa, major depressive disorder, and ADHD.

Abstract Fast and accurate fault location in DC power systems is of particular importance to ensure their reliable operation. One of the approaches for implementing a fast‐tripping protection scheme is to use Traveling waves (TW) initiated by a fault scenario. This paper proposes a physics‐informed machine learning approach that utilizes TWs for fault location in DC microgrids. TWs are extracted by the so‐called multiresolution analysis which identifies the TW's wavelet coefficients for multiple frequency ranges. This paper deploys Parseval's theorem to find the energy of wavelet coefficients as a quantitative metric for describing TWs. The hypothesis of this paper is that once the Parseval energy curves for a specific cable are extracted, they can be utilized to locate faults along with that cable regardless of the DC system in which the cable is deployed. The fault location algorithm uses Parseval energy curves to train a Gaussian Process (GP) estimator. With the Parseval energy values of measured current at the protection device location, the GP estimator is able to estimate fault locations with high accuracy. The effectiveness of the proposed algorithm is verified by simulating a DC microgrid system in PSCAD/EMTDC.

Abstract The tumor size ratio (TSR), time‐to‐tumor growth (TTG), and tumor growth rate (kG) are frequently suggested as model‐based predictors of overall survival (OS) for different types of tumors. When the tumor metrics are applied in forecasting of the outcome for individual patients at an early stage, the tumor data might be sparse resulting in imprecise prediction. This simulation study aimed to investigate how the tumor follow‐up data and estimation approaches influence the accuracy in the tumor size metrics and the predicted hazard of death for individual patients. Longitudinal tumor size and OS data were simulated using tumor growth inhibition and Weibull distribution models, respectively. Based on the model and increasing measurement durations, the accuracy (defined as 80–125% of the simulated “true” value) in individual metrics and hazard was computed. TSR week 6 (TSRw6) accuracy was adequate for 91% of the patients when tumor size was measured up to 12 weeks. For TTG and kG metrics, the highest accuracy observed was lower (43 and 77%, respectively) and occurred later (42 and 60 weeks, respectively). The simultaneous (joint) and sequential estimation approaches resulted in similar accuracies, however, in general, the sequential approach where individual tumor size parameters are fixed, demonstrated inferior estimation properties. The TSRw6 and the model‐predicted tumor time course (absolute or relative change) had better forecasting properties than TTG or kG. The population pharmacokinetic (PK) parameters and data approach performed similarly or better than the simultaneous approach and had a better accuracy in estimating individuals' hazard of death than the individual PK parameters method.

Abstract Photoelectrochemical (PEC) hydrogen evolution reaction (HER) was studied on exfoliated, pristine and Pt‐decorated tungsten diselenide (p‐WSe2) nanoflake samples, using a previously developed microdroplet PEC microscopy approach. The WSe2 nanoflakes had well‐defined thicknesses as measured by atomic force microscopy, and the Pt nanoparticles (NPs) were deposited by a variable number of atomic layer deposition (ALD) cycles. An exceptionally high photocurrent density of 49.6 mA cm−2 (under 220 mW cm−2 irradiation) and internal‐photon‐to‐electron‐conversion efficiency (∼90% at 550 nm) were demonstrated on these Pt‐decorated WSe2 (WSe2‐Pt) photocathodes. The Pt NP loading and thickness of WSe2 nanoflakes (in the 24–235 nm range) were used to fine‐tune their PEC activity for HER. We found similar charge transfer and surface recombination kinetics of pristine and WSe2‐Pt specimens (as assessed by intensity‐modulated photocurrent spectroscopy), which indicated significant differences in their bulk properties. X‐ray and ultraviolet photoelectron spectroscopies were performed to identify defect states and quantify the density of states around the valence band of WSe2. The elevated temperature of the ALD process and the evolving Pt NP phase conspired to passivate the sub‐surface (i.e., bulk) defects in the WSe2 nanoflakes, resulting in their vastly improved PEC performance.