Commercial Availability Research Articles

Isolation and Characterization of Porcine Endocardial Endothelial Cells.

The heart contains diverse endothelial cell types. We sought to characterize the endocardial endothelial cells (EECs), which line the chambers of the heart. EECs are relatively understudied, yet their dysregulation can lead to various cardiac pathologies. Due to the lack of commercial availability of these cells, we reported our protocol for isolating EECs from porcine hearts and for establishing an EEC population through cell sorting. In addition, we compared the EEC phenotype and fundamental behaviors to a well-studied endothelial cell line, human umbilical vein endothelial cells (HUVECs). The EECs stained positively for classic phenotypic markers such as CD31, von Willebrand Factor, and vascular endothelial (VE) cadherin. The EECs proliferated more quickly than HUVECs at 48 h (1310 ± 251 cells vs. 597 ± 130 cells, p = 0.0361) and at 96 h (2873 ± 257 cells vs. 1714 ± 342 cells, p = 0.0002). Yet EECs migrated more slowly than HUVECs to cover a scratch wound at 4 h (5% ± 1% wound closure vs. 25% ± 3% wound closure, p < 0.0001), 8 h (15% ± 4% wound closure vs. 51% ± 12% wound closure, p < 0.0001), and 24 h (70% ± 11% wound closure vs. 90% ± 3% wound closure, p < 0.0001). Finally, the EECs maintained their endothelial phenotype by positive expression of CD31 through more than a dozen passages (three populations of EECs showing 97% ± 1% CD31+ cells in over 14 passages). In contrast, the HUVECs showed significantly reduced CD31 expression over high passages (80% ± 11% CD31+ cells over 14 passages). These important phenotypic differences between EECs and HUVECs highlight the need for researchers to utilize the most relevant cell types when studying or modeling diseases of interest.

Integrating Remote Sensing and Weather Variables for Mango Yield Prediction Using a Machine Learning Approach

Accurate pre-harvest yield forecasting of mango is essential to the industry as it supports better decision making around harvesting logistics and forward selling, thus optimizing productivity and reducing food waste. Current methods for yield forecasting such as manually counting 2–3% of the orchard can be accurate but are very time inefficient and labour intensive. More recent evaluations of technological solutions such as remote (satellite) and proximal (on ground) sensing have provided very encouraging results, but they still require infield in-season sampling for calibration, the technology comes at a significant cost, and commercial availability is limited, especially for vehicle-mounted sensors. This study presents the first evaluation of a ”time series”—based remote sensing method for yield forecasting of mango, a method that does not require infield fruit counts and utilizes freely available satellite imagery. Historic yield data from 2015 to 2022 were sourced from 51 individual orchard blocks from two farms (AH and MK) in the Northern Territory of Australia. Time series measures of the canopy reflectance properties of the blocks were obtained from Landsat 7 and 8 satellite data for the 2015–2022 growing seasons. From the imagery, the following vegetation indices (VIs) were derived: EVI, GNDVI, NDVI, and LSWI, whilst corresponding weather variables (rainfall (Prec), temperature (Tmin/Tmax), evapotranspiration (ETo), solar radiation (Rad), and vapor pressure deficit (vpd)) were also sourced from SILO data. To determine the relationships among weather and remotely sensed measures of canopy throughout the growing season and the yield achieved (at the block level and the farm level), six machine learning (ML) algorithms, namely random forest (RF), support vector regression (SVR), eXtreme gradient boosting (XGBOOST), RIDGE, LASSO and partial least square regression (PLSR), were trialed. The EVI/GNDVI and Prec/Tmin were found to be the best RS and weather predictors, respectively. The block-level combined RS/weather-based RF model for 2021 produced the best result (MAE = 2.9 t/ha), marginally better than the RS only RF model (MAE = 3.4 t/ha). The farm-level model error (FLEM) was generally lower than the block-level model error, for both the combined RS/weather-based RF model (farm = 3.7%, block (NMAE) = 33.6% for 2021) and the RS-based model (farm = 4.3%, block = 38.4% for 2021). Further testing of the RS/weather-based RF models over six additional orchards (other than AH and MK) produced errors ranging between 24% and 39% from 2016 to 2020. Although accuracies of prediction did vary at both the block level and the farm level, this preliminary study demonstrates the potential of a ”time series” RS method for predicting mango yields. The benefits to the mango industry are that it utilizes freely available imagery, requires no infield calibration, and provides predictions several months before the commercial harvest. Therefore, this outcome not only presents a more adoptable option for the industry, but also better supports automation and scalability in terms of block-, farm-, regional, and national level forecasting.

Mixed Precision Iterative Refinement with Sparse Approximate Inverse Preconditioning

With the commercial availability of mixed precision hardware, mixed precision GMRES-based iterative refinement schemes have emerged as popular approaches for solving sparse linear systems. Existing analyses of these approaches, however, are based on using full LU factorizations to construct preconditioners for use within GMRES in each refinement step. In practical applications, inexact preconditioning techniques, such as incomplete LU or sparse approximate inverses, are often used for performance reasons. In this work, we investigate the use of sparse approximate inverse preconditioners based on Frobenius norm minimization within GMRES-based iterative refinement. We analyze the computation of sparse approximate inverses in finite precision and derive constraints under which user-specified stopping criteria will be satisfied. We then analyze the behavior of and convergence constraints for a five-precision GMRES-based iterative refinement scheme that uses sparse approximate inverse preconditioning, which we call SPAI-GMRES-IR. Our numerical experiments confirm the theoretical analysis and illustrate the resulting tradeoffs between preconditioner sparsity and GMRES-IR convergence rate.

Oxygen vacancies in the Spotlight: On the engineering of intrinsic defects in highly defective TiO2 photocatalysts

Nanostructured oxide semiconductors are widely used in energy conversion, catalysis, sensing and environmental applications, due to their high stability, commercial availability, efficiency and low cost. Despite its crucial importance for the design of more efficient materials, the interplay between intrinsic and extrinsic defects is yet to be clarified. For example, oxygen vacancies (VO’s) can be either beneficial or detrimental to the desired performances, depending on a variety of factors. Here, we synthesize TiO2-x samples by the addition of three different N chemical sources (NH3, triethylamine, urea). X-ray absorption spectroscopy, confocal microscopy, UV–vis absorbance and fluorescence, are employed to explore the occurrence and location of VO’s both in real and energy spaces. High–grade bulk DFT simulations complement the experimental picture. Synergy between theory and experiment, on the one hand, estimates the relative VO’s content in the different samples from local structural information. On the other hand, a sharp optical transition at ≈2.7 eV serves an unequivocal spectral signature of bulk VO’s, allowing a semi-quantitative analysis by confocal microscopy. Surface oxygen vacancies do not display fluorescence features under UV pumping, possibly due to the reaction of surface defects with atmospheric O2. Thus, the comparison between local structure and confocal microscopy can discriminate surface-localized and bulk VO’s. Concurrently, UV-induced photochromism and visible light photodegradation shed light on the most effective reactive defects. Eventually, surface-localized oxygen vacancies are predominant where actual N substitutional doping occurs, leading to materials exhibiting visible-light activity and characteristic photochromic behaviour. Implications on strategies for concomitant VO engineering and extrinsic doping are discussed.

Real-world safety and effectiveness of MVASI in metastatic colorectal cancer patients in Canada.

e15555 Background: MVASI is a biosimilar to the reference product, bevacizumab, and is the first biosimilar approved by Health Canada for the first-line (1L) treatment of metastatic colorectal cancer (mCRC). This study addresses the limited real-world evidence by describing the safety and effectiveness of MVASI as 1L therapy in mCRC. Methods: Retrospective data were collected in two waves of sites across Canada, at least 1 year (wave 1) or 2 years (wave 2) after commercial availability of MVASI at each site. Adult patients treated with ≥ 1 MVASI cycles as their 1L therapy for mCRC were included. Baseline demographic and clinical characteristics were collected 6 months prior to MVASI initiation (index date). Medical history, adjuvant treatment, and CRC diagnosis were collected within 5 years of pre-index date. Outcomes were gathered between index and chart review dates. Results: Among the 75 patients in wave 1, 36 (48.0%) were male and the median age was 62 years. Of the 164 patients in wave 2, 98 (59.8%) were male and the median age was 67 years. Most patients in wave 1 (42/69; 60.9%) and wave 2 (87/141; 61.7%) had a RAS mutation. The median time from mCRC diagnosis to MVASI initiation among wave 1 and 2 patients was 3.1 (IQR [2.1, 4.2]) and 2.3 months (IQR [1.6, 3.7]), respectively. At least one safety event of interest (EOI) was recorded for 26/75 (34.7%) wave 1 and 70/164 (42.7%) wave 2 patients (Table 1). The median progression free survival (PFS) for wave 1 and 2 patients were 9.47 and 21.38 months, respectively. Median overall survival (OS) for wave 1 patients was not estimable and was 26.45 months for wave 2 patients. Conclusions: In this real-world study, mCRC patients treated with 1L MVASI were generally representative of the Canadian mCRC population treated with 1L bevacizumab. Compared with clinical trials of MVASI and reference bevacizumab, the EOI profile and the OS data are similar, but lower rates of individual EOIs are observed in this real-world setting. The shorter PFS observed in wave 1 may be due to higher rates of comorbidities at baseline and longer time from mCRC diagnosis to index. [Table: see text]

Chemical looping combustion oxygen carrier production cost study

The objective of this study was to estimate the cost of commercial production of oxygen carriers (OCs) for large-scale application in a mature, chemical looping combustion (CLC) power generation industry. Estimates of cost were made for two production facility scenarios: (1) build and operate an on-site, OC production facility located at a 550 MW CLC power plant site; and (2) build and operate a central production facility to produce and distribute OCs to the U.S. CLC power generation industry. Two OC production techniques were addressed: mechanical mixing and co-precipitation. Representative OCs that have production raw materials with sufficient commercial availability to support a CLC industry are ilmenite, a natural OC, and four engineered OC types, Fe2O3-based, CuO-based, NiO-based, and CuFeAlO4-based, with candidate OC support materials Al2O3 and TiO2. The costs of the OC production raw materials represent the major portion of the OC product cost; the OC production cost, in dollars per kg, has been found to be nearly a linear function of the OC raw materials cost, in dollars per kg. The estimated OC product costs can be used to estimate the maximum OC loss rate yielding a designated CLC power plant cost-of-electricity (COE) target as a development guide, and it has been found that the maximum OC makeup rate, in kg per hour, achieving a designated COE reduction goal relative to a conventional pulverized coal (PC) power plant, will be nearly inversely proportional to the OC production raw materials cost, in dollars per kg.

Decarboxylative, Radical C–C Bond Formation with Alkyl or Aryl Carboxylic Acids: Recent Advances

AbstractThe ubiquity of carboxylic acids as naturally derived or man-made chemical feedstocks has spurred the development of powerful, decarboxylative C–C bond-forming transformations for organic synthesis. Carboxylic acids benefit not only from extensive commercial availability, but are stable surrogates for organohalides or organometallic reagents in transition-metal-catalysed cross-coupling. Open shell reactivity of carboxylic acids (or derivatives thereof) to furnish carbon-centred radicals is proving transformative for synthetic chemistry, enabling novel and strategy-level C(sp3)–C bond disconnections with exquisite chemoselectivity. This short review will summarise several of the latest advances in this ever-expanding area.1 Introduction2 Improved Decarboxylative Arylations3 sp3–sp3 Cross-Coupling of Carboxylic Acids with Aliphatic Bromides4 sp3–sp3 Cross-Coupling of Carboxylic Acids with Aliphatic Alcohols and Amines5 Doubly Decarboxylative sp3–sp3 Cross-Coupling of Carboxylic Acids6 Decarboxylative C–C Bond Formation from (Hetero)aryl Carboxylic Acids7 Conclusions

2D finger-printing and molecular docking studies identified potent mosquito repellents targeting odorant binding protein 1

Personal protection measures against the mosquitoes like the use of repellents constitute valuable tools in the effort to prevent the transmission of vector-borne diseases. Therefore, the discovery of novel repellent molecules which will be effective at lower concentrations and provide a longer duration of protection remains an urgent need.Mosquito Odorant-Binding Proteins (OBPs) involved in the initial steps of the olfactory signal transduction cascade have been recognized not only as passive carriers of odors and pheromones but also as the first molecular filter to discriminate semiochemicals, hence serving as molecular targets for the design of novel pest control agents. Among the three-dimensional structures of mosquito OBPs solved in the last decades, the OBP1 complexes with known repellents have been widely used as reference structures in docking analysis and molecular dynamics simulation studies for the structure-based discovery of new molecules with repellent activity.Herein, ten compounds known to be active against mosquitoes and/or displaying a binding affinity for Anopheles gambiae AgamOBP1 were used as queries in an in silico screening of over 96 million chemical samples in order to detect molecules with structural similarity. Further filtering of the acquired hits on the basis of toxicity, vapor pressure, and commercial availability resulted in 120 unique molecules that were subjected to molecular docking studies against OBP1. For seventeen potential OBP1-binders, the free energy of binding (FEB) and mode of interaction with the protein were further estimated by molecular docking simulations leading to the selection of eight molecules exhibiting the highest similarity with their parental compounds and favorable energy values. The in vitro determination of their binding affinity to AgamOBP1 and the evaluation of their repellent activity against female Aedes albopictus mosquitoes revealed that our combined ligand similarity screening and OBP1 structure-based molecular docking successfully detected three molecules with enhanced repellent properties. A novel DEET-like repellent with lower volatility (8.55 × 10−4 mmHg) but a higher binding affinity for OBP1 than DEET (1.35 × 10−3 mmHg). A highly active repellent molecule that is predicted to bind to the secondary Icaridin (sIC)-binding site of OBP1 with higher affinity than to the DEET-site and, therefore, represents a new scaffold to be exploited for the discovery of binders targeting multiple OBP sites. Finally, a third potent repellent exhibiting a high degree of volatility was found to be a strong DEET-site binder of OBP1 that could be used in slow-release formulations.

Bio-Based Tannin-Furanic-Silk Adhesives: Applications in Plywood and Chemical Cross-linking Mechanisms

Wood polyphenolic extracts, commonly called tannins, are excellent candidates for the production of bioplastics due to their abundance in nature, their commercial availability, and their reactivity. In particular, they were tested as wood adhesives with several hardeners, but their low moisture resistance and their rigidity reduced their technological interest. In the present study, we combined regenerated silk (RS) with tannin-furanic formulations to improve their properties. Three-layer plywood glued with these several fully renewable tannin-silk-furanic adhesives were tested for their mechanical properties: the modulus of elasticity, the modulus of rupture, and both dry and wet shear strength were enhanced when 20 wt % of RS was added. Initially, the cross section of the prepared samples was investigated by scanning electron microscopy, indicating a good dispersion of RS within the tannin-furanic matrix. Afterward, thermomechanical analysis of the adhesive highlighted that RS slows down the polymerization rate, decreasing the cross-linking kinetics of polyfurfuryl alcohol. Chemical investigations through ATR-FTIR and 13C-NMR show the formation of covalent bonds between RS and the furanic matrix. In summary, the combination of bioresources from the vegetal and animal kingdom allows the manufacturing of fully bio-based adhesives with enhanced mechanical properties and water resistance. This represents an important breakthrough in the exploitation of polyphenols, opening perspectives for their application in material science.

Hybridization Chain Reaction-Based Electrochemical Biosensors by Integrating the Advantages of Homogeneous Reaction and Heterogeneous Detection.

The conventional hybridization chain reaction (HCR)-based electrochemical biosensors usually require the immobilization of probes on the electrode surface. This will limit the applications of biosensors due to the shortcomings of complex immobilization processes and low HCR efficiency. In this work, we proposed astrategy for the design of HCR-based electrochemical biosensors by integrating the advantages of homogeneous reaction and heterogeneous detection. Specifically, the targets triggered the autonomous cross-opening and hybridization oftwobiotin-labeled hairpin probes to form long-nicked dsDNA polymers. The HCR products with many biotin tags were then captured by a streptavidin-covered electrode, thus allowing for the attachment of streptavidin-conjugated signal reporters through streptavidin-biotin interactions. By employing DNA and microRNA-21 as the model targets and glucose oxidase as the signal reporter, the analytical performances of the HCR-based electrochemical biosensors were investigated. The detection limits of this method were found to be 0.6 fM and 1 fM for DNA and microRNA-21, respectively. The proposed strategy exhibited good reliability for target analysis in serum and cellular lysates. The strategy can be used to develop various HCR-based biosensors for a wide range of applications because sequence-specific oligonucleotides exhibit high binding affinity to a series of targets. In light of the high stability and commercial availability of streptavidin-modified materials, the strategy can be used for the design of different biosensors by changing the signal reporter and/or the sequence of hairpin probes.

Generation of a Yeast Cell Model Potentially Useful to Identify the Mammalian Mitochondrial N-Acetylglutamate Transporter.

The human mitochondrial carrier family (MCF) consists of 53 members. Approximately one-fifth of them are still orphans of a function. Most mitochondrial transporters have been functionally characterized by reconstituting the bacterially expressed protein into liposomes and transport assays with radiolabeled compounds. The efficacy of this experimental approach is constrained to the commercial availability of the radiolabeled substrate to be used in the transport assays. A striking example is that of N-acetylglutamate (NAG), an essential regulator of the carbamoyl synthetase I activity and the entire urea cycle. Mammals cannot modulate mitochondrial NAG synthesis but can regulate the levels of NAG in the matrix by exporting it to the cytosol, where it is degraded. The mitochondrial NAG transporter is still unknown. Here, we report the generation of a yeast cell model suitable for identifying the putative mammalian mitochondrial NAG transporter. In yeast, the arginine biosynthesis starts in the mitochondria from NAG which is converted to ornithine that, once transported into cytosol, is metabolized to arginine. The deletion of ARG8 makes yeast cells unable to grow in the absence of arginine since they cannot synthetize ornithine but can still produce NAG. To make yeast cells dependent on a mitochondrial NAG exporter, we moved most of the yeast mitochondrial biosynthetic pathway to the cytosol by expressing four E. coli enzymes, argB-E, able to convert cytosolic NAG to ornithine. Although argB-E rescued the arginine auxotrophy of arg8∆ strain very poorly, the expression of the bacterial NAG synthase (argA), which would mimic the function of a putative NAG transporter increasing the cytosolic levels of NAG, fully rescued the growth defect of arg8∆ strain in the absence of arginine, demonstrating the potential suitability of the model generated.

Ferrocene-based catalysts for in-situ hydrothermal upgrading of heavy crude oil: Synthesis and application

In this work, the effect of synthesized Ferrocene-based ligand catalysts, including Mono-, Di- and Tri-Ferrocene, as additives for promoting the catalytic in-situ hydrothermal upgrading of Tatarstan (Russia) heavy crude oil was studied. In addition, the changes in composition of upgraded oil samples as well as the in-situ transformation and characteristics of used catalysts were evaluated in detail using comprehensive analyzing techniques. All of the catalytic and non-catalytic hydrothermal upgrading experiments were carried out under the steam stimulation conditions at 300 °C, 72 bar (1044.27 psi) and 24 h of reaction time. The results show that introducing Ferrocene-based ligand catalysts to the upgrading system promotes the in-situ upgrading of heavy crude oil and improves the physical and chemical properties of upgraded oil samples. The maximum viscosity reduction was observed in presence Tri-Ferrocene and reached around 40% compared to non-catalytic hydrothermal upgrading. In addition, the upgrading performance also reflects in increase of H/C ratio, reduction of sulfur content, increase of saturates and aromatics, and decrease of the content of resins and asphaltenes as well as a noticeable change (increase) in the light fractions of C10-C20 are observed for all upgraded oil samples. Mono-Ferrocene as an oil-soluble catalyst mainly transformed to the particles of Fe3O4 (Magnetite) and FeS, which can act as active forms of catalysts and accelerate the hydrothermal conversion of heavy crude oil and its heavy fractions including resins and asphaltenes. These transformations were confirmed using XRD, SEM-EDX and Mössbauer analyzing techniques. Generally, the good catalytic performance of used ferrocene-based ligand catalysts as well as their low cost and commercial availability makes them great potential catalysts for improving the efficiency of steam injection for heavy oil production and in-situ upgrading.

Iron-mediated modular decarboxylative cross-nucleophile coupling

Carboxylic acids are valuable building blocks for pharmaceutical discovery because of their chemical stability, commercial availability, and structural diversity. Decarboxylative coupling reactions enable versatile functionalization of these feedstock chemicals, but many of the most general methods require prefunctionalization of carboxylic acids with redox-active moieties. These internal oxidants can be costly, their installation impedes rapid library synthesis, and their use results in environmentally problematic organic byproducts. We report herein a method for the direct decarboxylative cross-coupling of native carboxylic acids with nucleophilic coupling partners mediated by inexpensive, terrestrially abundant, and nontoxic Fe(III) salts. This method involves an initial photochemical decarboxylation followed by radical-polar crossover, which enables the construction of diverse carbon-carbon, carbon-oxygen, and carbon-nitrogen bonds with remarkable generality.

How does digital infrastructure affect residents' healthcare expenditures? Evidence from Chinese microdata.

Healthcare expenditure is only one of the heavy burdens that families face in developing countries. Current research mainly focuses on analyzing the effects of financial policy. There is a lack of studies that examine the understanding and assessment of the impact of digital infrastructure on this issue. In this study, we used the Broadband China policy as a quasi-natural experiment to explore the impact of digital infrastructure on residents' healthcare expenditures in China. Using the differences-in-differences (DID) model and micro-survey data, we found that digital infrastructure has a positive impact on reducing the burden of healthcare expenditure in China. Our findings indicate that residents in cities can save up to 18.8% on healthcare expenses following large-scale digital infrastructure construction. Through mechanism analysis, we found that digital infrastructure reduces residents' healthcare expenditures by improving both commercial insurance availability and the healthcare efficiency of residents. In addition, the effects of digital infrastructure on reducing healthcare expenditure are more pronounced among middle-aged individuals, those with low levels of education, and those with low incomes, which indicates this digital construction wave helps bridge the social gap between the poor and the rich. This study provides compelling evidence of the positive impact of digital society construction on social health and wellbeing.

Clinical Adverse Events and Device Failures Reported for the Captivator and Duette Endoscopic Mucosal Resection (EMR) Systems: A MAUDE Database Analysis.

Endoscopic mucosal resection (EMR) is a widely used technique for the removal of precancerous or select cancerous mucosal-based lesions. Two systems used for EMR of upper gastrointestinal lesions are the Duette EMR kit and the Captivator EMR kit. The aim of this study is to analyze the reports submitted to the Food and Drug Administration's (FDA) Manufacturer and User Facility Device Experience (MAUDE) database for patient-related adverse events and device failures associated with these EMR kits. We analyzed postmarketing data from the FDA MAUDE from August 2004 to August 2021. Eighty-four MAUDE reports were found in the study period from August 2004 to August 2021. In total, device issues comprised 36.9% of the reports (n=31) and patient adverse events comprised 63.09% of the reports (n=53). Device issues that were reported included, but were not limited to, band placement/deployment failure (8.1%), suture breakage (7.31%), and snare breakage (4.94%). Patient adverse events that were reported included, but were not limited to, bleeding (25.9%), perforation (7.31%), and snare breakage (4.94%). Captivator EMR and Duette EMR have similar patterns of technical failure and clinical adverse events. More MAUDE reports exist for Duette EMR, possibly due to its longer duration of commercial availability.

Prism Worldwide commercializes TPE derived from end-of-life tires

On May 9, 2023, Prism Worldwide announced the commercial availability of Ancora™ C-1000 Thermoplastic Elastomer, which contains 50% post-consumer recycle content derived from end-of-life tires.

CBD hydroxyquinone photo-isomerises to a highly reactive intermediate

The legalisation of hemp has led to wide commercial availability of cannabidiol (CBD)-containing products. Here we show that the CBD-hydroxyquinone (HU-331), a readily formed oxidation product and common impurity in CBD isolates, undergoes a previously unknown photo-isomerisation to produce a highly reactive intermediate in solution. Studies supported by calculations indicate that this intermediate rapidly reacts with oxygen to form a multitude of cannabinoid products. The purple colour observed in light-aged CBD-containing solutions is largely due to the anions of these by-products and is not significantly due to the HU-331 anion. Our findings suggest that these uncharacterized cannabinoid derivatives can be present in CBD-containing e-liquids and solutions that have been stored under ambient light conditions, calling for quality control processes that manage HU-331 contamination.

Application of Phosphorylated Alpha Synuclein (p-syn) Skin Biopsy in Clinical Practice: Audit at an Academic Medical Center (P8-9.004)

<h3>Objective:</h3> To assess how p-syn skin biopsy is being applied clinically by auditing its use in an academic medical center. <h3>Background:</h3> Cutaneous deposition of p-syn is found in synucleinopathies including Parkinson’s disease (PD), multiple system atrophy (MSA), dementia with Lewy body (DLB), and pure autonomic failure (PAF). Skin biopsy assessing for the presence of p-syn is an emerging diagnostic tool with reported good sensitivity and high specificity for detecting synucleinopathies. Commercial cutaneous testing for p-syn is now available in the US, though not yet in widespread clinical use despite its minimally invasive nature and relative accessibility in comparison to other testings such as DaTscan and MIBG myocardial scintigraphy. <h3>Design/Methods:</h3> All patients followed at our center who had undergone p-syn skin biopsy since its commercial availability were identified and their electronic medical records reviewed. <h3>Results:</h3> 10 patients underwent skin biopsies for p-sync from June 2021 to August 2022. 7 had isolated autonomic dysfunction; 2 had parkinsonism but potential alternative explanations (i.e. hydrocephalus, antidopaminergic medications), and 1 had speech apraxia with a question of Alzheimer or DLB. 5 of 7 patients with autonomic dysfunction had positive biopsies, obviating the search for other etiologies such as autoimmune disease or amyloidosis. The other 3 patients were also found to be p-sync positive. Affirming this diagnosis positively impacted subsequent monitoring and management and enabled accurate prognostication. <h3>Conclusions:</h3> Skin biopsy is a useful tool for diagnosing synucleinopathy in patients presenting with autonomic dysfunction. It can also add diagnostic value in patients with parkinsonism and other potential competing explanations. <b>Disclosure:</b> Dr. Wang has nothing to disclose. Dr. Robbins has received personal compensation in the range of $0-$499 for serving as a Consultant for Guidepoint Global Inc. The institution of Dr. Robbins has received research support from Diamond Endowment Fund. The institution of Dr. Robbins has received research support from Reeves Endowment Fund. The institution of Dr. Robbins has received research support from Institute for Ethnomedicine. The institution of Dr. Robbins has received research support from Dartmouth Hitchcock Swigart Ethics Fellowship. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Neurohospitalist with Hayes Locums. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Vickery &amp; Shepherd. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Vaccine Injury Compensation Program. Dr. Robbins has received personal compensation in the range of $10,000-$49,999 for serving as a Medical Expert with Kraft Davies PLLC. Dr. Robbins has received personal compensation in the range of $500-$4,999 for serving as a Medical Expert with Northwestern University.

Treatment Outcomes for Patients With Amyotrophic Lateral Sclerosis Receiving Intravenous Edaravone From a Home and Alternative-Site Infusion Provider (P6-4.005)

<h3>Objective:</h3> To describe real-world treatment outcomes in patients with ALS treated with IV edaravone collected by a provider of home/alternative-site infusions. <h3>Background:</h3> Intravenous (IV) edaravone was US Food and Drug Administration approved in May 2017 after it was shown to slow the rate of physical functional decline in patients with amyotrophic lateral sclerosis (ALS). Information on real-world use of IV edaravone is limited. <h3>Design/Methods:</h3> A retrospective cohort study was conducted utilizing de-identified data collected from Amerita Specialty Infusion Services, a US-based provider of home/alternative-site infusions that has treated and collected data from patients with ALS receiving IV edaravone since the time of commercial availability. Patients with ALS who received their first IV edaravone dose between September 25, 2017, and December 31, 2020, were included. Patient status was confirmed through March 31, 2021. Variables collected included patient demographics, revised ALS Functional Rating Scale (ALSFRS-R) and forced vital capacity (FVC) scores, and treatment outcomes. <h3>Results:</h3> Patients (N=153) receiving IV edaravone were included in this analysis; 66.0% were male, mean±SD age was 61.4±10.8 years, and 27.5% were covered by commercial insurance. In patients who had healthcare provider-recorded ALSFRS-R (n=61) and FVC (n=38) assessed ±100 days from start of care, mean±SD scores were 33.7±9.3 and 66%±24%, respectively. At the end of the study period, 105 (68.6%) patients had discontinued treatment. The most frequent reason for discontinuation was death/hospice (42.9%), doctor choice (19.0%), patient choice (18.1%), and insurance/care change (14.3%). Mean±SD treatment duration for patients who discontinued was 314±260 days. As of March 31, 2021, 48 (31.4%) patients were still receiving treatment with IV edaravone and their mean±SD treatment duration was 446±292 days. <h3>Conclusions:</h3> This analysis describes treatment outcomes in IV edaravone-treated patients with ALS in a real-world setting. This information may be useful to clinicians who prescribe IV edaravone for patients with ALS. <b>Disclosure:</b> Mrs. Da Silva has nothing to disclose. Malgorzata Ciepielewska has received personal compensation for serving as an employee of Mitsubishi Tanable Pharma America . Mr. Do has nothing to disclose. Miss Anderson has nothing to disclose. Mrs. Martin has received personal compensation for serving as an employee of Amerita Specialty Infusion. Dr. Ortlip has nothing to disclose.

Role of cyanuric chloride in organic synthesis: A concise overview

AbstractCyanuric chloride, a chlorinated analog of 1,3,5‐triazine, is used as a catalyst, promoter, and activator to catalyze and initiate several reactions like Beckmann rearrangement, Lossen rearrangement, Biginelli reaction, Suzuki coupling reaction, Pictet Spengler reaction, Mannich reaction, etc. It is employed in several reactions due to its several properties like stable, non‐volatile, cost‐efficient, easy to handle, and easy commercial availability. Moreover, it is a very renowned precursor for the synthesis of triazine‐class pesticide atrazine, dyes, and crosslinking agents. Herein in this review article, the reactions initiated, catalyzed, and promoted by cyanuric chloride from 2010 to 2022 have been elaborated.