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To unlock the full promise of messenger (mRNA) therapies, expanding the toolkit of lipid nanoparticles is paramount. However, a pivotal component of lipid nanoparticle development that remains a bottleneck is identifying new ionizable lipids. Here we describe an accelerated approach to discovering effective ionizable lipids for mRNA delivery that combines machine learning with advanced combinatorial chemistry tools. Starting from a simple four-component reaction platform, we create a chemically diverse library of 584 ionizable lipids. We screen the mRNA transfection potencies of lipid nanoparticles containing those lipids and use the data as a foundational dataset for training various machine learning models. We choose the best-performing model to probe an expansive virtual library of 40,000 lipids, synthesizing and experimentally evaluating the top 16 lipids flagged. We identify lipid 119-23, which outperforms established benchmark lipids in transfecting muscle and immune cells in several tissues. This approach facilitates the creation and evaluation of versatile ionizable lipid libraries, advancing the formulation of lipid nanoparticles for precise mRNA delivery.
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Técnicas de Química Combinatória , Lipídeos , Aprendizado de Máquina , RNA Mensageiro , Lipídeos/química , RNA Mensageiro/genética , RNA Mensageiro/química , Nanopartículas/química , Animais , Humanos , CamundongosRESUMO
EXECUTIVE SUMMARY: Microbes are all pervasive in their distribution and influence on the functioning and well-being of humans, life in general and the planet. Microbially-based technologies contribute hugely to the supply of important goods and services we depend upon, such as the provision of food, medicines and clean water. They also offer mechanisms and strategies to mitigate and solve a wide range of problems and crises facing humanity at all levels, including those encapsulated in the sustainable development goals (SDGs) formulated by the United Nations. For example, microbial technologies can contribute in multiple ways to decarbonisation and hence confronting global warming, provide sanitation and clean water to the billions of people lacking them, improve soil fertility and hence food production and develop vaccines and other medicines to reduce and in some cases eliminate deadly infections. They are the foundation of biotechnology, an increasingly important and growing business sector and source of employment, and the centre of the bioeconomy, Green Deal, etc. But, because microbes are largely invisible, they are not familiar to most people, so opportunities they offer to effectively prevent and solve problems are often missed by decision-makers, with the negative consequences this entrains. To correct this lack of vital knowledge, the International Microbiology Literacy Initiative-the IMiLI-is recruiting from the global microbiology community and making freely available, teaching resources for a curriculum in societally relevant microbiology that can be used at all levels of learning. Its goal is the development of a society that is literate in relevant microbiology and, as a consequence, able to take full advantage of the potential of microbes and minimise the consequences of their negative activities. In addition to teaching about microbes, almost every lesson discusses the influence they have on sustainability and the SDGs and their ability to solve pressing problems of societal inequalities. The curriculum thus teaches about sustainability, societal needs and global citizenship. The lessons also reveal the impacts microbes and their activities have on our daily lives at the personal, family, community, national and global levels and their relevance for decisions at all levels. And, because effective, evidence-based decisions require not only relevant information but also critical and systems thinking, the resources also teach about these key generic aspects of deliberation. The IMiLI teaching resources are learner-centric, not academic microbiology-centric and deal with the microbiology of everyday issues. These span topics as diverse as owning and caring for a companion animal, the vast range of everyday foods that are produced via microbial processes, impressive geological formations created by microbes, childhood illnesses and how they are managed and how to reduce waste and pollution. They also leverage the exceptional excitement of exploration and discovery that typifies much progress in microbiology to capture the interest, inspire and motivate educators and learners alike. The IMiLI is establishing Regional Centres to translate the teaching resources into regional languages and adapt them to regional cultures, and to promote their use and assist educators employing them. Two of these are now operational. The Regional Centres constitute the interface between resource creators and educators-learners. As such, they will collect and analyse feedback from the end-users and transmit this to the resource creators so that teaching materials can be improved and refined, and new resources added in response to demand: educators and learners will thereby be directly involved in evolution of the teaching resources. The interactions between educators-learners and resource creators mediated by the Regional Centres will establish dynamic and synergistic relationships-a global societally relevant microbiology education ecosystem-in which creators also become learners, teaching resources are optimised and all players/stakeholders are empowered and their motivation increased. The IMiLI concept thus embraces the principle of teaching societally relevant microbiology embedded in the wider context of societal, biosphere and planetary needs, inequalities, the range of crises that confront us and the need for improved decisioning, which should ultimately lead to better citizenship and a humanity that is more sustainable and resilient. ABSTRACT: The biosphere of planet Earth is a microbial world: a vast reactor of countless microbially driven chemical transformations and energy transfers that push and pull many planetary geochemical processes, including the cycling of the elements of life, mitigate or amplify climate change (e.g., Nature Reviews Microbiology, 2019, 17, 569) and impact the well-being and activities of all organisms, including humans. Microbes are both our ancestors and creators of the planetary chemistry that allowed us to evolve (e.g., Life's engines: How microbes made earth habitable, 2023). To understand how the biosphere functions, how humans can influence its development and live more sustainably with the other organisms sharing it, we need to understand the microbes. In a recent editorial (Environmental Microbiology, 2019, 21, 1513), we advocated for improved microbiology literacy in society. Our concept of microbiology literacy is not based on knowledge of the academic subject of microbiology, with its multitude of component topics, plus the growing number of additional topics from other disciplines that become vitally important elements of current microbiology. Rather it is focused on microbial activities that impact us-individuals/communities/nations/the human world-and the biosphere and that are key to reaching informed decisions on a multitude of issues that regularly confront us, ranging from personal issues to crises of global importance. In other words, it is knowledge and understanding essential for adulthood and the transition to it, knowledge and understanding that must be acquired early in life in school. The 2019 Editorial marked the launch of the International Microbiology Literacy Initiative, the IMiLI. HERE, WE PRESENT: our concept of how microbiology literacy may be achieved and the rationale underpinning it; the type of teaching resources being created to realise the concept and the framing of microbial activities treated in these resources in the context of sustainability, societal needs and responsibilities and decision-making; and the key role of Regional Centres that will translate the teaching resources into local languages, adapt them according to local cultural needs, interface with regional educators and develop and serve as hubs of microbiology literacy education networks. The topics featuring in teaching resources are learner-centric and have been selected for their inherent relevance, interest and ability to excite and engage. Importantly, the resources coherently integrate and emphasise the overarching issues of sustainability, stewardship and critical thinking and the pervasive interdependencies of processes. More broadly, the concept emphasises how the multifarious applications of microbial activities can be leveraged to promote human/animal, plant, environmental and planetary health, improve social equity, alleviate humanitarian deficits and causes of conflicts among peoples and increase understanding between peoples (Microbial Biotechnology, 2023, 16(6), 1091-1111). Importantly, although the primary target of the freely available (CC BY-NC 4.0) IMiLI teaching resources is schoolchildren and their educators, they and the teaching philosophy are intended for all ages, abilities and cultural spectra of learners worldwide: in university education, lifelong learning, curiosity-driven, web-based knowledge acquisition and public outreach. The IMiLI teaching resources aim to promote development of a global microbiology education ecosystem that democratises microbiology knowledge.
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Microbiologia , Microbiologia/educação , Humanos , BiotecnologiaRESUMO
T Cell Receptor (TCR) antigen binding underlies a key mechanism of the adaptive immune response yet the vast diversity of TCRs and the complexity of protein interactions limits our ability to build useful low dimensional representations of TCRs. To address the current limitations in TCR analysis we develop a capacity-controlled disentangling variational autoencoder trained using a dataset of approximately 100 million TCR sequences, that we name TCR-VALID. We design TCR-VALID such that the model representations are low-dimensional, continuous, disentangled, and sufficiently informative to provide high-quality TCR sequence de novo generation. We thoroughly quantify these properties of the representations, providing a framework for future protein representation learning in low dimensions. The continuity of TCR-VALID representations allows fast and accurate TCR clustering and is benchmarked against other state-of-the-art TCR clustering tools and pre-trained language models.
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Receptores de Antígenos de Linfócitos T , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Receptores de Antígenos de Linfócitos T/genética , Humanos , Aprendizado Profundo , Algoritmos , Análise por Conglomerados , Biologia Computacional/métodos , Sequência de AminoácidosRESUMO
Alfalfa is a commonly grown forage in the Intermountain West region of the United States and is often included in the diet of dairy cattle. Alfalfa provides a variety of different nutrients, but the nutrient content of alfalfa varies depending on factors such as the soil, region, cutting, and climate. However, alfalfa leaves tend to have less variation in their nutrient content than alfalfa stems. Fractionating alfalfa may be one way to improve control of nutrients provided when developing a ration for developing dairy heifers. The purpose of this study was to determine whether including fractionated alfalfa in the diet impacts the growth or conception rates of developing dairy heifers. Heifers were allocated to one of three treatments: a control group fed a typical diet (CON; nâ =â 8), a diet that replaced alfalfa with fractionated alfalfa leaf pellets and alfalfa stems (ProLEAF MAXâ +â ProFiber Plus; PLMâ +â PFP; nâ =â 8), or a diet that replaced alfalfa with alfalfa stems (PFP; nâ =â 8) for 85 d. Heifers were fed individually twice daily and weight, hip height (HH), and wither height (WH) were recorded every 14 d. Additionally, blood was collected every 28 d, and conception rates were recorded at the end of the trial. Heifers receiving the PFP diet consumed less dry matter (Pâ =â 0.001) than the CON treatment. Analyses were then conducted to determine nutrient intake and heifers receiving the PFP diet also consumed less neutral detergent fiber (Pâ =â 0.02), acid detergent fiber (Pâ =â 0.02), crude protein (Pâ =â 0.001), and net energy for maintenance (Pâ =â 0.001) than heifers consuming the CON diet; however, no differences (Pâ >â 0.10) were observed between heifers fed the CON and PLMâ +â PFP diets. Analysis of body weight gain over the feeding period showed no difference (Pâ =â 0.52) among heifers consuming the different treatment diets. Additionally, treatment did not affect average daily gain (Pâ =â 0.49), gain:feed (Pâ =â 0.82), HH gain (Pâ =â 0.20), or WH gain (Pâ =â 0.44) among heifers receiving different diets. Treatmentâ ×â time altered (Pâ <â 0.001) blood urea nitrogen when analyzed as a repeated measure. Total feed cost was lowest (Pâ <â 0.001) for the PFP diet and cost of gain tended (Pâ =â 0.09) to be increased for the PLMâ +â PFP diet compared to the CON diet. Overall, these data indicate that including alfalfa stems in a developing heifer diet may decrease dry matter intake, lower input costs, and increase profitability, without negatively impacting growth.
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PURPOSE: Diffuse midline glioma (DMG) has seen a surge of research interest in recent years with the growth in knowledge of new avenues for potential treatments. However, no bibliometric review of the field has been conducted to visualize the current state of the field. Here, we use bibliometric mapping to visualize the knowledge structure, collaborations, and trends in the field. METHODS: A total of 1079 original and review articles from 1996 to 2023 on diffuse midline glioma were extracted from the Web of Science Core Collection on June 3, 2023. These files were analyzed with R and VOSviewer to construct bibliometric visualizations. RESULTS: Research interest in DMG has continued to grow, driven by publications of original research. Molecular characterization of DMG has been a key focus of recent literature, and terms relating to novel small molecules, mutations, immunotherapy, the blood-brain barrier, and liquid biopsy may be areas for future growth in the literature. Collaborating nations have generally been the North American and European nations, but other nations have begun to make their mark in the field. Leading and rising institutions and journals are described. CONCLUSION: Research in DMG may continue to focus on molecular characterization and new therapeutics based on this knowledge. Novel collaborations between rising nations and institutions in the field may aid in accelerating this research.
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Bibliometria , Glioma , Humanos , Criança , Barreira Hematoencefálica , Imunoterapia , Mutação , Glioma/terapiaRESUMO
PURPOSE: To quantify the safety and utility of biopsy of pediatric diffuse midline glioma (DMG). METHODS: This study was conducted in accordance with PRISMA guidelines. PubMed, Embase, Scopus, and Web of Science were queried for relevant articles from inception until June 2023. Two reviewers identified all articles that included diagnostic yield, morbidity, and mortality rates for pediatric DMG patients. Studies that did not present original data or were not in English or peer-reviewed were excluded. Meta-analysis was conducted in R using Freeman-Tukey or logit transformation and DerSimonian-Laird random-effects models. The risk of bias was assessed using the Newcastle-Ottawa Scale. A protocol for this review was not registered. RESULTS: We identified 381 patients from ten studies that met all criteria. DMG biopsy is safe overall (0% mortality, 95% CI: 0-0.6%; 11.0% morbidity, 95% CI: 4.8-18.9%) and has a high diagnostic yield (99.9%, 95% CI: 98.5-100%). The use of stereotactic biopsy is a significant moderator of morbidity (p = 0.0238). Molecular targets can be identified in approximately 53.4% of tumors (95% CI: 37.0-69.0%), although targeted therapies are only delivered in about 33.5% of all cases (95% CI: 24.4-44.1%). Heterogeneity was high for morbidity and identification of targets. The risk of bias was low for all studies. CONCLUSION: We conducted the first meta-analysis of DMG biopsy to show that it is safe, effective, and able to identify relevant molecular targets that impact targeted therapy.
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Glioma , Humanos , Criança , Biópsia/métodos , Glioma/diagnósticoRESUMO
Inhaled delivery of mRNA has the potential to treat a wide variety of diseases. However, nebulized mRNA lipid nanoparticles (LNPs) face several unique challenges including stability during nebulization and penetration through both cellular and extracellular barriers. Here we develop a combinatorial approach addressing these barriers. First, we observe that LNP formulations can be stabilized to resist nebulization-induced aggregation by altering the nebulization buffer to increase the LNP charge during nebulization, and by the addition of a branched polymeric excipient. Next, we synthesize a combinatorial library of ionizable, degradable lipids using reductive amination, and evaluate their delivery potential using fully differentiated air-liquid interface cultured primary lung epithelial cells. The final combination of ionizable lipid, charge-stabilized formulation and stability-enhancing excipient yields a significant improvement in lung mRNA delivery over current state-of-the-art LNPs and polymeric nanoparticles.
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Excipientes , Nanopartículas , Diferenciação Celular , Polímeros , RNA Mensageiro/genética , RNA Interferente PequenoRESUMO
In this study, a novel fabrication process, to the best of our knowledge, was developed to fabricate a glass harmonic diffractive lens. In this process, a polymethylmethacrylate master of the diffractive lens was machined using single-point diamond turning. Then an electrolytic plating process was conducted to grow a reverse nickel (Ni) mold. Precision compression molding was performed using the Ni mold to replicate the diffractive lens structures onto a glass surface. Surface measurements and optical testing show that the replicated diffractive lenses by the proposed method have high tolerances and require optical performance, demonstrating a high-volume, high-precision, and cost-effective process. The proposed method will be critical for consumer products where glass optics are increasingly used in lens assemblies.
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Importance: Polymicrogyria is the most commonly diagnosed cortical malformation and is associated with neurodevelopmental sequelae including epilepsy, motor abnormalities, and cognitive deficits. Polymicrogyria frequently co-occurs with other brain malformations or as part of syndromic diseases. Past studies of polymicrogyria have defined heterogeneous genetic and nongenetic causes but have explained only a small fraction of cases. Objective: To survey germline genetic causes of polymicrogyria in a large cohort and to consider novel polymicrogyria gene associations. Design, Setting, and Participants: This genetic association study analyzed panel sequencing and exome sequencing of accrued DNA samples from a retrospective cohort of families with members with polymicrogyria. Samples were accrued over more than 20 years (1994 to 2020), and sequencing occurred in 2 stages: panel sequencing (June 2015 to January 2016) and whole-exome sequencing (September 2019 to March 2020). Individuals seen at multiple clinical sites for neurological complaints found to have polymicrogyria on neuroimaging, then referred to the research team by evaluating clinicians, were included in the study. Targeted next-generation sequencing and/or exome sequencing were performed on probands (and available parents and siblings) from 284 families with individuals who had isolated polymicrogyria or polymicrogyria as part of a clinical syndrome and no genetic diagnosis at time of referral from clinic, with sequencing from 275 families passing quality control. Main Outcomes and Measures: The number of families in whom genetic sequencing yielded a molecular diagnosis that explained the polymicrogyria in the family. Secondarily, the relative frequency of different genetic causes of polymicrogyria and whether specific genetic causes were associated with co-occurring head size changes were also analyzed. Results: In 32.7% (90 of 275) of polymicrogyria-affected families, genetic variants were identified that provided satisfactory molecular explanations. Known genes most frequently implicated by polymicrogyria-associated variants in this cohort were PIK3R2, TUBB2B, COL4A1, and SCN3A. Six candidate novel polymicrogyria genes were identified or confirmed: de novo missense variants in PANX1, QRICH1, and SCN2A and compound heterozygous variants in TMEM161B, KIF26A, and MAN2C1, each with consistent genotype-phenotype relationships in multiple families. Conclusions and Relevance: This study's findings reveal a higher than previously recognized rate of identifiable genetic causes, specifically of channelopathies, in individuals with polymicrogyria and support the utility of exome sequencing for families affected with polymicrogyria.
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Polimicrogiria , Humanos , Polimicrogiria/diagnóstico por imagem , Polimicrogiria/genética , Sequenciamento do Exoma , Estudos Retrospectivos , Mutação de Sentido Incorreto , Irmãos , Proteínas do Tecido Nervoso/genética , Conexinas/genéticaRESUMO
The integration of inorganic components with bacterial biofilms is of great significance for expanding the functionality of artificial biological materials. However, so far, the complexities and functionalities of biofilm-based scaffolds assembled via metal-peptide coordination chemistries remain limited. Here, we present a platform for the multiplexed and specific coupling of recombinant protein-functionalized fluorescent red-green-blue (RGB) quantum dots (QDs) with engineered biofilms to form Jabuticaba-like nanostructures. Full-color living Jabuticaba-like nanostructures have been achieved through the interaction of extracellular peptides that are fabricated by biofilms with the proteins that modify the surface of the RGB QDs through orthogonal SpyTag/SpyCatcher, IsopeptagN/PilinN, and IsopeptagC/PilinC pairs. We envision that living cell populations will enable the multiplexable, scalable and bottom-up assembly of versatile materials that integrate both abiotic and biotic components into multifunctional systems.
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Nanoestruturas , Pontos Quânticos , Pontos Quânticos/química , Cor , Proteínas , Peptídeos , BiofilmesRESUMO
We offer a new biogenetic proposal for the origin of the complex alkaloid alstonlarsineâ A, through rearrangement of the Strychnos alkaloids alstolucinesâ B and F. Further, we provide evidence of the chemical feasibility of this proposal in the facile conversion of synthetic alstolucines into alstonlarsineâ A through a short, efficient sequence of N-methylation, ß-elimination, and a cascade 1,7-hydride shift/Mannich cyclization. We believe that this is the first biogenetic proposal involving the "tert-amino effect", a hydride-shift-based internal redox trigger of a Mannich cyclization. A further interesting feature of the cascade is that its stereochemical outcome most likely originates in conformational preferences during the hydride shift.
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Alcaloides , Estrutura Molecular , Estudos de Viabilidade , Alcaloides/química , Conformação Molecular , Ciclização , EstereoisomerismoRESUMO
BACKGROUND: Contingency management is an evidence-based yet underutilized approach for opioid use disorder (OUD). Reasons for limited adoption in real-world practice include ethical, moral, and philosophical concerns regarding use of monetary incentives, and lack of technological innovation. In light of surging opioid overdose deaths, there is a need for development of technology-enabled solutions leveraging the power of contingency management in a way that is viewed by both patients and providers as acceptable and feasible. OBJECTIVE: This mixed methods pilot study sought to determine the perceived acceptability and usability of PROCare Recovery, a reward-based, technology-enabled recovery monitoring smartphone app designed to automate contingency management by immediately delivering micropayments to patients for achieving recovery goals via smart debit card with blocking capabilities. METHODS: Participants included patients receiving buprenorphine for OUD (n=10) and licensed prescribers (n=5). Qualitative interviews were conducted by 2 PhD-level researchers via video conferencing to explore a priori hypotheses. Thematic analysis of interviews was conducted and synthesized into major themes. RESULTS: Participants were overwhelmingly in favor of microrewards (eg, US $1) to incentivize treatment participation (up to US $150 monthly). Participants reported high acceptability of the planned debit card spending restrictions (blocking cash withdrawals and purchases at bars or liquor stores, casinos or online gambling). Quantitative data revealed a high level of perceived usability of the PROCare Recovery app. CONCLUSIONS: Patients and providers alike appear receptive to microfinancial incentives in standard OUD treatment practices. Further pilot testing of PROCare is underway to determine acceptability, feasibility, and preliminary effectiveness in a rigorous randomized controlled trial.
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Background: Since December of 2019, coronavirus 19 (COVID-19) has spread rapidly around the world. Our understanding of the infection has grown over the past year, and its impact on older adults is particularly significant. Apart from the direct impacts of COVID-19 infections, it has also led to lockdowns which, in turn, result in isolation and loneliness. Method: We conducted a literature review of publicly available articles of the COVID-19 pandemic impact on the geriatric population between December 2019 and April 2021, a total of 748 articles. Results: The review will be presented with the Bio-Psycho-Social model, covering how the biological, psychological, and sociological aspects of health are intertwined and impact older adults. Early studies have also highlighted the prevalence of post-COVID infection symptoms that typically fall under geriatric medicine care. We highlight the bidirectional impact of isolation and COVID-19 infections on geriatric health, as well as discuss pertinent topics such as vaccine efficacy, long-term sequelae of COVID-19 infections, and ageism. Conclusion: This review seeks to present a one-year report of what is known about COVID-19 and geriatric medicine, as well as provide guidance to practitioners who care for older adults based on the most up-to-date literature.
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Purpose: To understand the degree and explore the possible causes of ocular graft-versus-host disease (oGVHD) underdiagnosis in patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT). Patients and Methods: A 15-question survey was emailed to 6032 subscribers to the Blood and Marrow Transplant Information Network. A total of 371 respondents confirmed the history of allo-HSCT, of which 335 were symptomatic. Their self-reported symptoms, onset, treatments tried, degree of symptom control and established diagnoses of systemic chronic graft-versus-host disease (cGVHD) and oGVHD were analyzed. Results: Among the 335 symptomatic survey respondents, 306 reported their ocular symptom onset was after allo-HSCT, with only 170 [55.6% (170/306)] ever receiving a diagnosis of oGVHD; 23 reported worsening pre-existing ocular symptoms after allo-HSCT, with only 5 [21.7% (5/23)] ever receiving a diagnosis of oGVHD; 6 reported stable symptoms before and after allo-HSCT, with 1 ever receiving a diagnosis of oGVHD. Of the 176 respondents carrying the diagnosis of oGVHD, 167 [94.9% (167/176)] also had the diagnosis of cGVHD. Logistic regression analysis showed that the diagnosis of oGVHD was highly correlated with the number of symptoms and treatments one reported. Furthermore, 35% of the respondents with new onset ocular symptoms reported onset within the first 6 months after allo-HSCT (previously reported), as well as 39% of the respondents with worsened existing symptoms. Conclusion: oGVHD underdiagnosis is likely associated with the previous diagnostic criteria, in which cGVHD of another organ system was required. The correct notion that oGVHD commonly causes severe dry eye disease has likely led to its underdiagnosis in patients with fewer number of symptoms and/or who tried fewer treatments.
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Purpose: To determine the outcomes of Ahmed glaucoma valve (AGV) and transscleral diode cyclophotocoagulation (CPC) in neovascular glaucoma (NVG). Methods: This was a single-center retrospective comparative case series involving chart review of consecutive patients who underwent AGV or CPC for treatment of NVG and had ≥6 months of follow-up. Surgical failure at 6 months, defined as an IOP of >21 or <6 mm Hg with hypotony maculopathy after 1 month, progression to no light perception (NLP) vision, glaucoma reoperation, or removal of AGV were the main outcome measures. Results: In total, 121 eyes of 121 patients were included (70 AGV and 51 CPC). Baseline demographics, visual acuity (VA), and intraocular pressure (IOP) were comparable between groups. At 6 months, failure was significantly higher in the CPC group than in the AGV group (43.1% vs. 17.1%, P = 0.020). Both groups had similar IOP and medication number at 6 months, but VA was significantly lower in the CPC group compared to the AGV group (2.4 ± 0.8 vs. 1.9 ± 1.0, P = 0.017). More CPC eyes required reoperation for glaucoma than AGV eyes (11.8% vs. 1.4%, P = 0.041). Multivariate regression analysis identified higher preoperative IOP (P = 0.001) and CPC surgery (P = 0.004) as independent predictors of surgical failure at 6 months. Age, sex, race, NVG etiology, bilaterality of the underlying retinal pathology, perioperative retina treatment, and prior or combined vitrectomy were not significant. Conclusion: AGV and CPC had comparable IOP and medication reduction in NVG eyes at 6 months. CPC was more frequently associated with failure, reoperation for glaucoma, and worse visual outcomes. High preoperative IOP and CPC surgery independently predicted surgical failure.
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Implantes para Drenagem de Glaucoma , Glaucoma Neovascular , Glaucoma , Seguimentos , Glaucoma/cirurgia , Glaucoma Neovascular/diagnóstico , Glaucoma Neovascular/cirurgia , Humanos , Pressão Intraocular , Fotocoagulação a Laser , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Graphene interacts with electromagnetic waves strongly in a wide range from ultra-violet to far-infrared, making the graphene coating suitable for a variety of applications. In this study, a novel localized rapid heating technique utilizing micro-patterned silicon stampers with carbide-bonded graphene coating, which directly heats up by absorbing mid-infrared light radiation, is implemented in rapid precision optical molding. The graphene network, as a functional coating to obtain thermal energy and improve the anti-adhesion of the mold surface, can heat up the mold surface rapidly (up to 18.16â K/s) and evenly above glass transition temperature over a large area within several seconds. Since the graphene coating was around tens of nanometers (â¼45â nm) thick, the rapid precision surface molding process can be shortened into tens of seconds. Furthermore, the thermal response and repeatability of the graphene coated silicon wafer is investigated by repeated thermal cycling. This novel rapid precision surface molding technique is successfully tested to replicate grating structures and periodic patterns from silicon molds to thermoplastic substrates with high accuracy. Compared with conventional methods, this new approach can achieve much higher replication fidelity with a shorter cycle time and lower energy consumption.
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Alfalfa is often included in the diets of beef animals; however, the nutrient content of alfalfa is variable depending on the region in which it is grown, climate, soil, and many other factors. The leaf portion of alfalfa has a less variable nutrient composition than the stem portion of the plant. The variability that is present in the alfalfa plant can make the development of total mixed rations of consistent nutrient content difficult. As such, the purpose of this study was to determine how the inclusion of fractionated alfalfa leaves and alfalfa stems impacts performance and carcass quality of finishing beef steers. Twenty-four steers were allocated to one of three treatments: a control group fed a typical finishing diet with alfalfa as the forage (CON; n = 8), a typical diet that replaced alfalfa with fractionated alfalfa leaf pellets and alfalfa stems (ProLEAF MAX™ + ProFiber Plus™; PLM+PFP; n = 8), or a typical diet that replaced alfalfa with alfalfa stems (PFP; n = 8) for 63 days. Steers were fed individually once daily, weighed every 14 days and ultrasound images were collected every 28 days. At the end of the feeding trial, steers were harvested at a commercial facility and carcass data was obtained. Analysis of dry matter intake demonstrated that steers receiving the PFP and CON diets consumed more feed (P < 0.001) than steers consuming the PLM+PFP diet. Steers receiving the PLM+PFP diet gained less (P < 0.001) weight than the steers receiving the other two dietary treatments. No differences (P > 0.10) in feed efficiency or carcass characteristics were observed. Steers receiving the PFP diet had improved (P = 0.016) cost of gain ($0.93 per kg) when compared with steers receiving PLM+PFP ($1.08 per kg) diet. Overall, our findings demonstrate that the inclusion of PFP in place of alfalfa hay in a finishing diet has the potential to improve cost of gain, without negatively affecting growth, performance, or carcass characteristics of finishing feedlot steers.