Let's talk about flux: the rising potential of autophagy rate measurements in disease.

Macroautophagy/autophagy is increasingly implicated in a variety of diseases, making it an attractive therapeutic target. However, many aspects of autophagy are not fully understood and its impact on many diseases remains debatable and context-specific. The lack of systematic and dynamic measurements in these cases is a key reason for this ambiguity. In recent years, Loos et al. 2014 and Beesabathuni et al. 2022 developed methods to quantitatively measure autophagy holistically. In this commentary, we pose some of the unresolved biological questions regarding autophagy and consider how quantitative measurements may address them. While the applications are ever-expanding, we provide specific use cases in cancer, virus infection, and mechanistic screening. We address how the rate measurements themselves are central to developing cancer therapies and present ways in which these tools can be leveraged to dissect the complexities of virus-autophagy interactions. Screening methods can be combined with rate measurements to mechanistically decipher the labyrinth of autophagy regulation in cancer and virus infection. Taken together, these approaches have the potential to illuminate the underlying mechanisms of various diseases.Abbreviation MAP1LC3/LC3: microtubule-associated protein 1 light chain 3; R1: rate of autophagosome formation; R2: rate of autophagosome-lysosome fusion; R3: rate of autolysosome turnover.

Water, Sanitation, and Hygiene (WASH) Factors Influencing the Effectiveness of Mass Drug Administration to Eliminate Trachoma as a Public Health Problem in Malawi.

PURPOSE: Following a national population-based trachoma survey in Malawi one round of azithromycin mass drug administration (MDA) was carried out, with a post-MDA impact survey showing TF prevalence below 5% and considered eliminated as a public health problem. However, active trachoma was still present in over 200 children. We assessed whether water, sanitation, and hygiene (WASH) factors were associated with ongoing presence of TF in children aged 1-9 years following MDA. METHODS: A secondary analysis was performed on a sub-set of the post-MDA impact survey data for children aged 1-9 years. We used a logistic regression analysis, adjusted for clustering at the household and village level. RESULTS: Among 16,142 children aged 1-9 years, 209 (1.3%) had TF after MDA. Factors associated with a significantly lower odds of TF after MDA were living in a household with a handwashing facility (aOR: 0.37) and living in a household where water for washing is located further away from the home (30 min away aOR: 0.39, p = .034, or more than 1 h away aOR: 0.31, p = .018) compared with water in the yard. CONCLUSION: The inverse association between a domestic handwashing facility and TF is consistent with previous findings, but the association of increasing distance to collect water for washing with a reduced risk of TF was unexpected and may reflect the impact of drought and unmeasured behavioural factors related to water usage. A more comprehensive collection of sociodemographic and WASH factor information in population-based trachoma surveys will provide insight into achieving and maintaining low levels of trachoma.

Multi-objective operation optimization of spent coffee ground torrefaction for carbon-neutral biochar production.

Many energy-intensive processes are employed to enhance biomass fuel properties to overcome the difficulties in utilizing biomass as fuel. Therefore, energy conservation during these processes is crucial for realizing a circular bioeconomy. This study develops a newly devised method to evaluate SCG biochars' higher heating value (HHV) and predict moisture content from power consumption. It is found that the increasing rates of HHV immediately follow decreases in power consumption, which could be used to determine the pretreatment time for energy conservation. The non-dominated sorting genetic algorithm II (NSGA-II) maximizes SCG biochar's HHV while minimizing energy consumption. The results show that producing SCG biochar with 23.98 MJ∙kg-1 HHV requires 20.042 MJ∙kg-1, using a torrefaction temperature of 244 °C and torrefaction time of 27 min and 43 sec. Every kilogram of biochar with an energy yield of 85.93 % is estimated to cost NT$ 12.21.

Design of biorefineries towards carbon neutrality: A critical review.

The increase in worldwide demand for energy is driven by the rapid increase in population and exponential economic development. This resulted in the fast depletion of fossil fuel supplies and unprecedented levels of greenhouse gas in the atmosphere. To valorize biomass into different bioproducts, one of the popular and carbon-neutral alternatives is biorefineries. This system is an appropriate technology in the circular economy model. Various research highlighted the role of biorefineries as a centerpiece in the carbon-neutral ecosystem of technologies of the circular economy model. To fully realize this, various improvements and challenges need to be addressed. This paper presents a critical and timely review of the challenges and future direction of biorefineries as an alternative carbon-neutral energy source.

Application of regression and artificial neural network analysis of Red-Green-Blue image components in prediction of chlorophyll content in microalgae.

This study presented a novel methodology to predict microalgae chlorophyll content from colour models using linear regression and artificial neural network. The analysis was performed using SPSS software. Type of extractant solvents and image indexes were used as the input data for the artificial neural network calculation. The findings revealed that the regression model was highly significant, with high R2 of 0.58 and RSME of 3.16, making it a useful tool for predicting the chlorophyll concentration. Simultaneously, artificial neural network model with R2 of 0.66 and low RMSE of 2.36 proved to be more accurate than regression model. The model which fitted to the experimental data indicated that acetone was a suitable extraction solvent. In comparison to the cyan-magenta-yellow-black model in image analysis, the red-greenblue model offered a better correlation. In short, the estimation of chlorophyll concentration using prediction models are rapid, more efficient, and less expensive.

CRISPR/Cas9-mediated Gene Knockout Followed by Negative Selection Leads to a Complete TCR Depletion in ortho CAR19 T Cells.

Genome-editing technologies, especially CRISPR (clustered regularly interspaced short palindrome repeats)/Cas9 (CRISPR-associated protein 9), endows researchers the ability to make efficient, simple , and precise genomic DNA changes in many eukaryotic cell types. CRISPR/Cas9-mediated efficient gene knockout holds huge potential to improve the efficacy and safety of chimeric antigen receptor (CAR) T cell-based immunotherapies. Here, we describe an optimized approach for a complete loss of endogenous T cell receptor (TCR) protein expression, by CRISPR/Cas9-mediated TCR α constant (TRAC) and TCR ß constant (TRBC) gene knockout, followed by subsequent CD3 negative selection in engineered human ortho CAR19 T cells. We believe this method can be expanded beyond CAR T cell application, and target other cell surface receptors. Graphical abstract: Schematic overview of the two-step process of endogenous TCR depletion in engineered human ortho CAR19 T cells using (1) CRISPR/Cas9-mediated gene knockout followed by (2) CD3 negative selection.

Life cycle assessment of microalgal biorefinery: A state-of-the-art review.

Microalgal biorefineries represent an opportunity to economically and environmentally justify the production of bioproducts. The generation of bioproducts within a biorefinery system must quantitatively demonstrate its viability in displacing traditional fossil-based refineries. To this end, several works have conducted life cycle analyses on microalgal biorefineries and have shown technological bottlenecks due to energy-intensive processes. This state-of-the-art review covers different studies that examined microalgal biorefineries through life cycle assessments and has identified strategic technologies for the sustainable production of microalgal biofuels through biorefineries. Different metrics were introduced to supplement life cycle assessment studies for the sustainable production of microalgal biofuel. Challenges in the comparison of various life cycle assessment studies were identified, and the future design choices for microalgal biorefineries were established.

Design of a Vaccine Passport Validation System Using Blockchain-based Architecture: Development Study.

BACKGROUND: COVID-19 is an ongoing global pandemic caused by SARS-CoV-2. As of June 2021, 5 emergency vaccines were available for COVID-19 prevention, and with the improvement of vaccination rates and the resumption of activities in each country, verification of vaccination has become an important issue. Currently, in most areas, vaccination and reverse transcription polymerase chain reaction (RT-PCR) test results are certified and validated on paper. This leads to the problem of counterfeit documents. Therefore, a global vaccination record is needed. OBJECTIVE: The main objective of this study is to design a vaccine passport (VP) validation system based on a general blockchain architecture for international use in a simulated environment. With decentralized characteristics, the system is expected to have the advantages of low cost, high interoperability, effectiveness, security, and verifiability through blockchain architecture. METHODS: The blockchain decentralized mechanism was used to build an open and anticounterfeiting information platform for VPs. The contents of a vaccination card are recorded according to international Fast Healthcare Interoperability Resource (FHIR) standards, and blockchain smart contracts (SCs) are used for authorization and authentication to achieve hierarchical management of various international hospitals and people receiving injections. The blockchain stores an encrypted vaccination path managed by the user who manages the private key. The blockchain uses the proof-of-authority (PoA) public chain and can access all information through the specified chain. This will achieve the goal of keeping development costs low and streamlining vaccine transit management so that countries in different economies can use them. RESULTS: The openness of the blockchain helps to create transparency and data accuracy. This blockchain architecture contains a total of 3 entities. All approvals are published on Open Ledger. Smart certificates enable authorization and authentication, and encryption and decryption mechanisms guarantee data protection. This proof of concept demonstrates the design of blockchain architecture, which can achieve accurate global VP verification at an affordable price. In this study, an actual VP case was established and demonstrated. An open blockchain, an individually approved certification mechanism, and an international standard vaccination record were introduced. CONCLUSIONS: Blockchain architecture can be used to build a viable international VP authentication process with the advantages of low cost, high interoperability, effectiveness, security, and verifiability.

An Interprofessional Approach to Chronic Pain Management and Education.

BACKGROUND AND OBJECTIVES: The opioid epidemic highlights the importance of evidence-based practices in the management of chronic pain and the need for improved resident education focused on chronic pain treatment and controlled substance use. We present the development, implementation, and outcomes of a novel, long-standing interprofessional safe prescribing committee (SPC) and resulting policy, protocol, and longitudinal curriculum to address patient care and educational gaps in chronic pain management for residents in training. METHODS: The SPC developed and implemented an opioid prescribing policy, protocol, and longitudinal curriculum in a single, community-based residency program. We conducted a postcurriculum survey for resident graduates to assess impact of knowledge gained. We conducted a retrospective chart review for patients on chronic opioid therapy to assess change in morphine equivalent dosing (MED) and pain scores pre- and postintervention. RESULTS: A postcurriculum survey was completed by 20/26 (77%) graduates; 18/20 (90%) felt well-equipped to manage chronic pain based on their residency training experience. We completed a retrospective chart review on 57 patients. We found a significant decrease in MED (-20.34 [SE 5.12], P<.0001) at intervention visit with MED reductions maintained through the postintervention period (-9.43 per year additional decrease [SE 5.25], P=.073). We observed improvement in postintervention pain scores (P=.017). CONCLUSIONS: Our study illustrates the effectiveness of an interprofessional committee in lowering prescribed opioid doses and enhancing chronic pain education in a community-based residency setting.

Catalytic microwave torrefaction of microalga Chlorella vulgaris FSP-E with magnesium oxide optimized via taguchi approach: A thermo-energetic analysis.

Biochar is a promising material and fuel for environmental sustainability. Microalgal biochar is produced using catalytic microwave torrefaction of Chlorella vulgaris FSP-E residue with magnesium oxide as a microwave absorber to enhance heating. Using Taguchi experimental design (TED) and Analysis of Variance (ANOVA), the effects of microwave power, catalyst concentration, and duration on energy yield are investigated. Both TED and ANOVA confirm the significant effects of microwave power and catalyst concentration, while only a slight effect from duration. The calorific values of produced biochar (21.12-26.22 MJ⋅kg-1) are close to coal. The maximum deoxygenation and carbonization extents are 56.69% and 35.23%, respectively. The optimal parameter combination of low microwave power (450 W), low duration (25 min), and high catalyst concentration (10 wt% MgO) poses the highest upgrading energy index (UEI) value. This confirms that better energy efficiency leans towards light torrefaction conditions with maximized catalyst concentration to produce the maximum energy yield while consuming the least electricity input.

Smart sustainable biorefineries for lignocellulosic biomass.

Lignocellulosic biomass (LCB) is considered as a sustainable feedstock for a biorefinery to generate biofuels and other bio-chemicals. However, commercialization is one of the challenges that limits cost-effective operation of conventional LCB biorefinery. This article highlights some studies on the sustainability of LCB in terms of cost-competitiveness and environmental impact reduction. In addition, the development of computational intelligence methods such as Artificial Intelligence (AI) as a tool to aid the improvement of LCB biorefinery in terms of optimization, prediction, classification, and decision support systems. Lastly, this review examines the possible research gaps on the production and valorization in a smart sustainable biorefinery towards circular economy.

Prioritizing the vulnerable over the susceptible for COVID-19 vaccination.

The COVID-19 pandemic led to a health crisis with widespread social and economic adverse effects. To address the fallout, vaccine development has been pursued in record time. Several vaccines have already been deployed in countries worldwide, but as the supply is limited, these have been provided selectively. Various allocation schemes, premised on ensuring an equitable distribution, have prioritized the elderly, given their apparent susceptibility. For the Philippines and possibly other countries with extremely limited supplies, the elderly need not always be given primary preference. The level of available supplies can be so low that the immediate focus of allocation should be on mitigating both infection and transmission. The proposed alternative vaccine allocation framework gives priority to groups rendered more vulnerable, such as those who are unable to avoid prolonged exposure to possibly infected people because of medical necessity or occupational conditions. Vulnerable groups include healthcare and other essential workers as well as patients requiring continued healthcare services. The proposed allocation scheme is meant to be complementary to concurrent public health measures, which have to be maintained though made less restrictive as the pandemic is brought under control.

Microplastic degradation as a sustainable concurrent approach for producing biofuel and obliterating hazardous environmental effects: A state-of-the-art review.

As plastics have been omnipresent in society ever since their introduction in 1907, global plastic production has ballooned in the 20th century or the Plasticene Era (Plastic Age). After their useful life span, they deliberately or accidentally, are disposed of in the environment. Influenced by different factors, plastics undergo fragmentation into microplastics (MPs) and present hazardous risks in all life forms including humans. Obliterating MPs from the environment has been a global challenge for the attainment of sustainable development goals (SDGs). This review aims to present MP degradation routes with a great focus on the thermodegradation and biodegradation routes as sustainable routes of MP degradation. These routes can achieve the reduction and obliteration of MPs in the environment, thus reducing their hazardous effects. Moreover, the thermodegradation of MPs can produce fuels that help solve the dilemma of energy security. Overall, continued research and development are still needed, however, these novel approaches and the increased awareness of the microplastics' hazards give us hope that we can achieve sustainable development in the near future.

Revision Breast Augmentation.

Breast augmentation is consistently one of the most commonly performed aesthetic operations every year. Unfortunately, revision rates following primary augmentation remain as high as 36%. There are several causes for revision breast augmentation; however, the most common and challenging of these include capsular contracture, implant malposition, and ptosis of the aging breast following augmentation. Successful management of these problems requires knowledge on how to best treat the implant and capsule with the corresponding soft tissue simultaneously. While surgical management is important, understanding the pathological causes of these entities during the primary operation can reduce the need for revision. This article utilizes the most up-to-date literature to review the appropriate clinical evaluation and surgical management of these complex cases.

Energy balance of torrefied microalgal biomass with production upscale approached by life cycle assessment.

Torrefaction is a thermochemical process used to convert the biomass into solid fuel. In this study, torrefaction increased the raw microalgal biomass' energy content from 20.22 MJ⋅kg-1 to 27.93 MJ⋅kg-1. To determine if more energy is produced than energy consumption from torrefaction, this study identified the energy balance of torrefied microalgal biomass production based on a life cycle approach. The energy analysis showed that, among all processes, torrefaction had the least amount of energy demand. The experimental setup, defined as scenario A, revealed that the principal source of energy demand, about 85%, was consumed on the microalgal growth using a photobioreactor system. A sensitivity analysis was also performed to determine the varying energy demand for torrefied microalgal biomass production. The different types of cultivation methods and various production scales were considered in scenarios B to D. Scenario D, which represented the commercial production-scale, the energy demand drastically decreased by 59.46% as compared to the experimental setup (scenario A). The open-pond cultivation system resulted in the least energy requirement, regardless of the production scale (scenarios B and C) among all the given scenarios. Unlike scenarios A and D, scenarios B and C identified the drying process to consume a high amount of energy. All the scenarios have shown an energy demand deficit. Therefore, efforts to decrease the energy demand on the upstream processes are needed to make the torrefied microalgal biomass a viable alternative energy source.

Epidemiology of soil-transmitted helminths following sustained implementation of routine preventive chemotherapy: Demographics and baseline results of a cluster randomised trial in southern Malawi.

Malawi has successfully leveraged multiple delivery platforms to scale-up and sustain the implementation of preventive chemotherapy (PCT) for the control of morbidity caused by soil-transmitted helminths (STH). Sentinel monitoring demonstrates this strategy has been successful in reducing STH infection in school-age children, although our understanding of the contemporary epidemiological profile of STH across the broader community remains limited. As part of a multi-site trial evaluating the feasibility of interrupting STH transmission across three countries, this study aimed to describe the baseline demographics and the prevalence, intensity and associated risk factors of STH infection in Mangochi district, southern Malawi. Between October-December 2017, a community census was conducted across the catchment area of seven primary healthcare facilities, enumerating 131,074 individuals across 124 villages. A cross-sectional parasitological survey was then conducted between March-May 2018 in the censused area as a baseline for a cluster randomised trial. An age-stratified random sample of 6,102 individuals were assessed for helminthiasis by Kato-Katz and completed a detailed risk-factor questionnaire. The age-cluster weighted prevalence of any STH infection was 7.8% (95% C.I. 7.0%-8.6%) comprised predominantly of hookworm species and of entirely low-intensity infections. The presence and intensity of infection was significantly higher in men and in adults. Infection was negatively associated with risk factors that included increasing levels of relative household wealth, higher education levels of any adult household member, current school attendance, or recent deworming. In this setting of relatively high coverage of sanitation facilities, there was no association between hookworm and reported access to sanitation, handwashing facilities, or water facilities. These results describe a setting that has reduced the prevalence of STH to a very low level, and confirms many previously recognised risk-factors for infection. Expanding the delivery of anthelmintics to groups where STH infection persist could enable Malawi to move past the objective of elimination of morbidity, and towards the elimination of STH. Trial registration: NCT03014167.

Time-aware deep neural networks for needle tip localization in 2D ultrasound.

PURPOSE: Accurate placement of the needle is critical in interventions like biopsies and regional anesthesia, during which incorrect needle insertion can lead to procedure failure and complications. Therefore, ultrasound guidance is widely used to improve needle placement accuracy. However, at steep and deep insertions, the visibility of the needle is lost. Computational methods for automatic needle tip localization could improve the clinical success rate in these scenarios. METHODS: We propose a novel algorithm for needle tip localization during challenging ultrasound-guided insertions when the shaft may be invisible, and the tip has a low intensity. There are two key steps in our approach. First, we enhance the needle tip features in consecutive ultrasound frames using a detection scheme which recognizes subtle intensity variations caused by needle tip movement. We then employ a hybrid deep neural network comprising a convolutional neural network and long short-term memory recurrent units. The input to the network is a consecutive plurality of fused enhanced frames and the corresponding original B-mode frames, and this spatiotemporal information is used to predict the needle tip location. RESULTS: We evaluate our approach on an ex vivo dataset collected with in-plane and out-of-plane insertion of 17G and 22G needles in bovine, porcine, and chicken tissue, acquired using two different ultrasound systems. We train the model with 5000 frames from 42 video sequences. Evaluation on 600 frames from 30 sequences yields a tip localization error of [Formula: see text] mm and an overall inference time of 0.064 s (15 fps). Comparison against prior art on challenging datasets reveals a 30% improvement in tip localization accuracy. CONCLUSION: The proposed method automatically models temporal dynamics associated with needle tip motion and is more accurate than state-of-the-art methods. Therefore, it has the potential for improving needle tip localization in challenging ultrasound-guided interventions.

Reduction of particulate matter and volatile organic compounds in biorefineries: A state-of-the-art review.

A biorefinery is an efficient approach to generate multiple bio-products from biomass. With the increasing demand for bioenergy and bio-products, biorefineries are essential industrial platforms that provide needed demand while significantly reducing greenhouse gas emissions. A biorefinery consists of various conversion technologies where particulate matter (PM) and volatile organic compounds (VOCs) are emitted. The released PM and VOCs pose detrimental health and environmental risks for society. Moreover, the projected rise of global bioenergy demand may lead to an increase in PM and VOCs from biorefineries. With the use of cleaner technologies and approaches, PM and VOCs can be avoided in biorefineries. The study presents the landscape of the research field through a bibliometric review of emissions from a biorefinery. A comprehensive review of works on the reduction of PM and VOCs in a biorefinery is outlined. The study includes a perspective of cleaner technologies and approaches utilized in biorefineries to mitigate these hazardous materials. The results reveal that the employment of life cycle assessment, safety assessment, and green chemistry processes can significantly reduce PM and VOC emissions as well as the consumption of hazardous substances in the biorefinery.