Overcoming Engineering Challenges to Enable Commercial-Scale mRNA Vaccine Manufacturing

Increasing production capacity may necessitate the facility to cater for higher hazardous area category (e.g., H-Occupancy) design features, such as specialized building construction and potential blast zones. [...]an assessment should cover: * Quantification of flammable material use for production steps, including buffer preparation and LNP storage * Equipment and facility cleaning strategies that contribute to the facility flammable materials inventory * Impact of HVAC design to avoid hazardous atmospheres (e.g., full fresh air), use of local exhaust ventilation (LEV) or fume hoods * Solvent distribution methods (e.g., closed solvent delivery and waste removal systems) * Location of solvent bulk storage outside of the processing area/ facility, and piping in what is necessary plus removing spent solvent in a timely manner (e.g., piped transfer to a waste tank for removal by a specialist contractor). At present, the process cannot be fully single-use, so thought needs to be put into the cleaning and sterilization processes, plus the analytical support infrastructure needed for reusable product-contact surfaces. [...]it is recommended that for each mRNA project, consideration is given to the following aspects to determine the link between the equipment available and the facility design: * Need for custom/proprietary equipment * Independent production rooms with "through-wall" buffer transfer through iris ports in from logistics corridor (Buffer Prep/Hold) * Room electrical classification needs versus process step. * Equipment selection versus electrical and fire code requirements * Benefits and limitations of implementing single-use technologies, given that the process will be hybrid (with stainless steel). [...]the limited capacity for outsourcing of supporting functions, such as facility environmental monitoring or product sterility testing, should be considered during concept design.

Quantifying optimal resource allocation strategies for controlling epidemics.

Frequent emergence of communicable diseases is a major concern worldwide. Lack of sufficient resources to mitigate the disease burden makes the situation even more challenging for lower-income countries. Hence, strategy development for disease eradication and optimal management of the social and economic burden has garnered a lot of attention in recent years. In this context, we quantify the optimal fraction of resources that can be allocated to two major intervention measures, namely reduction of disease transmission and improvement of healthcare infrastructure. Our results demonstrate that the effectiveness of each of the interventions has a significant impact on the optimal resource allocation in both long-term disease dynamics and outbreak scenarios. The optimal allocation strategy for long-term dynamics exhibits non-monotonic behaviour with respect to the effectiveness of interventions, which differs from the more intuitive strategy recommended in the case of outbreaks. Further, our results indicate that the relationship between investment in interventions and the corresponding increase in patient recovery rate or decrease in disease transmission rate plays a decisive role in determining optimal strategies. Intervention programmes with decreasing returns promote the necessity for resource sharing. Our study provides fundamental insights into determining the best response strategy when controlling epidemics in resource-constrained situations.

Lichen planus after COVID-19 infection and vaccination

Background: Lichen planus (LP) is an inflammatory disorder believed to result from CD8+ cytotoxic T-cell (CTL) mediated autoimmune reactions against basal keratinocytes. We present a review of LP following COVID-19 infection and vaccination. Method(s): Literature searches were conducted on PubMed and Google Scholar from 2019 to 7/2022. 35 articles were selected based on subject relevance, and references within articles were also screened. Result(s): 39 cases of post-vaccination LP and 6 cases of post-infection LP were found among case reports and case series. 150 cases of postvaccination LP and 12 cases of post-infection LP were found in retrospective and prospective studies. Conclusion(s): LP is a rare complication of COVID-19 infection and vaccination that may be mediated by overstimulation of T-cell responses and proinflammatory cytokine production. However, it does not represent a limitation against COVID-19 vaccination, and the benefits of vaccination considerably outweigh the risks.

Understanding Chinese international students in the U.S. in Times of the COVID-19 crisis: from a Chinese discourse studies perspective

Using the Chinese Discourse Studies (CNDS) as a theoretical framework, this study seeks to challenge the cultural essentialism and uncritical roots of existing literature, with an aim to expose long-standing patterns of Western totalizing discourse in the field of international education research. This exploratory article explores how Chinese international students as cultural agents respond to the global pandemic and pandemic-related stereotypes. Through a critical analysis of 21 Chinese students' narratives, this article identifies three culturally specific characteristics that pervade Chinese normative dialogues: (1) Chinese dialectics, (2) Chinese harmony, and (3) Chinese self-criticism. They are often employed to emphasize Chinese optimistic attitudes in times of crisis, avoidance of confrontation for harmonious communication, and moral character of self-introspection to conform to the social norm. This article offers new empirical evidence for the reconstruction of the Chinese paradigm of discourse studies and reveals the inappropriateness of Western scholarship for understanding non-Western linguistic and communicative events and practices. In sum, this article demonstrates that Chinese discourse studies can be a potential decolonial option to depart from deep-seated scholarship in Western intellectual supremacy and a visionary framework to advance multicultural discourses about international education against the backdrop of geopolitical tensions and anti-Asian racism.

Predicting the climate impact of aviation for en-route emissions: the algorithmic climate change function submodel ACCF 1.0 of EMAC 2.53

Using climate-optimized flight trajectories is one essential measure to reduce aviation's climate impact. Detailed knowledge of temporal and spatial climate sensitivity for aviation emissions in the atmosphere is required to realize such a climate mitigation measure. The algorithmic Climate Change Functions (aCCFs) represent the basis for such purposes. This paper presents the first version of the Algorithmic Climate Change Function submodel (ACCF 1.0) within the European Centre HAMburg general circulation model (ECHAM) and Modular Earth Submodel System (MESSy) Atmospheric Chemistry (EMAC) model framework. In the ACCF 1.0, we implement a set of aCCFs (version 1.0) to estimate the average temperature response over 20 years (ATR20) resulting from aviation CO2 emissions and non-CO2 impacts, such as NOx emissions (via ozone production and methane destruction), water vapour emissions, and contrail cirrus. While the aCCF concept has been introduced in previous research, here, we publish a consistent set of aCCF formulas in terms of fuel scenario, metric, and efficacy for the first time. In particular, this paper elaborates on contrail aCCF development, which has not been published before. ACCF 1.0 uses the simulated atmospheric conditions at the emission location as input to calculate the ATR20 per unit of fuel burned, per NOx emitted, or per flown kilometre.In this research, we perform quality checks of the ACCF 1.0 outputs in two aspects. Firstly, we compare climatological values calculated by ACCF 1.0 to previous studies. The comparison confirms that in the Northern Hemisphere between 150–300 hPa altitude (flight corridor), the vertical and latitudinal structure of NOx-induced ozone and H2O effects are well represented by the ACCF model output. The NOx-induced methane effects increase towards lower altitudes and higher latitudes, which behaves differently from the existing literature. For contrail cirrus, the climatological pattern of the ACCF model output corresponds with the literature, except that contrail-cirrus aCCF generates values at low altitudes near polar regions, which is caused by the conditions set up for contrail formation. Secondly, we evaluate the reduction of NOx-induced ozone effects through trajectory optimization, employing the tagging chemistry approach (contribution approach to tag species according to their emission categories and to inherit these tags to other species during the subsequent chemical reactions). The simulation results show that climate-optimized trajectories reduce the radiative forcing contribution from aviation NOx-induced ozone compared to cost-optimized trajectories. Finally, we couple the ACCF 1.0 to the air traffic simulation submodel AirTraf version 2.0 and demonstrate the variability of the flight trajectories when the efficacy of individual effects is considered. Based on the 1 d simulation results of a subset of European flights, the total ATR20 of the climate-optimized flights is significantly lower (roughly 50 % less) than that of the cost-optimized flights, with the most considerable contribution from contrail cirrus. The CO2 contribution observed in this study is low compared with the non-CO2 effects, which requires further diagnosis.

Enabling mRNA medicine for brain tumors

mRNA is a new class of drugs that has the potential to revolutionize the treatment of brain tumors. Thanks to the COVID-19 mRNA vaccines and numerous therapy-based clinical trials, it is now clear that lipid nanoparticles (LNPs) are a clinically viable means to deliver RNA therapeutics. However, LNP-mediated mRNA delivery to brain tumors remains elusive. Over the past decade, numerous studies have shown that tumor cells communicate with each other via small extracellular vesicles, which are around 100 nm in diameter and consist of lipid bilayer membrane similar to synthetic lipidbased nanocarriers. We hypothesized that rationally designed LNPs based on extracellular vesicle mimicry would enable efficient delivery of RNA therapeutics to brain tumors without undue toxicity. We synthesized LNPs using four components similar to the formulation used in the mRNA COVID19 vaccines (Moderna and Pfizer): ionizable lipid, cholesterol, helper lipid and polyethylene glycol (PEG)-lipid. For the in vitro screen, we tested ten classes of helper lipids based on their abundance in extracellular vesicle membranes, commercial availability, and large-scale production feasibility while keeping rest of the LNP components unchanged. The transfection kinetics of GFP mRNA encapsulated in LNPs and doped with 16 mol% of helper lipids was tested using GL261, U87 and SIM-A9 cell lines. Several LNP formations resulted in stable transfection (upto 5 days) of GFP mRNA in all the cell lines tested in vitro. The successful LNP candidates (enabling >80% transfection efficacy) were then tested in vivo to deliver luciferase mRNA to brain tumors via intrathecal administration in a syngeneic glioblastoma (GBM) mouse model, which confirmed luciferase expression in brain tumors in the cortex. LNPs were then tested to deliver Cre recombinase mRNA in syngeneic GBM mouse model genetically modified to express tdTomato under LoxP marker cassette that enabled identification of LNP targeted cells. mRNA was successfully delivered to tumor cells (70-80% transfected) and a range of different cells in the tumor microenvironment, including tumor-associated macrophages (80-90% transfected), neurons (31- 40% transfected), neural stem cells (39-62% transfected), oligodendrocytes (70-80% transfected) and astrocytes (44-76% transfected). Then, LNP formulations were assessed for delivering Cas9 mRNA and CD81 sgRNA (model protein) in murine syngeneic GBM model to enable gene editing in brain tumor cells. Sanger sequencing showed that CRISPR-Cas9 editing was successful in ~94% of brain tumor cells in vivo. In conclusion, we have developed a library of safe LNPs that can transfect GBM cells in vivo with high efficacy. This technology can potentially be used to develop novel mRNA therapies for GBM by delivering single or multiple mRNAs and holds great potential as a tool to study brain tumor biology.

Being a product consumer during the COVID-19 pandemic: profile of the Polish consumer in the organic dairy market

PurposeThe purpose of this paper was to determine the profile of dairy product consumers in the organic market.Design/methodology/approachThe study was based on a survey questionnaire developed by the author and administered to a total of 1,108 respondents. The statistical analysis (including descriptive statistics, the analysis of the discriminative function and the Chi2 test was performed with the use of Statistica 13.1 PL. The respondents' gender was the factor behind the differences in how they behaved.FindingsThe consumers indicated the channels they rely upon to find information on organic dairy products;in addition to trusting the opinions of their family members and experts, they also use web platforms. Further, they specified their preferred locations for buying favorite products during the pandemic: specialized organic food shops, large distribution chains and online stores.Practical implicationsThese outcomes will help in identifying target consumer segments and information channels for specific information and advertising messages. They also form an important resource for developing some potential strategies which the supply chain stakeholders could implement to promote organic consumption of dairy products.Originality/valueThis study identifies consumers' preferred dairy products;motives for purchasing organic dairy products;barriers that consumers believe exist in the market;sources of knowledge about products purchased by consumers;and consumers' preferred channels for purchasing organic dairy products. To the best of the author's knowledge, this is the first study of dairy product consumers in the organic market in Poland.

Economy and diversity of aquaculture production in Bulgaria: status and trends

Aquaculture production in Bulgaria has increased over the last decade, reaching 16 442 tonnes in 2019. Fish production has doubled in comparison with 2007, while that of mussels has increased tenfold. The Bulgarian contribution to EU aquaculture production has been increasing significantly in both volume and value over the years, making up 1.15% of the volume and 1.0% of the value of EU production in 2019. Freshwater aquaculture accounts for 78% of total production. Common carp dominates with about 29.4% (4836 t), followed by rainbow trout with 29.2% (4820 t) in 2019. The cultivation of sturgeon species and caviar production are among the most dynamically developing aquaculture segments. Mariculture in the Black Sea has increased in recent years, with the production of Mediterranean mussel reaching 2932 tonnes in 2019. An average of 405 farms operated during the period 2010-2019. Four regions (Plovdiv, Stara Zagora, Burgas and Montana) account for 50% of the total fish production. Pond aquaculture is the dominant technology used in Bulgaria, and it serves as the basis for numerous other activities, including management of fish stocks in various water bodies mainly for recreational fishing. Approximately 35 net-cage farms currently operate in bigger dams. Recirculating fish farms output made up only 0.15% of the total amount of aquaculture for the period 2010-2019. The aquaculture sector exhibited difficulties in recovering from the financial crisis of 2007-2008, manifested by a slow growth for the period 2010-2014. From 2015 to 2019 there has been a significant growth, manifested in a sharp increase of total revenue and profitability, especially among the larger enterprises in the sector, as well as an increase in the number of employees, and the labour productivity. As a result, in 2019 the registered total revenue per enterprise and total revenue per employee were more than double the respective figures for 2010. The profits of larger enterprises increased more than three times on average, but smaller entities, micro-enterprises with less than 5 employees, operated at the border line between profit and loss. The COVID-19 crisis could have lasting consequences. Despite EUR 1.2 million direct payments in the sector in 2020, there has been a significant drop in the export of aquaculture products. Consumption of fish and other aquaculture products remains low compared to those in the other EU countries.

FINANCIAL SECURITY in SMALL BUSINESS in PERIOD of DIGITAL ECONOMY: In CASE of UZBEKISTAN

In this paper has been proposed a methodology for ensuring the financial security of enterprises in the context of recession caused by the COVID-19 pandemic. Based on pre-crisis data related to the new coronavirus infection pandemic and multi-component modeling of the dynamics of industrial production in the Republic of Uzbekistan during the "corona crisis,"this study seeks to identify the dynamics of growth by economic activity type and recovery rate in order to identify areas of state support for industrial production. In this paper has been investigated issues of financial security management of textile enterprises. On the basis of secondary statistics, the growth of textile production in the regions of the Republic of Uzbekistan in 2008-2020 was analyzed and the factors influencing it were identified. By the author have been presented the main tasks and conditions for the financial security of enterprises, as well as developed scientific and practical recommendations for eliminating factors affecting the financial security of textile enterprises. © 2022 Owner/Author.

Research on the Optimal Energy Saving and Emission Reduction Path for Promoting High-Quality Industrial Development in Hubei Province

In December 2019, a novel coronavirus broke out in Wuhan City, Hubei Province, and, as the center of the coronavirus disease 2019 (COVID-19) epidemic, the economy and production throughout Hubei Province suffered huge temporary impacts. Based on the input–output and industrial pollution emissions data of 33 industrial industries in Hubei from 2010 to 2019, this article uses the non-parametric frontier analysis method to calculate the potential production losses and compliance costs caused by environmental regulations in Hubei's industrial sector by year and industry. Research has found that the environmental technology efficiency of the industrial sector in Hubei is showing a trend of increasing year-on-year, but the overall efficiency level is still not high, and there is great room for improvement. The calculation results with and without environmental regulatory constraints indicate that, generally, production losses and compliance costs may be encountered in the industrial sector in Hubei, and there are significant differences by industry. The potential production losses and compliance costs in pollution-intensive industries are higher than those in clean production industries. On this basis, we propose relevant policy recommendations to improve the technological efficiency of Hubei's industrial environment, in order to promote the high-quality development of Hubei's industry in the post-epidemic era.

Emotional risk work during the pandemic: Healthcare professionals' perceptions from a COVID-19 ward

In March 2020, COVID-19 wards were established in hospitals in Denmark. Healthcare professionals from a variety of specialities and wards were transferred to these new wards to care for patients admitted with severe COVID-19 infections. Based on ethnographic fieldwork in a COVID-19 ward at a hospital in Copenhagen, Denmark, including focus group interviews with nursing staff, we intended to explore practices in a COVID-19 ward by seeking insight into the relation between the work carried out and the professionals' ways of talking about it. We used a performative approach of studying how the institutional ways of handling pandemic risk work comes into being and relates to the health professionals' emerging responses. The empirical analysis pointed at emotional responses by the nursing staff providing COVID-19 care as central. To explore these emotional responses we draw on the work of Mary Douglas and Deborah Lupton's concept of the ‘emotion-risk-assemblage'. Our analysis provides insight into how emotions are contextually produced and linked to institutional risk understandings. We show that work in the COVID-19 ward was based on an institutional order that was disrupted during the pandemic, producing significant emotions of insecurity. Although these emotions are structurally produced, they are simultaneously internalised as feelings of incompetence and shame.

Transmission of broiler egg prices between surplus and deficit areas: exploring the dynamics

Broiler chicken eggs are one of the main and strategic foods for the people of Indonesia and contribute to regional and national inflation. Broiler egg production in Indonesia differs between regions. Areas with a surplus of eggs tend to have lower prices than areas with a deficit. This research is to measure the transmission of broiler egg prices between markets in surplus and deficit areas, using weekly price time series data for the period January 2018-December 2021. Areas of surplus broiler eggs, East Java Province (the highest broiler egg production in Indonesia) which become one of the main suppliers to the Province of East Nusa Tenggara as a deficit area. Using the Johannsen cointegration test it is found that there is no cointegration or there is no relationship between the surplus and deficit regions in the long term but not in the short term. Factors of marketing infrastructure, market information systems, and geographical conditions can be obstacles to the absence of cointegration. The VAR (Vector Auto-Regressive) Vector Error Correction model (VECM) test, found that price transmission occurred between surplus and deficit areas, meaning that between the two regions, there was market integration prior to Covid. The transmission has weakened, and due to the Covid situation, there have been restrictions on the movement of people and goods. The government and other market players need to study the response of the broiler egg market, in the short and long term so that market players can make the right policies.

Demonstrating the Value of Collaboration

[...]of the search for effective vaccines and treatments for COVID-19 being a priority, the development and manufacture of other treatments have been delayed, he adds. Through these industry collaborations, many developers have gained benefits, such as reduced time-to-market for new products, he specifies. [...]Quick believes that there will be more companies leaning towards outsourced services in the future, for development work and commercialization phases too. Given the disruption to the global pharmaceutical supply chain that has been experienced during the pandemic, O'Sullivan predicts that there will be opportunities for API suppliers in Europe, and elsewhere, to prosper from increased local demand, so long as the capacity and flexibility to deliver the required quantities are on available. [...]we will see significant investment by European API suppliers in expanded production capacity and capabilities in 2021 in order to attract Europe-based customers on the look-out for new local partners," he says. [...]Cruz emphasizes the rise of electronic health and customer records across Europe as an exciting prospect, particularly as it can lead to companies gaining a greater insight into treatments and customer needs.

Economic Aspects of a Resource Sharing Manufacturing Network under Turbulences

Nowadays, manufacturing companies face more difficulties than ever. Unrest in global supply chains triggered by fluctuating customer demand, raw material shortages and crises (Covid pandemic, global warming, wars) complicate the utilization of production resources necessary for economic success. Also, the rapidly changing environment causes existing production plans to be adapted, which results in order changes, causing additional costs for manufacturers. One solution to cope with these problems is cooperation and sharing resources: requesting capacity from partners when having shortages and offering them temporarily in case of excess capacity. In this paper, a platform-based resource sharing mechanism is investigated from the economic perspective. In the mechanism, requests and offers are matched by a central platform applying a complex matching logic. The platform provides valid alternatives based on the incoming ordersthat the requesting company can choose from. Companies are rating each other's performance after each interaction based on delivery accuracy;choosing between resource offers is made based on the cumulated rating about the offeror and the price of the offer. Within this paper, the aim is to investigate the resource sharing mechanism from the economic point of view based on an approach to the responsiveness of a supply chain structure to turbulence, to support decision-makers trying to cope with unexpected changes. For this purpose, here the mechanism is briefly introduced, and basic concepts about turbulences in supply chains are also presented. Cost types related to resource sharing manufacturing companies are distinguished, and the model is validated with agent-based simulation. A simulation experiment is performed to investigate the use-case of outsourced jobs having different price levels. Based on the experiment, it can be concluded that there is a price level limit in such a resource sharing federation, under which it is worth it to collaborate with partners by outsourcing certain jobs to them. © 2022 Authors. All rights reserved.

Mechanism of interferon induction by cannabidiol (CBD) and analogues in lung cancer cells

CBD, an FDA approved drug for epilepsy, may have therapeutic potential for other diseases and is currently being tested for efficacy in cancer-related clinical trials. As the literature about CBD, especially in vitro reports, is often contradictory, increasing our understanding of its specific action on a molecular level will allow to determine whether CBD can become a useful therapy or exacerbates specific cancers in a context-dependent manner. Due to its relative lipophilicity, CBD is challenging to dispense at therapeutic concentrations;therefore, one goal is to identify cannabinoid congeners with greater efficacy and reduced drug delivery challenges. We recently showed that CBD activates interferons as a mechanism of inhibiting SARS-CoV-2 replication in lung carcinoma cells. As factors produced by the innate immune system, interferons have been implicated in both pro-survival and growth arrest and apoptosis signaling in cancer. Here we show that CBD induces interferon production and interferon stimulated genes (ISGs) through a mechanism involving NRF2 and MAVS in lung carcinoma cells. We also show that CBDV, which differs from CBD by 2 fewer aliphatic tail carbons, has limited potency, suggesting that CBD specifically interacts with one or more cellular proteins rather than having a non-specific effect. We also identified other CBD-related cannabinoids that are more effective at inducing ISGs. Taken together, these results characterize a novel mechanism by which CBD activates the innate immune system in lung cancer cells and identify related cannabinoids that have possible therapeutic potential in cancer treatment.

Can Domestic Food Production Provide Future Urban Populations with Food and Nutrition Security?—Insights from Bangladesh, Kenya and Uganda

Population growth and urbanization increasingly put pressure on our planet's availability of areas needed for food production. The dependencies on domestically produced food are increasingly judged favourable, following the consequences of the Ukrainian war, with escalating fuel and grain prices and less accessibilities to low-income groups. It is, however, unclear whether land is domestically available. Applying a food system approach, the main aim of this article is to investigate spatial foodsheds and theoretical self-sufficiency for food production needed to supply increasing future populations in a selection of cities, including estimates for Dhaka in Bangladesh, Nairobi in Kenya and Kampala in Uganda. The projected foodshed scenario areas for the years 2020 and 2050 are estimated for the production of three core products currently extensively produced and consumed in the three countries. They show that it is not possible to feed an ever-increasing urban population based on domestic production alone. International trade, new technological developments and new consumer demands for less area-intensive food production systems may give solutions to the immense challenge of feeding the world's population with nutritious food in 2050. However, to ensure fair and inclusive transition pathways for low-income groups: (1) affordability and accessibility of trade opportunities, technologies and products, (2) a common vision aiming for the SDGs, including SDG2: Zero hunger and SDG11: Sustainable Cities and Communities as well as (3) best practices in co-creation and cooperation with the most vulnerable urban and rural populations, are highly needed.

CHALLENGES AND OPPORTUNITIES IN BEEKEEPING AND HONEY PRODUCTION DURING COVID-19 PANDEMIC – A SHORT REVIEW

Honey bees in beekeeping are commonly involved in honey production and as planned pollinators worldwide. However, at the beginning of the covid-19 pandemic, the hardworking little creatures suffered many difficulties. The entire supply chain was blocked. Consequently, the challenges directly affected honey and crop production worldwide. The pandemic issues like travel restrictions and limited access to apiaries had a detrimental influence on beekeepers' activity. Earlier sales decline during the crisis had an economic impact, with some beneficial impacts, like a rise in demand for health-related goods. However, the challenges come with opportunities, which lead to a pointy surge in demand for honey which paved the way for many women entrepreneurs as beekeepers to meet the local demands, which helps the rural economy to be sustained. Another intriguing benefit is that a drastic drop in pollution helped bees get back to their normal routine, which led to a drastic increase in honey production during the pandemic as opposed to what they experienced in normal times. This article briefly outlines such challenges faced by the beekeepers and the honey producers and also focuses on the new opportunities that rendered many values to the producers during the pandemic © Penerbit UMT

Effect of Process Variables on Pulp Yield of Indigenous Raw Materials

The biggest issue before pulp and paper producers is availability of quality raw material. India is fiber deficit country, this message has become more intense after covid when price of different raw materials are increased by 20-25%, . Chemical pulp is produced by chemical delignification of wood and non-wood plants. After kraft pulping the remaining lignin is removed by oxygen delignification and bleaching to produce higher purity cellulosic pulp. The goal of delignification processes is to remove lignin from the raw material without a negative effect on the cellulose and strength of pulp. The economics of pulp and paper production is more related to the yield of unbleached and bleached pulp production. Marginal increment in pulp yield reflects into savings of crore of rupees on yearly basis. An overall vigilant concern on process conditions and variables is required during production of pulp. BAT technology for pulping along with utilization of various additives and pretreatment methods allow to fine tune these process to obtain pulp with desired yield and quality. The primary aim of this paper is to review different process variables in respect to the yield of the pulp. © 2022 Indian Pulp and Paper Technical Association. All rights reserved.

Association Between Severe SARS-CoV-2 Infection and De Novo HLA Donor Specific Antibody Production in Lung Transplant Recipients: Single-center study

Objectives: The COVID-19 pandemic has led to significant morbidity and mortality in lung transplant recipients (LTR). Respiratory viral infections may be associated with de-novo HLA donor-specific antibody (DSA) production and impact lung transplant outcome. Since one of the immunomodulation strategies post-SARS-CoV-2 infection in LTR include decreasing or holding anti-metabolites, concerns have been raised for higher incidence of de-novo DSA production in LTR. Method(s): We performed a retrospective chart review of 80 consecutive LTR diagnosed with COVID-19 to investigate this concern. COVID-19 disease severity was divided into 3 groups: mild, moderate, and severe. Mild disease was defined as patients with COVID-19 diagnosis who were stable enough to be treated as out-patients. Moderate disease was defined as patients who required admission to the hospital and were on less than 10 liters of oxygen at rest. Severe disease was identified as patients who required hospitalization and were on more than 10 liters of oxygen with or without mechanical ventilation or extra corporal membrane oxygenation (ECMO). Groups were compared using the Kruskal-Wallis test. Result(s): A total of 23, 47, and 10 LTR were diagnosed with mild, moderate, and severe COVID-19 respectively. De-novo HLA DSAwere detected in 0/23 (0%), 3/47 (6.3%), and 4/10 (40%) LTR with mild, moderate, and severe COVID-19 respectively (p = 0.0007) within 6 months post-COVID-19 diagnosis. Conclusion(s): Severe COVID-19 may be associated with increased risk of de novo HLA DSA production resulting in allograft dysfunction.Copyright © 2023 Elsevier Inc.

Teclistamab in combination with daratumumab and lenalidomide in multiple myeloma (MajesTEC-2 study)

Introduction: Combination of daratumumab (Dara) and lenalidomide (Len) may enhance the function of teclistamab (Tec), potentially resulting in improved antimyeloma activity in a broader population. We present initial safety and efficacy data of Tec-Dara- Len combination in patients with multiple myeloma (MM) in a phase 1b study (MajesTEC-2;NCT04722146). Method(s): Eligible patients who received 1-3 prior lines of therapy (LOT), including a proteasome inhibitor and immune-modulatory drug, were given weekly doses of Tec (0.72-or- 1.5 mg/kg with step-up dosing) + Dara 1800 mg + Len 25 mg. Responses per International Myeloma Working Group criteria, adverse events (Aes) per CTCAE v5.0, and for cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS) per ASTCT guidelines, were assessed. Result(s): 32 patients received Tec-Dara- Len (0.72 mg/kg, n = 13;1.5 mg/kg, n = 19). At data cut-off (11 July 2022), median follow-up (range) was 5.78 months (1.0-10.4) and median treatment duration was 4.98 months (0.10-10.35). Median age was 62 years (38-75);87.5% were male. Median prior LOT was 2 (1-3), 18.8% were refractory to Dara and 28.1% refractory to Len. CRS was most frequent AE (81.3% [n = 26], all grade 1/2), 95% occurred during cycle1. Median time to onset was 2 days (1-8), median duration was 2 days (1-22). No ICANS were reported. Frequent Aes (>=25.0% across both dose levels) were neutropenia (75.0% [n = 24];grade 3/4: 68.8% [n = 22]), fatigue (43.8% [n = 14];grade 3/4: 6.3% [n = 2]), diarrhoea (37.5% [n = 12];all grade 1/2), insomnia (31.3% [n = 10];grade 3/4: 3.1% [n = 1]), cough (28.1% [n = 9];all grade 1/2), hypophosphatemia (25.0% [n = 8];all grade 1/2), and pyrexia (25% [n = 8];grade 3/4: 6.3% [n = 2]). Febrile neutropenia frequency was 12.5% (n = 4). Infections occurred in 24 patients (75.0%;grade 3/4: 28.1% [n = 9]). Most common were upper respiratory infection (21.9% [n = 7]), COVID-19 (21.9% [n = 7]), and pneumonia (21.9% [n = 7]). Three (9.4%) had COVID-19 pneumonia. One (3.1%) discontinued due to COVID-19 infection and this patient subsequently died of this infection. Overall response rate (ORR, median follow-up) was 13/13 (8.61 months) at 0.72 mg/kg and 13/16 evaluable patients (less mature at 4.17 months) at 1.5 mg/kg. 12 patients attained very good/better partial response at 0.72 mg/kg dose, and response was not mature for 1.5 mg/kg group. Median time to first response was 1.0 month (0.7-2.0). Preliminary pharmacokinetic concentrations of Tec-Dara- Len were similar as seen with Tec monotherapy. Tec-Dara- Len- treatment led to proinflammatory cytokine production and T-cell activation. Conclusion(s): The combination of Tec-Dara- Len has no new safety signals beyond those seen with Tec or Dara-Len individually. Promising ORR supports the potential for this combination to have enhanced early disease control through the addition of Tec. These data warrant further investigation.