Opening Up Opportunities in 2023

"The ongoing journey to standardization on more aspects of submission and data exchange will continue to have an impact," he notes. lan Crone, business unit director Europe-fme Life Sciences, which provides business and technology services, points out that the web-based human variations electronic application form (eAF) for centrally authorized products (CAPs) has been available for use since 4 Nov. 2022 on the European Medicines Agency's (EMA's) new product lifecycle management (PLM) portal. Renato Rjavec, Amplexor Life Sciences "Many biopharmaceutical functions have spent the last decade modernizing their base technologies, most often in a cloud/software as a service environment platform that brings foundational benefit to individual functions," states Steve Gens managing partner. Internal productivity and external regulatory requirements are both driving this data connectivity within industry, he adds, which "requires a clear cross functional digitization strategy and focus on cross-functional data governance, master data management, and ensuring all data from these various authoritative systems [are] at the same high level. " "Many biopharmaceutical functions have spent the last decade modernizing their base technologies, most often in a cloud/ software as a service environment platform that brings foundational benefit to individual functions." -

Suggesting Assess Queries for Interactive Analysis of Multidimensional Data

Assessment is the process of comparing the actual to the expected behavior of a business phenomenon and judging the outcome of the comparison. The ${{\sf assess}}$assess querying operator has been recently proposed to support assessment based on the results of a query on a data cube. This operator requires (i) the specification of an OLAP query to determine a target cube;(ii) the specification of a reference cube of comparison (benchmark), which represents the expected performance;(iii) the specification of how to perform the comparison, and (iv) a labeling function that classifies the result of this comparison. Despite the adoption of a SQL-like syntax that hides the complexity of the assessment process, writing a complete assess statement is not easy. In this paper we focus on making the user experience more comfortable by letting the system suggest suitable completions for partially-specified statements. To this end we propose two interaction modes: progressive refinement and auto-completion, both starting from an assess statement partially declared by the user. These two modes are evaluated both in terms of scalability and user experience, with the support of two experiments made with real users.

Countering Counterfeiters and Diverters

[...]the anticounterfeiting packaging market is projected to grow at a 7.8% compound annual growth rate to USS189.9 billion (€158 billion) in 2026 (1). [...]in anticipation of a spike in counterfeiting, the US Immigration and Customs Enforcement Homeland Security Investigations (HSI) has launched Operation Stolen Promise 2, to halt the production, distribution, and sale of illicit COVID-19 treatments and vaccines. The fact that the COVID-19 vaccines need to be shipped in stringent cold storage containers with radio frequency identification (RFID) temperature sensors along with specialized transportation methods will make it more difficult for counterfeiters to enter the supply chain, but not impossible." [...]Pitts predicts an increased focus on consumer engagement.

School Food Programming across Canada during the COVID 19 Pandemic: Program Reach and Modalities

In 2020, after the COVID-19 pandemic resulted in widespread school closures and a consequent pause in school food programs (SFP), stakeholder groups soon found alternate methods for delivering meals and snacks to students. This paper examines the breadth of school food programming in Canada during the pandemic. SFPs collectively offered meals (breakfast was most frequent), food boxes, and gift cards and average weekly distributions were over 10,000 meals. In most cases, the programs provided enough food/coupons to feed multiple or all household members. Almost half the programs received funding from provincial/territorial governments and around two-thirds received charitable contributions.Copyright © 2022 Taylor & Francis Group, LLC.

Renal Toxicity Boxed Warnings of Drugs Marketed in the US

Objectives: To assess the characteristics of FDA renal toxicity boxed warnings (formerly called Black Box Warning) included in the labels of drugs approved by the FDA and marked in the US. Method(s): We extracted the labels of human prescription drugs with renal toxicity boxed warnings from the "FDA Label: Full-Text Search of Drug Product Labeling" database, FDA regulatory information from drugs@FDA as of September 1, 2022. We extracted the therapeutic classification from the WHO ATC system. We conducted a descriptive analysis of the data. Result(s): The FDA listed 86 drugs including 72 active ingredients and 14 combinations with a boxed warning mentioning renal toxicity. Three drugs had emergency use authorizations for COVID-19, and all combinations included metformin. There were 8 (8.7%) drugs with renal toxicity boxed warnings approved before 1970, 6 (6.5%) in the 1970s, 14 (15.2%) in the 1980s, 34 (37.0%) in the 1990s, 17 (18.5%) in the 2000s, 9 (9.8%) in the 2010s, and 4 (4.3%) in 2020-Sep 2022. The therapeutic classes with the largest number of renal toxicity boxed warning included anti-infectives for systemic use 24 (26.1%), antineoplastic and immunomodulating agents 22 (23.9%), and alimentary tract and metabolism 17 (18.5%). The most common boxed warnings included renal impairment (n=21, 22.8%), nephrotoxicity (10, 10.9%), and nephrogenic systemic fibrosis (7, 7.6%). Additionally, 9 (9.8%) boxed warnings referred to the potential problems for patients with kidney transplants. Conclusion(s): Most drugs with a boxed warning were approved in the 1990s and 2000s. The therapeutic classes with the highest number of renal toxicity warnings were anti-infective for systemic use, antineoplastic and immunomodulating agents, and alimentary tract and metabolism. The most common warnings were renal impairment, nephrotoxicity, nephrogenic systemic fibrosis, and issues for patients with kidney transplants. Future research could expand the analysis to renal toxicity warnings, interactions, and precautions.Copyright © 2023

Best practices for pediatricians in diagnosing and treating asthma

Additionally, they can treat atopic comorbidities such as atopic dermatitis, chronic urticaria, nasal polyps, eosinophilic esophagitis, and hypereosinophilic syndrome, resulting in improved quality of life for our patients. Parents should be made aware of its updated black box warning for possible effects on mental health and behavior changes,3 including but not limited to suicidal ideation. FDA requires boxed warning about serious mental health side effects for asthma and allergy drug montelukast (Singulair);advises restricting use for allergic rhinitis.

Accessing isotopically labeled proteins containing genetically encoded phosphoserine for NMR with optimized expression conditions

Phosphoserine (pSer) sites are primarily located within disordered protein regions, making it difficult to experimentally ascertain their effects on protein structure and function. Therefore, the production of 15N- (and 13C)-labeled proteins with site-specifically encoded pSer for NMR studies is essential to uncover molecular mechanisms of protein regulation by phosphorylation. While genetic code expansion technologies for the translational installation of pSer in Escherichia coli are well established and offer a powerful strategy to produce site-specifically phosphorylated proteins, methodologies to adapt them to minimal or isotope-enriched media have not been described. This shortcoming exists because pSer genetic code expansion expression hosts require the genomic DELTAserB mutation, which increases pSer bioavailability but also imposes serine auxotrophy, preventing growth in minimal media used for isotopic labeling of recombinant proteins. Here, by testing different media supplements, we restored normal BL21(DE3) DELTAserB growth in labeling media but subsequently observed an increase of phosphatase activity and mis-incorporation not typically seen in standard rich media. After rounds of optimization and adaption of a high-density culture protocol, we were able to obtain >=10 mg/L homogenously labeled, phosphorylated superfolder GFP. To demonstrate the utility of this method, we also produced the intrinsically disordered serine/arginine-rich region of the SARS-CoV-2 Nucleocapsid protein labeled with 15N and pSer at the key site S188 and observed the resulting peak shift due to phosphorylation by 2D and 3D heteronuclear single quantum correlation analyses. We propose this cost-effective methodology will pave the way for more routine access to pSer-enriched proteins for 2D and 3D NMR analyses. GCE4All Biomedical Technology Development and Dissemination Center was supported by National Institute of General Medical Science, OSU NMR Facility funded in part by the National Institutes of Health, the Medical Research Foundation at OHSU and the Collins Medical Trust, National Science Foundation EAGER, and by the M. J. Murdock Charitable Trust.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Development of a spin-label model system for investigation of protein oligomerization states

The transmembrane domains of viral proteins are highly conserved and crucial to normal viral function. Oligomeric transmembrane domains present novel opportunities for drug development, as their disruption can prevent the assembly of the virus. The Reichart lab is particularly interested in developing retro-inverso peptide inhibitors. Retro-inverso peptides are peptides using D-amino acids mirroring a region of target protein, which allows the peptide to inhibit viral assembly, but they are also significantly less likely to be catabolized by natural metabolic or immunologic processes. The efficacy of these inhibitors is governed largely by the extent to which they mirror the target protein, making highly conserved regions, such as transmembrane domains, ideal target regions for these inhibitors. The primary technique in the literature for the investigation of oligomerization states uses fluorescence spectroscopy. We are now working on developing a novel alternative system to evaluate protein oligomerization using spin-labeled peptides that are directly incorporated into the peptide sequence. Direct incorporation of the spin-label into the peptide sequence is a more powerful technique than the standard procedures used in the literature. In particular, the ability to incorporate spin labels in various positions within the protein can give novel insights into the relative depth of the protein within a membrane, which is very difficult to study using other techniques and not possible using the fluorescence technique. The transmembrane domains of proteins with known and well-characterized monomer and trimer standard oligomerization states were synthesized using an Fmoc Solid- Phase Peptide Synthesis (SPPS) procedure incorporating an Fmoc-2,2,6,6-tetramethyl-N-oxyl-4-amino-4-carboxylic acid, (Fmoc-TOAC) instead of an alanine. Direct incorporation of stable N-oxide spin labels, which can be contrasted to labeling cysteine residues after the protein synthesis, has been used for the investigation of the secondary structure of proteins for decades, but the application of this spin labeling technique to study the oligomerization states of transmembrane domains of proteins is an understudied application. The products of SPPS were analyzed using a Liquid Chromatography Mass Spectroscopy instrument and purified using High Performance Liquid Chromatography. The spin-label was then deprotected and evaluated using Electron Spin Resonance (ESR) Spectroscopy. There are two primary future directions following this research project: first, the generation of viral proteins with spin labels incorporated in different positions to determine the relative depth of each position within the membrane;second, the incorporation of spin labels into SARS-CoV- 2 proteins to develop a model for in vitro evaluation of retro-inverso peptide assembly inhibitors. -Hampden-Sydney College Office of Undergraduate Research.Copyright © 2023 The American Society for Biochemistry and Molecular Biology, Inc.

Plasma expansion and renal perfusion in critical COVID-19 with AKI

Introduction: We have previously described decreased renal perfusion in acute kidney injury (AKI) due to critical COVID-19 [1]. The objective of this study was to compare the effects of plasma expansion with a standardized fluid bolus on renal perfusion in patients with AKI compared to similar patients without AKI. Method(s): A case control study design was used to investigate group differences before and after a standardized intervention. ICU-treated COVID-19 patients without underlying kidney disease were assigned to two groups based on KDIGO Creatinine criteria for AKI. Renal perfusion was assessed by magnetic resonance imaging using phase contrast and arterial spin labeling before and directly after plasma expansion with 7.5 ml/kg Ringer's Acetate (Baxter). Mean arterial pressure (MAP) was recorded before plasma infusion and compared with maximum value after. Data was analyzed with a mixed model repeated measures ANOVA for all kidneys using a random effect to account for research subjects. Result(s): Nine patients with AKI and eight without were included in the study. Patients in both groups were of similar mean age and weight, 66 (SD 8) years and 94 (SD 22) kg in AKI group and 64 (SD 15) years and 93 (SD 20) kg in patients without AKI. The response to plasma expansion was similar with increased MAP by 18 (CI 8-28) mmHg and 20 (CI 10-31) mmHg respectively (Table 1). Total renal perfusion and cortical perfusion was not significantly changed by plasma expansion, however there was a reduction of medullary perfusion in patients without AKI (Table 1). Conclusion(s): Plasma expansion with a standardized fluid bolus did not increase renal perfusion in critically ill patients with ARDS due to COVID-19.

Of Fear and Strangers: A History of Xenophobia by George Makari (review)

Sigmund Freud in his "Group Psychology and the Analysis of the Ego" (1921) outlined his take on this after World War I. British psychotherapists, including some of his English followers such as Wilfried Trotter, appropriated a psychology of difference popularized by Gustave Le Bon to define the valorous "Tommy" crusading against the inherently evil "Boche." In his 1921 essay, Freud began with the claim concerning collective behavior that had long been established in the psychological literature of the late 19th century—that "a group is extraordinarily credulous and open to influence, it has no critical faculty, and the improbable does not exist for it." In the first of many striking moments in this book, Makari locates the modern origin of xenophobia—and it is not where we expected to find it: the social fascination with the "phobias" had its origin in 19th-century medicine, which quickly devolved into social metaphor, as such diagnostic categories of behavior tend to do rather quickly. Makari begins his book locating his own discomfort with being seen as "different" and trying to understand his own family, Greek Orthodox inhabitants of Ottoman Lebanon, whose trek to the United States created (as many of us know from our own family experience) "better" Americans, initially struggling as peddlers and then establishing themselves in Texas as "real" Americans.

A molecular toolbox for ADP-ribosyl binding proteins.

Proteins interacting with ADP-ribosyl groups are often involved in disease-related pathways or viral infections, making them attractive drug targets. We present a robust and accessible assay applicable to both hydrolyzing or non-hydrolyzing binders of mono- and poly-ADP-ribosyl groups. This technology relies on a C-terminal tag based on a Gi protein alpha subunit peptide (GAP), which allows for site-specific introduction of cysteine-linked mono- and poly-ADP-ribosyl groups or analogs. By fusing the GAP-tag and ADP-ribosyl binders to fluorescent proteins, we generate robust FRET partners and confirm the interaction with 22 known ADP-ribosyl binders. The applicability for high-throughput screening of inhibitors is demonstrated with the SARS-CoV-2 nsp3 macrodomain, for which we identify suramin as a moderate-affinity yet non-specific inhibitor. High-affinity ADP-ribosyl binders fused to nanoluciferase complement this technology, enabling simple blot-based detection of ADP-ribosylated proteins. All these tools can be produced in Escherichia coli and will help in ADP-ribosylation research and drug discovery.

Specific pupylation as IDEntity reporter (SPIDER) for the identification of protein-biomolecule interactions.

Protein-biomolecule interactions play pivotal roles in almost all biological processes. For a biomolecule of interest, the identification of the interacting protein(s) is essential. For this need, although many assays are available, highly robust and reliable methods are always desired. By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin (SA)-biotin system, we developed the Specific Pupylation as IDEntity Reporter (SPIDER) method for identifying protein-biomolecule interactions. Using SPIDER, we validated the interactions between the known binding proteins of protein, DNA, RNA, and small molecule. We successfully applied SPIDER to construct the global protein interactome for m6A and mRNA, identified a variety of uncharacterized m6A binding proteins, and validated SRSF7 as a potential m6A reader. We globally identified the binding proteins for lenalidomide and CobB. Moreover, we identified SARS-CoV-2-specific receptors on the cell membrane. Overall, SPIDER is powerful and highly accessible for the study of protein-biomolecule interactions.

News

This section offers gastrointestinal health-related news briefs as of February 1, 2023, including a study which found that plant-based diet could reduce bowel cancer risk in men, a study which showed that the COVID-19 virus may have a profound effect on the gut microbiome balance, and the call by Coeliac UK for manufacturers to sign up for its labelling scheme in support of research which found that 76% of gluten-free consumers want to be labelled with the Crossed Grain trademark.

An exploration of learning-at-home experiences among families and children of color labeled with disabilities during COVID-19: A narrative inquiry

We are living in this historical moment of a COVID-19 global crisis that is continuing to impact marginalized families in our very own communities. Students of color, especially those who are already on the margins, and experience inequities in the classroom and in the community, have been further impacted by the quarantine as the educational system had not prioritized how to support students who face certain vulnerabilities due to lack of government funding, the historical oppressive tendency for schools to function within a medical model of standardization, along with the commodification of learning. Given the novelty of COVID-19 research, the full impact on these communities is yet to be fully known. Some students of color labeled with disabilities are faced with deeper struggles exacerbated by the pandemic's impact, while others may have improved performance during distance learning due to the removal of inherent bias in the classroom or the traditional inequities that may be perpetuated in a traditional school environment. Within a DisCrit theoretical framework that centers and celebrates the intersectional identities of these families and children, this study is about exploring the unique experiences of public, private and charter school students and their families in the San Francisco Bay area. Centering the narratives of families of color and their children labeled with learning disabilities is one way to shift the voice of power and dominant narratives, and to begin to understand their lived experiences as a way to decenter and dismantle white privilege, ableism and heteronormative supremacy. This qualitative narrative inquiry based study centers and celebrates the lived experiences of six families and their children of color labeled with learning disabilities during the COVID-19 pandemic-fueled remote learning crisis. The thematic findings from this study can inform policymakers and other stakeholders on how to best support these communities, advocate for school-based rights within a constructivist lens, and contribute to the dearth in scholarly research that supports disability justice. (PsycInfo Database Record (c) 2023 APA, all rights reserved)

Exploring the impacts of FDA temporary food labeling flexibility among the food allergy community during the Covid-19 pandemic

In an attempt to improve access to food distribution systems during the Covid-19 pandemic, the United States Food and Drug Administration (FDA) issued temporary flexibility in food labeling requirements. This requirement affects the Top 8 allergens and could lead to accidental allergen ingestion. The purpose of this study was to utilize a qualitative method to collect and analyze comments to FDA that were available via Allergic Living's website from May 22, 2020, to June 18, 2020, following the release of the food labeling change. In total, 3,033 comments were analyzed using the thematic analysis six-phase framework approach. Various themes were extracted relating to the emotional responses of the new labeling including fear, safety concerns, and trust of certain food product brands among the food allergy community. This research has implications for a broad spectrum of the U.S. food industry including restaurants, grocery stores, specialty food associations, and consumers. Stakeholders and experts in the food allergy community should be consulted when a policy change is occurring, especially during a pandemic affecting access to safe food.

Exploring the impacts of FDA temporary food labeling flexibility among the food allergy community during the COVID-19 pandemic. (Special Issue: The impact of the covid-19 pandemic and the foodservice industries.)

In an attempt to improve access to food distribution systems during the Covid-19 pandemic, the United States Food and Drug Administration (FDA) issued temporary flexibility in food labeling requirements. This requirement affects the Top 8 allergens and could lead to accidental allergen ingestion. The purpose of this study was to utilize a qualitative method to collect and analyze comments to FDA that were available via Allergic Living's website from May 22, 2020, to June 18, 2020, following the release of the food labeling change. In total, 3,033 comments were analyzed using the thematic analysis six-phase framework approach. Various themes were extracted relating to the emotional responses of the new labeling including fear, safety concerns, and trust of certain food product brands among the food allergy community. This research has implications for a broad spectrum of the U.S. food industry including restaurants, grocery stores, specialty food associations, and consumers. Stakeholders and experts in the food allergy community should be consulted when a policy change is occurring, especially during a pandemic affecting access to safe food.

Covid‐19‐tested food labels

While the transmission of virus SARS‐CoV‐2 via food is rare, some Chinese food retailers are considering a Covid‐19‐tested food label. However, how consumers may support such a label is unknown. We quantify Chinese consumers' willingness to pay (WTP) for food carrying a Covid‐19‐tested label using an online choice experiment. We find that the WTPs for such a label are always positive for all food products considered. The amount of WTP depends on the entities authenticating the labels, country of origin of the food, and consumers' socio‐demographic status. Contrary to expectation, the knowledge on Covid‐19 does not affect consumer preferences for the Covid‐19‐tested food labels. Our benefit and cost analysis suggests a possible large benefit of creating and administering a Covid‐19‐tested food label. This study provides insights for policymakers, global food manufacturers, and retailers to create marketing strategies to alleviate consumer food safety concerns associated with Covid‐19. [ABSTRACT FROM AUTHOR] Copyright of Canadian Journal of Agricultural Economics is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Understanding COVID-19 Vaccine Campaign on Facebook using Minimal Supervision

In the age of social media, where billions of internet users share information and opinions, the negative impact of pandemics is not limited to the physical world. It provokes a surge of incomplete, biased, and incorrect information, also known as an infodemic. This global infodemic jeopardizes measures to control the pandemic by creating panic, vaccine hesitancy, and fragmented social response. Platforms like Facebook allow advertisers to adapt their messaging to target different demographics and help alleviate or exacerbate the infodemic problem depending on their content. In this paper, we propose a minimally supervised multi-task learning framework for understanding messaging on Facebook related to the COVID vaccine by identifying ad themes and moral foundations. Furthermore, we perform a more nuanced thematic analysis of messaging tactics of vaccine campaigns on social media so that policymakers can make better decisions on pandemic control. © 2022 IEEE.

SIM imaging resolves endocytosis of SARS-CoV-2 spike RBD in living cells.

It is urgent to understand the infection mechanism of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the prevention and treatment of COVID-19. The infection of SARS-CoV-2 starts when the receptor-binding domain (RBD) of viral spike protein binds to angiotensin-converting enzyme 2 (ACE2) of the host cell, but the endocytosis details after this binding are not clear. Here, RBD and ACE2 were genetically coded and labeled with organic dyes to track RBD endocytosis in living cells. The photostable dyes enable long-term structured illumination microscopy (SIM) imaging and to quantify RBD-ACE2 binding (RAB) by the intensity ratio of RBD/ACE2 fluorescence. We resolved RAB endocytosis in living cells, including RBD-ACE2 recognition, cofactor-regulated membrane internalization, RAB-bearing vesicle formation and transport, RAB degradation, and downregulation of ACE2. The RAB was found to activate the RBD internalization. After vesicles were transported and matured within cells, RAB was finally degraded after being taken up by lysosomes. This strategy is a promising tool to understand the infection mechanism of SARS-CoV-2.

Medication Errors

No expiration date on COVID-19 vaccine label... STS abbreviation results in a close call...