Considerations and derivations of permitted daily exposure limits for impurities from intravitreal pharmaceutical products.

Intravitreal (IVT) injection is an uncommon route of parenteral administration for therapeutic medications, but one of the most important for the treatment of ocular diseases, especially those related to macular degeneration. Nonetheless, there are currently no regulatory guidelines that specifically address how to establish a permitted daily exposure (PDE) for impurities and residual process reagents in IVT pharmaceutical drug products given the unique vulnerability of ocular tissues. The establishment of PDEs for IVT administration is complicated by the limited understanding of metabolism and clearance of small molecular weight chemicals from the human vitreous humor (VH), a problem compounded by the limited IVT-specific toxicological data.

ETV2 transcriptionally activates Rig1 gene expression and promotes reprogramming of the endothelial lineage.

ETV2 is an essential transcription factor as Etv2 null murine embryos lack all vasculature, blood and are lethal early during embryogenesis. Previous studies have established that ETV2 functions as a pioneer factor and directly reprograms fibroblasts to endothelial cells. However, the underlying molecular mechanisms regulating this reprogramming process remain incompletely defined.

Large language models (LLMs) and the institutionalization of misinformation.

Large language models (LLMs), such as ChatGPT, flood the Internet with true and false information, crafted and delivered with techniques that psychological science suggests will encourage people to think that information is true. What's more, as people feed this misinformation back into the Internet, emerging LLMs will adopt it and feed it back in other models. Such a scenario means we could lose access to information that helps us tell what is real from unreal - to do 'reality monitoring.

To what extent does post-identification feedback translate into witness behaviour?

When eyewitness receive feedback implying they have accurately identified the perpetrator from a lineup, it boosts their confidence and possibly distorts their memory. Most research investigating this "post-identification feedback effect" (PIF effect) suggests the feedback changes eyewitness' retrospective memory of their actual experiences. But it remains unclear to what extent this feedback might change the eyewitness's subsequent behaviour.

Ferriphaselus amnicola strain GF-20, a new iron- and thiosulfate-oxidizing bacterium isolated from a hard rock aquifer.

Ferriphaselus amnicola GF-20 is the first Fe-oxidizing bacterium isolated from the continental subsurface. It was isolated from groundwater circulating at 20 m depth in the fractured-rock catchment observatory of Guidel-Ploemeur (France). Strain GF-20 is a neutrophilic, iron- and thiosulfate-oxidizer and grows autotrophically.

Networks that Govern Cardiomyocyte Proliferation to Facilitate Repair of the Injured Mammalian Heart.

Cardiovascular diseases are the number one cause of death worldwide and in the United States (US). Cardiovascular diseases frequently progress to end-stage heart failure, and curative therapies are extremely limited. Intense interest has focused on deciphering the cascades and networks that govern cardiomyocyte proliferation and regeneration of the injured heart.

Experimental and meta-analytic evidence that source variability of misinformation does not increase eyewitness suggestibility independently of repetition of misinformation.

Considerable evidence has shown that repeating the same misinformation increases its influence (i.e., repetition effects).

Hits and Misses: Digital Contact Tracing in a Pandemic.

Traditional contact tracing is one of the most powerful weapons people have in the battle against a pandemic, especially when vaccines do not yet exist or do not afford complete protection from infection. But the effectiveness of contact tracing hinges on its ability to find infected people quickly and obtain accurate information from them. Therefore, contact tracing inherits the challenges associated with the fallibilities of memory.

Barriers in chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) management: perspectives from health practitioners.

Objectives: Chronic prostatitis/Chronic Pelvic Pain Syndrome (CP/CPPS) is a complex condition which causes a significant burden on the diagnosed individuals. Assessment and management are perplexing, often resulting in unsatisfactory outcomes. Existing research has only focused on patients' perspectives of pain experiences, but scant evidence is available to understand the barriers that undermine effective pain management.

FOXK1 regulates Wnt signalling to promote cardiogenesis.

Aims: Congenital heart disease (CHD) is the most common genetic birth defect, which has considerable morbidity and mortality. We focused on deciphering key regulators that govern cardiac progenitors and cardiogenesis. FOXK1 is a forkhead/winged helix transcription factor known to regulate cell cycle kinetics and is restricted to mesodermal progenitors, somites, and heart.

The influence of the BDNF Val66Met genotype on emotional recognition memory in post-traumatic stress disorder.

Dysregulated consolidation of emotional memories is a core feature of posttraumatic stress disorder (PTSD). Brain Derived Neurotrophic Factor (BDNF) influences synaptic plasticity and emotional memory consolidation. The BDNF Val66Met polymorphism has been associated with PTSD risk and memory deficits respectively, although findings have been inconsistent, potentially due to a failure to control for important confounds such as sex, ethnicity, and the timing/extent of previous trauma experiences.

ETV2 and VEZF1 interaction and regulation of the hematoendothelial lineage during embryogenesis.

Ets variant 2 (Etv2), a member of the Ets factor family, has an essential role in the formation of endothelial and hematopoietic cell lineages during embryonic development. The functional role of ETS transcription factors is, in part, dependent on the interacting proteins. There are relatively few studies exploring the coordinated interplay between ETV2 and its interacting proteins that regulate mesodermal lineage determination.

Blastocyst complementation and interspecies chimeras in gene edited pigs.

The only curative therapy for many endstage diseases is allograft organ transplantation. Due to the limited supply of donor organs, relatively few patients are recipients of a transplanted organ. Therefore, new strategies are warranted to address this unmet need.

The importance of the smallest effect size of interest in expert witness testimony on alcohol and memory.

Memory experts are sometimes asked to evaluate the validity of accounts of witnesses, victims, or suspects. In some of these cases, they are asked what effect alcohol has on the validity of such accounts. In this article, we offer a guide on what expert witnesses can reliably say about how alcohol affects memory.

Collective memories serve similar functions to autobiographical memories.

People from the same country often hold shared, culturally-shaped memories about important events from that country's history, known as collective memories. Although empirical research has started to shed light on the properties of these memories, none has systematically examined the functions these memories. To what extent do collective memories serve functions? We hypothesised that collective memories serve functions for a collective similar to those that autobiographical memories serve for individuals-directive, identity, and social functions.

Xenotransplantation and exotransplantation: Strategies to expand the number of donor organs.

Cardiovascular disease is common and has a high mortality. Due to the limited number of organs available for orthotopic heart transplantation, alternative therapies have received intense interest. In this commentary we contrast xenotransplantation and blastocyst complementation to produce pigs that will serve as donors for organ transplantation.

Oversimplifications and Misrepresentations in the Repressed Memory Debate: A Reply to Ross.

Ross argued that false memory researchers misunderstand the concepts of repression and dissociation, as well as the writings of Freud. In this commentary, we show that Ross is wrong. He oversimplifies and misrepresents the literature on repressed and false memory.

Emerging technologies and ethics-exogenic chimeric humanized organs.

Organ transplantation is limited due to the scarcity of donor organs. In order to expand the supply of organs for transplantation, interspecies chimeras have been examined as a potential future source of humanized organs. Recent studies using gene editing technologies in combination with somatic cell nuclear transfer technology and hiPSCs successfully engineered humanized skeletal muscle in the porcine embryo.

Mechanisms and strategies to promote cardiac xenotransplantation.

End stage heart failure is a terminal disease, and the only curative therapy is orthotopic heart transplantation. Due to limited organ availability, alternative strategies have received intense interest for treatment of patients with advanced heart failure. Recent studies using gene-edited porcine organs suggest that cardiac xenotransplantation may provide a future source of organs.

Human muscle in gene edited pigs for treatment of volumetric muscle loss.

Focusing on complex extremity trauma and volumetric muscle loss (VML) injuries, this review highlights: 1) the current pathophysiologic limitations of the injury sequela; 2) the gene editing strategy of the pig as a model that provides a novel treatment approach; 3) the notion that human skeletal muscle derived from gene edited, humanized pigs provides a groundbreaking treatment option; and 4) the impact of this technologic platform and how it will advance to far more multifaceted applications. This review seeks to shed insights on a novel treatment option using gene edited pigs as a platform which is necessary to overcome the clinical challenges and limitations in the field.

Collective remembering and future forecasting during the COVID-19 pandemic: How the impact of COVID-19 affected the themes and phenomenology of global and national memories across 15 countries.

The COVID-19 pandemic created a unique set of circumstances in which to investigate collective memory and future simulations of events reported during the onset of a potentially historic event. Between early April and late June 2020, we asked over 4,000 individuals from 15 countries across four continents to report on remarkable (a) national and (b) global events that (i) had happened since the first cases of COVID-19 were reported, and (ii) they expected to happen in the future. Whereas themes of infections, lockdown, and politics dominated global and national past events in most countries, themes of economy, a second wave, and lockdown dominated future events.

Memories people no longer believe in can still affect them in helpful and harmful ways.

People can come to "remember" experiences they never had, and these false memories-much like memories for real experiences-can serve a variety of helpful and harmful functions. Sometimes, though, people realize one of their memories is false, and retract their belief in it. These "retracted memories" continue to have many of the same phenomenological characteristics as their believed memories.

ETV2 functions as a pioneer factor to regulate and reprogram the endothelial lineage.

The vasculature is an essential organ for the delivery of blood and oxygen to all tissues of the body and is thus relevant to the treatment of ischaemic diseases, injury-induced regeneration and solid tumour growth. Previously, we demonstrated that ETV2 is an essential transcription factor for the development of cardiac, endothelial and haematopoietic lineages. Here we report that ETV2 functions as a pioneer factor that relaxes closed chromatin and regulates endothelial development.