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Does a foreign country's prosecution of a family under a law that would be unconstitutional in the United States necessarily provide grounds for a claim of asylum upon arrival in the United States?...

This study aimed to investigate age-related injury incidence, severity, and burden over a 3-year period in U14 to U19 elite male soccer players in a German youth academy.Descriptive epidemiology study.Time-loss injuries of 166 unique players were prospectively documented and injury incidence, severity, and burden were calculated for each age group, body part, and type of injuries.A total of 562 time-loss injuries were recorded. Across all age groups (U14 to U19), injury incidence was 42.2 per squad season (ranging from 30.5 in the U19 to 67.7 in the U15), severity was 11.0 days lost (ranging from 8.0 in the U15 to 17.0 in the U17), and burden was 464.1 days lost per squad season (ranging from 304.9 in the U19 to 756.7 in the U14). The thigh, knee and ankle were the body parts with the highest injury incidence (9.2; 5.9; 5.9), severity (11.0; 16.0; 13.0), and burden (101.6; 94.9; 76.1). Cruciate ligament injuries had both the highest burden (164.4) and severity (137.0), and muscle injuries the highest incidence (11.0) of all types of injuries. U15 had the highest injury incidence (67.7) of all age groups. U14 and U17 had both the highest injury severity (15.0; 17.0) and burden (756.7; 618.8) of all age groups. Age-related patterns were observed for selected types of injuries such as muscle injuries, tendinopathy, bone-stress injury, and fractures.Injury incidence, severity, and burden substantially differed descriptively between age groups and clear age-related patterns for selected types of injuries were evident.

Opladen; Berlin; Toronto : Verlag Barbara Budrich 2023, 338 S. - (Wissenschaftliche Untersuchungen zur Arbeit der Stiftung „Haus der kleinen Forscher“; 9), “Scientific Studies on the Work of the ‘Haus der kleinen Forscher’ Foundation” is a regularly published series of scientific reports authored by distinguished experts from the field of early education. This series serves to pursue professional dialogue between the Foundation, academia and practice, with the aim of lending sound support to all child-care centres, after-school care centres and primary schools in Germany in their educational mission. This ninth volume of the series, with a foreword by Ilan Chabay, deals with the goals and requirements of computer science education in the elementary and primary sector. In their expert report, Nadine Bergner, Hilde Köster, Johannes Magenheim, Kathrin Müller, Ralf Romeike, Ulrik Schroeder and Carsten Schulte specify the pedagogical and content-related goal dimensions of computer science education at child-care centres and primary schools. In addition to establishing a theoretical basis for various goal dimensions, the authors discuss the success criteria for effective and efficient early computer science education in practice. They also provide recommendations for the further development of the Foundation’s offerings and scientific accompaniment of the work of the Foundation in the field of computer science. In their expert recommendation, Nadine Bergner and Kathrin Müller describe a selection of informatics systems for children at child-care centres and primary schools and offer suggestions for particularly suitable systems and their use in elementary and primary education based on professional criteria. The final chapter of the volume describes the implementation of these professional recommendations in the programmes of the “Haus der kleinen Forscher” Foundation – with and without computers. (DIPF/Verlag)

To investigate the influence of geographical origin, age, and sex on toxicologically relevant spontaneous histopathology findings in cynomolgus macaques ( Macaca fascicularis), we performed a comparative analysis of historical control data (HCD) from 13 test sites that included 3351 animals (1645 females and 1706 males) sourced from Mauritius, China, Vietnam, and Cambodia, aged from 2 to 9.5 years, and from 446 toxicology studies evaluated between 2016 and 2021. The most common findings were mononuclear infiltrates in the kidney, liver, brain, and lung, which showed highest incidences in Mauritian macaques, and heart, salivary glands, and gastrointestinal tract (GIT), which showed highest incidences of mononuclear infiltrates in mainland Asian macaques. Developmental and degenerative findings were more common in Mauritian macaques, while lymphoid hyperplasia and lung pigment showed higher incidences in Asian macaques. Various sex and age-related differences were also present. Despite origin-related differences, the similarities in the nature and distribution of background lesions indicate that macaques from all geographical regions are suitable for toxicity testing and show comparable lesion spectrum. However, in a toxicity study, it is strongly recommended to use animals from a single geographical origin and to follow published guidelines when using HCD to evaluate and interpretate commonly diagnosed spontaneous lesions.

Cell fate transitions depend on balanced rewiring of transcription and translation programs to mediate ordered developmental progression. Components of the nonsense-mediated mRNA decay (NMD) pathway have been implicated in regulating embryonic stem cell (ESC) differentiation, but the exact mechanism is unclear. Here we show that NMD controls expression levels of the translation initiation factor Eif4a2 and its premature termination codon-encoding isoform (Eif4a2PTC). NMD deficiency leads to translation of the truncated eIF4A2PTC protein. eIF4A2PTC elicits increased mTORC1 activity and translation rates and causes differentiation delays. This establishes a previously unknown feedback loop between NMD and translation initiation. Furthermore, our results show a clear hierarchy in the severity of target deregulation and differentiation phenotypes between NMD effector KOs (Smg5 KO > Smg6 KO > Smg7 KO), which highlights heterodimer-independent functions for SMG5 and SMG7. Together, our findings expose an intricate link between mRNA homeostasis and mTORC1 activity that must be maintained for normal dynamics of cell state transitions.

As a consequence of the increasing influence of machine learning on our lives, everyone needs competencies to understand corresponding phenomena, but also to get involved in shaping our world and making informed decisions regarding the influences on our society. Therefore, in K-12 education, students need to learn about core ideas and principles of machine learning. However, for this target group, achieving all of the aforementioned goals presents an enormous challenge. To this end, we present a teaching concept that combines a playful and accessible unplugged approach focusing on conceptual understanding with empowering students to actively apply machine learning methods and reflect their influence on society, building upon decision tree learning., To be published in the proceedings of the 3rd Teaching in Machine Learning Workshop, PMLR, 2022

Aims and objectives: Digital teaching, learning and assessment have been part of medical education and continuing education for decades. The objective of this review paper is to highlight developments and perspectives in these areas in the GMS Journal for Medical Education (GMS JME). Methodology: In the spring of 2020, we conducted a systematic literature search of the Journal for Medical Education (JME) and analysed the articles with regard to different categories such as article type, digital tools used or mode of data collection. Results: Of the 132 articles analysed, 78 were digital interventions (53 of which were exploratory-descriptive), 28 were project descriptions, 16 were surveys of needs or equipment and 10 were concept papers. About one-third of the studies and project reports each dealt with virtual patients or case-based learning, whereas no articles were published on trends such as serious games or virtual reality. Overall, our analysis shows that in many respects, the studies on digital teaching were more broadly based, especially between 2006 and 2010, after which this trend tended to decline again.Conclusions: Our analysis shows that publications in the JME consider some key aspects of digital teaching in medical education and continuing education, such as educational videos or virtual patients. The variability of information and methods of presentation advocate the use of guidelines to optimise the quality of scientific papers. Furthermore, clues for future research topics and experimental study designs are identified. Zielsetzung: Digitales Lehren, Lernen und Prüfen ist bereits seit Jahrzehnten Bestandteil der medizinischen Aus- und Weiterbildung. Das Ziel dieser Überblicksarbeit ist es, Entwicklungen und Perspektiven in diesen Bereichen im GMS Journal for Medical Education (GMS JME) aufzuzeigen. Methodik: Im Frühjahr 2020 haben wir eine systematische Literaturrecherche im Journal for Medical Education (JME) durchgeführt und die Artikel hinsichtlich verschiedener Kategorien wie Artikeltyp, eingesetzte digitale Tools oder Modus der Datenerhebung analysiert. Ergebnisse: Von den 132 analysierten Artikeln waren 78 digitale Interventionen (davon 53 explorativ-deskriptiv), 28 Projektbeschreibungen, 16 Erhebungen zu Bedarfen oder Ausstattungen und 10 Konzeptpapiere. Jeweils etwa ein Drittel der Studien und Projektberichte beschäftigten sich mit virtuellen Patient*innen bzw. fallbasiertem Lernen, während keine Artikel zu Trends wie Serious Games oder virtuellen Realitäten publiziert wurden. Unsere Analyse zeigt insgesamt, dass in vielerlei Hinsicht die Studien zu digitaler Lehre v.a. zwischen 2006 und 2010 breiter gefächert waren, danach war dieser Trend eher wieder rückläufig.Schlussfolgerungen: Unsere Analyse zeigt, dass Publikationen im JME einige Schwerpunkte der digitalen Lehre in der medizinischen Aus- und Weiterbildung, wie z.B. Lehrfilme oder virtuelle Patient*innen, berücksichtigen. Die Variabilität von Angaben und Darstellungsweisen befürworten den Einsatz von Leitlinien zur Optimierung der Qualität von wissenschaftlichen Arbeiten. Weiterhin werden Anhaltspunkte für zukünftige Forschungsthemen und experimentelle Studiendesigns identifiziert.

Technological advances in the context of digital transformation are the basis for rapid developments in the field of artificial intelligence (AI). Although AI is not a new topic in computer science (CS), recent developments are having an immense impact on everyday life and society. In consequence, everyone needs competencies to be able to adequately and competently analyze, discuss and help shape the impact, opportunities, and limits of artificial intelligence on their personal lives and our society. As a result, an increasing number of CS curricula are being extended to include the topic of AI. However, in order to integrate AI into existing CS curricula, what students can and should learn in the context of AI needs to be clarified. This has proven to be particularly difficult, considering that so far CS education research on central concepts and principles of AI lacks sufficient elaboration. Therefore, in this paper, we present a curriculum of learning objectives that addresses digital literacy and the societal perspective in particular. The learning objectives can be used to comprehensively design curricula, but also allow for analyzing current curricula and teaching materials and provide insights into the central concepts and corresponding competencies of AI., Comment: To be published in the proceedings of the proceedings of World Conference on Computers in Education, WCCE 2022

Written reflective practice is a regular exercise pre-service teachers perform during their higher education. Usually, their lecturers are expected to provide individual feedback, which can be a challenging task to perform on a regular basis. In this paper, we present the first open-source automated feedback tool based on didactic theory and implemented as a hybrid AI system. We describe the components and discuss the advantages and disadvantages of our system compared to the state-of-art generative large language models. The main objective of our work is to enable better learning outcomes for students and to complement the teaching activities of lecturers., Comment: 2 figures

Sequencing of the human genome and numerous advances in molecular techniques have launched the era of genetic medicine. Increasingly precise technologies for genetic modification, manufacturing, and administration of pharmaceutical-grade biologics have proved the viability of in vivo gene therapy (GTx) as a therapeutic modality as shown in several thousand clinical trials and recent approval of several GTx products for treating rare diseases and cancers. In recognition of the rapidly advancing knowledge in this field, the regulatory landscape has evolved considerably to maintain appropriate monitoring of safety concerns associated with this modality. Nonetheless, GTx safety assessment remains complex and is designed on a case-by-case basis that is determined by the disease indication and product attributes. This article describes our current understanding of fundamental biological principles and possible procedures (emphasizing those related to toxicology and toxicologic pathology) needed to support research and development of in vivo GTx products. This article is not intended to provide comprehensive guidance on all GTx modalities but instead provides an overview relevant to in vivo GTx generally by utilizing recombinant adeno-associated virus-based GTx—the most common in vivo GTx platform—to exemplify the main points to be considered in nonclinical research and development of GTx products.

Banken, Versicherungen, Asset Manager und weitere Finanzdienstleister spielen bei der Unterstützung der Transformation zu einer nachhaltigen Wirtschaft eine substantielle Rolle. Dabei werden sie von ökologischen, sozialen und politischen Risikofeldern herausgefordert. Wie Sie Ihr Risikomanagement unter diesen ESG-Kriterien (Environmental, Social, Governance) optimal ausrichten können, beleuchtet das innovative Praxisbuch systematisch – mit Beiträgen führender Finanzdienstleister, Aufsichtsbehörden, Hochschulen, Think Tanks und Beratungsgesellschaften: ein wichtiges, hochaktuelles Schlüsselthema für die gesamte Branche.

Hepatitis A virus (HAV) infects humans and non-human primates causing an acute self-limited illness. Three HAV genotypes have been described for humans and three genotypes have been described for non-human primates. We observed transiently elevated liver enzymes in Mauritius-origin laboratory-housed macaques in Germany and were not able to demonstrate HAV by serology and PCR. Using deep sequencing, we have identified a new HAV genotype with 86% nucleotide sequence homology to HAV genotype IV capsid proteins and approximately 80% nucleotide homology to other HAV genotypes. In situ hybridization indicates persistence in the biliary epithelium up to 3 months after liver enzymes were elevated. Vaccination using a commercial vaccine against human HAV prevented reoccurrence of liver enzyme elevations. Since available assays for HAV did not detect this new variant, knowledge of its existence may ameliorate potential significant epidemiological and research implications in laboratories globally.Article Summary LineA new genotype of hepatitis A virus, that was not identifiable by available diagnostic assays, caused liver enzyme elevations in laboratory-housed Mauritius-origin Cynomolgus macaques.

This article describes the Society of Toxicologic Pathology’s (STP) five recommended (“best”) practices for appropriate use of informed (non-blinded) versus masked (blinded) microscopic evaluation in animal toxicity studies intended for regulatory review. (1) Informed microscopic evaluation is the default approach for animal toxicity studies. (2) Masked microscopic evaluation has merit for confirming preliminary diagnoses for target organs and/or defining thresholds (“no observed adverse effect level” and similar values) identified during an initial informed evaluation, addressing focused hypotheses, or satisfying guidance or requests from regulatory agencies. (3) If used as the approach for an animal toxicity study to investigate a specific research question, masking of the initial microscopic evaluation should be limited to withholding only information about the group (control or test article-treated) and dose equivalents. (4) The decision regarding whether or not to perform a masked microscopic evaluation is best made by a toxicologic pathologist with relevant experience. (5) Pathology peer review, performed to verify the microscopic diagnoses and interpretations by the study pathologist, should use an informed evaluation approach. The STP maintains that implementing these five best practices has and will continue to consistently deliver robust microscopic data with high sensitivity for animal toxicity studies intended for regulatory review. Consequently, when conducting animal toxicity studies, the advantages of informed microscopic evaluation for maximizing sensitivity outweigh the perceived advantages of minimizing bias through masked microscopic examination.

Nonclinical toxicology studies that are required to support human clinical trials of new drug candidates are generally conducted in a rodent and a non-rodent species. These studies typically contain a vehicle control group and low, intermediate, and high dose test article groups. In addition, a dosing-free recovery phase is sometimes included to determine reversibility of potential toxicities observed during the dosing phase and may include additional animals in the vehicle control and one or more dose groups. Typically, reversibility is determined by comparing the test article–related changes in the dosing phase animals to concurrent recovery phase animals at the same dose level. Therefore, for interpretation of reversibility, it is not always essential to euthanize the recovery vehicle control animals. In the absence of recovery vehicle control tissues, the pathologist’s experience, historical control database, digital or glass slide repositories, or literature can be used to interpret the findings in the context of background pathology of the species/strain/age. Therefore, in most studies, the default approach could be not to euthanize recovery vehicle control animals. This article provides opinions on scenarios that may or may not necessitate euthanasia of recovery phase vehicle control animals in nonclinical toxicology studies involving dogs and nonhuman primates.

Zielsetzung: Digitales Lehren, Lernen und Prüfen ist bereits seit Jahrzehnten Bestandteil der medizinischen Aus- und Weiterbildung. Aufgrund unzureichender Übersicht, soll eine retrospektive Betrachtung der publizierten Beiträge im GMS Journal for Medical Education (JME) – vormals [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Hintergrund: Die digitale Transformation bietet in Medizin und medizinischer Ausbildung unbestritten vielfältige und nachhaltige Möglichkeiten und Chancen die Qualität und Effizienz der Lehre sowie klinischer Ausübung voranzutreiben. Obwohl dies empirisch eindeutig ist und es ein [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Lernziele: Teilnehmende finden unter [[link:https://kurzelinks.de/3DMdM*https://kurzelinks.de/3DMdM]] eine Sammlung von online frei zu betrachtende 3D-Modelle anatomischer und pathologischer Präparate sowie entsprechende digitale histologische [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Lernziele: Teilnehmende haben am Ende des Workshops ... das Prinzip des „Inverted Classroom“ durch eine interaktive asynchrone Vorbereitung und eine synchrone praktische Lernphase selber angewendet, die Vor- und Nachteile von Inverted-Classroom bzw. Blended-Learning oder Gamification [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Fragestellung/Zielsetzung: Aufgrund der Pandemie mit einem Mangel an klinisch-praktischer Lehre wurde im Sommersemester 2021 an der Universität Rostock ein digitales OSCE-Format (Objective Structured Clinical Examination) für 250 Medizinstudierende als Vorbereitung auf das Praktische [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Lernziel: Ziel des Workshops ist es, den Austausch zwischen verschiedenen Akteuren im Bereich der digitalen Lehre anzuregen und Lösungen für die aktuellen Herausforderungen der digitalen Transformation der Lehre zu finden. Ablauf der Veranstaltung mit Zeitplan inkl. eingesetzter didaktischer [zum vollständigen Text gelangen Sie über die oben angegebene URL]

Supplemental material, sj-docx-2-tpx-10.1177_01926233211041962 for Scientific and Regulatory Policy Committee Points to Consider: Nonclinical Research and Development of In Vivo Gene Therapy Products, Emphasizing Adeno-Associated Virus Vectors by Julie A. Hutt, Basel T. Assaf, Brad Bolon, Joy Cavagnaro, Elizabeth Galbreath, Branka Grubor, Lisa M. Kattenhorn, Annette Romeike and Laurence O. Whiteley in Toxicologic Pathology

Supplemental material, sj-docx-2-tpx-10.1177_01926233211041962 for Scientific and Regulatory Policy Committee Points to Consider: Nonclinical Research and Development of In Vivo Gene Therapy Products, Emphasizing Adeno-Associated Virus Vectors by Julie A. Hutt, Basel T. Assaf, Brad Bolon, Joy Cavagnaro, Elizabeth Galbreath, Branka Grubor, Lisa M. Kattenhorn, Annette Romeike and Laurence O. Whiteley in Toxicologic Pathology

Supplemental material, sj-docx-1-tpx-10.1177_01926233211041962 for Scientific and Regulatory Policy Committee Points to Consider: Nonclinical Research and Development of In Vivo Gene Therapy Products, Emphasizing Adeno-Associated Virus Vectors by Julie A. Hutt, Basel T. Assaf, Brad Bolon, Joy Cavagnaro, Elizabeth Galbreath, Branka Grubor, Lisa M. Kattenhorn, Annette Romeike and Laurence O. Whiteley in Toxicologic Pathology

Supplemental material, sj-pdf-1-tpx-10.1177_01926233221096424 for The Influence of Geographical Origin, Age, Sex, and Animal Husbandry on the Spontaneous Histopathology of Laboratory Cynomolgus Macaques (Macaca Fascicularis): A Contemporary Global and Multisite Review of Historical Control Data by Ronnie Chamanza, Stuart W. Naylor, Michela Gregori, Molly Boyle, Marcia E. Pereira Bacares, Elodie Drevon-Gaillot, Annette Romeike, Cynthia Courtney, Kelsey Johnson, Julie Turner, Nadine Swierzawski and Alok K. Sharma in Toxicologic Pathology

Stem cells intrinsically express a subset of genes which are normally associated with interferon stimulation and the innate immune response. However, the expression of these interferon-stimulated genes (ISG) in stem cells is independent from external stimuli such as viral infection. Here, we show that the interferon regulatory factor 1, Irf1, is directly controlled by the murine formative pluripotency gene regulatory network and transiently upregulated during the transition from naive to formative pluripotency. IRF1 binds to regulatory regions of a conserved set of ISGs and is required for their faithful expression upon exit from naive pluripotency. We show that in the absence of IRF1, cells exiting the naive pluripotent stem cell state are more susceptible to viral infection. Irf1 therefore acts as a link between the formative pluripotency network, regulation of innate immunity genes, and defense against viral infections during formative pluripotency.

Toxicologic Pathology is the official journal of the Society of Toxicologic Pathology (STP), the British Society of Toxicological Pathology (BSTP), and the European Society of Toxicologic Pathology (ESTP). Toxicologic Pathology publishes articles related to topics in various aspects of toxicologic pathology such as anatomic pathology, clinical pathology, experimental pathology, and biomarker research. Publications include society-endorsed Best Practice/Position and Points to Consider publications and ESTP Expert Workshop articles that are relevant to toxicologic pathology and scientific regulatory processes, Opinion articles under the banner of the STP Toxicologic Pathology Forum, Original Articles, Review Articles (unsolicited/contributed, mini, and invited), Brief Communications, Letters to the Editor, Meeting Reports, and Book Reviews. This article provides details on the various publication categories in Toxicologic Pathology and will serve as a reference for authors and readers.

Many potential drugs for treatment of neurodegenerative diseases, particularly antisense oligonucleotides (ASOs), are administered via lumbar intrathecal injection, because these drugs do not cross the blood–brain barrier. Intrathecal injection is a well-established method in cynomolgus monkeys, a species that is used in preclinical safety assessment when other nonrodent species cannot be used. The authors completed intrathecal ASO administration in over 30 preclinical safety studies (>1000 animals and >4500 dose administrations) during which we observed 3 cases of procedure-related spinal cord necrosis (incidence

In der Logistik geht es um Gestaltung, Planung, Steuerung, Bereitstellung, Optimierung und Sicherung des Material- und Warenflusses und der damit einhergehenden Informationen von der Entwicklung eines Produktes, beginnend beim Lieferanten, bis zum Absatz an den Endabnehmer. Häufig wird Logistik mit den „7 R“ beschrieben: Es geht darum, das richtige Produkt zur richtigen Zeit, am richtigen Ort, in der richtigen Menge, in der richtigen Qualität und zu den richtigen Kosten zum richtigen Kunden zu bringen. Ein Blick in die Gegenwart zeigt, dass logistischeProzessketten und Logistiknetze immer komplexer geworden sind – auch hinsichtlich Kosten, Zeit und Qualität. In diesem Kapitel bieten wir eine konkrete Arbeitshilfe für Praktiker und stellen anhand unterschiedlicher Beispiele Konzepte, Methoden und Instrumente vor, die es ermöglichen, Risiken in der Logistik zu identifizieren und effektiv zu handhaben. Für ein wirksames Logistik-Risikomanagement müssen die folgenden vier Erfolgsfaktoren berücksichtigt werden: 1. Methoden, 2. Organisation, 3. Prozess und 4. gelebte Risiko-/Fehlerkultur.

In einem Industrie- und Handelsunternehmen können Risiken an jedem Punkt entlang der Wertschöpfungskette entstehen. So hatte die Nuklearkatastrophe von Fukushima im März 2011 oder die COVID-19-Pandemie im Jahr 2020 massive Auswirkungen auf die Produktionsprozesse weltweit. Die Unterbrechung länderüberschreitender Lieferketten führte zu zumindest zeitweisen Produktionsstopps. Vor allem in der Folge der verstärkten Globalisierung der Wertschöpfungsnetzwerke sowie die Verschlankung derartiger Netzwerke ist die Risikoexponierung vieler produzierender Unternehmen in den vergangenen Jahren stark angestiegen. Das Kapitel "Risiko-Management in der Produktion" bietet eine Einführung in Methoden zum Aufbau eines wirksamens Risiko-Managements im Bereich der Produktion. So werden u.a. die Methoden Szenariotechnik/Szenarioanalyse (deterministisch), FMEA (Failure Mode and Effects Analysis), Fehlerbaumanalyse (Fault Tree Analysis), Bow-Tie-Analyse, CIRS, PAAG und HAZOP beschrieben.

To investigate the influence of geographical origin, age, and sex on toxicologically relevant spontaneous histopathology findings in cynomolgus macaques (

We provide a descriptive characterization of the unfolded protein response (UPR) in skeletal muscle of human patients with peritoneal sepsis and a sepsis model of C57BL/6J mice. Patients undergoing open surgery were included in a cross-sectional study and blood and skeletal muscle samples were taken. Key markers of the UPR and cluster of differentiation 68 (CD68) as surrogate of inflammatory injury were evaluated by real-time PCR and histochemical staining. CD68 mRNA increased with sepsis in skeletal muscle of patients and animals (p

p. 77-94.

Stem cells intrinsically express a subset of genes which are normally associated with interferon stimulation, and thus the innate immunity response. Expression of these interferon stimulated genes (ISG) in stem cells is independent of external stimuli such as viral infection. Here we show that the interferon regulatory factor 1, Irf1, is directly controlled by the murine formative pluripotency gene regulatory network and therefore upregulated in the transition from naive to formative pluripotency. IRF1 in turn binds to regulatory regions of a conserved set of ISGs and is required for their faithful expression in formative pluripotent cells. IRF1 also binds to an enhancer of the formative pluripotency transcription factor Oct6 and is partially required for upregulation of Oct6. IRF1 therefore acts as a link between the formative pluripotency network and the regulation of innate immunity genes in formative pluripotency.

Supplemental Material, sj-docx-2-tpx-10.1177_01926233211041962 for Scientific and Regulatory Policy Committee Points to Consider: Nonclinical Research and Development of In Vivo Gene Therapy Products, Emphasizing Adeno-Associated Virus Vectors by Julie A. Hutt, Basel T. Assaf, Brad Bolon, Joy Cavagnaro, Elizabeth Galbreath, Branka Grubor, Lisa M. Kattenhorn, Annette Romeike and Laurence O. Whiteley in Toxicologic Pathology