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Using Michigan Panel Study of Income Dynamics data, we study selection bias and the gender wage gap. Employing several methods, we find large declines in the total and unexplained gender gaps in wage offers between 1981 and 2015. Under our preferred selection correction method, the median total and unexplained gaps fell by 0.378 and 0.204 log points, respectively. These are larger declines than if we had not corrected for selection and simply measured convergence in observed wage gaps. However, substantial selectivity-corrected median gender wage gaps remain in 2015: 0.242 log points (total gap) and 0.206 log points (unexplained gap). [ABSTRACT FROM AUTHOR]

Therapy-related acute myeloid leukemia (t-AML) often exhibits adverse (genetic) features. There is ongoing discussion on the impact of t-AML on long-term outcome in AML. Therefore, we retrospectively analyzed clinical and biological characteristics of 1133 AML patients (225 t-AML patients and 908 de novo AML patients) with a median follow-up of 81.8 months. T-AML patients showed more adverse genetic alterations, higher age and more comorbidities as compared to de novo AML. Median OS in intensively treated t-AML patients was 13.7 months as compared to 39.4 months in de novo AML (p < 0.001). With non-intensive therapy, OS did not differ significantly (p = 0.394). With intensive therapy, significant differences in favor of de novo AML were observed in the ELN intermediate I/II (p = 0.009) and adverse (p = 0.016) risk groups but not within favorable risk groups (APL p = 0.927, ELN favorable p = 0.714). However, t-AML was no independent risk factor for OS (p = 0.103), RR (p = 0.982) and NRM (p = 0.320) in the multivariate analysis. A limitation of our study is an ELN 2010 risk stratification due to a lack of more comprehensive molecular data according to ELN 2022. We conclude that therapeutic algorithms in t-AML, in particular with regard to allo-HSCT, should be guided by ELN genetic risk rather than classification as t-AML alone. Our data support the WHO and ICC 2022 classifications, which include t-AML as diagnostic qualifier rather than a separate subcategory. [ABSTRACT FROM AUTHOR]

The process of locating and identifying missing persons presents a complex challenge that hinges on the collection and comparison of diverse data sets. This commentary offers an overview of some of the difficulties and considerations associated with data management in the context of large‐scale missing person identifications. Such complexities include the uniqueness of each disaster event, the response time to the event, the variable quality and quantity of data, and the involvement of numerous stakeholders, all of which contribute to the intricacies of data management. In addition, the paramount considerations of privacy and ethical standards further compound these challenges, especially when dealing with sensitive information such as genetic data. This commentary describes the integrated Data Management System (iDMS) developed by the International Commission on Missing Persons (ICMP) as one example of a comprehensive, freely available solution for data collection, storage, protection, and analysis in missing person cases. The various advantages of the system are discussed, including the system's interoperability among the diverse array of stakeholders involved. While the iDMS streamlines data management processes and therefore represents a significant advancement in the field of missing person identification, it is concluded that the pending issue extends beyond the software tools to encompass the lack of political will among stakeholders to collaborate there remains a pressing need for all stakeholders involved in the identification process to commit to a mechanism that facilitates compatibility and interoperability if different tools are used in disaster victim identification (DVI) scenarios. [ABSTRACT FROM AUTHOR]

Muscle stem cells (MuSCs) are specialized cells that reside in adult skeletal muscle poised to repair muscle tissue. The ability of MuSCs to regenerate damaged tissues declines markedly with aging and in diseases such as Duchenne muscular dystrophy, but the underlying causes of MuSC dysfunction remain poorly understood. Both aging and disease result in dramatic increases in the stiffness of the muscle tissue microenvironment from fibrosis. MuSCs are known to lose their regenerative potential if cultured on stiff plastic substrates. We sought to determine whether MuSCs harbor a memory of their past microenvironment and if it can be overcome. We tested MuSCs in situ using dynamic hydrogel biomaterials that soften or stiffen on demand in response to light and found that freshly isolated MuSCs develop a persistent memory of substrate stiffness characterized by loss of proliferative progenitors within the first three days of culture on stiff substrates. MuSCs cultured on soft hydrogels had altered cytoskeletal organization and activity of Rho and Rac guanosine triphosphate hydrolase (GTPase) and Yes-associated protein mechanotransduction pathways compared to those on stiff hydrogels. Pharmacologic inhibition identified RhoA activation as responsible for the mechanical memory phenotype, and single-cell RNA sequencing revealed a molecular signature of the mechanical memory. These studies highlight that microenvironmental stiffness regulates MuSC fate and leads to MuSC dysfunction that is not readily reversed by changing stiffness. Our results suggest that stiffness can be circumvented by targeting downstream signaling pathways to overcome stem cell dysfunction in aged and disease states with aberrant fibrotic tissue mechanics. [ABSTRACT FROM AUTHOR]

Background: Deletions and partial losses of chromosome 7 (chr7) are frequent in acute myeloid leukemia (AML) and are linked to dismal outcome. However, the genomic landscape and prognostic impact of concomitant genetic aberrations remain incompletely understood. Methods: To discover genetic lesions in adult AML patients with aberrations of chromosome 7 [abn(7)], 60 paired diagnostic/remission samples were investigated by whole-exome sequencing in the exploration cohort. Subsequently, a gene panel including 66 genes and a SNP backbone for copy-number variation detection was designed and applied to the remaining samples of the validation cohort. In total, 519 patients were investigated, of which 415 received intensive induction treatment, typically containing a combination of cytarabine and anthracyclines. Results: In the exploration cohort, the most frequently mutated gene was TP53 (33%), followed by epigenetic regulators (DNMT3A, KMT2C, IDH2) and signaling genes (NRAS, PTPN11). Thirty percent of 519 patients harbored ≥ 1 mutation in genes located in commonly deleted regions of chr7—most frequently affecting KMT2C (16%) and EZH2 (10%). KMT2C mutations were often subclonal and enriched in patients with del(7q), de novo or core-binding factor AML (45%). Cancer cell fraction analysis and reconstruction of mutation acquisition identified TP53 mutations as mainly disease-initiating events, while del(7q) or −7 appeared as subclonal events in one-third of cases. Multivariable analysis identified five genetic lesions with significant prognostic impact in intensively treated AML patients with abn(7). Mutations in TP53 and PTPN11 (11%) showed the strongest association with worse overall survival (OS, TP53: hazard ratio [HR], 2.53 [95% CI 1.66–3.86]; P < 0.001; PTPN11: HR, 2.24 [95% CI 1.56–3.22]; P < 0.001) and relapse-free survival (RFS, TP53: HR, 2.3 [95% CI 1.25–4.26]; P = 0.008; PTPN11: HR, 2.32 [95% CI 1.33–4.04]; P = 0.003). By contrast, IDH2-mutated patients (9%) displayed prolonged OS (HR, 0.51 [95% CI 0.30–0.88]; P = 0.0015) and durable responses (RFS: HR, 0.5 [95% CI 0.26–0.96]; P = 0.036). Conclusion: This work unraveled formerly underestimated genetic lesions and provides a comprehensive overview of the spectrum of recurrent gene mutations and their clinical relevance in AML with abn(7). KMT2C mutations are among the most frequent gene mutations in this heterogeneous AML subgroup and warrant further functional investigation. [ABSTRACT FROM AUTHOR]

This article examines how livelihood security is co-produced through multiple strategies in Southeast Asia's agrarian transformation, by considering the case of Cambodian migrant workers, who cobble together their livelihood through a combination of land, labour and debt. These workers leverage small landholdings as collateral to take on debts to finance migration to Thailand, where low wages and insecure employment inhibit their ability to repay such debts. The traditional social welfare role of land as a safety net is superseded by the use of land as collateral to access microfinance loans, which are also commonly used to respond to livelihood shocks. In this financialised context, social protection schemes insufficiently address the combined livelihood risks that are assumed by workers and do not provide meaningful protection to workers. Drawing on field interviews, we argue that these various supposed sources of livelihood security rather act to increase precarity for workers, by exacerbating labour discipline and dependence on employers. [ABSTRACT FROM AUTHOR]

Objective This study aimed to describe our experience with universal urine drug screening (UDS) with rapid confirmation (RC) via liquid chromatography mass spectrometry (LC-MS) before infant's discharge, in efforts to increase detection of neonates at risk of neonatal opioid withdrawal syndrome (NOWS) while reducing patient burden related to false positive results. Study Design Two-phase retrospective study of all pregnant women admitted to our labor and delivery (L&D) unit before (phase 1, April 2018–March 2019) and after (phase 2, October 2019–September 2020) RC of UDS was initiated. Urine samples were obtained on admission and screened for drugs using an enzyme immunoassay with positive results reflexed to confirmation via LC-MS. The turnaround time for LC-MS was 1 week in phase 1 and 24 hours in phase 2. For mothers with positive LC-MS confirmation, the infant's meconium was sent for drug screening. Positive results were determined to be true or false positive based on urinary LC-MS results. The primary outcome was the rate of opioid-positive mothers who were unanticipated. The secondary outcome was the difference in rate of neonates who were observed for NOWS, before and after implementation of RC with LC-MS. Results In phase 2, a total of 2,395 deliveries occurred of which 2,122 (88.6%) had available UDS results. Fifty-two (2.5%) women had a positive UDS for at least one drug with LC-MS confirmation. Of those, 25 were true positive and 27 were false positive. Twenty-one (84%) true positive mothers were taking opioids and 8 (37%) of them were unanticipated positives. Among mothers with positive UDS for opioids, the neonatal observation rate for development of NOWS was 100% (22/22) and 48% (21/44) before and after implementation of LC-MS RC, respectively. Conclusion Universal UDS and LC-MS RC in L&D may improve detection of unanticipated positive mothers whose infants are at risk of NOWS. RC of positive results allows intervention only for confirmed cases. Key Points Universal UDS can detect more infants at risk of NOWS. Rapid confirmation of positive UDS reduces burden. Only confirmed infants should be observed in the neonatal intensive care unit. Child Protective Services should only be notified of confirmed opioid-positive results. [ABSTRACT FROM AUTHOR]

Excessive calorie intake leads to mitochondrial overload and triggers metabolic inflexibility and insulin resistance. In this study, we examined how attenuated p38α activity affects glucose and fat metabolism in the skeletal muscles of mice on a high-fat diet (HFD). Mice exhibiting diminished p38α activity (referred to as p38αAF) gained more weight and displayed elevated serum insulin levels, as well as a compromised response in the insulin tolerance test, compared to the control mice. Additionally, their skeletal muscle tissue manifested impaired insulin signaling, leading to resistance in insulin-mediated glucose uptake. Examination of muscle metabolites in p38αAF mice revealed lower levels of glycolytic intermediates and decreased levels of acyl-carnitine metabolites, suggesting reduced glycolysis and β-oxidation compared to the controls. Additionally, muscles of p38αAF mice exhibited severe abnormalities in their mitochondria. Analysis of myotubes derived from p38αAF mice revealed reduced mitochondrial respiratory capacity relative to the myotubes of the control mice. Furthermore, these myotubes showed decreased expression of Acetyl CoA Carboxylase 2 (ACC2), leading to increased fatty acid oxidation and diminished inhibitory phosphorylation of pyruvate dehydrogenase (PDH), which resulted in elevated mitochondrial pyruvate oxidation. The expected consequence of reduced mitochondrial respiratory function and uncontrolled nutrient oxidation observed in p38αAF myotubes mitochondrial overload and metabolic inflexibility. This scenario explains the increased likelihood of insulin resistance development in the muscles of p38αAF mice compared to the control mice on a high-fat diet. In summary, within skeletal muscles, p38α assumes a crucial role in orchestrating the mitochondrial adaptation to caloric surplus by promoting mitochondrial biogenesis and regulating the selective oxidation of nutrients, thereby preventing mitochondrial overload, metabolic inflexibility, and insulin resistance. [ABSTRACT FROM AUTHOR]

Autologous(auto-) and allogeneic(allo-) hematopoietic stem cell transplantation (HSCT) are key treatments for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), although their roles are challenged by CAR-T-cells and other immunotherapies. We examined the transplantation trends and outcomes for DLBCL patients undergoing auto-/allo-HSCT between 1990 and 2021 reported to EBMT. Over this period, 41,148 patients underwent auto-HSCT, peaking at 1911 cases in 2016, while allo-HSCT saw a maximum of 294 cases in 2018. The recent decline in transplants corresponds to increased CAR-T treatments (1117 cases in 2021). Median age for auto-HSCT rose from 42 (1990–1994) to 58 years (2015–2021), with peripheral blood becoming the primary stem cell source post-1994. Allo-HSCT median age increased from 36 (1990–1994) to 54 (2015–2021) years, with mobilized blood as the primary source post-1998 and reduced intensity conditioning post-2000. Unrelated and mismatched allo-HSCT accounted for 50% and 19% of allo-HSCT in 2015–2021. Three-year overall survival (OS) after auto-HSCT improved from 56% (1990–1994) to 70% (2015–2021), p < 0.001, with a decrease in relapse incidence (RI) from 49% to 38%, while non-relapse mortality (NRM) remained unchanged (4%). After allo-HSCT, 3-year-OS increased from 33% (1990–1999) to 46% (2015–2021) (p < 0.001); 3-year RI remained at 39% and 1-year-NRM decreased to 19% (p < 0.001). Our data reflect advancements over 32 years and >40,000 transplants, providing insights for evaluating emerging DLBCL therapies. [ABSTRACT FROM AUTHOR]

We consider the problem of identifying the acoustic impedance of a wall surface from noisy pressure measurements in a closed room using a Bayesian approach. The room acoustics are modeled by the interior Helmholtz equation with impedance boundary conditions. The aim is to compute moments of the acoustic impedance to estimate a suitable density function of the impedance coefficient. For the computation of moments we use ratio estimators and Monte Carlo sampling. We consider two different experimental scenarios. In the first scenario, the noisy measurements correspond to a wall modeled by impedance boundary conditions. In this case, the Bayesian algorithm uses a model that is (up to the noise) consistent with the measurements and our algorithm is able to identify acoustic impedance with high accuracy. In the second scenario, the noisy measurements come from a coupled acoustic-structural problem, modeling a wall made of glass, whereas the Bayesian algorithm still uses a model with impedance boundary conditions. In this case, the parameter identification model is inconsistent with the measurements and therefore is not capable to represent them well. Nonetheless, for particular frequency bands the Bayesian algorithm identifies estimates with high likelihood. Outside these frequency bands the algorithm fails. We discuss the results of both examples and possible reasons for the failure of the latter case for particular frequency values. [ABSTRACT FROM AUTHOR]

Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models to study the mechanisms underlying cardiomyopathies and cardiotoxicity. Quantification of the contractile function in single hiPSC-CMs at high-throughput and over time is essential to disentangle how cellular mechanisms affect heart function. Here, we present CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time. Three software modules enable: parameter-based identification of single hiPSC-CMs; automated video acquisition of >200 cells/hour; and contractility measurements via traction force microscopy. We analyze >4,500 hiPSC-CMs over time in the same cells under orthogonal conditions of culture media and substrate stiffnesses; +/− drug treatment; +/− cardiac mutations. Using undirected clustering, we reveal converging maturation patterns, quantifiable drug response to Mavacamten and significant deficiencies in hiPSC-CMs with disease mutations. CONTRAX empowers researchers with a potent quantitative approach to develop cardiac therapies. Cardiomyocytes derived from human induced pluripotent stem cells (hiPSC-CMs) are powerful in vitro models. Here the authors report CONTRAX, an open-access, versatile, and streamlined pipeline for quantitative tracking of the contractile dynamics of single hiPSC-CMs over time at increased throughput. [ABSTRACT FROM AUTHOR]

Electrotactile stimulus is a form of sensory substitution in which an electrical signal is perceived as a mechanical sensation. The electrotactile effect could, in principle, recapitulate a range of tactile experience by selective activation of nerve endings. However, the method has been plagued by inconsistency, galvanic reactions, pain and desensitization, and unwanted stimulation of nontactile nerves. Here, we describe how a soft conductive block copolymer, a stretchable layout, and concentric electrodes, along with psychophysical thresholding, can circumvent these shortcomings. These purpose-designed materials, device layouts, and calibration techniques make it possible to generate accurate and reproducible sensations across a cohort of 10 human participants and to do so at ultralow currents (≥6 microamperes) without pain or desensitization. This material, form factor, and psychophysical approach could be useful for haptic devices and as a tool for activation of the peripheral nervous system. Editor's summary: Most haptic devices rely on mechanical actuators to stimulate the skin but are limited in range. Alternatively, electrical stimulation of mechanosensory neurons can be perceived as a mechanical force but often requires high currents and leads to unwanted effects, such as pain. Blau et al. developed an electrotactile device made from a conductive block copolymer in a serpentine shape that exhibited microscopic conformability with the skin. When tested on human participants, the device provided stimulation at very low currents and could toggle between pressure and vibration by changing the signal frequency. Safe and reliable electrotactile stimulation is a promising development for haptic devices such as human-machine interfaces and prosthetics. —Melisa Yashinski [ABSTRACT FROM AUTHOR]

Based on the lack of differences in progression-free and overall survival after a median follow-up of 93 months in our HOVON-65/GMMG-HD4 trial (German part; n = 395) randomizing VAD induction (vincristin/adriamycin/dexamthasone)/tandem-transplantation/thalidomide-maintenance vs. PAD induction (bortezomib/adriamycin/dexamethasone)/tandem transplantation/bortezomib maintenance, we discern how chromosomal aberrations determine long-term prognosis by different patterns of association with proliferation and treatment-dependent response, whether responses achieved by different regimens are equal regarding prognosis, and whether subpopulations of patients could be defined as treatable without upfront "novel agents" in cases of limited resources, e.g., in low- or middle-income countries. Serum parameters and risk factors were assessed in 395 patients. CD138-purified plasma cells were subjected to fluorescence in situ hybridization (n = 354) and gene expression profiling (n = 204). We found chromosomal aberrations to be associated in four patterns with survival, proliferation, and response: deletion (del) del17p13, del8p21, del13q14, (gain) 1q21+, and translocation t(4;14) (all adverse) associate with higher proliferation. Of these, del17p is associated with an adverse response (pattern 1), and 1q21+, t(4;14), and del13q14 with a treatment-dependent better response (pattern 2). Hyperdiploidy associates with lower proliferation without impacting response or survival (pattern 3). Translocation t(11;14) has no association with survival but a treatment-dependent adverse response (pattern 4). Significantly fewer patients reach a near-complete response or better with "conventional" (VAD) vs. bortezomib-based treatment after induction or high-dose melphalan. These patients, however, show significantly better median progression-free and overall survival. Molecularly, patients responding to the two regimens differ in gene expression, indicating distinct biological properties of the responding myeloma cells. Patients with normal renal function (89.4%), low cytogenetic risk (72.5%), or low proliferation rate (37.9%) neither benefit in progression-free nor overall survival from bortezomib-based upfront treatment. We conclude that response level, the treatment by which it is achieved, and molecular background determine long-term prognosis. Chromosomal aberrations are associated in four patterns with proliferation and treatment-dependent responses. Associations with faster and deeper responses can be deceptive in the case of prognostically adverse aberrations 1q21+ and t(4;14). Far from advocating a return to "outdated" treatments, if resources do not permit state-of-the-art-treatment, normal renal function and/or molecular profiling identifies patient subpopulations doing well without upfront "novel agents". [ABSTRACT FROM AUTHOR]

Background: ARDS is a heterogeneous syndrome with distinct clinical phenotypes. Here we investigate whether the presence or absence of large pulmonary ultrasonographic consolidations can categorize COVID-19 ARDS patients requiring mechanical ventilation into distinct clinical phenotypes. Methods: This is a retrospective study performed in a tertiary-level intensive care unit in Israel between April and September 2020. Data collected included lung ultrasound (LUS) findings, respiratory parameters, and treatment interventions. The primary outcome was a composite of three ARDS interventions: prone positioning, high PEEP, or a high dose of inhaled nitric oxide. Results: A total of 128 LUS scans were conducted among 23 patients. The mean age was 65 and about two-thirds were males. 81 scans identified large consolidation and were classified as "C-type", and 47 scans showed multiple B-lines with no or small consolidation and were classified as "B-type". The presence of a "C-type" study had 2.5 times increased chance of receiving the composite primary outcome of advanced ARDS interventions despite similar SOFA scores, Pao2/FiO2 ratio, and markers of disease severity (OR = 2.49, %95CI 1.40–4.44). Conclusion: The presence of a "C-type" profile with LUS consolidation potentially represents a distinct COVID-19 ARDS subphenotype that is more likely to require aggressive ARDS interventions. Further studies are required to validate this phenotype in a larger cohort and determine causality, diagnostic, and treatment responses. [ABSTRACT FROM AUTHOR]

Benzene, emitted from automobile exhaust and biomass burning, is ubiquitous in ambient air. Benzene is a precursor hydrocarbon (HC) that forms secondary organic aerosol (SOA), but its SOA formation mechanism is not well studied. To accurately predict the formation of benzene SOA, it is important to understand the gas mechanisms of phenol, which is one of the major products formed from the atmospheric oxidation of benzene. Laboratory data presented herein highlight the impact of the aqueous phase on SOA generated through benzene and phenol oxidation. The roles of the aqueous phase consist of (1) suppression of the aging of hydrocarbon and (2) conventional acid-catalyzed reactions in the inorganic phase. To explain this unusual effect, it is hypothesized that a persistent phenoxy radical (PPR) effectively forms via a heterogeneous reaction of phenol and phenol-related products in the presence of wet inorganic aerosol. These PPR species are capable of catalytically consuming ozone during an NO x cycle and negatively influencing SOA growth. In this study, explicit gas mechanisms were derived to produce the oxygenated products from the atmospheric oxidation of phenol or benzene. Gas mechanisms include the existing Master Chemical Mechanism (MCM v3.3.1), the reaction path for peroxy radical adducts originating from the addition of an OH radical to phenols forming low-volatility products (e.g., multi-hydroxy aromatics), and the mechanisms to form heterogeneous production of PPR. The simulated gas products were classified into volatility- and reactivity-based lumped species and incorporated into the Unified Partitioning Aerosol Reaction (UNIPAR) model that predicts SOA formation via multiphase reactions of phenol or benzene. The predictability of the UNIPAR model was examined using chamber data, which were generated for the photooxidation of phenol or benzene under controlled experimental conditions (NO x levels, humidity, and inorganic seed types). The SOA formation from both phenol and benzene still increased in the presence of wet inorganic seed because of the oligomerization of reactive organic species in the aqueous phase. However, model simulations show a significant suppression of ozone, the oxidation of phenol or benzene, and SOA growth compared with those without PPR mechanisms. The production of PPR is accelerated in the presence of acidic aerosol and this weakens SOA growth. In benzene oxidation, up to 53 % of the oxidation pathway is connected to phenol formation in the reported gas mechanism. Thus, the contribution of PPR to gas mechanisms is less than that of phenol. Overall, SOA growth in phenol or benzene is negatively related to NO x levels in the high-NO x region (HC ppbC / NO x ppb < 5). However, the simulation indicates that the significance of PPR rises with decreasing NO x levels. Hence, the influence of NO x levels on SOA formation from phenol or benzene is complex under varying temperature and seed type conditions. Adding the comprehensive reaction of phenolic compounds will improve the prediction of SOA formation from aromatic HCs due to the missing mechanisms in the current air quality model. [ABSTRACT FROM AUTHOR]

There are very few explicit evaluations of path integrals for topological gauge theories in more than 3 dimensions. Here we provide such a calculation for the path integral representation of the Ray-Singer Torsion of a flat connection on a vector bundle on base manifolds that are themselves S1 bundles of any dimension. The calculation relies on a suitable algebraic choice of gauge which leads to a convenient factorisation of the path integral into horizontal and vertical parts. [ABSTRACT FROM AUTHOR]

While the process of teaching student perfusionists has been in development since the 1950s, the publication of the processes to improve perfusion clinical education has been largely lacking. Publications regarding education from other allied health and medical fields have shown the value of student-centered learning. The use of reflective practice to move perfusion students from thinking about actions after cardiopulmonary bypass (CPB) to reflecting and reacting on actions during CPB is better encouraged by moving from a teacher-centered to a student-centered clinical model. Our institution's teaching process has developed into a multi-point procedure to make our students into reflective practicing clinicians. Student preceptor evaluations were reversed to allow the students to evaluate themselves first, with feedback from the preceptor given subsequently. Additionally, a biweekly student educational session, where the student chooses a topic and reviews current evidence-based practice, was instituted. The clinical program director serves as the moderator and clinical expert to facilitate problem-based learning during the sessions. Students were also given three skill/experience levels with goals to reach and move through during the rotation. These student levels were also helpful to our preceptors in knowing what each student's skill level was throughout their rotation. Overall, moving from a teacher-centered to a student-centered clinical rotation has helped make students familiar with reflective practice, self-evaluation, evidence-based practice, and problem-based learning. The incorporation of these processes will hopefully lead students to become lifelong reflective perfusionists. [ABSTRACT FROM AUTHOR]

Intellectual history is usually seen as essentially historical. It is – but it is also essentially philosophical, both when theorising intellectual history, which some intellectual historians do, and when interpreting texts, which all intellectual historians do. I demonstrate this symbiosis between history and philosophy via critical reflections on Martin Jay's recent book Genesis and Validity. Philosophical analysis, closely integrated with historical examples, suggests that we should significantly rethink Jay's theorisation of the relationship between genesis and validity (e.g. whether ideas from one context are valid in others). But the symbiosis between history and philosophy matters more when interpreting texts. Philosophical analysis is a powerful tool for recovering what authors meant, understanding how their ideas fit together, and seeing similarities and differences between ideas, as I show with examples from Quentin Skinner's interpretations of Machiavelli, Hobbes and others. Yet even Jay and Skinner – two of the world's most philosophically astute intellectual historians – overlook the crucial symbiosis between history and philosophy. [ABSTRACT FROM AUTHOR]

Second allogeneic stem cell transplantation (alloSCT2) is among the most effective treatments for acute myeloid leukemia (AML) relapse after first alloSCT (alloSCT1). Long-term EBMT registry data were used to provide large scale, up-to-date outcome results and to identify factors for improved outcome. Among 1540 recipients of alloSCT2, increasing age, better disease control and performance status before alloSCT2, more use of alternative donors and higher conditioning intensity represented important trends over time. Between the first (2000–2004) and last (2015–2019) period, two-year overall and leukemia-free survival (OS/LFS) increased considerably (OS: 22.5–35%, LFS: 14.5–24.5%). Cumulative relapse incidence (RI) decreased from 64% to 50.7%, whereas graft-versus-host disease and non-relapse mortality (NRM) remained unchanged. In multivariable analysis, later period of alloSCT2 was associated with improved OS/LFS (HR = 0.47/0.53) and reduced RI (HR = 0.44). Beyond, remission duration, disease stage and patient performance score were factors for OS, LFS, RI, and NRM. Myeloablative conditioning for alloSCT2 decreased RI without increasing NRM, leading to improved OS/LFS. Haploidentical or unrelated donors and older age were associated with higher NRM and inferior OS. In summary, outcome after alloSCT2 has continuously improved over the last two decades despite increasing patient age. The identified factors provide clues for the optimized implementation of alloSCT2. [ABSTRACT FROM AUTHOR]

Background: Human papillomavirus (HPV) poses a significant public health concern, as it is linked to various serious health conditions such as cancer and genital warts. Despite the vaccine's safety, efficacy, and availability through national school programs, HPV vaccination rates remain low in Israel, particularly within the ultra-Orthodox community due to religious and cultural barriers. Decision aids have shown promise in facilitating shared decision making and promoting informed choices in health care. This study aimed to assess the impact of a novel Web-based decision aid on HPV vaccination intentions, knowledge, decision self-efficacy, and decisional conflict among Israeli parents and young adults, with a specific focus on exploring differences between religious groups. Methods: Two Web-based decision aids were developed for parents of children aged 10 to 17 y (n = 120) and young adults aged 18 to 26 y (n = 160). A quasi-experimental study was conducted among Hebrew-speaking parents and young adults eligible for HPV vaccination. Participants completed pre- and postintervention questionnaires assessing vaccination intentions, knowledge about HPV, decision self-efficacy, and decisional conflict. Results: The decision aid significantly improved intentions toward HPV vaccination among most religious groups, except the Jewish ultra-Orthodox community. Ultra-Orthodox participants exhibited reluctance to vaccinate themselves or their children (odds ratio [OR] = 0.23, P < 0.001 for parents' group; OR = 0.43, P < 0.001 for young adults' group). Parental preference for vaccinating girls over boys (OR = 2.66, P < 0.001) and increased inclination for vaccination among Muslim-Arabs were observed (OR = 3.12, P < 0.001). Knowledge levels improved among ultra-Orthodox participants but not decisional conflict and self-efficacy. Conclusions: The Web-based decision aid positively influenced the quality of HPV vaccination decision making among various religious groups in Israel, except for the ultra-Orthodox community. Culturally tailored approaches that address specific community concerns are essential for informed decision making. Highlights: Human papillomavirus (HPV) vaccination rates in Israel are substantially lower than those of other routine vaccinations, particularly among religious and ultra-Orthodox communities, largely due to sociocultural beliefs and misinformation. A newly developed Web-based decision aid was implemented in a study involving parents and young adults to evaluate its impact on vaccination intent, knowledge about HPV, decision self-efficacy, and decisional conflict. While the decision aid significantly enhanced vaccination intention, knowledge, and perceived behavioral control among various religious groups, it did not yield the same outcomes within the ultra-Orthodox Jewish community. This study highlights the vital role of cultural adaptation in HPV vaccine decision aids within Israel, revealing significant disparities in vaccination perceptions and decisions among diverse religious and cultural groups. [ABSTRACT FROM AUTHOR]

Purpose: Treatment decisions for leptomeningeal disease (LMD) rely on patient risk stratification, since clinicians lack objective prognostic tools. The introduction of rare cell capture technology for identification of cerebrospinal fluid tumor cells (CSF-TCs), such as CNSide assay, improved the sensitivity of LMD diagnosis, but prognostic value is unknown. This study assesses the prognostic value of CSF-TC density in patients with LMD from solid tumors. Methods: We conducted a retrospective cohort study of patients with newly diagnosed or previously treated LMD from a single institution who had CNSide assay testing for CSF-TCs from 2020 to 2023. Univariable and multivariable survival analyses were conducted with Cox proportional-hazards modeling. Maximally-selected rank statistics were used to determine an optimal cutpoint for CSF-TC density and survival. Results: Of 31 patients, 29 had CSF-TCs detected on CNSide. Median (interquartile range [IQR]) CSF-TC density was 67.8 (4.7–639) TCs/mL. CSF cytology was positive in 16 of 29 patients with positive CNSide (CNSide diagnostic sensitivity = 93.5%, negative predictive value = 85.7%). Median (IQR) survival from time of CSF-TC detection was 176 (89–481) days. On univariable and multivariable analysis, CSF-TC density was significantly associated with survival. An optimal cutpoint for dichotomizing survival by CSF-TC density was 19.34 TCs/mL. The time-dependent sensitivity and specificity for survival using this stratification were 76% and 67% at 6 months and 65% and 67% at 1 year, respectively. Conclusions: CSF-TC density may carry prognostic value in patients with LMD from solid tumors. Integrating CSF-TC density into LMD patient risk-stratification may help guide treatment decisions. [ABSTRACT FROM AUTHOR]

Rationale: The strongest genetic risk factor for childhood-onset asthma, the 17q21 locus, is associated with increased viral susceptibility and disease-promoting processes. Objectives: To identify biological targets underlying the escalated viral susceptibility associated with the clinical phenotype mediated by the 17q21 locus. Methods: Genome-wide transcriptome analysis of nasal brush samples from 261 children (78 healthy, 79 with wheezing at preschool age, 104 asthmatic) within the ALLIANCE (All-Age-Asthma) cohort, with a median age of 10.0 (range, 1.0–20.0) years, was conducted to explore the impact of their 17q21 genotype (SNP rs72163891). Concurrently, nasal secretions from the same patients and visits were collected, and high-sensitivity mesoscale technology was employed to measure IFN protein levels. Measurements and Main Results: This study revealed that the 17q21 risk allele induces a genotype- and asthma/wheeze phenotype–dependent enhancement of mucosal GSDMB expression as the only relevant 17q21-encoded gene in children with preschool wheeze. Increased GSDMB expression correlated with the activation of a type-1 proinflammatory, cell-lytic immune, and natural killer signature, encompassing key genes linked to an IFN type-2-signature (IFNG, CXCL9, CXCL10, KLRC1, CD8A, GZMA). Conversely, there was a reduction in IFN type 1 and type 3 expression signatures at the mRNA and protein levels. Conclusions: This study demonstrates a novel disease-driving mechanism induced by the 17q21 risk allele. Increased mucosal GSDMB expression is associated with a cell-lytic immune response coupled with compromised airway immunocompetence. These findings suggest that GSDMB-related airway cell death and perturbations in the mucosal IFN signature account for the increased vulnerability of 17q21 risk allele carriers to respiratory viral infections during early life, opening new options for future biological interventions. The All-Age-Asthma (ALLIANCE) cohort is registered at www.clinicaltrials.gov (pediatric arm, NCT 02496468). [ABSTRACT FROM AUTHOR]

The COVID-19 pandemic taught us that homes can double as offices. But when a teleworker opens her laptop across state lines from her employer, may she claim the statutory worker protections provided in the employer's state? Too often, courts misunderstand this recurring problem and refuse to extend an employer's state protections to an out-of-state teleworker, granting a defendant's motion to dismiss. Because each statute is analyzed in isolation, a teleworker may be relegated to lawless nowhere land, unable to recover under any state statutory scheme. This Note argues that, in the absence of legislative direction, a court should always find that the scope of an employer's state statute is broad enough to extend to an out-of-state remote teleworker. Telework is performed using entirely virtual technology and has no physical connection to the place in which it is performed. In contrast, the employer is tethered to earth and therefore should permissibly regulate the employer-teleworker relationship. This Note advocates for a judicial solution by examining existing judicial considerations. It argues that, because of the quasi-territorial nature of remote work, a teleworker should always fall within the legislative jurisdiction of an employer's state. [ABSTRACT FROM AUTHOR]

The article "Ecological Aesthetics: An Afterword" published in Ecological Psychology explores the study of aesthetic experience from an ecological perspective. The papers collected in the article discuss the relationships between artists and their art, as well as between observers and the art they view. The article emphasizes the subjective and unique nature of aesthetic experiences, which are influenced by factors such as the context in which the art is experienced. It also highlights the importance of studying art as a means of deepening our understanding of perception and valuing the aesthetic experience in its own right. The article concludes by questioning the distinction between art and everyday experiences, suggesting that both can evoke aesthetic responses. [Extracted from the article]

Bone density is one of many interacting variables that influence fracture initiation and propagation. Thus, average density values of the human neurocranium are an important consideration in skull trauma interpretation. However, neurocranial bone density has not previously been systematically evaluated. This study aimed to develop reference ranges for average neurocranial bone density and correlate this density with previously recorded average bone thickness. Using post-mortem computed tomography head scans of 604 deceased individuals, bone density (Hounsfield units) was measured at 20 locations across the neurocranium. Descriptive and inferential statistics were applied to establish bone density means; assess how age, sex and ancestry interact with density, and correlate density with thickness means. Mean density ranged from 78 Hu (mastoid process) to 1323 Hu (temporal squama); age, sex and ancestry significantly affected density, and a moderate negative correlation was found between density and thickness. Subsequently, reference measurements for density are presented here by age, sex and ancestry and are based upon a 95% confidence interval about the mean. These data provide a baseline for neurocranial density measurements that may be of use to forensic practitioners to assess if a cranium is of average (within the interval) or atypical (outside the interval) density. [ABSTRACT FROM AUTHOR]

There is an increased risk of GVHD and of non-relapse mortality (NRM) after allogeneic stem cell transplantations (alloSCT) when mismatched unrelated donors (MMUD) are used. In Europe, it is standard practice to use rabbit anti-thymocyte globulin (rATG) to reduce the high NRM and GVHD risks after MMUD alloSCT. As an alternative to rATG, post-transplantation Cyclophosphamide (PTCy) is in increasing clinical use. It is currently impossible to give general recommendations regarding preference for one method over another since comparative evidence from larger data sets is lacking. To improve the evidence base, we analyzed the outcome of rATG vs. PTCy prophylaxis in adult patients with hematologic malignancies undergoing first peripheral blood alloSCT from MMUD (9/10 antigen match) between Jan 2018 and June 2021 in the database of the European Society for Blood and Marrow Transplantation (EBMT). We performed multivariate analyses using the Cox proportional-hazards regression model. We included 2123 patients in the final analyses (PTCy, n = 583; rATG, n = 1540). p values and hazard ratios (HR) presented here are multivariate outcomes. Two years after alloSCT we found a lower NRM in the PTCy group of 18% vs. 24.9% in the rATG group; p = 0.028, HR 0.74. Overall survival in the PTCy cohort was higher with 65.7% vs. 55.7% in the rATG cohort; p < 0.001, HR 0.77. Progression-free survival was also better in the PTCy patients with 59.1% vs. 48.8% when using rATG; p = 0.001, 0.78. The incidences of chronic GVHD and acute GVHD were not significantly different between the groups. We found significantly lower NRM as well as higher survival in recipients of peripheral blood alloSCTs from MMUD receiving PTCy as compared to rATG. The results of the current analysis suggest an added value of PTCy as GVHD prophylaxis in MMUD alloSCT. [ABSTRACT FROM AUTHOR]

The routine of the dental profession exposes dentists not only to medical challenges but also to ethical and legal ones. Compared to other physicians, dentists are more likely to encounter children who are victims of domestic violence. This reality exposes them to legal liability due to the reporting obligations and the risk of misdiagnosing injuries. This paper aims to examine the importance of dentists in diagnosing injuries to children caused by domestic violence and the inherent dangers of failing to make such a diagnosis. [ABSTRACT FROM AUTHOR]

Despite extensive research on severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) vaccination responses in healthy individuals, there is comparatively little known beyond antibody titers and T‐cell responses in the vulnerable cohort of patients after allogeneic hematopoietic stem cell transplantation (ASCT). In this study, we assessed the serological response and performed longitudinal multimodal analyses including T‐cell functionality and single‐cell RNA sequencing combined with T cell receptor (TCR)/B cell receptor (BCR) profiling in the context of BNT162b2 vaccination in ASCT patients. In addition, these data were compared to publicly available data sets of healthy vaccinees. Protective antibody titers were achieved in 40% of patients. We identified a distorted B‐ and T‐cell distribution, a reduced TCR diversity, and increased levels of exhaustion marker expression as possible causes for the poorer vaccine response rates in ASCT patients. Immunoglobulin heavy chain gene rearrangement after vaccination proved to be highly variable in ASCT patients. Changes in TCRα and TCRβ gene rearrangement after vaccination differed from patterns observed in healthy vaccinees. Crucially, ASCT patients elicited comparable proportions of SARS‐CoV‐2 vaccine‐induced (VI) CD8+ T‐cells, characterized by a distinct gene expression pattern that is associated with SARS‐CoV‐2 specificity in healthy individuals. Our study underlines the impaired immune system and thus the lower vaccine response rates in ASCT patients. However, since protective vaccine responses and VI CD8+ T‐cells can be induced in part of ASCT patients, our data advocate early posttransplant vaccination due to the high risk of infection in this vulnerable group. [ABSTRACT FROM AUTHOR]

Aims: Given the increasing number of individuals developing metabolic dysfunction‐associated steatotic liver disease (MASLD) and the low rate of those with progressive liver disease, there is a pressing need to conceive affordable biomarkers to assess MASLD in general population settings. Herein, we aimed to investigate the performance of the ultrasound‐derived fat fraction (UDFF) for hepatic steatosis in high‐risk individuals. Methods: A total of 302 Europeans with obesity, type 2 diabetes, or a clinical history of hepatic steatosis were included in the analyses. Clinical, laboratory, and imaging data were collected using standardized procedures during a single screening visit in Rome, Italy. Hepatic steatosis was defined by controlled attenuation parameter (CAP) or ultrasound‐based Hamaguchi's score. UDFF performance for hepatic steatosis was estimated by the area under the receiver operating characteristic curve (AUC). Results: Overall, median (IQR) UDFF was 12% (7–20). UDFF was positively correlated with CAP (ρ = 0.73, p < 0.0001) and Hamaguchi's score (ρ = 0.79, p < 0.0001). Independent predictors of UDFF were circulating triglycerides, alanine aminotransferase (ALT), and ultrasound‐measured visceral adipose tissue (VAT). UDFF AUC was 0.89 (0.85–0.93) and 0.92 (0.88–0.95) for CAP‐ and ultrasound‐diagnosed hepatic steatosis, respectively. UDFF AUC for hepatic steatosis was higher than those of fatty liver index (FLI), hepatic steatosis index (HSI), CAP‐score (CAPS), and ALT (p < 0.0001). Lower age, ALT, and VAT were associated with discordance between UDFF and ultrasound. Conclusions: UDFF may be a simple and accurate imaging biomarker to assess hepatic steatosis and monitor changes in hepatic fat content over time or in response to therapeutic interventions beyond clinical trials. [ABSTRACT FROM AUTHOR]

Amyloids, protein, and peptide assemblies in various organisms are crucial in physiological and pathological processes. Their intricate structures, however, present significant challenges, limiting our understanding of their functions, regulatory mechanisms, and potential applications in biomedicine and technology. This study evaluated the AlphaFold2 ColabFold method's structure predictions for antimicrobial amyloids, using eight antimicrobial peptides (AMPs), including those with experimentally determined structures and AMPs known for their distinct amyloidogenic morphological features. Additionally, two well‐known human amyloids, amyloid‐β and islet amyloid polypeptide, were included in the analysis due to their disease relevance, short sequences, and antimicrobial properties. Amyloids typically exhibit tightly mated β‐strand sheets forming a cross‐β configuration. However, certain amphipathic α‐helical subunits can also form amyloid fibrils adopting a cross‐α structure. Some AMPs in the study exhibited a combination of cross‐α and cross‐β amyloid fibrils, adding complexity to structure prediction. The results showed that the AlphaFold2 ColabFold models favored α‐helical structures in the tested amyloids, successfully predicting the presence of α‐helical mated sheets and a hydrophobic core resembling the cross‐α configuration. This implies that the AI‐based algorithms prefer assemblies of the monomeric state, which was frequently predicted as helical, or capture an α‐helical membrane‐active form of toxic peptides, which is triggered upon interaction with lipid membranes. [ABSTRACT FROM AUTHOR]

ABSTRACT Using qualitative open item analysis, MBA alumni were asked their perceptions of competencies, skills and concepts developed or reinforced in a client-focused team project MBA capstone course. The replies from 167 respondents were aggregated together over a nineyear period from 2013 to 2021. Conversion of coded responses to managerial competencies indicated eight competencies: client relationship management, communication, financial modeling, presentation, project management, research and analysis, strategic deliverable recommendation, and team leadership. This coding structure provided partial convergent validation for prior theoretical and empirical work linking MBA learned-to-needed managerial competencies. In addition, several differences were found between competencies/skills developed or reinforced in the MBA capstone by type of undergraduate major, i.e., business, liberal arts or STEM. [ABSTRACT FROM AUTHOR]

This document explores the challenges and implications of using generative AI in scientific research. It emphasizes the need for transparency, accountability, and responsible practices in the use of AI tools and algorithms. The authors stress the importance of disclosing the use of generative AI in research, accurately identifying human and AI contributions, and citing prior literature. The document also highlights the need for model creators to provide detailed information about their models, including data used and any limitations or biases. It calls for ethics and equity in AI use, continuous monitoring and oversight, and public engagement. The establishment of a Strategic Council on the Responsible Use of AI in Science is suggested to provide guidance and address emerging concerns. The text urges the scientific community to adhere to existing guidelines and contribute to AI governance efforts. Overall, it emphasizes the importance of maintaining the integrity of science while utilizing the potential of AI. [Extracted from the article]

Purpose: Management of CNS involvement in leukemia may include craniospinal irradiation (CSI), though data on CSI efficacy are limited. Methods: We retrospectively reviewed leukemia patients who underwent CSI at our institution between 2009 and 2021 for CNS involvement. CNS local recurrence (CNS-LR), any recurrence, progression-free survival (PFS), CNS PFS, and overall survival (OS) were estimated. Results: Of thirty-nine eligible patients treated with CSI, most were male (59%) and treated as young adults (median 31 years). The median dose was 18 Gy to the brain and 12 Gy to the spine. Twenty-five (64%) patients received CSI immediately prior to allogeneic hematopoietic cell transplant, of which 21 (84%) underwent total body irradiation conditioning (median 12 Gy). Among 15 patients with CSF-positive disease immediately prior to CSI, all 14 assessed patients had pathologic clearance of blasts (CNS-response rate 100%) at a median of 23 days from CSI start. With a median follow-up of 48 months among survivors, 2-year PFS and OS were 32% (95% CI 18–48%) and 43% (95% CI 27–58%), respectively. Only 5 CNS relapses were noted (2-year CNS-LR 14% (95% CI 5–28%)), which occurred either concurrently or after a systemic relapse. Only systemic relapse after CSI was associated with higher risk of CNS-LR on univariate analysis. No grade 3 or higher acute toxicity was seen during CSI. Conclusion: CSI is a well-tolerated and effective treatment option for patients with CNS leukemia. Control of systemic disease after CSI may be important for CNS local control. CNS recurrence may reflect reseeding from the systemic space. [ABSTRACT FROM AUTHOR]

Clostridioides difficile is an important human pathogen causing antibiotic-associated diarrhoea worldwide. Besides using antibiotics for treatment, the interest in bacteriophages as an alternative therapeutic option has increased. Prophage abundance and genetic diversity are well-documented in clinical strains, but the carriage of prophages in environmental strains of C. difficile has not yet been explored. Thus, the prevalence and genetic diversity of integrated prophages in the genomes of 166 environmental C. difficile isolates were identified. In addition, the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas systems were determined in the genomes of prophage regions. Predicted prophages and CRISPR-Cas systems were identified by using the PHASTER web server and CRISPRCasFinder, respectively. Phylogenetic relationships among predicated prophages were also constructed based on phage-related genes, terminase large (TerL) subunits and LysM. Among 372 intact prophages, the predominant prophages were phiCDHM1, phiCDHM19, phiMMP01, phiCD506, phiCD27, phiCD211, phiMMP03, and phiC2, followed by phiMMP02, phiCDKM9, phiCD6356, phiCDKM15, and phiCD505. Two newly discovered siphoviruses, phiSM101- and phivB_CpeS-CP51-like Clostridium phages, were identified in two C. difficile genomes. Most prophages were found in sequence types (STs) ST11, ST3, ST8, ST109, and ST2, followed by ST6, ST17, ST4, ST5, ST44, and ST58. An obvious correlation was found between prophage types and STs/ribotypes. Most predicated prophages carry CRISPR arrays. Some prophages carry several gene products, such as accessory gene regulator (Agr), putative spore protease, and abortive infection (Abi) systems. This study shows that prophage carriage, along with genetic diversity and their CRISPR arrays, may play a role in the biology, lifestyle, and fitness of their host strains. [ABSTRACT FROM AUTHOR]

This study provides the manufacturing process and the main physicochemical characteristics to describe the Guatemalan artisanal beverages Boj and Suchiles. Flow charts were established for the manufacturing processes of these two indigenous fermented beverages of Guatemala. Physicochemical characteristics were analyzed to determine the degree of action of the microorganisms responsible for the alcoholic fermentations. Boj and Suchiles are produced throughout the year using regional ingredients such as sugarcane and pineapple. Boj is especially popular in the northern city of Coban and Suchiles in Guatemala City and Antigua, Guatemala. Although they have cultural relevance, few scientific studies about these beverages exist. The process and raw materials used to elaborate Boj and Suchiles were documented, and samples were taken to conduct the physicochemical characterization of both beverages. Boj and Suchiles showed the following results: pH, 3.3 ± 0.1 and 3.0 ± 0.1 units; alcohol, 6.9 ± 0.9 and 0.79 ± 0.4%(v/v); total soluble solids (TSS), 3.1 ± 0.3 and 15.4 ± 1.2 (g/100 g); reducing sugars 8.6 and 85.2 g/L; lactic acid, 8.7 ± 1.6 and 10.7 ± 3.0 g/L; acetic acid, 2.8 ± 0.6 and 6.9 ± 2.9 g/L. Essential and nonessential amino acids, sugars, protein, organic acids, and B vitamins were analyzed. [ABSTRACT FROM AUTHOR]

Effective surveillance of adverse events following immunization (AEFIs) primarily relies on the collaboration of two partners: national regulatory authorities (NRAs) and national expanded programs on immunization (EPIs). In December 2020, the World Health Organization (WHO) Global Advisory Committee for Vaccine Safety recommended a new case-based indicator of national capacity to monitor immunization safety: at least one serious AEFI reported per 1 million total population per year. To achieve this indicator, WHO-affiliated countries and territories (WHO countries) rely upon data generated from functional AEFI surveillance systems. This report describes 2020-2022 global, regional, and national progress in use of the newly introduced immunization safety monitoring indicator and progress on joint AEFI reporting from national EPIs and NRAs. Among WHO countries, 51 (24%) of 214 implemented the new indicator in 2020, 111 (52%) of 214 implemented it in 2021, and 92 (43%) of 215 in 2022. In 2020, 41 (19%) WHO countries reported AEFI data jointly from EPIs and NRAs; this increased to 55 (26%) in 2021 and 57 (27%) in 2022. These findings, resulting in part from the intensified support for COVID-19 vaccination, demonstrate that national AEFI surveillance systems increasingly support the timely use and sharing of case-based immunization safety data, but work is still needed to strengthen global vaccine safety monitoring. [ABSTRACT FROM AUTHOR]