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Summary: Stem cell therapies for degenerative cartilage disease are limited by an incomplete understanding of hyaline cartilage formation and maintenance. Human bone marrow stromal cells/skeletal stem cells (hBMSCs/SSCs) produce stable hyaline cartilage when attached to hyaluronic acid-coated fibrin microbeads (HyA-FMBs), yet the mechanism remains unclear. In vitro, hBMSC/SSC/HyA-FMB organoids exhibited reduced BMP signaling early in chondrogenic differentiation, followed by restoration of BMP signaling in chondrogenic IGFBP5+/MGP+ cells. Subsequently, human-induced pluripotent stem cell (hiPSC)-derived sclerotome cells were established (BMP inhibition) and then treated with transforming growth factor β (TGF-β) −/+ BMP2 and growth differentiation factor 5 (GDF5) (BMP signaling activation). TGF-β alone elicited a weak chondrogenic response, but TGF-β/BMP2/GDF5 led to delamination of SOX9+ aggregates (chondrospheroids) with high expression of COL2A1, ACAN, and PRG4 and minimal expression of COL10A1 and ALP in vitro. While transplanted hBMSCs/SSCs/HyA-FMBs did not heal articular cartilage defects in immunocompromised rodents, chondrospheroid-derived cells/HyA-FMBs formed non-hypertrophic cartilage that persisted until at least 5 months in vivo.

The goal of Community Service activities with the theme Writing and Publication of Classroom Action Research (CAR) is to increase educators' competence in the field of CAR, inspire innovation and improve learning, disseminate CAR knowledge and practice in the classroom, and encourage collaboration and knowledge sharing. The activity's goal was to reach 35 junior high school teachers in Kupang Regency, NTT Province. Carried out through the use of andragogy learning methodologies, including needs assessment, content preparation, and interactive training. The end findings demonstrate that the training participants' understanding of CAR has greatly expanded, their desire and self-innovation have developed, and they have continued with a commitment to use the outcomes of the CAR training, as well as subsequent training activities will be carried out in order to improve instructors' capacities to enhance their understanding and skills in CAR-related issues.

In the last decade the world has experienced a number of global crises which triggered economic downturns. Impacts from the global financial crisis, the global COVID pandemic, and Russia’s invasion of Ukraine trigger instability in financial markets. This paper explores similarities and differences between these crises based on inflation and its energy-related components. A Vector Autoregressive (VAR) model is used to analyze both EU-level trends, as well as data for Romania. The findings indicate idiosyncratic shifts in the relationships between variables. The changes are often specific to individual shocks and the policy context. How policy makers respond to these shocks will also impact the fiscal space, the borrowing costs of countries, and the cost of servicing debt, which risks a return to the type of austerity policies that slowed down the post-financial crisis recovery. There is a need for more detailed research and investigations in policy responses designed to respond to ongoing events.

Abstract Background The prevalence of sedentary behaviour has concurrently risen with multiple cardiometabolic risk markers independent of physical activity levels. Office-based workers accumulate the highest levels of sitting time during occupational times. This study aims to investigate the short-term effects of using height-adjustable sit-to-stand workstations on cardiometabolic risk markers of office-based workers in South Africa. Results Sixty-two office-based workers were randomized into intervention (n = 44), and the control group (n = 18). Small improvements were observed in BMI, blood pressure, and cholesterol levels in this cohort. Conclusion This preliminary investigation confirms that short-term height-adjustable sit-stand interventions are effective in reducing workplace sitting time and selected health outcomes. South Africa has been attributed with the highest burden of obesity in Sub-Saharan Africa, as a result, there is a need to implement long-term workplace intervention to reverse these implications. Trial registration Pan African Clinical Trial Registry, PACTR201911656014962 on the 12th of November 2019.

Using Montenegro as a case study, this paper evaluates the viability of currency substitution, in this case euroization, as a response to increased financial volatility. Proponents of euroization outline a series of expected benefits, while critics point to what they perceive as much larger costs. The paper contrasts the macroeconomic developments of Montenegro and how it fared during the Global Financial Crisis and the shock triggered by the Covid-19 pandemic with the performance of its regional peers and the euro area overall. The findings are contrasted to how the various expectations played out for Montenegro, drawing further lessons on the role of monetary policy and domestic monetary sovereignty.

This paper compares the actual and potential resources derived from the G20’s Debt Service Suspension Initiative and the actual and potential resources from International Monetary Fund’s 2021 allocation of Special Drawing Rights. These programs were two main sources of support for 73 vulnerable countries during height of the COVID-19 pandemic. For these countries, Special Drawing Rights provided much greater potential support when compared to the Debt Service Suspension Initiative. Special Drawing Rights deployed more actual resources as well. When these programs are evaluated from the perspective of the countries receiving assistance, Special Drawing Rights are found to have several characteristics that are more desirable. As such, as a tool, Special Drawing Rights have several advantages that should be taken into account during discussions about policy responses to global challenges in the future.

SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)-as generated by the immune system following infection or vaccination-has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG), and ACE2 binding inhibition capacity in asymptomatic individuals between January 2021 and May 2022. These data were generated as part of a large university COVID monitoring program in Ohio, United States of America, and demonstrate that COVID incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva CoV2 viral loads becoming progressively higher in our community until vaccine mandates were established. Among the unvaccinated, infection with each CoV2 lineage (pre-Omicron) resulted in saliva Spike-specific IgM, IgA, and IgG responses, the latter increasing significantly post-infection and being more pronounced than N-specific IgG responses. Vaccination resulted in significantly higher Spike-specific IgG levels compared to unvaccinated infected individuals, and uninfected vaccinees' saliva was more capable of inhibiting Spike function. Vaccinees with breakthrough Delta infections had Spike-specific IgG levels comparable to those of uninfected vaccinees; however, their ability to inhibit Spike binding was diminished. These data are consistent with COVID vaccines having achieved hoped-for effects in our community, including the generation of mucosal antibodies that inhibit Spike and lower community viral loads, and suggest breakthrough Delta infections were not due to an absence of vaccine-elicited Ig, but instead limited Spike binding activity in the face of high community viral loads.

In light of two recent global economic shocks, the global financial crisis of 2007/08 and the COVID-19 pandemic, this paper analyzes the relationships between global shocks and the national stock markets, looking to trends in volatility for the leading stock indices in six CEE countries, namely Austria, Bulgaria, Czech Republic, Hungary, Poland, and Romania, and indices from Germany (DAX) and the United States (S&P 500). The selected indices include the largest domestic companies in each country and make up most of the domestic market capitalization. For the analysis we used Garman-Klass (GK) volatility estimator, as the volatility was considered the most important proxy for market uncertainty. Then we used a simple correlation matrix to show initial tendencies. Also, the Johansen's test was used to determine if the indices are cointegrated and if this relationship has changed significantly in the non-crisis periods. We analyze Granger causality and the network approach as proposed by Diebold and Yilmaz (2015). The GK volatility results were individualized in three periods: 2007-2011 as a proxy for the global financial crisis and European sovereign debt; 2012-2019 representing a period of economic recovery and ultimately 2020-2021 representing the data points for the COVID-19 global pandemic. We find that particularly during periods of global distress, correlations between patterns of volatility for the stock market indices from these countries increase, and they exhibit stronger patterns of cointegration. These findings highlight the increasing connectivity in global financial markets and added challenges in crafting portfolio diversification strategies based on geography of stock holdings.

The initial shock from and response to the Global Financial Crisis (GFC) in 2008 had a profound impact on the fiscal balances and subsequently the government debt ratios of countries in the European Union (EU). This paper examines the relationship fiscal consolidation measures and the changes in debt ratios that followed. The findings highlight that the negative feedback of fiscal consolidation on economic growth in this context can translate into increases, rather than decreases in government debt ratios. As debt levels in most European Union countries are reaching record levels in the aftermath of Covid-19, these results warn of the risks of a stunted recovery if a similar approach as in the aftermath of the GFC is pursued.

Introduction: Erythropoietin (EPO), produced in the kidney in a hypoxia responsive manner, is required for red blood cell production. In non-erythroid tissue, EPO increases endothelial cell production of nitric oxide (NO) and endothelial nitric oxide synthase (eNOS) that regulates vascular tone to improve oxygen delivery. This contributes to EPO cardioprotective activity in mouse models. Nitric oxide treatment in mice shifts hematopoiesis toward the erythroid lineage, increases red blood cell production and total hemoglobin. In erythroid cells, nitric oxide can also be generated by hydroxyurea metabolism that may contribute to hydroxyurea induction of fetal hemoglobin. We find that during erythroid differentiation, EPO induces neuronal nitric oxide synthase (nNOS) and that neuronal nitric oxide synthase is required for normal erythropoietic response.Methods: Wild type (WT) mice and mice with targeted deletion of nNOS (nNOS−/−) and eNOS (eNOS−/−) were assessed for EPO stimulated erythropoietic response. Bone marrow erythropoietic activity was assessed in culture by EPO dependent erythroid colony assay and in vivo by bone marrow transplantation into recipient WT mice. Contribution of nNOS to EPO stimulated cell proliferation was assessed in EPO dependent erythroid cells and in primary human erythroid progenitor cell cultures.Results: EPO treatment increased hematocrit similarly in WT and eNOS−/− mice and showed a lower increase in hematocrit nNOS−/− mice. Erythroid colony assays from bone marrow cells were comparable in number from wild type, eNOS−/− and nNOS−/− mice at low EPO concentration. Colony number increased at high EPO concentration is seen only in cultures from bone marrow cells of wild type and eNOS−/− mice but not from nNOS−/− mice. Colony size with high EPO treatment also exhibited a marked increase in erythroid cultures from wild type and eNOS−/− mice but not from nNOS−/− mice. Bone marrow transplant from nNOS−/− mice into immunodeficient mice showed engraftment at comparable levels to WT bone marrow transplant. With EPO treatment, the increase in hematocrit was blunted in recipient mice that received with nNOS−/− donor marrow compared with recipient mice that received WT donor marrow. In erythroid cell cultures, addition of nNOS inhibitor resulted in decreased EPO dependent proliferation mediated in part by decreased EPO receptor expression, and decreased proliferation of hemin induced differentiating erythroid cells.Discussion: EPO treatment in mice and in corresponding cultures of bone marrow erythropoiesis suggest an intrinsic defect in erythropoietic response of nNOS−/− mice to high EPO stimulation. Transplantation of bone marrow from donor WT or nNOS−/− mice into recipient WT mice showed that EPO treatment post-transplant recapitulated the response of donor mice. Culture studies suggest nNOS regulation of EPO dependent erythroid cell proliferation, expression of EPO receptor and cell cycle associated genes, and AKT activation. These data provide evidence that nitric oxide modulates EPO dose dependent erythropoietic response.

Cut-and-paste |$K$| -theory has recently emerged as an important variant of higher algebraic |$K$| -theory. However, many of the powerful tools used to study classical higher algebraic |$K$| -theory do not yet have analogues in the cut-and-paste setting. In particular, there does not yet exist a sensible notion of the Dennis trace for cut-and-paste |$K$| -theory. In this paper we address the particular case of the |$K$| -theory of polyhedra, also called scissors congruence |$K$| -theory. We introduce an explicit, computable trace map from the higher scissors congruence groups to group homology, and use this trace to prove the existence of some nonzero classes in the higher scissors congruence groups. We also show that the |$K$| -theory of polyhedra is a homotopy orbit spectrum. This fits into Thomason's general framework of |$K$| -theory commuting with homotopy colimits, but we give a self-contained proof. We then use this result to re-interpret the trace map as a partial inverse to the map that commutes homotopy orbits with algebraic |$K$| -theory. [ABSTRACT FROM AUTHOR]

Traditional IP multicast (IPMC) maintains state per IPMC group in core devices to distribute one-to-many traffic along tree-like structures through the network. This limits its scalability because whenever subscribers of IPMC groups change, forwarding state in the core network needs to be updated. Bit Index Explicit Replication (BIER) has been proposed by the IETF for efficient transport of IPMC traffic without the need of IPMC-group-dependent state in core devices. However, legacy devices do not offer the required features to implement BIER. P4 is a programming language which follows the software-defined networking (SDN) paradigm. It provides a programmable data plane by programming the packet processing pipeline of P4 devices. The contribution of this article is threefold. First, we provide a hardware-based prototype of BIER and BIER fast reroute (BIER-FRR) which leverages packet recirculation. Our target is the P4-programmable high-performance switching ASIC Tofino; the source code is publicly available. Second, we perform an experimental evaluation, with regard to failover time and throughput, which shows that up to 100 Gb/s throughput can be obtained and that failures affect BIER forwarding for less than 1 ms. However, throughput can decrease if switch-internal packet loss occurs due to missing recirculation capacity. As a remedy, we add more recirculation capacity by turning physical ports into loopback mode. To quantify the problem, we derive a prediction model for reduced throughput whose results are in good accordance with measured values. Third, we provide a provisioning rule for recirculation ports, that is applicable to general P4 programs, to avoid switch-internal packet loss due to packet recirculation. In a case study we show that BIER requires only a few such ports under realistic mixes of unicast and multicast traffic.

Nontuberculous mycobacteria (NTM) are an increasingly common cause of respiratory infection in people with cystic fibrosis (PwCF). Relative to those with no history of NTM infection (CF-NTMNEG), PwCF and a history of NTM infection (CF-NTMPOS) are more likely to develop severe lung disease and experience complications over the course of treatment. In other mycobacterial infections (e.g., tuberculosis), an overexuberant immune response causes pathology and compromises organ function; however, since the immune profiles of CF-NTMPOS and CF-NTMNEG airways are largely unexplored, it is unknown which, if any, immune responses distinguish these cohorts or concentrate in damaged tissues. Here, we evaluated lung lobe–specific immune profiles of 3 cohorts (CF-NTMPOS, CF-NTMNEG, and non-CF adults) and found that CF-NTMPOS airways are distinguished by a hyperinflammatory cytokine profile. Importantly, the CF-NTMPOS airway immune profile was dominated by B cells, classical macrophages, and the cytokines that support their accumulation. These and other immunological differences between cohorts, including the near absence of NK cells and complement pathway members, were enriched in the most damaged lung lobes. The implications of these findings for our understanding of lung disease in PwCF are discussed, as are how they may inform the development of host-directed therapies to improve NTM disease treatment.

Despite a rich literature on the effects of self-efficacy (SE) on various outcomes, there is little discussion of its effects on obsessive-compulsive disorder (OCD). The purpose of this study was to develop and validate the Facing-Contamination Self-Efficacy Scale (FC-SES), a measure of beliefs about one's capability to face OCD-relevant contamination triggers. The final sample consisted of 129 participants, age 18 and over, who were recruited through Amazon's Mechanical Turk. Factor structure, reliability, and validity were assessed using exploratory factor analysis, Cronbach's alpha, and correlational analyses, respectively. Factor analysis yielded 2 clearly interpretable factors: human-related contamination (9 items), and animal-related contamination (5 items). The 14-item FC-SES demonstrated very good internal consistency reliability ([alpha] = .87), as well as good convergent and discriminant validity. Results suggest the FC-SES is a valid and reliable tool that can be used in future research exploring the relationship between SE and contamination-related OCD symptoms., Author(s): Lori F. Merling [sup.1] , Jedidiah Siev [sup.2] , Keith Lit [sup.1] Author Affiliations: (1) grid.261241.2, 0000 0001 2168 8324, College of Psychology, Nova Southeastern University, , 3301 College [...]

The climate crisis prompted the International Monetary Fund (IMF), an international lender of last resort, to implement wholesale reforms to incorporate climate policy into its operations. At the IMF, selected countries from the Global North—historically the largest emitters of greenhouse gases—dominate decision‐making. This raises several questions. Can the Fund implement an ambitious and effective climate policy? How are climate‐vulnerable developing countries and their interests represented in everyday decision‐making at the institution? Drawing on scholarship on the political economy and legitimacy of international organizations, we focus on the formal distribution of decision‐making power within the IMF to evaluate the IMF's shift toward climate change. Our empirical analysis of the representation of 57 self‐identifying climate‐vulnerable developing countries (the V20) at the IMF and within its Executive Board shows that these countries, speaking for almost a third of the Fund's membership, command a vote share of merely 5.6%. Our assessment of the Climate Strategy adopted by the IMF amplifies equity concerns over its climate policies and further attests to the disregard of requests by developing countries. Barring meaningful governance reform to increase the voice and representation of climate‐vulnerable developing countries, the IMF's approach to addressing climate change is unlikely to translate into legitimate and effective climate policy. [ABSTRACT FROM AUTHOR]

By 2040, roughly two-thirds of humanity are expected to live in urban areas. As cities expand, humans irreversibly transform natural ecosystems, creating both opportunities and challenges for wildlife. Here, we investigate how the Northern Goshawk (Accipiter gentilis) is adjusting to urban environments. We measured a variety of behavioural and ecological parameters in three urban and four rural study sites. City life appeared related to all parameters we measured. Urban female goshawks were overall 21.7 (CI95% 5.13–130) times more likely to defend their nestlings from humans than rural females. Urban goshawks were 3.64 (CI95% 2.05–6.66) times more likely to feed on pigeons and had diets exhibiting lower overall species richness and diversity. Urban females laid eggs 12.5 (CI95% 7.12–17.4) days earlier than rural individuals and were 2.22 (CI95% 0.984–4.73) times more likely to produce a brood of more than three nestlings. Nonetheless, urban goshawks suffered more from infections with the parasite Trichomonas gallinae, which was the second most common cause of mortality (14.6%), after collisions with windows (33.1%). In conclusion, although city life is associated with significant risks, goshawks appear to thrive in some urban environments, most likely as a result of high local availability of profitable pigeon prey. We conclude that the Northern Goshawk can be classified as an urban exploiter in parts of its distribution.

Background: Sedentary behaviour is associated with cardiometabolic diseases amongst office-bound workers, mostly through extended sitting and engaging in low-energy-demanding activities during work hours. The aim of this study is to assess the effectiveness of standing desks and healthy messages on cardiovascular parameters in a cohort of office-based workers and to explore the perceptions of these workers about the suitability of this intervention to lower occupation-related sedentariness. Methods/design: The protocol will use a mixed-methods study design. Phase 1 of this study is a 12-month, single blinded, randomised controlled trial, which will include baseline, 3-month, 6-month and 12-month post-intervention assessments of plausible cardiometabolic risk biomarkers in office-bound workers at a South African credit and information management company. These biomarkers include anthropometry, sedentary behaviour and physical activity, sleep duration, blood pressure, glucose, glycated haemoglobin (HbA1c), lipid profile and cardiorespiratory fitness. Participants will be randomised into an intervention or control group. The intervention group will be provided with an adjustable sit–stand desk and receive weekly health-promoting messages for the intervention period. Phase 2 will use focus group discussions conducted post-intervention to explore the study participants’ perceptions of the effectiveness of the intervention. Cardiometabolic risk biomarkers and changes in these variables will be compared between the intervention group and the control group at the four time points using descriptive and inferential statistics. Discussion: Regression analysis will be undertaken to determine the association of cardiometabolic risk biomarkers with cardiometabolic diseases. A thematic content analysis approach will be used to explore emerging themes from focus group discussions. Protocol identification: Pan African Clinical Trial Registry, PACTR201911656014962.

In this case report, we focus on Muenke syndrome (MS), a disease caused by the p.Pro250Arg variant in fibroblast growth factor receptor 3 (FGFR3) and characterized by uni- or bilateral coronal suture synostosis, macrocephaly without craniosynostosis, dysmorphic craniofacial features, and dental malocclusion. The clinical findings of MS are further complicated by variable expression of phenotypic traits and incomplete penetrance. As such, unraveling the mechanisms behind MS will require a comprehensive and systematic way of phenotyping patients to precisely identify the impact of the mutation variant on craniofacial development. To establish this framework, we quantitatively delineated the craniofacial phenotype of an individual with MS and compared this to his unaffected parents using three-dimensional cephalometric analysis of cone beam computed tomography scans and geometric morphometric analysis, in addition to an extensive clinical evaluation. Secondly, given the utility of human induced pluripotent stem cells (hiPSCs) as a patient-specific investigative tool, we also generated the first hiPSCs derived from a family trio, the proband and his unaffected parents as controls, with detailed characterization of all cell lines. This report provides a starting point for evaluating the mechanistic underpinning of the craniofacial development in MS with the goal of linking specific clinical manifestations to molecular insights gained from hiPSC-based disease modeling.

Abstract: Pseudogenes are duplicated genes with mutations rendering them nonfunctional. For single-gene disorders with homologous pseudogenes, the pseudogene might be a target for genetic correction. Autosomal-recessive p47phox-deficient chronic granulomatous disease (p47-CGD) is a life-threatening immune deficiency caused by mutations in NCF1, a gene with 2 pseudogenes, NCF1B and NCF1C. The most common NCF1 mutation, a GT deletion (ΔGT) at the start of exon 2 (>90% of alleles), is constitutive to NCF1B and NCF1C. NCF1 ΔGT results in premature termination, undetectable protein expression, and defective production of antimicrobial superoxide in neutrophils. We examined strategies for p47-CGD gene correction using engineered zinc-finger nucleases targeting the exon 2 ΔGT in induced pluripotent stem cells or CD34+ hematopoietic stem cells derived from p47-CGD patients. Correction of ΔGT in NCF1 pseudogenes restores oxidase function in p47-CGD, providing the first demonstration that targeted restoration of pseudogene function can correct a monogenic disorder.

Summary: Chlamydial infection requires the formation of a membrane-bound vacuole, termed the inclusion, that undergoes extensive interactions with select host organelles. The importance of the Inc protein CT229 in the formation and maintenance of the chlamydial inclusion was recently highlighted by studies demonstrating that its absence during infection results in reduced bacterial replication, premature inclusion lysis, and host cell death. Previous reports have indicated that CT229 binds Rab GTPases; however, the physiological implications of this interaction are unknown. Here, we show that CT229 regulates host multivesicular trafficking by recruiting multiple Rab GTPases and their cognate effectors to the inclusion. We demonstrate that CT229 specifically modulates clathrin-coated vesicle trafficking and regulates the trafficking of transferrin and the mannose-6-phosphate receptor, both of which are crucial for proper chlamydial development. This study highlights CT229 as a master regulator of multiple host vesicular trafficking pathways essential for chlamydial infection. : Faris et al. use genetic approaches to demonstrate that the disruption of the essential Chlamydia trachomatis Inc protein CT229 impairs recruitment of Rab GTPases, specific Rab effector proteins, transferrin, and the mannose-6-phosphate receptor to the periphery of the inclusion. Understanding how C. trachomatis hijacks host vesicular transport will help define how chlamydiae acquire essential substrates, such as iron and lipids, from the host cell. Keywords: Chlamydia trachomatis, CT229 (CpoS), Rab GTPase, transferrin, M6PR

This paper analyses the available data on external debt burdens of low- and middle-income countries and identifies 79 countries that are considered by international institutions as being in or at risk of debt distress. In the context of the ongoing climate crisis, high debt burdens hamper the ability of these country to invest in climate resilience. This paper shows the effects that servicing debt has on these countries' ability to respond to climate disasters, as well as provide services to their population. The paper shows how developing countries are trapped in a vicious cycle, which keeps them indebted and perpetuates vulnerability to the effects of climate change, as well as hampering their development path. The response so far from the international financial community has been inadequate to help countries break this vicious cycle. [ABSTRACT FROM AUTHOR]

In the last decade the world has experienced a number of global crises which triggered economic downturns. Impacts from the global financial crisis, the global COVID pandemic, and Russia's invasion of Ukraine trigger instability in financial markets. This paper explores similarities and differences between these crises based on inflation and its energy-related components. A Vector Autoregressive (VAR) model is used to analyze both EU-level trends, as well as data for Romania. The findings indicate idiosyncratic shifts in the relationships between variables. The changes are often specific to individual shocks and the policy context. How policy makers respond to these shocks will also impact the fiscal space, the borrowing costs of countries, and the cost of servicing debt, which risks a return to the type of austerity policies that slowed down the post-financial crisis recovery. There is a need for more detailed research and investigations in policy responses designed to respond to ongoing events. [ABSTRACT FROM AUTHOR]

The educational inclusion imposes challenges to the National System of Education, to optimize the attention to the students with upsets of the oral communication. Is the objective of the article to share the design of an investigation that assists to the scientific problem how to contribute to the improvement of the educational inclusion of the students with upsets of the oral communication? The employment of the investigation-action-participativa it drives to the execution of the objective related with the construction of a pedagogic model for the improvement of this process. The results of the investigation will constitute a necessary contribution to the educational inclusion in the National System of Education

SARS-CoV-2 (CoV2) infected, asymptomatic individuals are an important contributor to COVID transmission. CoV2-specific immunoglobulin (Ig)—as generated by the immune system following infection or vaccination—has helped limit CoV2 transmission from asymptomatic individuals to susceptible populations (e.g. elderly). Here, we describe the relationships between COVID incidence and CoV2 lineage, viral load, saliva Ig levels (CoV2-specific IgM, IgA and IgG), and ACE2 binding inhibition capacity in asymptomatic individuals between January 2021 and May 2022. These data were generated as part of a large university COVID monitoring program in Ohio, United States of America, and demonstrate that COVID incidence among asymptomatic individuals occurred in waves which mirrored those in surrounding regions, with saliva CoV2 viral loads becoming progressively higher in our community until vaccine mandates were established. Among the unvaccinated, infection with each CoV2 lineage (pre-Omicron) resulted in saliva Spike-specific IgM, IgA, and IgG responses, the latter increasing significantly post-infection and being more pronounced than N-specific IgG responses. Vaccination resulted in significantly higher Spike-specific IgG levels compared to unvaccinated infected individuals, and uninfected vaccinees' saliva was more capable of inhibiting Spike function. Vaccinees with breakthrough Delta infections had Spike-specific IgG levels comparable to those of uninfected vaccinees; however, their ability to inhibit Spike binding was diminished. These data are consistent with COVID vaccines having achieved hoped-for effects in our community, including the generation of mucosal antibodies that inhibit Spike and lower community viral loads, and suggest breakthrough Delta infections were not due to an absence of vaccine-elicited Ig, but instead limited Spike binding activity in the face of high community viral loads. Author summary: Our study identified relationships between specific SARS-CoV-2 (CoV2) variants of concern (VOCs) and CoV2-specific immunoglobulin (Ig) among asymptomatic young adults in our university community. Asymptomatic young adults are important source of CoV2 transmission in the United States of America and other countries. Major findings from our study which we believe inform our understanding of CoV2 transmission and immunity, and may potentially influence COVID monitoring policies at other universities include the following: (1) CoV2 positivity occurred in waves which mirrored those in regions surrounding our university campuses, and were driven by newly emerged VOCs. (2) Only after university vaccine requirements went into effect did net viral loads among all community members decline. (3) Breakthrough infections among vaccinees were not due to an absence of vaccine-elicited Ig, but rather diminished inhibitory capacity during a period when community viral loads peaked. In other words, vaccination efforts achieved their intended goal of increasing CoV2-specific Ig; in individuals with breakthrough infections, however, the capacity of this Ig to inhibit Spike function was limited and corresponded to when community viral loads were at their highest. [ABSTRACT FROM AUTHOR]