Strong Evidence Research Articles

Seasonal and geographical impact on the Irish raw milk microbiota correlates with chemical composition and climatic variables.

The microbiota of raw milk is influenced by many factors that encourage or prevent the introduction and growth of both beneficial and undesirable microorganisms. The seasonal and geographical impacts on the microbial communities of raw milk have been previously seen, but the relationships with environmental factors and the chemical composition has yet to be investigated. In this year-long study, we found that while raw milk is highly diverse, a core microbiota was detected for Irish raw milk, with strong evidence of seasonal and geographical influence. We also found associations between groups of microorganisms, environmental factors, and milk composition, which expand current knowledge on the relationships between microbial and chemical composition and the climate. These results provide evidence for the development of a tool to allow for the prediction of raw milk quality and safety.

TOP2A modulates signaling via the AKT/mTOR pathway to promote ovarian cancer cell proliferation

ABSTRACT Ovarian cancer (OC) is a form of gynecological malignancy that is associated with worse patient outcomes than any other cancer of the female reproductive tract. Topoisomerase II α (TOP2A) is commonly regarded as an oncogene that is associated with malignant disease progression in a variety of cancers, its mechanistic functions in OC have yet to be firmly established. We explored the role of TOP2A in OC through online databases, clinical samples, in vitro and in vivo experiments. And initial analyses of public databases revealed high OC-related TOP2A expression in patient samples that was related to poorer prognosis. This was confirmed by clinical samples in which TOP2A expression was elevated in OC relative to healthy tissue. Kaplan-Meier analyses further suggested that higher TOP2A expression levels were correlated with worse prognosis in OC patients. In vitro, TOP2A knockdown resulted in the inhibition of OC cell proliferation, with cells entering G1 phase arrest and undergoing consequent apoptotic death. In rescue assays, TOP2A was confirmed to regulate cell proliferation and cell cycle through AKT/mTOR pathway activity. Mouse model experiments further affirmed the key role that TOP2A plays as a driver of OC cell proliferation. These data provide strong evidence supporting TOP2A as an oncogenic mediator and prognostic biomarker related to OC progression and poor outcomes. At the mechanistic level, TOP2A can control tumor cell growth via AKT/mTOR pathway modulation. These preliminary results provide a foundation for future research seeking to explore the utility of TOP2A inhibitor-based combination treatment regimens in platinum-resistant recurrent OC patients.

Improving the Efficiency of Outbound CATI As a Nonresponse Follow-Up Mode in Address-Based Samples: A Quasi-Experimental Evaluation of a Dynamic Adaptive Design

Abstract This article evaluates the use of dynamic adaptive design methods to target outbound computer-assisted telephone interviewing (CATI) in the California Health Interview Survey (CHIS). CHIS is a large-scale, annual study that uses an address-based sample (ABS) with push-to-Web mailings, followed by outbound CATI follow-up for addresses with appended phone numbers. CHIS 2022 implemented a dynamic adaptive design in which predictive models were used to end dialing early for some cases. For addresses that received outbound CATI follow-up, dialing was paused after three calls. A response propensity (RP) model was applied to predict the probability that the address would respond to continued dialing, based on the outcomes of the first three calls. Low-RP addresses were permanently retired with no additional dialing, while the rest continued through six or more attempts. We use a difference-in-difference design to evaluate the effect of the adaptive design on calling effort, completion rates, and the demographic composition of respondents. We find that the adaptive design reduced the mean number of calls per sampled unit by about 14 percent (relative to a modeled no-adaptive-design counterfactual) with a minimal reduction in the completion rate and no strong evidence of changes in the prevalence of target demographics. This suggests that RP modeling can meaningfully distinguish between ABS sample units for which additional dialing is and is not productive, helping to control outbound dialing costs without compromising sample representativeness.

Academic Stress Interventions in High Schools: A Systematic Literature Review.

The experience of academic stress is common during high school and can have significant negative consequences for students' educational achievement and wellbeing. High school students frequently report heightened levels of school-related distress, particularly as they approach high-stakes assessments. Programs designed to reduce or prevent academic stress are needed, and their delivery in school settings is ideal to improve treatment access. The current review aimed to examine the effectiveness of high school-based programs in reducing or preventing academic stress. A systematic search returned 31 eligible studies across 13 countries. Programs were categorised according to intervention type, format, and facilitator. Results showed that the methodological quality of most studies was poor, and many used an inactive control group. As predicted by theories of academic stress, the strongest evidence was for programs grounded in cognitive-behavioural therapy (CBT). There was evidence that both universal and targeted approaches can be beneficial. The unique implementation issues for these two formats are discussed. Most programs were delivered by psychologists and were generally effective, but almost all of these were CBT programs. A smaller proportion of programs delivered by teachers were effective. Therefore, future studies should evaluate the implementation success of programs to improve the rate of effective delivery by school staff. Overall, the field will benefit from more randomised controlled trials with comparisons to active control groups, larger sample sizes and longer-term follow-ups.

Discovery of Red-Shifting Mutations in Firefly Luciferase Using High-Throughput Biochemistry.

Photinus pyralis luciferase (FLuc) has proven a valuable tool for bioluminescence imaging, but much of the light emitted from the native enzyme is absorbed by endogenous biomolecules. Thus, luciferases displaying red-shifted emission enable higher resolution during deep-tissue imaging. A robust model of how protein structure determines emission color would greatly aid the engineering of red-shifted mutants, but no consensus has been reached to date. In this work, we applied deep mutational scanning to systematically assess 20 functionally important amino acid positions on FLuc for red-shifting mutations, predicting that an unbiased approach would enable novel contributions to this debate. We report dozens of red-shifting mutations as a result, a large majority of which have not been previously identified. Further characterization revealed that mutations N229T and T352M, in particular, bring about unimodal emission with the majority of photons being >600 nm. The red-shifting mutations identified by this high-throughput approach provide strong biochemical evidence for the multiple-emitter mechanism of color determination and point to the importance of a water network in the enzyme binding pocket for altering the emitter ratio. This work provides a broadly applicable mutational data set tying FLuc structure to emission color that contributes to our mechanistic understanding of emission color determination and should facilitate further engineering of improved probes for deep-tissue imaging.

Another look at the price clustering behavior: evidence from the Muscat stock exchange

PurposeThe price clustering behavior is becoming a core part of the market efficiency theory especially with the development of trading strategies and the occurrence of major and unprecedented shocks which have led to severe inquiry regarding asset price dynamics and their distribution. However, research on emerging stock market is scant. The study contributes to the literature on price clustering by investigating an active emerging stock market, the Muscat stock market one of the Arabian Gulf Markets.Design/methodology/approachThis research adopts the artificial intelligence technique and other statistical estimation procedure in understanding the price clustering patterns in Muscat stock market and their main determinants.FindingsThe findings reveal that stock prices are marked by clustering behavior as commonly highlighted in the previous studies. However, we found strong evidence of price preferences to cluster on numbers closer to zero than to one. We also show that the nature of firm’s activity matters for price clustering behavior. In addition, firms with traded bonds in Oman market experienced a substantial less stock price clustering than other firms. Clustered stock prices are more likely to have higher prices and higher volatility of price. Finally, clustering raised when the market became highly uncertain during the Covid-19 crisis especially for the financial firms.Originality/valueThis study provides novel results on price clustering literature especially for an active emerging market and during the Covid-19 pandemic crisis.

(022) Penile Implant Reservoir Placement: The Current Utilized Various Techniques and the Associated Outcome: Systematic Review and Meta-Analysis

Abstract Introduction Many innovations in the field of inflatable penile prosthesis (IPP) has been emerged. Since the introduction of the IPP, reservoir positioning in the space of Retzius (SOR) was considered the classical approach that had been utilized for many years. However, in certain group of patients, reservoir insertion in such space might be difficult or even risky. As a result, many alternatives for the reservoir placement outside the SOR has emerged with the intent of safe and reliable reservoir placement. Objective To conduct a systematic review for the studies evaluating the outcomes of different techniques used for IPP reservoir placement to look for possible superiority of any approach over others. Methods A systemic review was performed utilizing (PRISMA) statement. The PubMed and Google scholar were used to look for articles published up to January 2023. Original articles reporting different techniques for IPP reservoir placement and evaluating the associated outcomes were included. Data regarding study design, sample size, approach of reservoir placement, surgical technique, device type and reported outcomes (infection rate, bladder/bowel/vascular injury, reservoir herniation, mechanical failure, auto-inflation, reservoir palpability and patients’ satisfaction) were collected. Pooled proportion was calculated and included in the meta-analysis. The Newcastle-Ottawa scale was used for assessing the quality of the studies. Results A total of 23 articles meeting the inclusion criteria, all were retrospective reviews. 11 compared more than one technique for reservoir placement whereas 12 described a single technique. In total, techniques for 6 main different reservoir locations has been reported, including SOR (7 studies), submuscular/subrectus (6 studies), Lateral retroperitoneal (1 study), subcutaneous (1 study), sub external oblique (1 study) and intraperitoneal (1 study). Another 7 modifications have been described for the SOR technique (traditional SOR, accessing SOR using blunt scissor in post-prostatectomy patients, accessing SOR using blunt scissor in virgin cases, dilating SOR using catheter balloon, accessing SOR under direct vision, accessing SOR through external oblique fascia incision, and the addition of The Tubing Hitch&Lasso, Intussusception Anchor technique (THALIA)). Another 6 modifications for the submuscular/subrectus approach have been described (posterior to transversalis fascia (PTF), anterior to transversalis fascia (ATF), high submuscular, subrectus using counter incision, subrectus with the addition of THALIA, low submuscular with trans-fascial-fixation (TFF)). None of the studies have proven the superiority of one technique over others, with most of the techniques has comparable intra-operative and post-operative outcomes (table 1). The addition of anchoring step (THALIA or TFF) resulted in neglected risk of reservoir herniation, however, related studies has small sample size with no comparison groups. Meta-analysis for the studies of SOR (n=7) and submuscular/subrectus (n=6) groups showed a statistically significant difference only in the herniation rates (figure 1). 10 studies were of strong quality (8 stars) while the remaining 13 studies were of poor quality. Conclusions Modest evidence suggests a comparable favorable outcome of various approaches used for IPP reservoir placement. The lack of enough prospective trials, short term follow up, and diversity in the techniques prescribed prevent the ability to build strong evidence. For the purpose of supporting the superiority of any technique, further prospective studies on a larger number of patients with long-term follow up are needed to reach a solid verdict. Disclosure No.

Evaluation of pre-plant incorporated manure and phosphorus fertilizers on alfalfa yield, nutritive value, and residual soil characteristics

Managing adequate levels of plant available P in soil is an important management practice for boosting alfalfa (Medicago sativa L.) yields and nutritive value. Although several ways of supplementing P at various stages of plant growth are in practice, pre-plant application of P through various organic and inorganic nutrient sources are largely under-investigated. Therefore, a three-year study was conducted at the New Mexico State University Rex. E. Kirksey Agricultural Science Center, Tucumcari, NM USA, to investigate the impact of manure (pre-plant applied @ 22.5 Mg ha−1vs. no manure) and inorganic P sources (00-46-00 or 11-52-00) applied to soil either in one-time bulk (336 kg P2O5 ha−1 preplant incorporated) or split applications (112 kg P2O5 ha−1 preplant incorporated with an additional 112 kg P2O5 ha−1 surface-applied annually) on the yield and nutritive value of alfalfa and residual soil characteristics. Results demonstrated that pre-plant manure application had statistically no advantage in improving the alfalfa forage yield compared to control (p > 0.05), although there was strong evidence of a consistent yield increase trend in all manure treatments. Forage nutritive value parameters such as ADF (Acid Detergent Fiber), NDF (Neutral Detergent Fiber), K, and Zn were significantly improved by manure supplementation. Manure application improved most soil quality parameters, especially the soil Nitrate-N, Olsen P, K, S, and Zn contents. Inorganic P fertilizer type or application strategy had no significant impact on alfalfa yield and nutritive value and soil characteristics. Most interactions (both two-way and three-way) among the tested treatments had no significant impact on the study parameters.

Insufficiency of informal alignment: why did Finland choose formal NATO membership?

Abstract In May 2022, less than three months after Russia started its war of aggression against Ukraine, both Finland and Sweden applied for membership in NATO, thereby revoking their longstanding policies of non-alliance. What led to this shift? And what made formal NATO membership more attractive to these countries than their previous relationship with the alliance, which already amounted to informal alignment between them and NATO? To answer these questions, this article reviews the process and debates preceding the Finnish NATO application, which also proved decisive for Sweden's alliance bid. In doing so, the article contributes to the existing literature on Finland's NATO process as well as the broader scholarly debate about alliance formation. It argues that two factors prompted the Finnish NATO application: first, a dramatic shift in Finnish public opinion on NATO membership and, second, the emergence of a broadly shared view among Finland's elites of the insufficiency of Finland's existing security arrangements in view of Russia's increased threat potential, with NATO membership seen as the only viable remedy. The article duly highlights the role of public opinion in shaping a state's alignment preferences. Moreover, it finds strong evidence for realist (threat) and rationalist (efficiency) explanations for alliance formation.

Influence of ploidy, genetic and environment on production traits of the Pacific oyster Crassostrea gigas

Pacific oysters, Crassostrea gigas, are one of the most widely farmed shellfish. To meet demand, the advantages of growth and increased sterility are currently being exploited in the commercial culture of triploid C. gigas. However, the extent of the triploid advantage can vary, environmental conditions and rearing methods. In the present study, the performance of diploid and triploid oysters was compared at two sites (Rongcheng and Rushan) to determine whether the triploidization would result in any advantage on production traits that could be utilized for aquaculture of this species. Triploid oysters were also produced using the wild broodstock and selected line to verify whether selectively bred oysters maintain their improved traits after triploidization. In this study, we found that the survival advantage of triploid is “site-dependent” and that Rongcheng's triploids did not exhibit significantly higher cumulative survival than diploids. Notably, incremental survival of triploid oysters was consistently higher than that of diploids during the second summer, which may be related to gonad development and spawning in diploids. At both sites, growth traits (shell height and individual weight) were always higher for triploids than in diploids in both the selected and control groups, which is strong evidence of a superior growth advantage for triploids. In addition, we found that the production performance (growth, survival and yield) of the selected group was consistently better than that of the control group (either diploid or triploid), suggesting that the superior traits of diploids can be converted to triploids through ploidy manipulation. Our results support the notion that yield can be further optimized by reducing mortality through a selective breeding program coupled with triploid production to increase growth rates. This study provides meaningful information on the potential of triploid C. gigas for oyster culture in northern China.

(207) Premature Ejaculation and Varicocele, are they Associated? Systematic Review

Abstract Introduction Premature ejaculation (PE) is one of the most common sexual disorders that negatively impacts couple’s satisfaction. Varicocele on the other hand is a highly prevalent condition affecting men population. A higher incidence of PE is observed among patients with varicocele, which incited several authors to evaluate the possible correlation between varicocele and PE. Others went beyond that to investigate whether varicocele repair can lead to an improvement in PE. Objective To systematically review the literature for all the studies exploring the relationship between PE and varicocele. Methods A systemic review was performed utilizing (PRISMA) statement. The PubMed, Google scholar and Scopus databases were used to look for articles published up to June 2023 using the appropriate keywords. Articles reporting an association between the presence of varicocele and PE and exploring changes in ejaculation latency time after varicocele correction were included. Data including study design, sample size, varicocele details, PE diagnostic method, outcome measured and tools used to measure it were collected. The Newcastle-Ottawa scale was used for assessing the quality of the included studies. Results A total of eight studies were identified, two of them were retrospective and six were prospective. Intravaginal ejaculation latency time (IELT) was used as a diagnostic tool for PE in 5 studies, Premature Ejaculation Diagnostic Tool (PEDT) in 1 study, Chinese Index of Sexual Function for Premature Ejaculation-5 (CIPE-5) scores in 1 study, and subjective assessment in 2 studies. Two studies looked for the prevalence of PE among patients with and without varicocele. Both studies showed a significantly higher frequency of PE among varicocele patients. Whereas six studies evaluated the improvement in ejaculatory function after varicocelectomy; five of them revealed a statistically significant improvement. Quality check: only one study was of strong quality while the remaining 7 studies were of fair quality. Conclusions Limited evidence suggests the presence of positive relation between varicocele and PE. The small number of studies and patients, lack of enough prospective clinical trials, short term follow up, heterogenous study design and absence or diversity in the diagnostic tools used prevent our ability to build strong evidence. For the purpose of supporting the relation and validate it, further prospective studies on a larger number of patients with long-term follow up are needed to reach a solid verdict. Disclosure No.

Sequence signatures within the genome of SARS-CoV-2 can be used to predict host source.

We conducted an in silico analysis to better understand the potential factors impacting host adaptation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in white-tailed deer, humans, and mink due to the strong evidence of sustained transmission within these hosts. Classification models trained on single nucleotide and amino acid differences between samples effectively identified white-tailed deer-, human-, and mink-derived SARS-CoV-2. For example, the balanced accuracy score of Extremely Randomized Trees classifiers was 0.984 ± 0.006. Eighty-eight commonly identified predictive mutations are found at sites under strong positive and negative selective pressure. A large fraction of sites under selection (86.9%) or identified by machine learning (87.1%) are found in genes other than the spike. Some locations encoded by these gene regions are predicted to be B- and T-cell epitopes or are implicated in modulating the immune response suggesting that host adaptation may involve the evasion of the host immune system, modulation of the class-I major-histocompatibility complex, and the diminished recognition of immune epitopes by CD8+ T cells. Our selection and machine learning analysis also identified that silent mutations, such as C7303T and C9430T, play an important role in discriminating deer-derived samples across multiple clades. Finally, our investigation into the origin of the B.1.641 lineage from white-tailed deer in Canada discovered an additional human sequence from Michigan related to the B.1.641 lineage sampled near the emergence of this lineage. These findings demonstrate that machine-learning approaches can be used in combination with evolutionary genomics to identify factors possibly involved in the cross-species transmission of viruses and the emergence of novel viral lineages.IMPORTANCESevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a highly transmissible virus capable of infecting and establishing itself in human and wildlife populations, such as white-tailed deer. This fact highlights the importance of developing novel ways to identify genetic factors that contribute to its spread and adaptation to new host species. This is especially important since these populations can serve as reservoirs that potentially facilitate the re-introduction of new variants into human populations. In this study, we apply machine learning and phylogenetic methods to uncover biomarkers of SARS-CoV-2 adaptation in mink and white-tailed deer. We find evidence demonstrating that both non-synonymous and silent mutations can be used to differentiate animal-derived sequences from human-derived ones and each other. This evidence also suggests that host adaptation involves the evasion of the immune system and the suppression of antigen presentation. Finally, the methods developed here are general and can be used to investigate host adaptation in viruses other than SARS-CoV-2.

Self-Assessment Survey: Evaluation of a Revised Measure Assessing Positive Behavioral Interventions and Supports

The purpose of this study was to evaluate the psychometric properties of the Self-Assessment Survey (SAS) 4.0, an updated measure assessing implementation fidelity of positive behavioral interventions and supports (PBIS). A total of 627 school personnel from 33 schools in six U.S. states completed the SAS 4.0 during the 2021–2022 school year. We evaluated data demonstrating the measure’s reliability (internal consistency, interrater reliability between PBIS team and non-team members), internal structure, and convergent validity for assessing implementation of Tier 1, 2, and 3 systems. We found strong internal consistency (overall and across subscales) and evidence regarding the internal structure as a four-factor measure. In addition, we found the SAS 4.0 (overall score and subscales) to be statistically significantly correlated with another widely used and empirically evaluated PBIS fidelity measure, the Tiered Fidelity Inventory (TFI). We found a statistically significant correlation between the SAS 4.0 and the SAS 3.0 for the Schoolwide Systems subscale but not other subscales. We discuss limitations given the current sample and describe implications for how PBIS teams can use the measure for school improvement and decision making.

Autistic and nonautistic adolescents do not differ in adaptation to gaze direction.

Predictive processing accounts of autism posit that autistic individuals' perception is less biased by expectations than nonautistic individuals', perhaps through stronger precision-weighting of prediction errors. Since precision-weighting is fundamental to all information processing, under this theory, the differences between autistic and nonautistic individuals should be domain-general and observable in both behavior and brain responses. This study used EEG, behavioral responses, and eye-tracking co-registration during gaze-direction adaptation, to investigate whether increased precision-weighting of prediction errors is evident through smaller adaptation after-effects in autistic adolescents compared with nonautistic peers. Multilevel modeling showed that autistic and nonautistic adolescents' responses were consistent with behavioral adaptation, with Bayesian statistics providing extremely strong evidence for the absence of a group difference. Cluster-based permutation testing of ERP responses did not show the expected adaptation after-effect but did show habituation to repeated stimulus presentation, and no group difference was detected, a result not consistent with the theoretical account. Combined with the few other available studies, the current findings raise challenges for the theory, suggesting no fundamental difference in precision-weighting of prediction errors in autism.

How do animals weigh conflicting information about reward sources over time? Comparing dynamic averaging models

Optimal foraging theory suggests that animals make decisions which maximize their food intake per unit time when foraging, but the mechanisms animals use to track the value of behavioral alternatives and choose between them remain unclear. Several models for how animals integrate past experience have been suggested. However, these models make differential predictions for the occurrence of spontaneous recovery of choice: a behavioral phenomenon in which a hiatus from the experimental environment results in animals reverting to a behavioral allocation consistent with a reward distribution from the more distant past, rather than one consistent with their most recently experienced distribution. To explore this phenomenon and compare these models, three free-operant experiments with rats were conducted using a serial reversal design. In Phase 1, two responses (A and B) were baited with pellets on concurrent variable interval schedules, favoring option A. In Phase 2, lever baiting was reversed to favor option B. Rats then entered a delay period, where they were maintained at weight in their home cages and no experimental sessions took place. Following this delay, preference was assessed using initial responding in test sessions where levers were presented, but not baited. Models were compared in performance, including an exponentially weighted moving average, the Temporal Weighting Rule, and variants of these models. While the data provided strong evidence of spontaneous recovery of choice, the form and extent of recovery was inconsistent with the models under investigation. Potential interpretations are discussed in relation to both the decision rule and valuation functions employed.

Global Functional Connectivity is Associated with Mind Wandering Domain of Comfort.

The resting-state paradigm is frequently applied to study spontaneous activity of the brain in normal and clinical conditions. To assess the relationship between brain activity and subjective experiences, various questionnaires are used. Previous studies using Amsterdam Resting State Questionnaire were focusing on fMRI functional connectivity or EEG microstates and spectral aspect. Here, we utilized Global Field Synchronization as the parameter to estimate global functional connectivity. By re-analyzing the resting-state data from 226 young healthy participants we showed a strong evidence of relationship between ARSQ domain of Comfort and GFS values in the alpha range (r = 0.210, BF10 = 12.338) and substantial evidence for positive relationship between ARSQ domain of Comfort and GFS in the beta frequency range (r = 196, BF10 = 6.307). Our study indicates the relevance of assessments of spontaneous thought occurring during the resting-state for the understanding of the individual intrinsic electrical brain activity.

The New Racial Spillover: Donald Trump, Racial Attitudes, and Public Opinion Toward Accountability for Perpetrators and Planners of the January 6 Capitol Attack

Abstract Since the violent January 6 attack on the U.S. Capitol, federal authorities have sought to hold participants and organizers accountable for their assault on American democracy. Troublingly, however, a substantial fraction of the public opposes the prosecution of participants in the assault on the Capitol and rejects charging former president Trump with crimes relating to the planning and execution of the attack. Why does a substantial fraction of the American public oppose accountability for perpetrators of the January 6 attack? In this article, we argue that racial attitudes play a central role in determining individuals' attitudes toward accountability for the Capitol attack. Elaborating on the theory of “racial spillover,” we argue that former president Trump's frequent use of racial rhetoric—which established a racialized identity and cemented a close relationship between negative racial attitudes and support for his presidency among members of the mass public—created conditions in which these attitudes were likely to “spill over” into the ostensibly non-racialized domain of attitudes toward holding perpetrators, planners, and inciters accountable for the attack. Because attitudes toward accountability for the Capitol attack are inextricable from Trump's racialized persona, we hypothesize that negative racial attitudes should be associated with increased opposition to accountability for those responsible for the attack. Using data from four original, nationally representative surveys fielded between 2021 and 2023, we find strong evidence for our racial spillover hypothesis and show that individuals with more negative racial attitudes are more opposed to accountability for those responsible for the Capitol attack.

The Relationship between Soluble Angiotensin-Converting Enzyme Level and Coronavirus Disease 2019 in Children: A Prospective Cohort Study

Abstract Objective Our objective was to investigate soluble angiotensin-converting enzyme (sACE) levels in pediatric patients with coronavirus disease 2019 (COVID-19) and to identify factors associated with the occurrence and severity of pediatric COVID-19. Methods This was a prospective cohort study conducted between April 2020 and July 2020. The study population consisted of 143 children (between 1 month and 18 years old), 103 of whom had COVID-19 and 40 of whom were negative for COVID-19 (randomly selected). The sACE levels and other laboratory data of all participants were measured at admission (day 0, baseline). Repeat measurements were performed in patients on the 5th day. Disease severity was documented at baseline and on the 5th day, and the change in severity between these time points was recorded. Results Age and sex distribution were similar in the two groups. At baseline, 31 (30.1%) of the patients were asymptomatic, 58 (56.3%) had mild disease, and 14 (13.6%) had moderate disease. Baseline sACE levels were similar in the groups (p = 0.120). Higher weight was independently associated with low sACE levels in children (p = 0.037). The sACE level of patients on the 5th day was significantly lower compared with baseline (p = 0.007). Patients who experienced a decrease in disease severity were compared with those who did not demonstrate a decrease. Baseline sACE levels were significantly lower in those who experienced decreased severity (p = 0.039). Multiple linear regression revealed that COVID-19 severity at baseline was independently associated with the low sACE level at baseline (p = 0.023). Conclusion Lower sACE at diagnosis was associated with COVID-19 severity in children. However, no strong evidence was found that could suggest the sACE level as an important predictor for the occurrence or severity of COVID-19 in children.

Tracking subjects' strategies in behavioural choice experiments at trial resolution.

Investigating how, when, and what subjects learn during decision-making tasks requires tracking their choice strategies on a trial-by-trial basis. Here, we present a simple but effective probabilistic approach to tracking choice strategies at trial resolution using Bayesian evidence accumulation. We show this approach identifies both successful learning and the exploratory strategies used in decision tasks performed by humans, non-human primates, rats, and synthetic agents. Both when subjects learn and when rules change the exploratory strategies of win-stay and lose-shift, often considered complementary, are consistently used independently. Indeed, we find the use of lose-shift is strong evidence that subjects have latently learnt the salient features of a new rewarded rule. Our approach can be extended to any discrete choice strategy, and its low computational cost is ideally suited for real-time analysis and closed-loop control.

Exploring the emerging bidirectional association between inflamm-aging and cellular senescence in organismal aging and disease.

There is strong evidence that most individuals in the elderly population are characterized by inflamm-aging which refers to a subtle increase in the systemic pro-inflammatory environment and impaired innate immune activation. Although a variety of distinct factors are associated with the progression of inflamm-aging, emerging research is demonstrating a dynamic relationship between the processes of cellular senescence and inflamm-aging. Cellular senescence is a recognized factor governing organismal aging, and through a characteristic secretome, accumulating senescent cells can induce and augment a pro-inflammatory tissue environment that provides a rationale for immune system-independent activation of inflamm-aging and associated diseases. There is also accumulating evidence that inflamm-aging or its components can directly accelerate the development of senescent cells and ultimately senescent cell burden in tissues in a likely vicious inflammatory loop. The present review is intended to describe the emerging senescence-based molecular etiology of inflamm-aging as well as the dynamic reciprocal interactions between inflamm-aging and cellular senescence. Therapeutic interventions concurrently targeting cellular senescence and inflamm-aging are discussed and limitations as well as research opportunities have been deliberated. An effort has been made to provide a rationale for integrating inflamm-aging with cellular senescence both as an underlying cause and therapeutic target for further studies.