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Brain oscillations in humans play a role in a wide range of cognitive processes, including navigation and memory. The oscillatory dynamics contributing to successful spatial memory recall in humans are not well-understood. To investigate specific oscillatory frequency bands during the recall process in human navigation, we recorded electroencephalographic (EEG) activity during a recall trial in healthy young adults (n = 15) following the learning of a goal location in a Virtual Water Maze task. We compared this to the activity during the same trial length, in a group of participants who did not learn a target location and navigated freely but were time-matched to the learning group (non-learning, n = 15). We compared relative power in Delta (2–4 Hz), Theta (5–7 Hz), Alpha (8–12 Hz), Beta (15–29 Hz), and Gamma (30–40 Hz) bands across the scalp. We found that delta and theta activity were greater during recall in our learning group, as opposed to our non-learning group. We also demonstrated clear suppression in the alpha band at posterior sites during memory-guided navigation compared to our non-learning group. Additionally, when goal-directed navigation switches to focused searching behavior, power becomes greater at the frontal region; with increases in the delta and theta bands reflecting this strategy change. There was also greater beta and gamma activity at posterior sites in our learning group. We discuss the results further in terms of the possible roles and functions of these oscillations during human navigation and hope this exploratory analysis can provide hypotheses for future spatial navigation and memory work.

BackgroundThe effects of SARS-CoV-2 have varied between significant waves of hospitalization.Research questionAre cardiovascular complications different among the first, delta and omicron waves of hospitalized COVID-19 pneumonia patients?Study design and methodsThis was a multi-centre retrospective study of patients hospitalized with SARS-CoV-2 pneumonia: 632 were hospitalized during the first wave (March–July 2020), 1013 during the delta wave (September 2020–March 2021), and 323 during the omicron wave (January 2022–July 2022). Patients were stratified by wave and occurrence of cardiovascular events.ResultsAmong all hospitalized patients with cardiovascular events, patients in the omicron wave were younger (62.4 ± 14 years) than patients in the first wave (67.4 ± 7.8 years) and the delta wave (66.9 ± 12.6 years) and had a higher proportion of non-Hispanic White people than in the first wave (78.6% vs. 61.7%). For COVID-19 patients who suffered from cardiovascular events, the omicron wave patients had significantly higher neutrophil/lymphocyte ratio, white blood cell and platelet counts when compared to the first wave. Omicron wave patients had significantly lower albumin and B-type natriuretic peptide levels (only 5.8% of the first wave and 14.6% of the delta wave) when compared to either the first wave or delta wave patients. In COVID-19 patients who suffered cardiovascular events during hospitalization, mortality rate in the omicron wave (26.8%) was significantly lower than the first wave (48.3%), time to mortality for non-survivors of COVID-19 patients who suffered cardiovascular events was significantly longer in the omicron wave (median 16 days) than in the first wave (median 10 days).ConclusionsYounger and white patients were affected with cardiovascular complications more often by the omicron variant. Despite higher neutrophil/lymphocyte ratio and WBC counts, the omicron patients with cardiovascular events showed lower heart injuries, lower mortality and longer time to mortality for non-survivors when compared to the first and delta waves.

BackgroundThis study is the extension of the COVAG study. We compared two RATs, the Panbio COVID-19 Ag Rapid Test (Abbott) and the SD Biosensor Q SARS-CoV-2 Rapid Antigen Test (Roche), against RT-PCR on the foil of new variants.MethodsWe included 888 all-comers at a diagnostic center between October 20, 2021, and March 18, 2022. RT-PCR-positive samples with a Ct value ≤32 were examined for SARS-CoV-2 variants.FindingsThe sensitivity of the Abbott-RAT and Roche-RAT were 65 and 67%, respectively. For both RATs, lower Ct values were significantly correlated with higher sensitivity. For samples with Ct values ≤25, the sensitivities of the Roche-RAT and of the Abbott-RAT were 96 and 95%, for Ct values 25–30 both were 19%, and for Ct values ≥30 they were 6 and 2%, respectively. The RATs had substantially higher sensitivities in symptomatic than asymptomatic participants (76, 77%, vs. 29, 31%, for Abbott-RAT, Roche-RAT, respectively) and in participants referred to testing by their primary care physician (84, 85%) compared to participants who sought testing due to referral by the health department (55, 58%) or a warning by the Corona-Warn-App (49, 49%). In persons with self-reported previous COVID-19 sensitivities were markedly lower than in patients without previous COVID-19: 27% vs. 75% for Roche-RAT and 27% vs. 73% for Abbott-RAT. We did not find significant correlation between vaccination status and sensitivity. The Omicron variant was detected with a sensitivity of 94 and 92%, the delta variant with a sensitivity of 80 and 80% for Abbott-RAT and Roche-RAT, respectively. This difference is attributable to the lower Ct values of the Omicron samples compared to the Delta samples. When adjusted for the Ct value, a multivariate logistic regression did not show a significant difference between Omicron and Delta. In terms of sensitivity, we found no significant difference between the wild-type and the Omicron and Delta variants, but a significantly lower sensitivity to the alpha variant compared to the other variants.The specificities were > 99% overall.

Background Transcranial alternating current stimulation (tACS) is a brain stimulation method for modulating ongoing endogenous oscillatory activity at specified frequency during sensory and cognitive processes. Given the overlap between event-related potentials (ERPs) and event-related oscillations (EROs), ERPs can be studied as putative biomarkers of the effects of tACS in the brain during cognitive/sensory task performance. Objective This preliminary study aimed to test the feasibility of individually tailored tACS based on individual P3 (latency and frequency) elicited during a cued premature response task. Thus, tACS frequency was individually tailored to match target-P3 ERO for each participant. Likewise, the target onset in the task was adjusted to match the tACS phase and target-P3 latency. Methods Twelve healthy volunteers underwent tACS in two separate sessions while performing a premature response task. Target-P3 latency and ERO were calculated in a baseline block during the first session to allow a posterior synchronization between the tACS and the endogenous oscillatory activity. The cue and target-P3 amplitudes, delta/theta ERO, and power spectral density (PSD) were evaluated pre and post-tACS blocks. Results Target-P3 amplitude significantly increased after activetACS, when compared to sham. Evoked-delta during cue-P3 was decreased after tACS. No effects were found for delta ERO during target-P3 nor for the PSD and behavioral outcomes. Conclusion The present findings highlight the possible effect of phase synchronization between individualized tACS parameters and endogenous oscillatory activity, which may result in an enhancement of the underlying process (i.e., an increase of target-P3). However, an unsuccessful synchronization between tACS and EEG activity might also result in a decrease in the evoked-delta activity during cue-P3. Further studies are needed to optimize the parameters of endogenous activity and tACS synchronization. The implications of the current results for future studies, including clinical studies, are further discussed since transcranial alternating current stimulation can be individually tailored based on endogenous event-related P3 to modulate responses.

Objectives: Different SARS-CoV-2 variants can differentially affect the prevalence of Post Covid-19 Condition (PCC). This prospective study assesses prevalence and severity of symptoms three months after an Omicron infection, compared to Delta, test-negative and population controls. This study also assesses symptomology after reinfection and breakthrough infections. Methods: After a positive SARS-CoV-2 test, cases were classified as Omicron or Delta based on ≥ 85% surveillance prevalence. Three months after enrolment, participants indicated point prevalence for 41 symptoms and severity, using validated questionnaires for four symptoms. PCC prevalence was estimated as the difference in prevalence of at least one significantly elevated symptom, identified by permutation test, in cases compared to population controls. Results: At three months follow-up, five symptoms and severe dyspnea were significantly elevated in Omicron cases (n = 4138) compared to test-negative (n = 1672) and population controls (n = 2762). PCC prevalence was 10·4% for Omicron cases and 17·7% for Delta cases (n = 6855). In Omicron cases, severe fatigue and dyspnea were more prevalent in reinfected than primary infected, while severity of symptoms did not significantly differ between cases with a booster or primary vaccination course. Conclusions: Prevalence of PCC is 41% lower after Omicron than Delta at three months. Reinfection seems associated with more severe long-term symptoms compared to first infection.

The paper deals with the poetics of the novels of the Peruvian writer Mario Vargas Llosa and the evolution of his style. To solve research problems, it is used the Delta method which is the most authoritative and reliable stylometric tool that allows you to compare texts based on the distribution of most frequent words. The work poses three questions: 1) Do Vargas Llosa's early total novels The Time of the Hero, The Green House, and Conversation in the Cathedral differ at the level of style from the later novels, forming a separate group, as the literary hypothesis claims? Answer: the hypothesis is confirmed; 2) Is it possible to divide the fifteen texts of the second period into smaller groups based on stylistic similarities? Answer: novels of the second period are divided into three large groups. Moreover, an interesting correlation is revealed: the novels grouped into separate groups have similarities not only at the level of style, but also at the level of themes, composition and narrative features; 3) Whether the “boom” is a stylistically isolated period in the poetics of its key authors? Answer: the novels written by Latin American authors during the boom period (1960–1970s) are not stylistically isolated: the authorial signal is stronger, and the case of Vargas Llosa with a clear differentiation of groups of novels is unique.

Abstract Background The COVID-19 pandemic has made devastating impacts on public health and global economy. While most people experience mild symptoms, it is highly transmissible and deadly in at-risk populations. Telemedicine has the potential to prevent hospitalization and provide remote care. Methods This retrospective study included 336 people with COVID-19, among which 141 (42%) and 195 (58%) were in Delta and Omicron dominant groups, respectively. Patients were confirmed to have COVID-19 by PCR or rapid test and were cared for via telemedicine. Severe cases were hospitalized for more intensive treatment. Results The majority of individuals recovered at home (97.02%), while 2.98% required hospitalization. All hospital admissions were in Delta dominant group. No deaths were reported. Delta dominant group was more likely to develop loss of taste and smell, decreased appetite and need longer treatment time than those in Omicron dominant group. Conclusions Telemedicine is a safe measure to provide at-home care for people with COVID-19 infections caused by both Delta and Omicron variants. Trial registration This study was approved by the Institutional Review Board Committee of University of Medicine and Pharmacy at Ho Chi Minh City (IRB No: 22115–DHYD).

Abstract Introduction The randomized, placebo-controlled, double-blind MOVe-OUT trial demonstrated molnupiravir (800 mg every 12 h for 5 days) as safe and effective for outpatient treatment of mild-to-moderate COVID-19, significantly reducing the risk of hospitalization/death in high-risk adults. At the time of that report, virologic assessments from the trial were partially incomplete as a result of their time-intensive nature. Here we present final results from all prespecified virology endpoints in MOVe-OUT based on the full trial dataset. Methods Nasopharyngeal swabs were collected at baseline (day 1, prior to first dose) and days 3, 5 (end-of-treatment visit), 10, 15, and 29. From these samples, change from baseline in SARS-CoV-2 RNA titers (determined by quantitative PCR), detection of infectious SARS-CoV-2 (by plaque assay), and SARS-CoV-2 viral error induction (determined by whole genome next-generation sequencing) were assessed as exploratory endpoints. Results Molnupiravir was associated with greater mean reductions from baseline in SARS-CoV-2 RNA than placebo (including 50% relative reduction at end-of-treatment) through day 10. Among participants with infectious virus detected at baseline (n = 96 molnupiravir, n = 97 placebo) and evaluable post-baseline samples, no molnupiravir-treated participant had infectious SARS-CoV-2 by day 3, whereas infectious virus was recovered from 21% of placebo-arm participants on day 3 and 2% at end-of-treatment. Consistent with molnupiravir’s mechanism of action, sequence analysis demonstrated that molnupiravir was associated with an increased number of low-frequency transition errors randomly distributed across the SARS-CoV-2 RNA genome compared with placebo (median 143.5 molnupiravir, 15 placebo), while transversion errors were infrequent overall (median 2 in both arms). Outcomes were consistent regardless of baseline SARS-CoV-2 clade, presence of SARS-CoV-2-specific immune response, or viral load. Conclusions A 5-day course of orally administered molnupiravir demonstrated a consistently greater virologic effect than placebo, including rapidly eliminating infectious SARS-CoV-2, in high-risk outpatients with mild-to-moderate COVID-19. Trial Registration ClinicalTrials.gov, NCT04575597.

Abstract Background Ubiquitylation (ubi) of the intracellular domain of the Notch ligand Delta (Dl) by the E3 ligases Neuralized (Neur) and Mindbomb1 (Mib1) on lysines (Ks) is thought to be essential for the its signalling activity. Nevertheless, we have previously shown that DlK2R-HA, a Dl variant where all Ks in its intracellular domain (ICD) are replaced by the structurally similar arginine (R), still possess weak activity if over-expressed. This suggests that ubi is not absolutely required for Dl signalling. However, it is not known whether the residual activity of DlK2R-HA is an effect of over-expression and, if not, whether DlK2R can provide sufficient activity for the whole development of Drosophila. Results To clarify these issues, we generated and analysed Dl attP -DlK2R-HA, a knock-in allele into the Dl locus. Our analysis of this allele reveals that the sole presence of one copy of Dl attP -DlK2R-HA can provide sufficient activity for completion of development. It further indicates that while ubi is required for the full activity of Dl in Mib1-dependent processes, it is not essential for Neur-controlled neural development. We identify three modes of Dl signalling that are either dependent or independent of ubi. Importantly, all modes depend on the presence of the endocytic adapter Epsin. During activation of Dl, direct binding of Epsin appears not to be an essential requirement. In addition, our analysis further reveals that the Ks are required to tune down the cis-inhibitory interaction of Dl with Notch. Conclusions Our results indicate that Dl can activate the Notch pathway without ubi of its ICD. It signals via three modes. Ubi is specifically required for the Mib1-dependent processes and the adjustment of cis-inhibition. In contrast to Mib1, Neur can efficiently activate Dl without ubi. Neur probably acts as an endocytic co-adapter in addition to its role as E3 ligase. Endocytosis, regulated in a ubi-dependent or ubi-independent manner is required for signalling and also suppression of cis-inhibition. The findings clarify the role of ubi of the ligands during Notch signalling.

The gastrointestinal (GI) tract may be a significant entrance or interaction site for SARS-CoV-2; therefore, the gut mucosal immune system participates in virus interaction as a first-line physical and immunological defense, leading to GI involvement and symptoms. This review focuses on the GI symptoms associated with SARS-CoV-2 infection while providing specific results on variant-specific signs and syndromes related to coronavirus disease 2019 (COVID-19). The pattern of symptoms changed during the virus evolution, since the data provided a current and thorough picture of the symptoms experienced by SARS-CoV-2 infected people, and variations in symptom patterns occurred as the Alpha, Delta, and Omicron variants have spread. Since the beginning of the pandemic, GI symptoms have been linked to SARS-CoV-2 infections, even though most infected people do not report them. For example, diarrhea (28.2%) was the most frequently reported GI symptom in the early phase of the pandemic. The most observed GI tract symptoms during COVID-19 were anorexia (loss of appetite), nausea, vomiting, diarrhea, and abdominal pain, usually in at least one-third of the patients. Mesenteric ischemia and GI bleeding were less observed but more severe. While GI symptoms are not associated with increased mortality, they complicate the disease, increase the duration of the illness, and result in worse outcomes. Nevertheless, it is accepted that symptoms between variants differ significantly, i.e., the Omicron variant causes milder COVID-19 than the Delta. Still, the rate of GI symptoms has declined in the following variant-dominated phases of the pandemic (Alpha: 19.4%, Delta: 17.9%, Omicron: 13.8%), which was also demonstrated for other GI signs associated with COVID-19.

This study evaluates the effectiveness of the previously proposed Standard Penetration Test (SPT) N and shear wave velocity (VS) models in relation to the geological attributes of the Busan region, situated in the southeastern part of the Korean peninsula. The multiple empirical N-VS models, which used datasets collected from different regions in South Korea, resulted in distinct N-VS trends across models. To validate the predictive capabilities of each model, this study gathered boring logs containing SPT N and VS measurements within the Busan region, followed by a thorough residual analysis. The Busan area encompasses a delta region to the west and erosion basins within the mountains and hills to the east. Despite the relatively confined geographical scope, we found that models developed using data from fill areas exhibit superior performance for the delta region (western Busan), while models constructed from datasets within erosion basins perform better for the erosion basin region (eastern Busan). This comparative examination supports the dependence of the N-VS model on geologic attributes and offers the valuable insight that N-VS models developed with analogous geological attributes should be employed when estimating VS from SPT N values.

Abstract Background Persistent SARS-CoV-2 infection in immunocompromised hosts is thought to contribute to viral evolution by facilitating long-term natural selection and viral recombination in cases of viral co-infection or superinfection. However, there are limited data on the longitudinal intra-host population dynamics of SARS-CoV-2 co-infection/superinfection, especially in pediatric populations. Here, we report a case of Delta-Omicron superinfection in a hospitalized, immunocompromised pediatric patient. Methods We conducted Illumina whole genome sequencing (WGS) for longitudinal specimens to investigate intra-host dynamics of SARS-CoV-2 strains. Topoisomerase PCR cloning of Spike open-reading frame and Sanger sequencing of samples was performed for four specimens to validate the findings. Analysis of publicly available SARS-CoV-2 sequence data was performed to investigate the co-circulation and persistence of SARS-CoV-2 variants. Results Results of WGS indicate the patient was initially infected with the SARS-CoV-2 Delta variant before developing a SARS-CoV-2 Omicron variant superinfection, which became predominant. Shortly thereafter, viral loads decreased below the level of detection before resurgence of the original Delta variant with no residual trace of Omicron. After 54 days of persistent infection, the patient tested negative for SARS-CoV-2 but ultimately succumbed to a COVID-19-related death. Despite protracted treatment with remdesivir, no antiviral resistance mutations emerged. These results indicate a unique case of persistent SARS-CoV-2 infection with the Delta variant interposed by a transient superinfection with the Omicron variant. Analysis of publicly available sequence data suggests the persistence and ongoing evolution of Delta subvariants despite the global predominance of Omicron, potentially indicative of continued transmission in an unknown population or niche. Conclusion A better understanding of SARS-CoV-2 intra-host population dynamics, persistence, and evolution during co-infections and/or superinfections will be required to continue optimizing patient care and to better predict the emergence of new variants of concern.

Since the beginning of the COVID-19 pandemic, SARS-CoV-2 has demonstrated its ability to rapidly and continuously evolve, leading to the emergence of thousands of different sequence variants, many with distinctive phenotypic properties. Fortunately, the broad application of next generation sequencing (NGS) across the globe has produced a wealth of SARS-CoV-2 genome sequences, offering a comprehensive picture of how this virus is evolving so that accurate diagnostics, reliable therapeutics, and prophylactic vaccines against COVID-19 can be developed and maintained. The millions of SARS-CoV-2 sequences deposited into genomic sequencing databases, including GenBank, BV-BRC, and GISAID, are annotated with the dates and geographic locations of sample collection, and can be aligned to and compared with the Wuhan-Hu-1 reference genome to extract their constellation of nucleotide and amino acid substitutions. By aggregating these data into concise datasets, the spread of variants through space and time can be assessed. Variant tracking efforts have initially focused on the Spike protein due to its critical role in viral tropism and antibody neutralization. To identify emerging variants of concern as early as possible, we developed a computational pipeline to process the genomic data and assign risk scores based on both epidemiological and functional parameters. Epidemiological dynamics are used to identify variants exhibiting substantial growth over time and spread across geographical regions. Experimental data that quantify Spike protein regions targeted by adaptive immunity and critical for other virus characteristics are used to predict variants with consequential immunogenic and pathogenic impacts. The growth assessment and functional impact scores are combined to produce a Composite Score for any set of Spike substitutions detected. With this systematic method to routinely score and rank emerging variants, we have established an approach to identify threatening variants early and prioritize them for experimental evaluation.

Opioid tolerance is well-described physiologically but its mechanistic basis remains incompletely understood. An important site of opioid action in vivo is the presynaptic terminal, where opioids inhibit transmitter release. This response characteristically resists desensitization over minutes yet becomes gradually tolerant over hours, and how this is possible remains unknown. Here, we delineate a cellular mechanism underlying this longer-term form of opioid tolerance in cultured rat medium spiny neurons. Our results support a model in which presynaptic tolerance is mediated by a gradual depletion of cognate receptors from the axon surface through iterative rounds of receptor endocytosis and recycling. For the μ-opioid receptor (MOR), we show that the agonist-induced endocytic process which initiates iterative receptor cycling requires GRK2/3-mediated phosphorylation of the receptor's cytoplasmic tail, and that partial or biased agonist drugs with reduced ability to drive phosphorylation-dependent endocytosis in terminals produce correspondingly less presynaptic tolerance. We then show that the δ-opioid receptor (DOR) conforms to the same general paradigm except that presynaptic endocytosis of DOR, in contrast to MOR, does not require phosphorylation of the receptor's cytoplasmic tail. Further, we show that DOR recycles less efficiently than MOR in axons and, consistent with this, that DOR tolerance develops more strongly. Together, these results delineate a cellular basis for the development of presynaptic tolerance to opioids and describe a methodology useful for investigating presynaptic neuromodulation more broadly.

Delta opioid receptor (DOR) agonists alleviate nociceptive behaviors in various chronic pain models, including neuropathic pain, while having minimal effect on sensory thresholds in the absence of injury. The mechanisms underlying nerve injury-induced enhancement of DOR function are unclear. We used a peripheral nerve injury (PNI) model of neuropathic pain to assess changes in the function and localization of DORs in mice and rats. Intrathecal administration of DOR agonists reversed mechanical allodynia and thermal hyperalgesia. The dose-dependent thermal antinociceptive effects of DOR agonists were shifted to the left in PNI rats. Administration of DOR agonists produced a conditioned place preference in PNI, but not in sham, animals, whereas the DOR antagonist naltrindole produced a place aversion in PNI, but not in sham, mice, suggesting the engagement of endogenous DOR activity in suppressing pain associated with the injury. GTPγS autoradiography revealed an increase in DOR function in the dorsal spinal cord, ipsilateral to PNI. Immunogold electron microscopy and in vivo fluorescent agonist assays were used to assess changes in the ultrastructural localization of DORs in the spinal dorsal horn. In shams, DORs were primarily localized within intracellular compartments. PNI significantly increased the cell surface expression of DORs within lamina IV-V dendritic profiles. Using neonatal capsaicin treatment, we identified that DOR agonist-induced thermal antinociception was mediated via receptors expressed on primary afferent sensory neurons but did not alter mechanical thresholds. These data reveal that the regulation of DORs following PNI and suggest the importance of endogenous activation of DORs in regulating chronic pain states.

Evolutionary analysis using viral sequence data can elucidate the epidemiology of transmission. Using publicly available SARS-CoV-2 sequence and epidemiological data, we developed discrete phylogeographic models to interrogate the emergence and dispersal of the Delta and Omicron variants in 2021 between and across California and Mexico. External introductions of Delta and Omicron in the region peaked in early July (2021-07-10 [95% CI: 2021-04-20, 2021-11-01]) and mid-December (2021-12-15 [95% CI: 2021-11-14, 2022-01-09]), respectively, 3 months and 2 weeks after first detection. These repeated introductions coincided with domestic migration events with no evidence of a unique transmission hub. The spread of Omicron was most consistent with gravity centric patterns within Mexico. While cross-border events accounted for only 5.1% [95% CI: 4.3-6] of all Delta migration events, they accounted for 20.6% [95% CI: 12.4-29] of Omicron movements, paralleling the increase in international travel observed in late 2021. Our investigations of the Delta and Omicron epidemics in the California/Mexico region illustrate the complex interplay and the multiplicity of viral and structural factors that need to be considered to limit viral spread, even as vaccination is reducing disease burden. Understanding viral transmission patterns may help intra-governmental responses to viral epidemics.

BackgroundWe examined school reopening policies amidst ongoing transmission of the highly transmissible Delta variant, accounting for vaccination among individuals ≥12 years.MethodsWe collected data on social contacts among school-aged children in the California Bay Area and developed an individual-based transmission model to simulate transmission of the Delta variant of SARS-CoV-2 in schools. We evaluated the additional infections in students and teachers/staff resulting over a 128-day semester from in-school instruction compared to remote instruction when various NPIs (mask use, cohorts, and weekly testing of students/teachers) were implemented, across various community-wide vaccination coverages (50%, 60%, 70%), and student (≥12 years) and teacher/staff vaccination coverages (50% - 95%).FindingsAt 70% vaccination coverage, universal masking reduced infections by >57% among students. Masking plus 70% vaccination coverage enabled achievement of

Functional interactions between G protein-coupled receptors are poised to enhance neuronal sensitivity to neuromodulators and therapeutic drugs. Mu and delta opioid receptors (MORs and DORs) can interact when overexpressed in the same cells, but whether co-expression of endogenous MORs and DORs in neurons leads to functional interactions is unclear. Here, in mice, we show that both MORs and DORs inhibit parvalbumin-expressing basket cells (PV-BCs) in hippocampal CA1 through partially occlusive signaling pathways that terminate on somato-dendritic potassium channels and presynaptic calcium channels. Using photoactivatable opioid neuropeptides, we find that DORs dominate the response to enkephalin in terms of both ligand sensitivity and kinetics, which may be due to relatively low expression levels of MOR. Opioid-activated potassium channels do not show heterologous desensitization, indicating that MORs and DORs signal independently. In a direct test for heteromeric functional interactions, the DOR antagonist TIPP-Psi does not alter the kinetics or potency of either the potassium channel or synaptic responses to photorelease of the MOR agonist [d-Ala2, NMe-Phe4, Gly-ol5]enkephalin (DAMGO). Thus, aside from largely redundant and convergent signaling, MORs and DORs do not functionally interact in PV-BCs in a way that impacts somato-dendritic potassium currents or synaptic transmission. These findings imply that cross-talk between MORs and DORs, either in the form of physical interactions or synergistic intracellular signaling, is not a preordained outcome of co-expression in neurons.

Objective: To analyze and compare chest computed tomography (CT) findings and evolutionary characteristics of different strains of novel corona virus pneumonia and to explore the correlation of CT findings and strain characteristics with clinical outcomes. Methods: Chest CT images of 75 cases of the original strain, 130 cases of the Delta variant, and 562 cases of the Omicron variant from the Inner Mongolia Autonomous Region, were collected and sorted. The CT manifestations and their changes for different strains were analyzed and compared. Results: The proportion of patients with mild disease in the Omicron variant group (499 cases, 88.79%) was significantly higher than that in the original strain (9 cases, 12.00%) and Delta variant groups (47 cases, 36.15%). Compared to the original strain group, the Delta variant group showed higher incidences of mild cases% (47 cases, 36.15% vs. 9 cases, 12.00%) and lower incidences of severe cases (14 cases, 16.87% vs. 19 cases, 28.79%). A total of 96.97% (64 cases) of the original strain group, 93.98% (78 cases) of the Delta variant group, and 98.41% (62 cases) of the Omicron variant group showed ground-glass opacities, which were the main manifestations on the first CT scan. There was no statistically significant difference among the three groups. In terms of morphology and distribution of ground-glass opacity, 12 cases (19.05%) of the Omicron group showed acinular nodule ground-glass opacity, which was significantly higher than that shown by the original strain group (2 cases, 3.03%) and the Delta variant group (3 cases, 3.61%). The lesions in the three groups were mainly distributed along the subpleural lung regions. However, the Omicron variant group had a higher distribution ratio along the bronchial vascular bundle than the original strain and Delta variant groups. In terms of concomitant signs, concomitant consolidation and cable proportion were significantly lower on the first CT image. The proportions of concurrent consolidation in the original strain, Delta variant, and Omicron variant groups were 3.03% (2 cases), 6.02% (5 cases), and 5.00% (1 case), respectively. The proportions of accompanying cables in the original strain, Delta variant, and Omicron variant groups were 12.12% (8 cases), 15.66% (13 cases), and 20.00% (4 cases), respectively. The imaging findings of the lesions in the original strain and Delta variant groups changed over the course of the disease. In the original strain group, 39.39% (26 cases) had realistic changes based on the original ground-glass opacity and 53.03% (35 cases) had a cord based on the original ground-glass opacity. This proportion was significantly higher than the proportion of consolidation and cord based on the first CT. In the Delta variant group, 44.58% (37 cases) of patients showed inflammatory consolidation based on the original ground-glass opacity and 61.45% (51 cases) of patients showed a cord based on the original ground-glass opacity. In the Omicron variant group, 34.38% (11 cases) had inflammatory consolidation based on the original ground-glass opacity and 71.88% (23 cases) had cord based on the original ground-glass opacity, both of which were significantly higher than the proportions of primary inflammatory consolidation and cord. The median number of days from apparent absorption to onset in the original strain, Delta variant and Omicron variant groups were 16 days, 16 days, and 9 days, respectively. Conclusions: The dynamic changes in chest CT findings of cases infected with different strains of COVID-19 can reflect the evolution of lesions with the clinical course of the disease. This prediction has clinical application value in determining the course of COVID-19 and disease management.

Background. Constant assessment of the dynamics of the main characteristics of the epidemic process is the basic function of epidemiological surveillance of infectious diseases. The search for factors that determine changes in the characteristics of the epidemic process makes it possible to develop timely management decisions and reduce the risk of an increase in the scale of the pandemic. Moscow is the main centre of attraction for the population of other Russian regions with the most complex structure of social links and the highest population density. The purpose of the study is to identify factors that potentially determine the trends of observed changes using a molecular epidemiological analysis of the main characteristics of the epidemic process of a new coronavirus infection (COVID-19). Materials and methods. For the analysis, the data of Russian national genome sequence database of SARS-CoV-2 virus (VGARus) were combined with information on morbidity and mortality presented at the official internet resources стопкоронавирус.рф and Yandex DataLens, the dynamics of vaccination, COVID-19 disease incidence and hospitalization from the portal Gogov.ru. A multicentre retrospective observational epidemiological study was conducted to examine the sex and age structure of hospitalised patients. Anonymized case histories of patients with COVID-19 collected at different follow-up periods in the institutions of Moscow (41,561 cases) served as a source of data for the sex and age structure analysis. Results. We identified 11 periods with significantly different complex epidemiological characteristics. A decrease in the incidence among young people of working age during the period of restrictive measures was revealed. In 3 out of 11 worsening of the epidemic situation coincided with the beginning of the circulation of a new genetic variant of the pathogen COVID-19 (variants Wuhan, Delta, Omicron). A decrease in the incidence in the summer period was noted, regardless of the circulating genetic variants. Conclusion. A significant part of the observed dynamics of the characteristics of the epidemic process in Moscow can be explained by the properties of the pathogen, seasonality and dynamics of magnitude of the herd immunity. The influence of the dynamics of the herd immunity indicators on the course of the epidemic process is to be studied further.

Objective: To quantitatively analyze and compare the chest computed tomography (CT) imaging features of patients infected with delta and omicron variants of COVID-19 using artificial intelligence (AI). Method: The clinical data of 294 patients infected with the novel coronavirus delta variant diagnosed at the Fourth Hospital of Inner Mongolia Autonomous Region from February 20, 2022 to April 19, 2022 and 222 patients infected with the omicron variant diagnosed at the People's Hospital of Inner Mongolia Autonomous Region from December 1, 2022 to December 30, 2022 were retrospectively analyzed. CT imaging data were analyzed and divided into delta and omicron groups. Quantitative calculation was performed using deductive predictive pulmonary infection auxiliary diagnostic software, and CT imaging signs and quantitative CT data between groups were compared and analyzed. Results: No statistical significance was noted between the delta and omicron groups in imaging signs, such as ground-glass opacity, ground-glass nodule, cord-like lesion, consolidation, paving stone sign, thickened interlobular septum, and thickened vessels in the lesion. The distribution of lesions along the bronchial vascular bundle was more likely in the omicron than in the delta group. The total lung lesion volume, volume proportion, right middle lobe lesion volume, volume proportion, right inferior lobe lesion volume, and volume proportion in the delta group were higher than those in the omicron group. The proportions of lesions in the delta group in −570 ~ −470 HU, −470 ~ −370 HU, −370 ~ −270 HU, and −270 ~ −170 HU volumes were higher than those in the omicron group. Conclusion: In the early stage of COVID-19, the volume of CT lesions in the patients infected with the delta variant was higher than that in the omicron group, and the distribution of lesions in the omicron group was more likely to have atypical distribution along the bronchial vascular bundle than that in the delta group. The volume and volume proportion of the pneumonia-infected area in patients with COVID-19 were quantitatively evaluated using the AI-assisted diagnosis system for COVID-19 to provide objective reference data for patients' condition assessment.

The Danube Delta is a unique natural object influenced by natural and human factors. According to the available observation and remote sensing data, the features of the water temperature in the Danube Delta, as well as in nearby lakes and the adjacent area of the Black Sea, have been determined. The water temperature in the Danube River was found to be much higher than the air temperature, especially in autumn. Generally, it is also higher than in nearby lakes and the adjacent part of the Black Sea. During 1961–2021 the mean annual water temperature in the Danube Delta increased significantly, especially during the last three decades. It has been determined that water temperature is affected not only by air temperature, but also by water discharge and wind. With a large water discharge the mixing of water is intensified and it causes the decrease of surface water temperature during the main part of the year with the exception of the coldest months. The greatest impact of water discharge on the water temperature is observed in June. The cool breeze in summer months also has some effect on the surface water temperature of the river near the seashore. The results show the potential of remote sensing to track the changes of water temperature along the river and to identify the shallow sections.

Objectives: The Omicron BA.2 variant is probably the main epidemic strain worldwide at present. Comparing the epidemiological characteristics, transmissibility, and influencing factors of SARS-CoV-2, the results obtained in this paper will help to provide theoretical support for disease control. Methods: This study was a historical information analysis, using the R programming language and SPSS 24.0 for statistical analysis. The Geoda and Arc GIS were used for spatial autocorrelation analysis. Results: Local spatial autocorrelations of the incidence rate were observed in Delta and Omicron BA.1 outbreaks, whereas Omicron BA.2 outbreaks showed a random distribution in incidence rate. The time-dependent reproduction number of Delta, Omicron BA.1, and Omicron BA.2 were 3.21, 4.29, and 2.96, respectively, and correspondingly, the mean serial interval were 4.29 days (95% confidence interval [CI]: 0.37-8.21), 3.84 days (95% CI: 0-8.37), and 2.77 days (95% CI: 0-5.83). The asymptomatic infection rate of cases in Delta, Omicron BA.1, and Omicron BA.2 outbreaks were 21.71%, 6.25%, and 4.35%, respectively. Conclusion: The Omicron BA.2 variant had the greatest serial interval, transmissibility, and transmission speed, followed by BA.1, and then Delta. Compared with Delta and Omicron BA.1 variants, the Omicron BA.2 variant may be less pathogenic and more difficult to control than Omicron BA.1 and Delta.

La ciudad de Rosario, provincia de Santa Fe, Argentina, surge y se desarrolla junto a la ribera occidental del río Paraná y, a pesar de la cercanía con la orilla oriental ubicada a 60 km de distancia, en jurisdicción de Entre Ríos, hasta el siglo XXI la relación entre ambas es escasa y las transformaciones costeras disímiles. Sin embargo, son remotos y heterogéneos los imaginarios interesados en su conexión y, fundamentalmente, en la generación de vínculos con el espacio insular intermedio. La presente investigación se propone reconocer aquellas representaciones que, a lo largo de más de un siglo, tendieron a enlazar la ciudad de Rosario, su frente costero, el vasto ámbito isleño y la margen oriental entrerriana, a fin de comprender el rol que las mismas cumplieron en la constitución de imaginarios sociales, diversos y móviles, que se tradujeron en cada momento histórico en proyectos de apropiación del territorio fluvial.

Background: Modern response to pandemics, critical for effective public health measures, is shaped by the availability and integration of diverse epidemiological outbreak data. Tracking variants of concern (VOC) is integral to understanding the evolution of SARS-CoV-2 in space and time, both at the local level and global context. This potentially generates actionable information when integrated with epidemiological outbreak data. Methods: A city-wide network of researchers, clinicians, and pathology diagnostic laboratories was formed for genome surveillance of COVID-19 in Pune, India. The genomic landscapes of 10,496 sequenced samples of SARS-CoV-2 driving peaks of infection in Pune between December-2020 to March-2022, were determined. As a modern response to the pandemic, a “band of five” outbreak data analytics approach was used. This integrated the genomic data (Band 1) of the virus through molecular phylogenetics with key outbreak data including sample collection dates and case numbers (Band 2), demographics like age and gender (Band 3–4), and geospatial mapping (Band 5). Results: The transmission dynamics of VOCs in 10,496 sequenced samples identified B.1.617.2 (Delta) and BA(x) (Omicron formerly known as B.1.1.529) variants as drivers of the second and third peaks of infection in Pune. Spike Protein mutational profiling during pre and post-Omicron VOCs indicated differential rank ordering of high-frequency mutations in specific domains that increased the charge and binding properties of the protein. Time-resolved phylogenetic analysis of Omicron sub-lineages identified a highly divergent BA.1 from Pune in addition to recombinant X lineages, XZ, XQ, and XM. Conclusions: The band of five outbreak data analytics approach, which integrates five different types of data, highlights the importance of a strong surveillance system with high-quality meta-data for understanding the spatiotemporal evolution of the SARS-CoV-2 genome in Pune. These findings have important implications for pandemic preparedness and could be critical tools for understanding and responding to future outbreaks.

Objectives: COVID-19 was severe in the Delta variant-dominated epidemic wave (fifth wave) in Japan. The clinical characteristics and effectiveness of COVID-19 vaccination are not fully understood in the Omicron variant-dominated wave (sixth and seventh waves), especially in hospitalized patients. We investigated the relationship between vaccination and disease severity in the Omicron-dominated wave and compared these variant-dominated waves. Methods: The nationwide COVID-19 database (Japan COVID-19 Task Force) was used to compare clinical characteristics and critical outcomes in patients hospitalized with Delta (fifth, N = 735) vs Omicron-dominated waves (sixth, N = 495; seventh, N = 128). Results: Patients in the sixth and seventh waves had a lower incidence of critical outcomes and respiratory outcomes, and a higher incidence of bacterial infection, although the mortality rate did not differ significantly between waves. In the sixth and seventh waves, 138 (27.9%) and 29 (22.7%) patients with COVID-19 were unvaccinated, respectively. Multivariable analysis adjusted with previously reported factors revealed that the proportion of (1) critical outcomes and (2) respiratory outcomes decreased in a frequency-dependent manner. Thus, (1) (the number of vaccinations): 1-2 times: adjusted odds ratio (aOR) 0.37 (95% confidence interval [CI]; 0.20-0.69); 3-4 times: aOR 0.25 (95% CI; 0.11-0.58); and (2) 1-2 times: aOR 0.43 (95% CI; 0.27-0.66); 3-4 times: aOR 0.36 (95% CI; 0.21-0.60). Conclusions: Patients hospitalized with COVID-19 with Omicron infections showed a lower incidence of critical outcomes than those with Delta infections, and COVID-19 vaccination may contribute to preventing respiratory failure.

Within-host infection dynamics of Omicron dramatically differs from previous variants of SARS-CoV-2. However, little is still known about which parameters of virus-cell interplay contribute to the observed attenuated replication and pathogenicity of Omicron. Mathematical models, often expressed as systems of differential equations, are frequently employed to study the infection dynamics of various viruses. Adopting such models for results of in vitro experiments can be beneficial in a number of aspects, such as model simplification (e.g., the absence of adaptive immune response and innate immunity cells), better measurement accuracy, and the possibility to measure additional data types in comparison with in vivo case. In this study, we consider a refinement of our previously developed and validated model based on a system of integro-differential equations. We fit the model to the experimental data of Omicron and Delta infections in Caco-2 (human intestinal epithelium model) and Calu-3 (lung epithelium model) cell lines. The data include known information on initial conditions, infectious virus titers, and intracellular viral RNA measurements at several time points post-infection. The model accurately explains the experimental data for both variants in both cell lines using only three variant- and cell-line-specific parameters. Namely, the cell entry rate is significantly lower for Omicron, and Omicron triggers a stronger cytokine production rate (i.e., innate immune response) in infected cells, ultimately making uninfected cells resistant to the virus. Notably, differences in only a single parameter (e.g., cell entry rate) are insufficient to obtain a reliable model fit for the experimental data.

Abstract Objectives Existing evidence suggests a link between ABO blood type and severe outcomes in coronavirus disease 2019 (COVID‐19). We aimed to assess the relationship between blood type and severe outcomes across variant strains throughout the pandemic. Methods This was a multicenter retrospective observational cohort analysis from a large health system in southeastern Michigan using electronic medical records to evaluate emergency encounters, hospitalization, and severe outcomes in COVID‐19 based on ABO blood type. Consecutive adult patients presenting to the emergency department with a primary diagnosis of COVID‐19 (U07.1) from March 1, 2020 through December 31, 2022 were assessed. Patients who presented during three distinct time intervals that coincided with Alpha, Delta, and Omicron variant predominance were included in the analysis. Exclusions included no record of ABO blood type, positive PCR COVID‐19 test within the preceding 28 days, and if transferred from out of the health system. Severe outcomes were inclusive of intensive care unit admission, mechanical ventilation, or death, which, as a composite, represented our primary outcome. Secondary outcomes were hospital admission and length of stay. A logistic regression model was employed to test the association between ABO blood type and severe outcome, adjusting for age, sex, race, vaccination status, Elixhauser comorbidity indices, and the dominant variant time period in which the encounter occurred. Results Of the 33,796 COVID‐19 encounters, 9416 met inclusion criteria; 4071 (43.2%) were type O, 3417 (36.3%) were type A, 459 (4.9%) were type AB, and 1469 (15.6%) were type B blood. Note that 66.4% of the cohort was female (p = 0.18). The proportion of composite severe disease among the four blood types was similar and ranged between 8.6% and 8.9% (p = 0.98). Note that 53.0% of type A blood patients required hospital admission, compared to 51.9%, 50.4%, and 48.1% of type AB, B, and O blood, respectively (p

BackgroundDespite decreasing COVID-19 disease severity during the Omicron waves, a proportion of patients still require hospitalization and intensive care.ObjectiveTo compare demographic characteristics, comorbidities, vaccination status, and previous infections in patients hospitalized for community-associated COVID-19 (CAC) in predominantly Delta, Omicron BA.1 and BA.4/5 SARS-CoV-2 waves.MethodsData were extracted from three national databases—the National COVID-19 Database, National Vaccination Registry and National Registry of Hospitalizations.ResultsAmong the hospitalized CAC patients analyzed in this study, 5,512 were infected with Delta, 1,120 with Omicron BA.1, and 1,143 with the Omicron BA.4/5 variant. The age and sex structure changed from Delta to BA.4/5, with the proportion of women (9.5% increase), children and adolescents (10.4% increase), and octa- and nonagenarians increasing significantly (24.5% increase). Significantly more patients had comorbidities (measured by the Charlson Comorbidity Index), 30.3% in Delta and 43% in BA.4/5 period. The need for non-invasive ventilatory support (NiVS), ICU admission, mechanical ventilation (MV), and in-hospital mortality (IHM) decreased from Delta to Omicron BA.4/5 period for 12.6, 13.5, 11.5, and 6.3%, respectively. Multivariate analysis revealed significantly lower odds for ICU admission (OR 0.68, CI 0.54–0.84, p < 0.001) and IHM (OR 0.74, CI 0.58–0.93, p = 0.011) during the Delta period in patients who had been fully vaccinated or boosted with a COVID-19 vaccine within the previous 6 months. In the BA.1 variant period, patients who had less than 6 months elapsed between the last vaccine dose and SARS-CoV-2 positivity had lower odds for MV (OR 0.38, CI 0.18-0.72, p = 0.005) and IHM (OR 0.56, CI 0.37- 0.83, p = 0.005), but not for NIVS or ICU admission.ConclusionThe likelihood of developing severe CAC in hospitalized patients was higher in those with the Delta and Omicron BA.1 variant compared to BA.4/5.

The aim: of our study was to identify and characterize the SARS-CoV-2 variants in COVID-19 patients’ samples collected from different regions of Ukraine to determine the relationship between SARS-CoV-2 phylogenetics and COVID-19 epidemiology. Patients and methods: Samples were collected from COVID-19 patients during 2021 and the beginning of 2022 (401 patients). The SARS-CoV-2 genotyping was performed by parallel whole genome sequencing. Results: The obtained SARS-CoV-2 genotypes showed that three waves of the COVID-19 pandemic in Ukraine were represented by three main variants of concern (VOC), named Alpha, Delta and Omicron; each VOC successfully replaced the earlier variant. The VOC Alpha strain was presented by one B.1.1.7 lineage, while VOC Delta showed a spectrum of 25 lineages that had different prevalence in 19 investigated regions of Ukraine. The VOC Omicron in the first half of the pandemic was represented by 13 lines that belonged to two different clades representing B.1 and B.2 Omicron strains. Each of the three epidemic waves (VOC Alpha, Delta, and Omicron) demonstrated their own course of disease, associated with genetic changes in the SARS-CoV-2 genome. The observed epidemiological features are associated with the genetic characteristics of the different VOCs, such as point mutations, deletions and insertions in the viral genome. A phylogenetic and transmission analysis showed the different mutation rates; there were multiple virus sources with a limited distribution between regions. Conclusions: The evolution of SARS-CoV-2 virus and high levels of morbidity due to COVID-19 are still registered in the world. Observed multiple virus sourses with the limited distribution between regions indicates the high efficiency of the anti-epidemic policy pursued by the Ministry of Health of Ukraine to prevent the spread of the epidemic, despite the low level of vaccination of the Ukrainian population.

The execution of a Notch signal at the plasma membrane relies on the mechanical force exerted onto Notch by its ligand. It has been appreciated that the DSL ligands need to collaborate with a ubiquitin (Ub) ligase, either Neuralized or Mindbomb1, in order to exert this pulling force, but the role of ubiquitylation per se is uncertain. Regarding the Delta–Neur pair, it is documented that neither the Neur catalytic domain nor the Delta intracellular lysines (putative Ub acceptors) are needed for activity. Here, we present a dissection of the Delta activity using the Delta–Notch-dependent expression of Hey in newborn Drosophila neurons as a sensitive in vivo assay. We show that the Delta–Neur interaction per se, rather than ubiquitylation, is needed for activity, pointing to the existence of a Delta–Neur signaling complex. The Neur catalytic domain, although not strictly needed, greatly improves Delta–Neur complex functionality when the Delta lysines are mutated, suggesting that the ubiquitylation of some component of the complex, other than Delta, can enhance signaling. Since Hey expression is sensitive to the perturbation of endocytosis, we propose that the Delta–Neur complex triggers a force-generating endocytosis event that activates Notch in the adjacent cell. [ABSTRACT FROM AUTHOR]

Objective: Mutations in coronavirus 2 [severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)] are a considerable issue. It could affect the infectivity and outcome of coronavirus disease-2019 (COVID-19) infection. In this prospective study, we compared the characteristics and outcomes of the main SARS-CoV-2 variants in our non-intensive care unit pandemic service inpatients. Methods: In this study, 2,090 COVID-19 inpatients were included. The numbers of patients with alpha (group 1), delta (group 2), and omicron (group 3) variants were 701, 699, and 690, respectively. Results: The median age of group 3 patients was significantly higher than that of the others, and the female/male ratio and presence of diabetes mellitus of group 1 patients were significantly lower than those of the others (p<0.05, both). Regarding the hospital stay period and outcome, group 1 patients had the highest mortality rate (p<0.05, Eta square =0.12). Regression analysis showed that the presence of the alpha variant, severe chest computed tomography findings and chronic kidney disease, long hospital stay, and high serum C-reactive protein and D-dimer levels at admission were risk factors for a poor outcome. Conclusion: Early admission and/or easily obtainable clinical and laboratory determinant parameters of poor outcome could be a pathfinder for clinicians and/or researchers dealing with this challenging contagious viral disease. [ABSTRACT FROM AUTHOR]

The gastrointestinal (GI) tract may be a significant entrance or interaction site for SARS-CoV- 2; therefore, the gut mucosal immune system participates in virus interaction as a first-line physical and immunological defense, leading to GI involvement and symptoms. This review focuses on the GI symptoms associated with SARS-CoV-2 infection while providing specific results on variant-specific signs and syndromes related to coronavirus disease 2019 (COVID-19). The pattern of symptoms changed during the virus evolution, since the data provided a current and thorough picture of the symptoms experienced by SARS-CoV-2 infected people, and variations in symptom patterns occurred as the Alpha, Delta, and Omicron variants have spread. Since the beginning of the pandemic, GI symptoms have been linked to SARS-CoV-2 infections, even though most infected people do not report them. For example, diarrhea (28.2%) was the most frequently reported GI symptom in the early phase of the pandemic. The most observed GI tract symptoms during COVID-19 were anorexia (loss of appetite), nausea, vomiting, diarrhea, and abdominal pain, usually in at least one-third of the patients. Mesenteric ischemia and GI bleeding were less observed but more severe. While GI symptoms are not associated with increased mortality, they complicate the disease, increase the duration of the illness, and result in worse outcomes. Nevertheless, it is accepted that symptoms between variants differ significantly, i.e., the Omicron variant causes milder COVID-19 than the Delta. Still, the rate of GI symptoms has declined in the following variant-dominated phases of the pandemic (Alpha: 19.4%, Delta: 17.9%, Omicron: 13.8%), which was also demonstrated for other GI signs associated with COVID-19. [ABSTRACT FROM AUTHOR]

Fukasawa introduced in Fukasawa [The normalizing transformation of the implied volatility smile. Math. Finance, 2012, 22(4), 753-762] two necessary conditions for no butterfly arbitrage on a given implied volatility smile which require that the functions d1 and d2 of the Black-Scholes formula have to be decreasing. In this article, we characterize the set of smiles satisfying these conditions, using the parametrization of the smile in delta. We obtain a parametrization of the set of such smiles via one real number and three positive functions, which can be used by practitioners to calibrate a weak arbitrage-free smile. We also show that such smiles and their symmetric smiles can be transformed into smiles in the strike space by a bijection. Our result motivates the study of the challenging question of characterizing the subset of butterfly arbitrage-free smiles using the parametrization in delta. [ABSTRACT FROM AUTHOR]

Introduction: The randomized, placebo-controlled, double-blind MOVe-OUT trial demonstrated molnupiravir (800 mg every 12 h for 5 days) as safe and effective for outpatient treatment of mild-to-moderate COVID-19, significantly reducing the risk of hospitalization/death in high-risk adults. At the time of that report, virologic assessments from the trial were partially incomplete as a result of their time-intensive nature. Here we present final results from all prespecified virology endpoints in MOVe-OUT based on the full trial dataset. Methods: Nasopharyngeal swabs were collected at baseline (day 1, prior to first dose) and days 3, 5 (end-of-treatment visit), 10, 15, and 29. From these samples, change from baseline in SARS-CoV-2 RNA titers (determined by quantitative PCR), detection of infectious SARS-CoV-2 (by plaque assay), and SARS-CoV-2 viral error induction (determined by whole genome next-generation sequencing) were assessed as exploratory endpoints. Results: Molnupiravir was associated with greater mean reductions from baseline in SARS-CoV-2 RNA than placebo (including 50% relative reduction at end-of-treatment) through day 10. Among participants with infectious virus detected at baseline (n = 96 molnupiravir, n = 97 placebo) and evaluable post-baseline samples, no molnupiravir-treated participant had infectious SARS-CoV-2 by day 3, whereas infectious virus was recovered from 21% of placebo-arm participants on day 3 and 2% at end-of-treatment. Consistent with molnupiravir's mechanism of action, sequence analysis demonstrated that molnupiravir was associated with an increased number of low-frequency transition errors randomly distributed across the SARS-CoV-2 RNA genome compared with placebo (median 143.5 molnupiravir, 15 placebo), while transversion errors were infrequent overall (median 2 in both arms). Outcomes were consistent regardless of baseline SARS-CoV-2 clade, presence of SARS-CoV-2-specific immune response, or viral load. Conclusions: A 5-day course of orally administered molnupiravir demonstrated a consistently greater virologic effect than placebo, including rapidly eliminating infectious SARS-CoV-2, in high-risk outpatients with mild-to-moderate COVID-19. Trial Registration : ClinicalTrials.gov, NCT04575597. [ABSTRACT FROM AUTHOR]

The threat of environmental pollution in Nigeria, particularly in the Niger Delta region, cannot be solely ascribed to oil spillages; rather, it also encompasses the discharge of cassava mill effluent (CME), frequently disposed off in an unregulated manner. Existing studies on CME have focused on its potential environmental consequences on soil characteristics, microbial populations, and heavy metal levels. There is limited study on the awareness of the impact of CME on the environment. Thus, this study contributes to the literature on CME by examining the awareness of its effect on the environment in Ika North East Local Government Area of Delta State, Nigeria. The study used interviews, observation, and questionnaires administered to 399 respondents for data collection. A Student t-test, ANOVA, and Pearson's correlation were employed to analyse the data in Statistical Package for the Social Sciences. Results revealed limited awareness, with 51.3% unaware of CME's environmental impact. Slight, moderate, and extreme awareness were reported by 7.5%, 17.3%, and 23.8%, respectively. Gender's influence on awareness was insignificant, but age showed a significant influence (p < 0.05), while education, occupation, and income correlated positively with awareness (p < 0.001). The source of information significantly predicted awareness (r = −0.727, p < 0.001). It indicates that gender's influence on awareness might depend on education levels. Socio-economic factors are strongly related to awareness. Reliable information sources are vital for understanding CME's environmental impact. The study underscores the need for enhanced environmental education and reliable information dissemination to promote sustainable practices. [ABSTRACT FROM AUTHOR]

A general geographic characteristic of the Vistula basin and mouth area is given; brief data on the modern hydrological regime of the river mouth are presented. The history of floods in the Vistula delta and their studies is considered in detail, as well as delta evolution and the dynamics of its hydrographic network. [ABSTRACT FROM AUTHOR]

We summarized through systematic review and meta-analysis of observational studies the risk of mortality as well as severe illness of COVID-19 caused by omicron variant relative to delta variant of SARS-CoV-2. A total of twelve studies were included. Our results showed significantly reduced odds of mortality (pooled OR = 0.33; 95% CI: 0.16–0.67) and significantly reduced odds of severe illness (pooled OR = 0.24; 95% CI: 0.21–0.28) in patients infected with the omicron variant of SARS-CoV-2 relative to their counterparts infected with the delta variant. Findings of lower disease severity following infection with the omicron variant of SARS-CoV-2 than the delta variant are encouraging during the ongoing transition from the pandemic phase into the endemic phase of COVID-19. [ABSTRACT FROM AUTHOR]

This study evaluates the effectiveness of the previously proposed Standard Penetration Test (SPT) N and shear wave velocity (VS) models in relation to the geological attributes of the Busan region, situated in the southeastern part of the Korean peninsula. The multiple empirical N-VS models, which used datasets collected from different regions in South Korea, resulted in distinct N-VS trends across models. To validate the predictive capabilities of each model, this study gathered boring logs containing SPT N and VS measurements within the Busan region, followed by a thorough residual analysis. The Busan area encompasses a delta region to the west and erosion basins within the mountains and hills to the east. Despite the relatively confined geographical scope, we found that models developed using data from fill areas exhibit superior performance for the delta region (western Busan), while models constructed from datasets within erosion basins perform better for the erosion basin region (eastern Busan). This comparative examination supports the dependence of the N-VS model on geologic attributes and offers the valuable insight that N-VS models developed with analogous geological attributes should be employed when estimating VS from SPT N values. [ABSTRACT FROM AUTHOR]

Despite the ever-increasing occurrences of the coronavirus disease (COVID-19) cases around the world, very few medications have been validated in the clinical trials to combat COVID-19. Although several vaccines have been developed in the past quarter, the time elapsed between deployment and administration remains a major impediment. Repurposing of pre-approved drugs, such as phosphodiesterase 5 (PDE5) inhibitors, could be a game-changer while lessening the burden on the current healthcare system. Repurposing and developing phosphodiesterase 5 (PDE5) inhibitors could extrapolate their utility to combat the SARS-CoV-2 infection, and potentially aid in the management of the symptoms associated with its newer variants such as BF.7, BQ.1, BQ.1.1, XBB.1.5, and XBB.1.16. Administration of PDE5 inhibitors via the oral and intravenous route demonstrates other potential off-label benefits, including anti-apoptotic, anti-inflammatory, antioxidant, and immunomodulatory effects, by intercepting several pathways. These effects can not only be of clinical importance in mild-to-moderate, but also moderate-to-severe SARS-CoV-2 infections. This article explores the various mechanisms by which PDE5 inhibitors alleviates the symptoms associated with COVID-19 as well as well as highlights recent studies and findings. These benefits of PDE5 inhibitors make it a potential drug in the physicians' armamentarium in alleviating symptoms associated with SARS-CoV-2 infection. However, adequate clinical studies must be instituted to eliminate any untoward adverse events. [ABSTRACT FROM AUTHOR]

Background: The Notch signaling pathway plays a significant role in the gene regulatory network of development of vertebrate and invertebrate. However, as a ligand for the Notch signaling pathway, the mechanism of Delta in the development of Exopalaemon carinicauda is still unclear. Methods and results: The Delta's molecular characteristics, tissue distribution and their association with development in E. carinicauda were studied by RACE (rapid amplification of cDNA end), qRT-PCR (quantitative Real-time PCR) and SNP (single nucleotide polymorphism), respectively. The delta in E. carinicauda had a full-length cDNA of 2807 bp and its Delta of 808 amino-acid residue had the highest identity with the Delta of Homarus americanus (identity = 76.63%). Delta had the highest expression in the ovary, and its expression varied with different stages of embryonic, larval, and ovarian development. After delta RNA interference (with a highest interference efficiency of 66% at 24 h), the expression of Notch signaling pathway genes and developmental related genes was significantly reduced, and the ovarian development was significantly delayed. Further study found that there were 4 SNPs (ds1-4) in delta cDNA, of which two (ds2 T1521G caused a mutation Asn422Lys and ds3 G1674A caused a mutation Tyr473Cys in the EGF-like domain) were associated with the development of E. carinicauda. The Gonadosomatic Index (GSI) of the ds2 TT genotypes was 37.28% and 134.60% higher than E. carinicauda of GT and GG genotype respectively (P < 0.05). Conclusion: Our research indicated that delta was involved in the development of E. carinicauda and provided new insights for molecular breeding with SNP markers in E. carinicauda. [ABSTRACT FROM AUTHOR]

Background: The COVID-19 pandemic has made devastating impacts on public health and global economy. While most people experience mild symptoms, it is highly transmissible and deadly in at-risk populations. Telemedicine has the potential to prevent hospitalization and provide remote care. Methods: This retrospective study included 336 people with COVID-19, among which 141 (42%) and 195 (58%) were in Delta and Omicron dominant groups, respectively. Patients were confirmed to have COVID-19 by PCR or rapid test and were cared for via telemedicine. Severe cases were hospitalized for more intensive treatment. Results: The majority of individuals recovered at home (97.02%), while 2.98% required hospitalization. All hospital admissions were in Delta dominant group. No deaths were reported. Delta dominant group was more likely to develop loss of taste and smell, decreased appetite and need longer treatment time than those in Omicron dominant group. Conclusions: Telemedicine is a safe measure to provide at-home care for people with COVID-19 infections caused by both Delta and Omicron variants. Trial registration: This study was approved by the Institutional Review Board Committee of University of Medicine and Pharmacy at Ho Chi Minh City (IRB No: 22115–DHYD). [ABSTRACT FROM AUTHOR]

SARS-CoV-2, the virus responsible for the COVID-19 pandemic, belongs to the betacoronavirus genus. This virus has a high mutation rate, which rapidly evolves into new variants with different properties, such as increased transmissibility or immune evasion. Currently, the most prevalent global SARS-CoV-2 variant is Omicron, which is more transmissible than previous variants. Current available vaccines may be less effective against some currently existing SARS-CoV-2 variants, including the Omicron variant. The S1 subunit of the spike protein of SARS-CoV-2 has been a major target for COVID-19 vaccine development. It plays a crucial role in the virus’s entry into host cells and is the primary target for neutralizing antibodies. In this study, the S1 subunit of the spike protein of SARSCoV-2 was engineered and produced at a high level in Nicotiana benthamiana plant. The expression level of the recombinant S1 protein was greater than the 0.5-g/kg fresh weight, and the purification yield was at least ~0.3 g of pure protein/kg of plant biomass, which would make a plant-produced S1 antigen an ideal vaccine candidate for commercialization. Purified, the plant-produced SARS-CoV-2 S1 protein exhibited significantly higher binding to the SARSCoV-2 receptor, angiotensin-converting enzyme 2 (ACE2). Moreover, we also show that recombinant S1 protein/antigen-elicited antibodies can neutralize the Delta or Omicron variants. Collectively, our results demonstrate that a plantproduced S1 antigen could be a promising vaccine candidate against SARS-CoV2 variants including Omicron. [ABSTRACT FROM AUTHOR]

Background: Ubiquitylation (ubi) of the intracellular domain of the Notch ligand Delta (Dl) by the E3 ligases Neuralized (Neur) and Mindbomb1 (Mib1) on lysines (Ks) is thought to be essential for the its signalling activity. Nevertheless, we have previously shown that DlK2R-HA, a Dl variant where all Ks in its intracellular domain (ICD) are replaced by the structurally similar arginine (R), still possess weak activity if over-expressed. This suggests that ubi is not absolutely required for Dl signalling. However, it is not known whether the residual activity of DlK2R-HA is an effect of over-expression and, if not, whether DlK2R can provide sufficient activity for the whole development of Drosophila. Results: To clarify these issues, we generated and analysed DlattP-DlK2R-HA, a knock-in allele into the Dl locus. Our analysis of this allele reveals that the sole presence of one copy of DlattP-DlK2R-HA can provide sufficient activity for completion of development. It further indicates that while ubi is required for the full activity of Dl in Mib1-dependent processes, it is not essential for Neur-controlled neural development. We identify three modes of Dl signalling that are either dependent or independent of ubi. Importantly, all modes depend on the presence of the endocytic adapter Epsin. During activation of Dl, direct binding of Epsin appears not to be an essential requirement. In addition, our analysis further reveals that the Ks are required to tune down the cis-inhibitory interaction of Dl with Notch. Conclusions: Our results indicate that Dl can activate the Notch pathway without ubi of its ICD. It signals via three modes. Ubi is specifically required for the Mib1-dependent processes and the adjustment of cis-inhibition. In contrast to Mib1, Neur can efficiently activate Dl without ubi. Neur probably acts as an endocytic co-adapter in addition to its role as E3 ligase. Endocytosis, regulated in a ubi-dependent or ubi-independent manner is required for signalling and also suppression of cis-inhibition. The findings clarify the role of ubi of the ligands during Notch signalling. [ABSTRACT FROM AUTHOR]

Lithofacies and biostratigraphical analysis has enabled the establishment of a stratigraphic event framework for Ludfordian and Pridoli strata in south Wales and the Welsh Borderland. In SW Wales, the Golden Grove Axis acted as a structural hinge separating the shallow marine storm-influenced Cae'r mynach Seaway from a pediment surface above which Ludfordian colluvium (Abercyfor Formation) was deposited. The Axis seeded four NW-derived river-influenced delta progrades of Leintwardinian to early Pridoli age (Tilestones Formation). A NE-sourced early Pridoli wave-influenced delta deposited the Downton Castle Sandstone Formation (DCSF), coeval to the youngest Tilestones prograde, with a lateral interface existing between Mynydd Epynt and the Clun Forest area. Except for the Malverns area, the DCSF is no longer recognized south of the Neath Disturbance. Early Pridoli forced regression promoted widespread subaerial exposure north of the Neath Disturbance, with incision into tracts close to the Welsh Borderland Fault System. The basinward-shift in facies belts resulted in marine erosion and deposition of a phosphatic ravinement pebble lag. The wave-influenced Clifford's Mesne Sandstone Formation delta subsequently seeded on the Gorsley Axis with tidally influenced Rushall Formation accumulating in a back-barrier setting. The Pwll-Mawr Formation records the easterly advance of coeval coastal deposits on the western side of the remnant Cae'r mynach Seaway. Behind migrating delta coastlines, green muds accumulated on coastal plains (Temeside Mudstone Formation) with better drained red dryland alluvium (Moor Cliffs Formation) charting expansion of Old Red Sandstone lithofacies. Mid-Pridoli incision preserves the Pont ar Llechau Formation estuarine valley fill. [ABSTRACT FROM AUTHOR]

Background We compared homologous and heterologous boosting in adults in the Philippines primed with 2 or 3 doses of CoronaVac, with recombinant protein vaccine, SCB-2019. Methods CoronaVac-immunized adults (18–72 years) received a homologous or heterologous full or half dose SCB-2019 booster. We assessed all neutralizing antibody (NAb) responses against prototype SARS-CoV-2 after 15 days and NAb against SARS-CoV-2 Delta and Omicron variants in subsets (30‒50 per arm). Participants recorded adverse events. Results In 2-dose CoronaVac-primed adults prototype NAb geometric mean titers (GMT) were 203 IU/mL (95% confidence interval [CI], 182–227) and 939 IU/mL (95% CI, 841–1049) after CoronaVac and SCB-2019 boosters; the GMT ratio (4.63; 95% CI, 3.95–5.41) met predefined noninferiority and post-hoc superiority criteria. After 3-dose CoronaVac-priming prototype NAb GMTs were 279 IU/mL (95% CI, 240–325), 1044 IU/mL (95% CI, 898–1213), and 668 IU/mL (95% CI, 520–829) following CoronaVac, full and half-dose SCB-2019 boosters, respectively. NAb GMT ratios against Delta and Omicron comparing SCB-2019 with CoronaVac were all greater than 2. Mild to moderate reactogenicity was evenly balanced between groups. No vaccine-related serious adverse events were reported. Conclusions Full or half dose SCB-2019 boosters were well tolerated with superior immunogenicity than homologous CoronaVac, particularly against newly emerged variants. Clinical Trials Registration. NCT05188677. [ABSTRACT FROM AUTHOR]

The Peace–Athabasca Delta (PAD) in northern Alberta is one of the world's largest inland freshwater deltas and is home to many species of fish, mammals, and birds. Over the past five decades, the PAD has experienced prolonged dry periods in between rare floods, accompanied by a reduction in the area comprised of lakes and ponds that provide a habitat for aquatic life. In the Peace sector of the PAD, this likely resulted from a reduced frequency of spring flooding caused by major ice jams that form in the lower Peace River. There is debate in the literature regarding the factors that promote or inhibit the formation of such ice jams, deriving from physical process studies, paleolimnological studies, and—recently—statistical analysis founded in logistic regression. Logistic regression attempts to quantify ice-jam flood (IJF) probability, given the values of assumed explanatory variables, involve considerable uncertainty. Herein, different sources of uncertainty are examined and their effects on statistical inferences are evaluated. It is shown that epistemic uncertainty can be addressed by selecting direct explanatory variables, such as breakup flow and ice cover thickness, rather than through more convenient, albeit weak, proxies that rely on winter precipitation and degree-days of frost. Structural uncertainty, which derives from the unknown mathematical relationship between IJF probability and the selected explanatory variables, leads to different probability predictions for different assumed relationships but does not modify assessments of statistical significance. The uncertainty associated with the relatively small sample size (number of years of record) may be complicated by known physical constraints on IJF occurrence. Overall, logistic regression corroborates physical understanding that points to breakup flow and freezeup level as primary controls of IJF occurrence. Additional influences, related to the thermal decay of the ice cover and the flow gradient during the advance of the breakup front towards the PAD, are difficult to quantify at present. Progress requires increased monitoring of processes and an enhanced numerical modelling capability. [ABSTRACT FROM AUTHOR]

Introduction: To explore whether the reported lower pathogenicity in infected individuals of variant of concern (VoC) Omicron and its current subvariants compared to VoC Delta may be related to fundamental differences in the initial virus-tissue interaction, we assessed their ability to penetrate, replicate and cause damage in a human 3D respiratory model. Methods: For this, we used TEER measurements, real-time PCR, LDH, cytokine and complex confocal imaging analyses. Results and discussion: We observed that Delta readily penetrated deep into the respiratory epithelium and this was associated withmajor tissue destruction, high LDH activity, high viral loads and pronounced innate immune activation as observed by intrinsic C3 activation and IL-6 release at infection sites. In contrast, Omicron subvariants BA.5, BQ.1.1 and BF7 remained superficially in the mucosal layer resulting merely in outward-directed destruction of cells, maintenance of epithelial integrity, minimal LDH activity and low basolateral release of virus at infection sites, as well as significantly smaller areas of complement activation and lower IL-6 secretion. Interestingly, also within Omicron subvariants differences were observed with newer Omicron subvariants BQ.1.1 and BF.7 illustrating significantly reduced viral loads, IL-6 release and LDH activity compared to BA.5. Our data indicate that earliest interaction events after SARS-CoV-2 transmission may have a role in shaping disease severity. [ABSTRACT FROM AUTHOR]