Forecast of omicron wave time evolution

Adopting an early doubling time of three days for the rate of new infections with the omicron mutant the temporal evolution of the omicron wave in different countries is predicted. The predictions are based on the susceptible-infectious-recovered/removed (SIR) epidemic compartment model with a constant stationary ratio k=mu(t)/a(t) between the infection (a(t)) and recovery (mu(t)) rate. The fixed early doubling time then uniquely relates the initial infection rate a0 to the ratio k, which therefore determines the full temporal evolution of the omicron waves. For each country three scenarios (optimistic, pessimistic, intermediate) are considered and the resulting pandemic parameters are calculated. These include the total number of infected persons, the maximum rate of new infections, the peak time and the maximum 7-day incidence per 100000 persons. Among the considered European countries Denmark has the smallest omicron peak time and the recently observed saturation of the 7-day incidence value at 2478 is in excellent agreement with the prediction in the optimistic scenario. For Germany we predict peak times of the omicron wave ranging from 32 to 38 and 45 days after the start of the omicron wave in the optimistic, intermediate and pessimistic scenario, respectively, with corresponding maximum SDI values of 7090, 13263 and 28911, respectively. Adopting Jan 1st, 2022 as the starting date our predictions implies that the maximum of the omicron wave is reached between Feb 1 and Feb 15, 2022. Rather similar values are predicted for Switzerland. Due to an order of magnitude smaller omicron hospitalization rate, due to the high percentage of vaccinated and boostered population, the German health system can cope with maximum omicron SDI value of 2800 which is about a factor 2.5 smaller than the maximum omicron SDI value 7090 in the optimistic case. By either reducing the duration of intensive care during this period of maximum, and/or by making use of the nonuniform spread of the omicron wave across Germany, it seems that the German health system can barely cope with the omicron wave avoiding triage decisions. The reduced omicron hospitalization rate also causes significantly smaller mortality rates compared to the earlier mutants in Germany. In the optimistic scenario one obtains for the total number of fatalities 7445 and for the maximum death rate 418 per day which are about one order of magnitude smaller than the beta fatality rate and total number.

Pazopanib in Patients with Osteosarcoma Metastatic to the Lung: Phase 2 Study Results and the Lessons for Tumor Measurement

Background. This single-arm, multicenter, phase 2 study evaluated the safety and antitumor activity of pazopanib in patients with unresectable, pulmonary metastatic osteosarcoma. Patients and Methods. Patients with pulmonary metastatic osteosarcoma unresponsive to chemotherapy were eligible. Patients who received prior tyrosine kinase inhibitor therapy were excluded. Pazopanib at 800 mg once daily was administered for 28-day cycles. Tumor responses were evaluated by local radiology assessment 1 month prior to and after initiation of treatment to calculate tumor doubling time and after every even numbered cycle. The primary endpoints were progression-free survival at 4 months, concomitant with a demonstrated 30% increase in tumor doubling time relative to the pretreatment growth rate. Results. 12 patients (7 female) were enrolled. The study was terminated prematurely due to withdrawal of financial support by the sponsor. 8 subjects were eligible for the primary analysis, whereas 4 patients were in a predefined exploratory “slow-growing” cohort. In the “fast-growing” cohort, 3 of the 8 patients (37.5%) eligible for first-stage analysis were deemed “success” by the preplanned criteria, adequate to proceed to second-stage accrual. In addition, 1 of the 4 patients in the “slow-growing” cohort experienced a partial remission. Grade 1-2 diarrhea was the most common adverse event, and grade 3 events were infrequent. Conclusion. This study illustrates a novel method of demonstrating positive drug activity in osteosarcoma by increasing tumor doubling time, and this is further supported by a partial response in a patient with “slow-growing” disease. This trial is registered with NCT01759303.

Modeling the USA Winter 2021 Resurgence

The current USA 2021 CoVID-19 Winter Resurgence is modeled here with the same function used for analyzing prior USA CoVID-19 waves: N(t)= max[N/o\exp{+(t/[t/R\(1+α/s\t)]exp(-δ/o\t)}]. Here, N(t) gives the total number of CoVID-19 cases above the previous baseline, and t/R\ sets the initial t/dbl\ = [t/R\ ln(2)] pandemic t/dbl\ doubling time. Larger α/s\ values indicate that uninfected people are improving their pandemic mitigation efforts, such as Social Distancing and vaccinations; while δ/o\>0 accelerates the post-peak [(d/dt)N(t)] tail-off, and is empirically associated with mask-wearing. The pandemic wave end is when N(t) no longer increases. Results from the USA Summer 2021 Resurgence (see prior medrxiv.org preprints*) were used as a baseline. By 11/15/2021, an additional N/o\(11/15/2021)=107,000 cases above baseline were found, signaling the USA Winter 2021 Resurgence. This CoVID-19 wave is still in its initial stages. Presently, our analysis indicates that this CoVID-19 wave can infect virtually all susceptible persons; just like the initial stage of the USA Summer 2021 Resurgence. Data up through 12/30/2021 gives these parameter values: t/R\=8.05 days; α/s\=0.011/day. These values are identical to the prior 2020 USA Winter Resurgence results. Also, the present N/o\(11/15/2021) and the prior N/o\(9/25/2020)=89,900 values are similar. However, while the Winter 2020 Resurgence showed a significant mask-wearing effect: δ/o\(2020)= 1.748 x 10^-3 / day, this initial USA Winter 2021 Resurgence shows practically no mask-wearing effects: δ/o\(2021)< 0.001 x 10^-3 / day. If mask-wearing were to quickly rise to the Winter 2020 levels, it would give these projected totals: N(t=[1/1/2022])= 54,705,400; N(t=[3/21/2022])= 83,371,000; N(t=[3/21/2024])= 92,399,000. More robust mask-wearing and enhanced Social Distancing measures could further reduce these values (with 3 Figures). * (10.1101_2021.08.16.21262150; 10.1101_2021.10.15.21265078)

Influence of cyclonic and anti-cyclonic eddies on plankton biomass, activity and diversity in the southeastern Mediterranean Sea

Planktonic food-webs were studied contemporaneously in a mesoscale cyclonic (upwelling, ~13 months old) and an anti-cyclonic (down-welling, ~2 months old) eddies, as well as in an uninfluenced-background situation in the oligotrophic southeastern Mediterranean Sea (SEMS) during late summer 2018. We show that integrated nutrients concentrations were higher at the cyclone compared to the anti-cyclone or the background stations by 2–13 fold. Concurrently, Synechococcus and Prochlorococcus were the dominant community component abundance-wise in the oligotrophic anti-cyclone (~300 × 1010 cells m−2). In the cyclone, pico- and nanoeukaryotes such as dinoflagellates, Prymnesiophyceae and Ochrophyta contributed substantially to the total phytoplankton abundnce (~14 × 1010 cells m−2) which was ~65 % lower in the anti-cyclone/background stations (~5 × 1010 cells m−2). Primary production was highest in the cyclonic eddy (191 mg C m−2 d−1) and was 2–5 fold lower outside the eddy area. The calculated doubling time of phytoplankton was ~3 days in the cyclone and ~5–10 days at the anti-cyclone/background stations, further reflecting the nutritional differences between these environments. Heterotrophic prokaryotic cell-specific activity was highest in the cyclone (~10 fg C cell−1 d−1), while the least productive cells were found in the anti-cyclone (4 fg C cell−1 d−1). The calculated doubling time of heterotrophic bacteria were 1.4 days in the cyclone and 2.5–3.5 days at the anti-cyclone/background stations. Total zooplankton biomass in the upper 300 m was tenfold higher in the cyclone compared with the anti-cyclone or background stations (1337 vs. 112–133 mg C m−2, respectively). Copepod diversity was much higher in the cyclone (44 species), compared to the anti-cyclone (6 small-size species). Our results highlight that cyclonic and anti-cyclonic eddies show significantly different community compositions and food-web dynamics in oligotrophic environments, with cyclones representing productive oases in the marine desert of the SEMS.

Elimination of [PSI+] Prion and Influence on Yeast Cell Growth

Background Prions are proteinaceous infectious particles that act as pathogens and cause the development of lethal neurodegenerative diseases in humans and other animals. Yeast Saccharomyces cerevisiae is a widespread model system in which mechanisms of prion induction and elimination have been identified. New and safe substances and methods are being sought to cure cells of prion proteins. It is particularly important that by treating cells from prions and restoring them from the [PSI+] to the [psi−] form, the primary growth of the cells is restored. One of the main objectives of this study was to determine the growth dynamics of S. cerevisiae cells with different [PSI+] prion variants, cells that have lost [PSI+] prion variants, and cells that never had [PSI+] prion variants. Results In this research, we applied GuHCl and combined GuHCl and PEF treatment against [PSI+] prion. We evaluated cells culture growth dynamics – optical density and doubling time and determined that method of [PSI+] prion elimination does not affect cell doubling time. Also, we found that both elimination methods affect the optical density reached by [psi−] cells. However, the cells in which the [PSI+] prion has been eliminated by GuHCl alone are able to reach the same optical density as unaffected [psi−] cells and higher optical density than the affected [psi−] cells by GuHCl alone. Conclusions These findings indicate the potential long-term positive effect of [PSI+] prion on cell growth, which persists after [PSI+] removal.

Characterization of mesenchymal stem cells isolated from Wharton’s jelly of the human umbilical cord

Background Isolation of post-partum umbilical cord Wharton’s jelly stem cells has gained attention as an alternative source of the bone marrow. Because easy isolation, lack of ethical concerns, and the presence of both embryonic and adult stem cells have made them a valuable source for use in therapeutic applications and regenerative medicine. The study utilized a modified protocol using in-house human pooled cord blood serum for isolation and expansion of the mesenchymal stem cells obtained from the human umbilical cord Wharton’s jelly. Cell proliferation and population doubling time and tri-lineage differentiation were assessed, and the expressions of mesenchymal cell surface markers CD44, CD90, CD105, and CD34 were assessed by flow cytometry and RT-PCR. The genetic stability of the isolated cells was assessed by chromosomal karyotype. Results The isolated cells displayed fibroblastic-like morphology and tri-lineage differentiation into adipocyte, chondrocyte, and osteocyte. The isolated cells maintained the proliferative competence with a doubling time ranged from 38 to 42h and corresponded well with the standard positive and negative molecular markers (CD44+, CD90+, CD 105+, and CD34−). Cell senescence occurred at the later passage of the cells (P15) affecting, about 25% of the population. Metaphases spread of the cells showed normal diploid karyotypes, with typical chromosomal plates indicating genetic stability of the isolated cells. Conclusion The primary cultures exhibited success in isolating the umbilical cord Wharton’s jelly mesenchymal stem cells, which maintained their tri-lineage differentiation potential, phenotypes and karyotype characteristics on further passage and expansion.

Production of Microalgal Biomass at Different Growth Phases to Use as Biofuel Feedstock

The growth of microalgae under optimized conditions was determined for assessing their growth rate and biomass production. In this study, the growth of both green algae (Chlamydomonas noctigama and Chlorella vulgaris) and cyanobacteria (Anabaena variabilis and Nostoc spongiaeforme) was measured as optical density. Chlamydomonas noctigama and Chlorella vulgaris showed the doubling time of 9.5 and 8.0 hours, respectively, whereas Anabaena variabilis and Nostoc spongiaeforme showed the doubling time of 14.8 and 16.6 hours, respectively. All the species exhibited the highest growth in terms of biomass at the phase in between stationary and death phases. J. Asiat. Soc. Bangladesh, Sci. 47(2): 161-171, December 2021

Genetic Drift Versus Climate Region Spreading Dynamics of COVID-19

Background: The current propagation models of COVID-19 are poorly consistent with existing epidemiological data and with evidence that the SARS-CoV-2 genome is mutating, for potential aggressive evolution of the disease.Objectives: We looked for fundamental variables that were missing from current analyses. Among them were regional climate heterogeneity, viral evolution processes versus founder effects, and large-scale virus containment measures.Methods: We challenged regional versus genetic evolution models of COVID-19 at a whole-population level, over 168,089 laboratory-confirmed SARS-CoV-2 infection cases in Italy, Spain, and Scandinavia at early time-points of the pandemic. Diffusion data in Germany, France, and the United Kingdom provided a validation dataset of 210,239 additional cases.Results: Mean doubling time of COVID-19 cases was 6.63 days in Northern versus 5.38 days in Southern Italy. Spain extended this trend of faster diffusion in Southern Europe, with a doubling time of 4.2 days. Slower doubling times were observed in Sweden (9.4 days), Finland (10.8 days), and Norway (12.95 days). COVID-19 doubling time in Germany (7.0 days), France (7.5 days), and the United Kingdom (7.2 days) supported the North/South gradient model. Clusters of SARS-CoV-2 mutations upon sequential diffusion were not found to clearly correlate with regional distribution dynamics.Conclusion: Acquisition of mutations upon SARS-CoV-2 spreading failed to explain regional diffusion heterogeneity at early pandemic times. Our findings indicate that COVID-19 transmission rates are rather associated with a sharp North/South climate gradient, with faster spreading in Southern regions. Thus, warmer climate conditions may not limit SARS-CoV-2 infectivity. Very cold regions may be better spared by recurrent courses of SARS-CoV-2 infection.

PSA and PSA Kinetics as Predictors for 18F-Fluciclovine PET/CT Positivity in Biochemically Recurrent Prostate Cancer

<b><i>Introduction:</i></b> ¹⁸F-Fluciclovine PET/CT is one of the imaging techniques currently employed to restage prostate cancer (PCa). Due to the conflicting results reported in the literature, it is not yet known at what PSA threshold ¹⁸F-fluciclovine PET/CT could reliably demonstrate the presence of recurring disease. We explored the association between ¹⁸F-fluciclovine PET/CT positivity and prescan PSA, PSA doubling time, and PSA velocity in patients with biochemical recurrence (BCR) of PCa after curative-intent treatment. <b><i>Methods:</i></b> Data from 59 patients who underwent ¹⁸F-fluciclovine PET/CT for BCR after radical prostatectomy or radiotherapy were retrieved from a single institution database. Patients already undergone salvage treatments at the time of PET/CT, with newly diagnosed PCa or with initial diagnosis of metastatic PCa were excluded. A 2-sided independent samples Bayesian <i>t</i> test and Bayesian Mann-Whitney U test were used to assess the association between PET/CT and prescan PSA, PSA doubling time, and PSA velocity. <b><i>Results:</i></b> Evidence for no difference between PET/CT-positive and -negative patients for log-transformed PSA was found (BF₀₁ 3.61, % error: 0.01). Robustness check and sequential analysis showed stability across a wide range of prior distribution specifications. The hypothesis of no difference in terms of PSA-dt and for PSA-vel between groups was found to be more likely compared to the alternative hypothesis (BF₀₁ of 3.44 and 3.48, respectively). <b><i>Conclusion:</i></b> PSA and PSA kinetics are unlikely to be associated with ¹⁸F-fluciclovine PET/CT positivity in patients with BCR, and none of these serum biomarkers might be used as single predictors of PET/CT detection. Larger studies might be needed to evaluate the role of different predictors.

Omicron strain spreads with the doubling time of 3.2-3.6 days in South Africa province of Gauteng that achieved herd immunity to Delta variant

Omicron, the novel, highly mutated SARS-CoV-2 Variant of Concern (belonging to the Pango lineage B.1.1.529), was first collected on November 8, 2021, in Gauteng province of South Africa. By the end of November 2021 it has spread towards fixation in Gauteng and was detected on all continents. Based on data collected till December 7, 2021, we showed the exponential growth of the Omicron variant over the four-week period in Gauteng (November 8-December 5, 2021) with the doubling time equal 3.38 day [CI 95%: 3.18-3.61 day]. Log-linear regression suggests that the spread began around October 10, 2021, however due to stochasticity in the initial spread this estimate is likely inaccurate. Phylogenetic analysis indicates that the Omicron strain started to diverge in between October 28 and November 5, 2021. This implies that the hidden spread of Omicron before October 10, 2021 (which would suggest slower strain growth) is unlikely. The very short doubling time of Omicron in Gauteng, a province that has reached herd immunity to the Delta variant (implied by the decrease of the weekly number of cases between July and October, 2021, at no significant mobility restrictions), suggests that Omicron will cause abrupt outbreaks of COVID-19 epidemics across the world, and will become the (temporarily) dominant strain.