Sequential Waves Research Articles

COVID-19 Waves with Associated Variants & Scenario in Pakistan

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is an enveloped RNA beta-coronavirus virus that is coronaviridae-related. It originated in Wuhan, China in December 2019 and is known to cause COVID-19 illness. SARS-CoV-2 posed a major threat to the world in concern of health along with trade and medical facilities. COVID-19 patients experience comorbid conditions like severe fever, typhoid, myocarditis, and a fatal black fungus attack. World Health Organization declared COVID-19 as an emergency on 30th January 2020 and a pandemic on 11th March. As of right now, COVID-19 has been verified to have infected over 100 million people across 210 nations, and 2 million of those infections have resulted in death. RT-qPCR (Reverse transcriptase qualitative PCR) test is performed if any symptoms exist, and isolation is necessary for three to five days after the confirmation. In Pakistan, it was reported firstly on 26th February 2020 by the Pakistan government when two persons were found infected with the disease. SARS-CoV-2 changes its genome constantly and results in the emergence of different variants in different waves. Pakistan has faced 6 sequential waves since 2020 to date, each associated with different variants and overlapping variants. The first wave was associated with B.1, B.1.471, B.1.36, second with B.1.36.31, B.1.247, B.1.1.1, B.1.160, B.1.471, B.1.562, B.1.1.7, B.1.1.250, B.1.261, B.1.351, P.1, third with B.1.1.7, B.1.351, P.1, B.1.617.2, B.1.36, B.1.468, B.1.1.413, A.27, fourth with P.1, B.1.617.2, fifth with Omicron (B.1.1.529) and sixth with new subvariants of Omicron (BA.4 & BA.5). In terms of severity and infectivity, Omicron and its subvariants differ from Delta and other SARS-CoV-2 variants. In this review, we have discussed SARS-CoV-2 spike mutations, its variants along with their origin & association to wave(s), and its scenario in Pakistan.

Multimodal chromatin profiling using nanobody-based single-cell CUT&Tag

Probing histone modifications at a single-cell level in thousands of cells has been enabled by technologies such as single-cell CUT&Tag. Here we describe nano-CUT&Tag (nano-CT), which allows simultaneous mapping of up to three epigenomic modalities at single-cell resolution using nanobody-Tn5 fusion proteins. Multimodal nano-CT is compatible with starting materials as low as 25,000–200,000 cells and has significantly higher sensitivity and number of fragments per cell than single-cell CUT&Tag. We use nano-CT to simultaneously profile chromatin accessibility, H3K27ac, and H3K27me3 in juvenile mouse brain, allowing for discrimination of more cell types and states than unimodal single-cell CUT&Tag. We also infer chromatin velocity between assay for transposase-accessible chromatin (ATAC) and H3K27ac in the oligodendrocyte lineage and deconvolute H3K27me3 repressive states, finding two sequential waves of H3K27me3 repression at distinct gene modules during oligodendrocyte lineage progression. Given its high resolution, versatility, and multimodal features, nano-CT allows unique insights in epigenetic landscapes in complex biological systems at the single-cell level.

Deciphering Transcriptional Networks during Human Cardiac Development

Human heart development is governed by transcription factor (TF) networks controlling dynamic and temporal gene expression alterations. Therefore, to comprehensively characterize these transcriptional regulations, day-to-day transcriptomic profiles were generated throughout the directed cardiac differentiation, starting from three distinct human- induced pluripotent stem cell lines from healthy donors (32 days). We applied an expression-based correlation score to the chronological expression profiles of the TF genes, and clustered them into 12 sequential gene expression waves. We then identified a regulatory network of more than 23,000 activation and inhibition links between 216 TFs. Within this network, we observed previously unknown inferred transcriptional activations linking IRX3 and IRX5 TFs to three master cardiac TFs: GATA4, NKX2-5 and TBX5. Luciferase and co-immunoprecipitation assays demonstrated that these five TFs could (1) activate each other's expression; (2) interact physically as multiprotein complexes; and (3) together, finely regulate the expression of SCN5A, encoding the major cardiac sodium channel. Altogether, these results unveiled thousands of interactions between TFs, generating multiple robust hypotheses governing human cardiac development.

Disease severity and efficacy of homologous vaccination among patients infected with SARS-CoV-2 Delta or Omicron VOCs, compared to unvaccinated using main biomarkers.

From March 2021, various countries including Iraq issued prompted recommendations for increased COVID‐19 vaccine protection in individuals especially those at risk of catching the virus (i.e., lifestyle, health sector workers, and chronic diseases). It is critically important to understand the impact of COVID‐19 vaccinations with the most commonly used vaccines (Pfizer and AstraZeneca) among populations either on the severity of the disease or the transmissibility of SARS‐CoV‐2 variants of concern (VOCs) and in sequential waves. This study was conducted to establish the clinical severity of COVID‐19 caused by Delta and Omicron SARS‐CoV‐2 variants among patients who either attended or were admitted to hospitals and to compare the effectiveness of Pfizer and AstraZeneca COVID‐19 vaccines (single or double doses) at least to prevent hospitalizations if not eradicating the pandemic. A case–control study was done of 570 hospitalized patients; including 328 COVID‐19 confirmed patients (166 males, 160 females) who received homologous vaccinations and 242 unvaccinated patients (128 males, 114 females) during the studied waves. The study showed that unvaccinated COVID‐19 patients in both waves had expressed significantly a higher number and longer periods of symptoms than vaccinated ones. Additionally, there was no significant effect of vaccine types, Pfizer and AstraZeneca or vaccine shot numbers on the PCR‐Ct in the last (Omicron) wave of the pandemic. However, in the previous (Delta) wave of the pandemic, fully vaccinated (double doses) COVID‐19 patients had higher PCR‐Ct values. Whether among vaccinated or unvaccinated patients, lower CRP levels recorded during the Omicron wave than that of the Delta wave, and regardless of the vaccine type or shot numbers, there were no significant differences between the two waves. Lower WBCs were observed in patients (vaccinated and unvaccinated) infected with the Delta variant in comparison to those infected with the Omicron variant and without any remarkable effect of the vaccine type or shot numbers. This is the first molecular and investigational study of the Delta variant and circulated Omicron in Iraq, regarding the severity of these two waves of SARS‐CoV‐2 pandemic and the efficacy of homologous vaccination, indicating the insufficiency of two doses and the demand for booster dose(s) as the most effective way of keeping on the safe‐side against SARS‐CoV‐2.

Collisional interactions and the transition between lava dome sector collapse and pyroclastic density currents at Tutupaca volcano (Southern Peru)

We describe sedimentological variations of the block-rich debris avalanche deposits and associated pyroclastic density current deposits emplaced around 1802 CE from Tutupaca volcano in southern Peru. We use these exceptionally well-preserved features to document the collisional shearing contact between the avalanche and coeval pyroclastic density currents. Furthermore, we show how the first stages of the edifice collapse and syn-cataclastic emplacement process affect the block-size distributions.With field observations, we describe imbricated block clusters, jigsaw cracks and striations related to elongated ridge structures on the deposit surface. Sedimentological and statistical methods (Fourier Shape analysis and Shape Preferred Orientation measured on 208 blocks and 566 mesoscale structures) help us to characterize the cataclastic gradient and establish the collisional relationships between different units. We determine that the proximal impacted deposits and block lithofacies from ridges may be related to distal block units around ∼10 km run-out distance. Different block clusters indicate a kinematic transition between avalanche units to pyroclastic density currents. Block shape parameters help to differentiate rounded blocks resulting from matrix abrasion with and striated blocks from ridges related to proximal imbricated block clusters. From the statistical dataset, a few equations have been developed indicating a common cataclastic origin with a co-genetic evolution of block lithofacies during sequential syn-cataclastic emplacement.The dome collapse is associated with a specific granular flow regime between avalanche and pyroclastic density currents with secondary reworking. Cyclic impact waves contribute to block cluster growth. Clusters are disaggregated during shock propagation. The inherited shapes of the block lithofacies with a/b = 1.2–2 and ellipse = 0.2–2.5 indicate the reworking by impact waves. A multidirectional switch to mass spreading in the median zone between 2 and 6 km may be considered with secondary flow and segregation waves. A basal frictional regime with striations is differentiated from collisional cataclastic flow, generating polymodal grooves during peak velocity at the flow front. Impact forces around ∼15.7 × 1010 N are implied by suggested clast velocities around 8.86 m.s−1 and the transitional regime between avalanche units and pyroclastic density currents between 15.5 and 39.6 m.s−1. An extensional disaggregation with the fractal dimensions (D) of the surrounded matrix between 0.6 and 2.8 characterizes the granular transport. A collisional shearing contact probably operated between avalanche units and pyroclastic density currents, which contribute to co-genetic evolution of block clusters from median to frontal distal zones. In the distal zone, abraded block clusters and tilted blocks are related to frontal reworking by impact wave.The cataclastic gradient of avalanche units is correlated with the pyroclastic flow regime. Semi-quantitative analysis of block clusters provides information about syn-emplacement processes during sequential impact waves related to volcanic debris-avalanche units and pyroclastic density currents.

Changing faces and habitat of mucormycosis epidemic in sequential COVID waves

The Corona virus poses a greater challenge in the form of the deadly fungal infection, mucormycosis. To study the histopathological features giving emphasis on the varying presentation of mucormycosis in sequential covid waves.A prospective study comprising 31 patients histopathologically diagnosed with mucormycosis were included in the study. Demographic features, predisposing conditions, and clinical features were obtained from medical records. Tissue sections were reviewed with hematoxylin and eosin (H and E), and special stains like Gomori's methenamine silver (GMS), and periodic acid Schiff (PAS) potassium hydroxide (KOH) examination and fungal culture. The study included 21 males and 10 females with age ranging from 35-75 years. On histopathological examination, inflammation, granulomas, foreign body giant cells along with necrosis was seen. Invasion into soft tissues, muscles, and adipose tissues along with Angioinvasion, perineural spread was identified. Fungal balls, round to ovoid mature sporangia with column-shaped columella, presence of proliferating hyphae in tissues like skeletal muscle, cartilage etc which are supposed to be relatively resistant for inflammatory pathology got noted as one of our astounded histopathological findings insinuating how a human body acts as a culture media exhibiting diversity of a human makeup. The trend of presentation and severity kept changing with successive covid wave. Diagnosis of mucormycosis is gruesome and more difficult as compared to other infectious organism. In addition, like any malignant pathology, perivascular and neural infiltration is one of the important histological features of invasive mucormycosis as it indicates the severity and prognosis. There is drastically different trend of presentation in covid and its different mutant waves.

Modular, cascade-like transcriptional program of regeneration in Stentor.

The giant ciliate Stentor coeruleus is a classical model system for studying regeneration and morphogenesis in a single cell. The anterior of the cell is marked by an array of cilia, known as the oral apparatus, which can be induced to shed and regenerate in a series of reproducible morphological steps, previously shown to require transcription. If a cell is cut in half, each half regenerates an intact cell. We used RNA sequencing (RNAseq) to assay the dynamic changes in Stentor's transcriptome during regeneration, after both oral apparatus shedding and bisection, allowing us to identify distinct temporal waves of gene expression including kinases, RNA -binding proteins, centriole biogenesis factors, and orthologs of human ciliopathy genes. By comparing transcriptional profiles of different regeneration events, we identified distinct modules of gene expression corresponding to oral apparatus regeneration, posterior holdfast regeneration, and recovery after wounding. By measuring gene expression after blocking translation, we show that the sequential waves of gene expression involve a cascade mechanism in which later waves of expression are triggered by translation products of early-expressed genes. Among the early-expressed genes, we identified an E2F transcription factor and the RNA-binding protein Pumilio as potential regulators of regeneration based on the expression pattern of their predicted target genes. RNAi-mediated knockdown experiments indicate that Pumilio is required for regenerating oral structures of the correct size. E2F is involved in the completion of regeneration but is dispensable for earlier steps. This work allows us to classify regeneration genes into groups based on their potential role for regeneration in distinct cell regeneration paradigms, and provides insight into how a single cell can coordinate complex morphogenetic pathways to regenerate missing structures.

Leveraging South African HIV research to define SARS-CoV-2 immunity triggered by sequential variants of concern.

Severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), the virus that causes coronavirus disease 2019 (COVID‐19), has shifted our paradigms about B cell immunity and the goals of vaccination for respiratory viruses. The development of population immunity, through responses directed to highly immunogenic regions of this virus, has been a strong driving force in the emergence of progressively mutated variants. This review highlights how the strength of the existing global virology and immunology networks built for HIV vaccine research enabled rapid adaptation of techniques, assays, and skill sets, to expeditiously respond to the SARS‐CoV‐2 pandemic. Allying real‐time genomic surveillance to immunological platforms enabled the characterization of immune responses elicited by infection with distinct variants, in sequential epidemic waves, as well as studies of vaccination and hybrid immunity (combination of infection‐ and vaccination‐induced immunity). These studies have shown that consecutive variants of concern have steadily diminished the ability of vaccines to prevent infection, but that increasing levels of hybrid immunity result in higher frequencies of cross‐reactive responses. Ultimately, this rapid pivot from HIV to SARS‐CoV‐2 enabled a depth of understanding of the SARS‐CoV‐2 antigenic vulnerabilities as population immunity expanded and diversified, providing key insights for future responses to the SARS‐CoV‐2 pandemic.

Learning Methods During School Closure and Its Correlation With Anxiety and Health Behavior of Thai Students.

BackgroundThe sequential waves of epidemic spread of COVID-19 in Thailand have caused periodic closures of schools, and exposed students to different learning methods that require multiple adjustment strategies. This study aimed to examine how different learning methods may correlate with anxiety and health behavior (e.g., physical activity, active play, screen time, sleep) of primary and secondary school students in Thailand.MethodsThailand Report Card (TRC) Data (2021) was employed. The sample of the TRC was drawn by multi-stages random sampling stratified by region, district, urban/rural, school size, sex, and age to ensure national representativeness. A total of 6,078 Thai primary (64%) and secondary (36%) school students were included in the analysis.ResultsAbout two-thirds (66.4%) of the sample experienced a shift from traditional classroom to fully online learning, 6.9% experienced partial online instruction, 23.6% received handouts or written assignments, and 3.1% resumed traditional classroom learning. Compared to fully online learning, students who experienced traditional classroom (onsite) teaching were 37.8% less likely to report moderate-to severe anxiety (OR 0.6; p-value 0.021). There was no significant correlation between school closure-induced anxiety with overall physical activity (PA) and active play, but anxiety was significantly associated with screen time and sleep duration. Receiving handouts/written assignments only as the learning method was significantly correlated with PA, but two methods (handouts and onsite/traditional classroom) was significantly correlated with active play. Students who experienced classroom learning were also more likely to comply with recommended durations of screen time and sleep.ConclusionAlthough online learning was probably the most convenient choice during COVID-19 containment measures in Thailand, this method did not provide sufficient opportunity for PA and play. Online learning also encouraged an excessive use of screen media, and disrupted sleeping patterns. Online learning also pressured Thai students to make various adjustments in their daily routines that may have further aggravated anxiety.

Establishing content validity for the migraine Global Impression Item (mGI-I) assessment: a modified single-item migraine symptom severity questionnaire

ObjectiveTo establish content validity of a single-item, migraine-specific symptom severity questionnaire for completion by migraine patients, key family members (KFMs) of migraine patients, and Healthcare Professionals (HCPs) who treat migraine patients.BackgroundMigraine is a common disabling primary headache disorder with high prevalence and significant socioeconomic burden and personal impacts. There is a need for a global assessment of migraine symptom severity to evaluate potential new therapies from multiple perspectives.MethodsThe migraine Global Impression Item (mGI-I) was drafted and tested in a non-interventional, qualitative study comprising telephone interviews with 15 migraine patients, 15 KFMs of migraine patients, and 15 migraine treating HCPs. The mGI-I was drafted with two different item stem options and two different response scale options to ask about the patient’s migraine from the perspective of each respondent. Cognitive interviews were conducted to test comprehensiveness, clarity and ease of completion of the different versions of the mGI-I iteratively in three sequential waves of respondents.ResultsRevisions were made to the draft mGI-I after Wave 1 and Wave 2 of the interviews. Changes were made to simplify the item stem (removing unnecessary text), make language more patient-friendly (e.g. use of “migraine attack”), and add clarity to the item stem for consistent interpretation (include descriptive language of migraine attacks). Across both waves there was a preference for a 5-point response scale compared to a 7-point scale. In Wave 3, all respondents found the revised instructions, item stem, and 5-point response scale comprehensive, easy to understand and to answer. No further changes to the mGI-I were made after Wave 3.ConclusionsThis qualitative study of 45 total respondents across 3 subpopulations, established the content validity and appropriateness of the mGI-I in migraine patients, KFMs, and migraine-treating HCPs. The study specifically confirmed that the mGI-I is comprehensive, easily understood and answered for each respondent population.

Multiscale models of Covid-19 with mutations and variants

<p style='text-indent:20px;'>This paper focuses on the multiscale modeling of the COVID-19 pandemic and presents further developments of the model [<xref ref-type="bibr" rid="b7">7</xref>] with the aim of showing how relaxations of the confinement rules can generate sequential waves. Subsequently, the dynamics of mutations into new variants can be modeled. Simulations are developed also to support the decision making of crisis managers.</p>

The natural history of COVID-19 in patients with inflammatory bowel disease: a nationwide study by the Hellenic Society for the study of IBD.

COVID-19 has evolved into a global health crisis, variably affecting the management of patients with chronic illnesses. Patients with inflammatory bowel disease (IBD) may represent a vulnerable population due to frequent administration of immune-modifying treatments. We aimed to depict the natural history of COVID-19 infection in Greek patients with IBD at a nationwide level via unbiased reporting of all cases that were registered during the sequential waves of the pandemic. Following a national call from the Hellenic Society for the study of IBD, we enrolled all IBD patients with established diagnoses of COVID-19. Clinical and epidemiological data, including COVID-19 modifying factors and IBD-associated therapies, were analyzed against adverse outcomes (hospitalization, ICU admission and death). We identified 154 IBD patients who were diagnosed with COVID-19 (men: 58.4%; mean age=41.7 years [SD = 14.9]; CD: 64.3%). Adverse outcomes were reported in 34 patients (22.1%), including 3 ICU admissions (1.9%) and two deaths (1.3%). Multivariate logistic regression analysis showed that age (OR = 1.04, 95% CI, 1-1.08) and dyspnea at presentation (OR = 7.36, 95% CI, 1.84-29.46) were associated with worse outcomes of COVID-19 infection. In contrast, treatment with biologics, in particular anti-TNF agents, exerted a protective effect against an unfavorable COVID-19 disease course (OR = 0.4, 95% CI, 0.16-0.99). Patients on subcutaneous biologics were more likely to halt treatment due to the infection as compared to those on intravenous biologics. IBD patients who developed COVID-19 had a benign course with adverse outcomes being infrequent. Treatment with anti-TNF biologics had a protective effect, thus, supporting continuation of therapy during the pandemic.

The Temporal Mechanisms Guiding Interneuron Differentiation in the Spinal Cord.

Neurogenesis timing is an essential developmental mechanism for neuronal diversity and organization throughout the central nervous system. In the mouse spinal cord, growing evidence is beginning to reveal that neurogenesis timing acts in tandem with spatial molecular controls to diversify molecularly and functionally distinct post-mitotic interneuron subpopulations. Particularly, in some cases, this temporal ordering of interneuron differentiation has been shown to instruct specific sensorimotor circuit wirings. In zebrafish, in vivo preparations have revealed that sequential neurogenesis waves of interneurons and motor neurons form speed-dependent locomotor circuits throughout the spinal cord and brainstem. In the present review, we discuss temporal principals of interneuron diversity taken from both mouse and zebrafish systems highlighting how each can lend illuminating insights to the other. Moving forward, it is important to combine the collective knowledge from different systems to eventually understand how temporally regulated subpopulation function differentially across speed- and/or state-dependent sensorimotor movement tasks.

Cardiovascular Risk Factor and Disease Measures from the Population Assessment of Tobacco and Health (PATH) Study.

Background: Cardiovascular disease is a key health condition associated with tobacco use; however, clinical measures are not typically possible in population-based studies. In this paper, we assess the reliability and validity of self-reported cardiovascular risk factors and diseases in a large nationally representative study of tobacco use and health outcomes. Methods: This paper analyzes self-reported cardiovascular risk factors and disease among adults age 40 years and older based on U.S. nationally representative data from the Population Assessment of Tobacco and Health (PATH) Study. Prevalence of cardiovascular risk factors (self-reported high blood pressure, high cholesterol, diabetes and family history of premature heart disease, BMI ≥ 35, and tobacco use) and cardiovascular disease (self-reported heart attack, stroke and/or congestive heart failure (CHF)) were considered along with ratings of physical functioning, fatigue, and general health. Results: Self-reported cardiovascular disease was found to be associated with functional health measures (walking up a flight of stairs) and general ratings of health. Prospective analyses found strong correlations between sequential data collection waves for history of hypertension, elevated cholesterol and CHF, while more modest correlations were noted for stroke and heart attack. The overall prevalence of cardiovascular disease and hypertension was comparable to those from the National Health and Nutrition Examination Survey (NHANES). Conclusions: These analyses suggest reliability and concurrent validity regarding self-reported cardiovascular risk factors and disease assessed in the PATH Study.

Government responses and COVID-19 deaths: Global evidence across multiple pandemic waves.

We provide an assessment of the impact of government closure and containment measures on deaths from COVID-19 across sequential waves of the COVID-19 pandemic globally. Daily data was collected on a range of containment and closure policies for 186 countries from January 1, 2020 until March 11th, 2021. These data were combined into an aggregate stringency index (SI) score for each country on each day (range: 0-100). Countries were divided into successive waves via a mathematical algorithm to identify peaks and troughs of disease. Within our period of analysis, 63 countries experienced at least one wave, 40 countries experienced two waves, and 10 countries saw three waves, as defined by our approach. Within each wave, regression was used to assess the relationship between the strength of government stringency and subsequent deaths related to COVID-19 with a number of controls for time and country-specific demographic, health system, and economic characteristics. Across the full period of our analysis and 113 countries, an increase of 10 points on the SI was linked to 6 percentage points (P < 0.001, 95% CI = [5%, 7%]) lower average daily deaths. In the first wave, in countries that ultimately experiences 3 waves of the pandemic to date, ten additional points on the SI resulted in lower average daily deaths by 21 percentage points (P < .001, 95% CI = [8%, 16%]). This effect was sustained in the third wave with reductions in deaths of 28 percentage points (P < .001, 95% CI = [13%, 21%]). Moreover, interaction effects show that government policies were effective in reducing deaths in all waves in all groups of countries. These findings highlight the enduring importance of non-pharmaceutical responses to COVID-19 over time.

A Preliminary Investigation of Insect Succession Patterns on Decomposing Carrion on Rottnest Island (WA)

Introduction: Pivotal component of medico-legal investigations is the determination of time since death, or (minimum) postmortem interval, (min) PMI. Forensic entomology can provide reliable estimates of (min) PMI using carrion insect species. Carrion insect arrival and departure occurs in predictable and sequential waves, however, successions may vary depending on geographical location and environmental conditions. Hence, it is crucial to refer to insect succession data of the same region where the death scene occurs. A current gap in forensic entomology research is on carrion-breeding species and succession on decomposition remains/carrions on small islands. Rottnest Island is located off the south-west coast of Perth. The aim of this study was to establish baseline data of carrion insect fauna present on this island, and to provide entomological evidence that may aid in any future investigations on the island. Methods: A list of the insect taxa associated with two decomposing swine hindquarters during the summer season was compiled over a 15-day study period and compared with published mainland data obtained during the same period of the year. Results: Ten insect taxa representing four families were collected and identified in association with the decomposing carrion. The first wave of colonising Diptera species included Calliphoridae species and Sarcophagidae species. The second wave of Diptera comprised Muscidae species, in addition to beetles. Furthermore, ants and spiders were noted throughout the trial. Conclusions: Comparing the results on Rottnest Island with currently available data from mainland WA, showed that the composition of insect speciesand the patterns of succession were similar.

Factor and 6th Polynomial Regression Analyses of COVID19 Data from 35 Countries Reveal 4 Patterns of Epidemic Evolution that Includes up to 4 Sequential Waves.

COVID Pandemics is now one year old, and virus not only spread across the world but also drastically changes by means of a high mutation rate, many of them appearing simultaneously at different geographic regions. Because of this mutation capacity the virus cannot be considered single entity as proposed current epidemiologic models, but has to be assumed as a fuzzy being that expresses itself as a family of variants, requiring its dynamics to be understood by means of new theoretical approaches and new epidemic data analyses. The purpose of the present paper is to discuss actual knowledge about COVID19 to better model its dynamics and analyze worldwide epidemic data under this point of view. To accomplish this, actual knowledge about the virus genome structure and replication process, as well as about its known mutations are reviewed, resulting in the proposal that: SARS Cov2 evolved from animals and/or other Human CoVs following the rules of natural selection due to its high rate of mutations that transformed its ancestors to better infect humans using ACE2 receptors, simultaneously in many distinct and widely distributed geographic regions, and it continues, nowadays, this kind of evolution across the world, largely independent from human mobility. Therefore, COVID19 concurrently appeared at many different world regions and have not one but multiple concurrent ancestors. Because of this, the theory of Formal Languages is proposed as an adequate tool to model the structure of COVID19 genome; its mutations and actual virus mutational evolution. This model justifies the use of Factor Analysis as a statistical tool to investigate patterns of covariation in a large number of variables and to determine if information may be condensed into small sets of these variables called principal components . Results shows that 4 patterns explain 75% of covariance of the Daily New Cases reported by 35 countries, indicating the existence of 4 worldwide epidemic patterns. 6th Polynomial regression was used to further investigation the national particularities of the epidemics of the different countries associated to each of these patterns. Results suggest that COVID19 high mutational rate creates simultaneously a large number of virus lineages across the world that submitted to natural selection, promotes distinct epidemic evolution in different countries, mostly dictated by the local virus mutational development rather than influenced by foreigner lineage importation. Based on this, actual Pandemic Dogmatic Management based on lockdown; stay home orders and indiscriminate mobility restriction is discussed and alternative solutions are suggested.

Single-cell transcriptomics reveal temporal dynamics of critical regulators of germ cell fate during mouse sex determination.

Despite the importance of germ cell (GC) differentiation for sexual reproduction, the gene networks underlying their fate remain unclear. Here, we comprehensively characterize the gene expression dynamics during sex determination based on single-cell RNA sequencing of 14914 XX and XY mouse GCs between embryonic days (E) 9.0 and 16.5. We found that XX and XY GCs diverge transcriptionally as early as E11.5 with upregulation of genes downstream of the bone morphogenic protein (BMP) and nodal/Activin pathways in XY and XX GCs, respectively. We also identified a sex-specific upregulation of genes associated with negative regulation of mRNA processing and an increase in intron retention consistent with a reduction in mRNA splicing in XY testicular GCs by E13.5. Using computational gene regulation network inference analysis, we identified sex-specific, sequential waves of putative key regulator genes during GC differentiation and revealed that the meiotic genes are regulated by positive and negative master modules acting in an antagonistic fashion. Finally, we found that rare adrenal GCs enter meiosis similarly to ovarian GCs but display altered expression of master genes controlling the female and male genetic programs, indicating that the somatic environment is important for GC function. Our data are available on a web platform and provide a molecular roadmap of GC sex determination at single-cell resolution, which will serve as a valuable resource for future studies of gonad development, function, and disease.

Toward a New Urban Cycle? A Closer Look to Sprawl, Demographic Transitions and the Environment in Europe

Urban growth is a largely debated issue in social science. Specific forms of metropolitan expansion—including sprawl—involve multiple and fascinating research dimensions, making mixed (quali-quantitative) analysis of this phenomenon particularly complex and challenging at the same time. Urban sprawl has attracting the attention of multidisciplinary studies defining nature, dynamics, and consequences that dispersed low-density settlements are having on biophysical and socioeconomic contexts worldwide. The present commentary provides a brief overview on nature and implications of the latent relationship between sprawl, demographic dynamics, and background socio-environmental contexts with special focus on Europe. Empirical evidence supports the idea that spatial planning should cope more effectively with the increasing environmental and socioeconomic exposure of European regions to sprawl and demographic transitions, being progressively far away from a traditional urban cycle with sequential waves of urbanization, suburbanization, counter-urbanization, and re-urbanization. Growing socio-ecological vulnerability of metropolitan regions was evaluated based on a literature review demonstrating how a better comprehension of the intimate linkage between long-term demographic dynamics and urban cycles is necessary to inform fine-tuned policies controlling sprawl and promoting a sustainable management of peri-urban land.

Recession, Local Fertility, and Urban Sustainability: Results of a Quasi-Experiment in Greece, 1991–2018

Fertility is a spatially non-stationary property of regional demographic systems. Despite the wealth of quantitative (micro–macro) information delineating short-term population dynamics in advanced economies, the contribution of economic downturns to local fertility has still been under-investigated along urban–rural gradients, especially in low-fertility contexts. Recent studies have assumed suburban fertility rates as systematically higher than urban and rural fertility rates. This assumption (hereafter known as the “suburban fertility hypothesis”) has been grounded on stylized facts and spatial regularities in advanced economies that reflect a significant role of both macro (contextual) and micro (behavioral) factors that positively influence fertility in suburban locations. To test the suburban fertility hypothesis at the macro-scale, the present study compares gross fertility rates from seven regional units of the Athens metropolitan area between 1991 and 2018. A refined spatial analysis of gross fertility rates during an economic expansion (1999–2008) and recession (2009–2018) was carried out in 115 urban, suburban, and rural municipalities of the same area. Experiencing sequential waves of economic expansion and recession, Athens’ socio-demographic dynamics were considered a sort of “quasi-experiment” for Southern Europe, linking late suburbanization with the multiple impacts of (rapid) economic downturns. Compared with both urban and rural locations, a higher fertility rate in suburban municipalities (15–20 km away from downtown Athens) was observed during the study period. However, a subtle distinction was observed during the economic expansion versus the recession. In the first period, the highest birth rates were recorded in industrial locations west of Athens, hosting economically disadvantaged communities with a relatively young population structure. With the recession, the highest fertility was associated with residential and service-specialized (wealthier) locations east of Athens, attracting resident population from neighboring areas, and better responding to crisis. The results of our study document how recent urban expansion and economic downturns have intrinsically shaped fertility dynamics, with implications for urban sustainability and social cohesion of metropolitan regions.