Molecular Characterization of Severe Acute Respiratory Syndrome Coronavirus 2 Isolates From Central Inner Sardinia

BackgroundThe SARS-CoV-2 pandemic stimulated an outstanding global sequencing effort, which allowed to monitor viral circulation and evolution. Nuoro province (Sardinia, Italy), characterized by a relatively isolated geographical location and a low population density, was severely hit and displayed a high incidence of infection.MethodsAmplicon approach Next Generation Sequencing and subsequent variant calling in 92 respiratory samples from SARS-CoV-2 infected patients involved in infection clusters from March 2020 to May 2021.ResultsPhylogenetic analysis displayed a coherent distribution of sequences in terms of lineage and temporal evolution of pandemic. Circulating lineage/clade characterization highlighted a growing diversity over time, with an increasingly growing number of mutations and variability of spike and nucleocapsid proteins, while viral RdRp appeared to be more conserved. A total of 384 different mutations were detected, of which 196 were missense and 147 synonymous ones. Mapping mutations along the viral genome showed an irregular distribution in key genes. S gene was the most mutated gene with missense and synonymous variants frequencies of 58.8 and 23.5%, respectively. Mutation rates were similar for the S and N genes with one mutation every ∼788 nucleotides and every ∼712 nucleotides, respectively. Nsp12 gene appeared to be more conserved, with one mutation every ∼1,270 nucleotides. The frequency of variant Y144F in the spike protein deviated from global values with higher prevalence of this mutation in the island.ConclusionThe analysis of the 92 viral genome highlighted evolution over time and identified which mutations are more widespread than others. The high number of sequences also permits the identification of subclusters that are characterized by subtle differences, not only in terms of lineage, which may be used to reconstruct transmission clusters. The disclosure of viral genetic diversity and timely identification of new variants is a useful tool to guide public health intervention measures.

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Modelling the evolution of COVID-19 in high-incidence European countries and regions: estimated number of infections and impact of past and future intervention measures

10.1101/2020.05.09.20096735 ◽

2020 ◽

Author(s):

Juan Fernandez-Recio

Keyword(s):

Reproduction Number ◽

Mechanistic Model ◽

Control Measures ◽

European Countries ◽

Intervention Measures ◽

High Incidence ◽

Long Term Impact ◽

The Impact ◽

Over Time

A previously developed mechanistic model of COVID-19 transmission has been adapted and applied here to study the evolution of the disease and the effect of intervention measures in some European countries and territories where the disease had major impact. A clear impact of the major intervention measures on the reproduction number (Rt) has been found in all studied countries and territories, as already suggested by the drop in the number of deaths over time. Interestingly, the impact of such major intervention measures seems to be the same in most of these countries. The model has also provided realistic estimates of the total number of infections, active cases and future outcome. While the predictive capabilities of the model are much more uncertain before the peak of the outbreak, we could still reliably predict the evolution of the disease after a major intervention by assuming the afterwards reproduction number from current study. More challenging is to foresee the long-term impact of softer intervention measures, but this model can estimate the outcome of different scenarios and help planning changes in the implementation of control measures in a given country or region.

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A Profile of Bicycle-Related Injuries in Tai Po

Hong Kong Journal of Emergency Medicine ◽

10.1177/102490790301000204 ◽

2003 ◽

Vol 10 (2) ◽

pp. 81-87 ◽

Cited By ~ 1

Author(s):

LLY Lee ◽

KL Yeung ◽

JTS Chan ◽

RCI Chen

Keyword(s):

District Hospital ◽

Geographical Location ◽

Female Gender ◽

Bicycle Safety ◽

School Aged Children ◽

Intervention Measures ◽

High Incidence ◽

The Common ◽

Serious Injury ◽

Bicycle Injury

Background Implementation of prevention programs for bicycle safety should be based on a good understanding of the profile of bicycle accidents. The objective of this study was to investigate the differences in the severity of bicycle-related injuries when comparing with various risk factors, and to utilize this information to formulate the intervention measures. Methods A retrospective review was conducted on all patients (n=116) who were treated for bicycle-related injuries within a period of 66 days at the emergency department of a district hospital in Tai Po, New Territories. Results School-aged children, especially boys, were more commonly injured. The head and lower extremities were the common sites of injuries. Female gender (χ2=4.39; P<0.05) and injuries involving head and upper extremities (χ2=12.61; P<0.05) were associated with higher chance of serious injury. Conclusion Tai Po district had a high incidence of bicycle accidents due to its geographical location. Population at a greater risk for bicycle injury was the male gender school-aged children and therefore prevention program should be targeted at them.

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Clinical characterization of dysautonomia in long COVID-19 patients

Scientific Reports ◽

10.1038/s41598-021-93546-5 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nicolas Barizien ◽

Morgan Le Guen ◽

Stéphanie Russel ◽

Pauline Touche ◽

Florent Huang ◽

...

Keyword(s):

Mixed Models ◽

Repeated Measures ◽

Physical Medicine ◽

Persistent Symptoms ◽

Index Changes ◽

Changes Over Time ◽

And Control ◽

Testing Group ◽

Over Time

AbstractIncreasing numbers of COVID-19 patients, continue to experience symptoms months after recovering from mild cases of COVID-19. Amongst these symptoms, several are related to neurological manifestations, including fatigue, anosmia, hypogeusia, headaches and hypoxia. However, the involvement of the autonomic nervous system, expressed by a dysautonomia, which can aggregate all these neurological symptoms has not been prominently reported. Here, we hypothesize that dysautonomia, could occur in secondary COVID-19 infection, also referred to as “long COVID” infection. 39 participants were included from December 2020 to January 2021 for assessment by the Department of physical medicine to enhance their physical capabilities: 12 participants with COVID-19 diagnosis and fatigue, 15 participants with COVID-19 diagnosis without fatigue and 12 control participants without COVID-19 diagnosis and without fatigue. Heart rate variability (HRV) during a change in position is commonly measured to diagnose autonomic dysregulation. In this cohort, to reflect HRV, parasympathetic/sympathetic balance was estimated using the NOL index, a multiparameter artificial intelligence-driven index calculated from extracted physiological signals by the PMD-200 pain monitoring system. Repeated-measures mixed-models testing group effect were performed to analyze NOL index changes over time between groups. A significant NOL index dissociation over time between long COVID-19 participants with fatigue and control participants was observed (p = 0.046). A trend towards significant NOL index dissociation over time was observed between long COVID-19 participants without fatigue and control participants (p = 0.109). No difference over time was observed between the two groups of long COVID-19 participants (p = 0.904). Long COVID-19 participants with fatigue may exhibit a dysautonomia characterized by dysregulation of the HRV, that is reflected by the NOL index measurements, compared to control participants. Dysautonomia may explain the persistent symptoms observed in long COVID-19 patients, such as fatigue and hypoxia. Trial registration: The study was approved by the Foch IRB: IRB00012437 (Approval Number: 20-12-02) on December 16, 2020.

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Identification and Characterization of Multiple Myeloma Stem Cell-Like Cells

Cancers ◽

10.3390/cancers13143523 ◽

2021 ◽

Vol 13 (14) ◽

pp. 3523

Author(s):

Wancheng Guo ◽

Haiqin Wang ◽

Peng Chen ◽

Xiaokai Shen ◽

Boxin Zhang ◽

...

Keyword(s):

Multiple Myeloma ◽

Drug Resistance ◽

Stem Cell ◽

New Drugs ◽

Cell Therapies ◽

High Relapse Rate ◽

High Incidence ◽

Poorly Differentiated ◽

Identification And Characterization

Multiple myeloma (MM) is a B-cell tumor of the blood system with high incidence and poor prognosis. With a further understanding of the pathogenesis of MM and the bone marrow microenvironment, a variety of adjuvant cell therapies and new drugs have been developed. However, the drug resistance and high relapse rate of MM have not been fundamentally resolved. Studies have shown that, in patients with MM, there is a type of poorly differentiated progenitor cell (MM stem cell-like cells, MMSCs). Although there is no recognized standard for identification and classification, it is confirmed that they are closely related to the drug resistance and relapse of MM. This article therefore systematically summarizes the latest developments in MMSCs with possible markers of MMSCs, introduces the mechanism of how MMSCs work in MM resistance and recurrence, and discusses the active pathways that related to stemness of MM.

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520. Longitudinal Analysis of SARS-CoV-2 Viruses in Hospitalized Adults

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.714 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S325-S326

Author(s):

Lacy Simons ◽

Ramon Lorenzo-Redondo ◽

Hannah Nam ◽

Scott C Roberts ◽

Michael G Ison ◽

...

Keyword(s):

Viral Load ◽

Genome Sequencing ◽

Viral Genome ◽

Temporal Dynamics ◽

Population Level ◽

Hospital Staff ◽

Therapeutic Interventions ◽

Viral Loads ◽

Qrt Pcr ◽

Over Time

Abstract Background The rapid spread of SARS-CoV-2, the causative agent of Coronavirus disease 2019 (COVID-19), has been accompanied by the emergence of viral mutations, some of which may have distinct virological and clinical consequences. While whole genome sequencing efforts have worked to map this viral diversity at the population level, little is known about how SARS-CoV-2 may diversify within a host over time. This is particularly important for understanding the emergence of viral resistance to therapeutic interventions and immune pressure. The goal of this study was to assess the change in viral load and viral genome sequence within patients over time and determine if these changes correlate with clinical and/or demographic parameters. Methods Hospitalized patients admitted to Northwestern Memorial Hospital with a positive SARS-CoV-2 test were enrolled in a longitudinal study for the serial collection of nasopharyngeal specimens. Swabs were administered to patients by hospital staff every 4 ± 1 days for up to 32 days or until the patients were discharged. RNA was extracted from each specimen and viral loads were calculated by quantitative reverse transcriptase PCR (qRT-PCR). Specimens with qRT-PCR cycle threshold values less than or equal to 30 were subject to whole viral genome sequencing by reverse transcription, multiplex PCR, and deep sequencing. Variant populations sizes were estimated and subject to phylogenetic analysis relative to publicly available SARS-CoV-2 sequences. Sequence and viral load data were subsequently correlated to available demographic and clinical data. Results 60 patients were enrolled from March 26th to June 20th, 2020. We observed an overall decrease in nasopharyngeal viral load over time across all patients. However, the temporal dynamics of viral load differed on a patient-by-patient basis. Several mutations were also observed to have emerged within patients over time. Distribution of SARS-CoV-2 viral loads in serially collected nasopharyngeal swabs in hospitalized adults as determined by qRT-PCR. Samples were collected every 4 ± 1 days (T#1–8) and viral load is displayed by log(copy number). Conclusion These data indicate that SARS-CoV-2 viral loads in the nasopharynx decrease over time and that the virus can accumulate mutations during replication within individual patients. Future studies will examine if some of these mutations may provide fitness advantages in the presence of therapeutic and/or immune selective pressures. Disclosures Michael G. Ison, MD MS, AlloVir (Consultant)

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Identity Politics and Refugee Policies in Kupang, Eastern Indonesia: A Politico-Historical Perspective

Asian Journal of Law and Society ◽

10.1017/als.2021.6 ◽

2021 ◽

pp. 1-14

Author(s):

Andrey Damaledo

Keyword(s):

Identity Politics ◽

Host Country ◽

Historical Perspective ◽

Geographical Location ◽

Policy Implications ◽

Refugee Status ◽

Timor Leste ◽

Displaced People ◽

Over Time

Abstract This article assesses the implementation of Presidential Regulation No. 125 of 2016 concerning the Treatment of Refugees and how it relates to different kinds of bureaucratic labelling of refugees as it unfolds in Indonesia’s region of Kupang. From a politico-historical perspective, Kupang is a useful case-study for elucidating the policy implications of the labelling of refugees, as the region has been hosting different kinds of refugees due to its strategic geographical location that borders Australia and Timor-Leste. Drawing on my fieldwork in Kupang between October 2012 and October 2013, and my intermittent return to the region between January 2017 and February 2019, this article argues that labels for refugees evolve over time in response to the larger sociopolitical situation, but they are formed mostly to serve the interest of the host country rather than those of displaced people. Furthermore, while labelling displaced people as “refugees” has been effective in justifying funding and support, it can also lead to a manipulation of refugee status, and the marginalization and exclusion of refugees.

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Segmentation analysis in the volumetric measurement and tissue characterization of MS lesions over time

Journal of Neuroimmunology ◽

10.1016/0165-5728(95)98985-k ◽

1995 ◽

Vol 56-63 ◽

pp. 40-40

Author(s):

CF Gonzalez ◽

S. Vlnltski ◽

S. Shehagiri ◽

F.D. Lublin ◽

R.L. Knobler

Keyword(s):

Tissue Characterization ◽

Volumetric Measurement ◽

Segmentation Analysis ◽

Over Time

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Communal versus Competitive Feasting: Comment on Kassabaum

American Antiquity ◽

10.1017/aaq.2020.66 ◽

2020 ◽

Vol 85 (4) ◽

pp. 795-798

Author(s):

Brian Hayden

Keyword(s):

Social Solidarity ◽

Monumental Architecture ◽

High Incidence ◽

Egalitarian Society ◽

Made In

Megan Kassabaum has developed a useful approach for interpreting feasting remains, but its application to the Feltus site demonstrates that modifications need to be made. In particular, the characterization of competitive feasting is too simplistic, and her model does not include work types of feasts, which may be responsible for the remains at the Feltus site. The interpretation of feasting at the Feltus site as resulting from social solidarity needs of a dispersed egalitarian society appear questionable on the basis of a high incidence of special meat, the occurrence of smoking pipes, monumental architecture, and indications of possible human sacrifices.

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Spectral characterization of ciliary beating: variations of frequency with time

AJP Cell Physiology ◽

10.1152/ajpcell.1985.249.1.c160 ◽

1985 ◽

Vol 249 (1) ◽

pp. C160-C165 ◽

Cited By ~ 57

Author(s):

D. Eshel ◽

Y. Grossman ◽

Z. Priel

Keyword(s):

Mathematical Model ◽

Power Spectra ◽

Ciliary Beating ◽

Isolated Lung ◽

Ciliary Cell ◽

The Mathematical Model ◽

Beating Frequency ◽

Over Time ◽

Dominant Frequencies

Ciliary beating frequency in tissue culture from frog palate and isolated lung was optically examined using instrumentation that was adjusted to measure a fraction of the surface area of a single ciliary cell. Consecutive 1-s segments of the analogue signal were fast Fourier transformed (FFT) to obtain a power spectrum. At room temperature, these power spectra changed over time from 1 s to the next. Each spectrum contained several dominant frequencies of similar intensities. Cooling the preparation resulted in a single-peak spectrum that was constant over time. A mathematical model is proposed to simulate these findings. The results and the mathematical model support the hypothesis that ciliary beating frequency fluctuates over short periods of time.

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