bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Health Navigators to Connect At-Risk Clients to Community Resources
Authors: Menendez Telma , Barragan Noel C. , Kuo Tony , Morrison Janina L.
Published: July 2021

Context:

The coupling of health care services with complementary resources that address unmet social needs is a progressively popular approach for improving health outcomes among low-income populations. Community health workers are increasingly recognized as a helpful intermediary for clients navigating community and clinical services.

Program:

The Wellness Center at the Historic General Hospital in East Los Angeles employs a team of community health workers, referred to as Health Navigators, who are trained to link low-income clients to resources such as chronic disease management programs, food pantries, free or low-cost legal aid, health insurance enrollment, group fitness classes, and counseling and peer support services.

Implementation:

The Center's model of practice has evolved over time, continuously increasing the breadth and depth of services provided by the Health Navigator team. Its goal has been to address clients' unmet social needs while optimizing their health outcomes through the building of stronger community-clinical linkages.

Evaluation:

A program review showed that Health Navigators serve as a critical bridge for clients navigating a complex network of health and social services. They actively engage, recruit, and deliver services to clients. Since 2014, the Health Navigator team has connected more than 28 000 unique clients to resources for health and well-being.

Discussion:

By using Health Navigators to assist clients with community resource engagement, the Center has prototyped and promoted an approach that complements clinical care, strengthening the community-clinical linkages that are needed to meaningfully manage chronic disease outside of the hospital or clinic setting.
Liability Waivers for COVID-19: Law, Policy, and Practice
Authors: Yang Y. Tony , Chen Brian K.
Published: July 2021

As businesses reopen, the practice of asking customers to sign COVID-19 liability waivers is increasing throughout the United States. Although the courts have not yet decided the enforceability of COVID-19–related liability waivers, existing case law, as well as new executive and legislative actions, suggests that such waivers may offer some protection to businesses from liability. Nevertheless, we believe that the legal and ethical rationales underlying liability waivers are not applicable to a pandemic. We further argue that the challenging nature of and the substantial unknowns about the novel coronavirus make waivers contrary to public policy. Fears over floods of litigation appear thus far unfounded, and businesses should not be relieved from their obligation of taking reasonable safety precautions. Waivers are not a panacea to reopen businesses in an ongoing pandemic, and the ultimate protection against liability is to operate in a manner that minimizes the spread of the virus consistent with evidence-based guidelines.
A Prospective US National Trauma Center Study of Firearm Injury Survivors Weapon Carriage and Posttraumatic Stress Disorder Symptoms
Authors: Nehra Deepika , Bulger Eileen M. , Maier Ronald V. , Moloney Kathleen E. , Russo Joan , Wang Jin , Anderson Kristina , Zatzick Douglas F.
Published: July 2021

Objective:

To describe the demographic, injury-related, and mental health characteristics of firearm injury patients and trace firearm weapon carriage and PTSD symptoms over the year after injury.

Summary and Background Data:

Based on the increasing incidence of firearm injury and need for novel injury prevention strategies, hospital-based violence intervention programs are being implemented in US trauma centers. There is limited data on the long-term outcomes and risk behaviors of firearm injury survivors to guide this work.

Methods:

We conducted a secondary analysis of a pragmatic 25-trauma center randomized trial (N = 635). Baseline characteristics of firearm-injured patients (N = 128) were compared with other trauma patients. Mixed model regression was used to identify risk factors for postinjury firearm weapon carriage and PTSD symptoms.

Results:

Firearm injury patients were younger and more likely to be black, male and of lower socioeconomic status, and more likely to carry a firearm in the year before injury. Relative to preinjury, there was a significant drop in firearm weapon carriage at 3- and 6-months postinjury, followed by a return to preinjury levels at 12-months. Firearm injury was significantly and independently associated with an increased risk of postinjury firearm weapon carriage [relative risk = 2.08, 95% confidence interval (1.34, 3.22), P < 0.01] and higher PTSD symptom levels [Beta = 3.82, 95% confidence interval (1.29, 6.35), P < 0.01].

Conclusions:

Firearm injury survivors are at risk for firearm carriage and high PTSD symptom levels postinjury. The significant decrease in the high-risk behavior of firearm weapon carriage at 3–6 months postinjury suggests that there is an important postinjury “teachable moment” that should be targeted with preventive interventions.

Trial Registration:

ClinicalTrials.gov NCT02655354
The effect of obesity on inpatient outcomes in lower extremity trauma: A systematic review and meta-analysis
Authors: Liu Qinxin , Wu Mengfan , Orgill Dennis P. , Bai Xiangjun , Panayi Adriana C.
Published: July 2021

BACKGROUND

Obesity is a growing global health problem and a well-recognized risk factor for many medical conditions. This meta-analysis was conducted to assess the effect of obesity on overall complication occurrence, mortality, and hospital length of stay in patients with nonpathological lower limb trauma.

METHODS

The EMBASE, PUBMED, and MEDLINE electronic databases were searched from inception to April 1, 2020, for studies published in English. References cited by chosen studies were also checked manually for inclusion. Studies chosen for the analysis were prospective observational or retrospective cohort studies reporting on total complications of patients with acute traumatic, nonpathological, lower limb fractures that required internal fixation, with or without other underlying conditions. Two investigators independently reviewed the full text of eligible studies for inclusion and extracted data. Inconsistency was resolved through consultation with other authors.

RESULTS

Sixteen studies with 404,414 patients were investigated in this study. The data showed obesity was related with increased total complications (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.51–0.83; p < 0.01), increased wound complications (OR, 0.41; 95% CI, 0.25–0.66; p < 0.01), and increased mortality rate (OR, 0.64; 95% CI, 0.45–0.91; p < 0.05). Six cohort studies also showed prolonged hospital length of stay in obese patients.

CONCLUSION

Our results suggest that obesity is associated with increased complication and mortality rates, as well as longer hospital length of stay in patients with lower-limb trauma who required surgical treatment. These findings may raise attention to optimize surgical technique and develop individualized treatment for obese patients.

LEVEL OF EVIDENCE

Systematic reviews, level IV.
A global transcriptomic analysis of Staphylococcus aureus biofilm formation across diverse clonal lineages
Authors: Tomlinson Brooke R. , Malof Morgan E. , Shaw Lindsey N.
Published: July 2021

A key characteristic of

Staphylococcus aureus

infections, and one that also varies phenotypically between clones, is that of biofilm formation, which aids in bacterial persistence through increased adherence and immune evasion. Though there is a general understanding of the process of biofilm formation – adhesion, proliferation, maturation and dispersal – the tightly orchestrated molecular events behind each stage, and what drives variation between

S. aureus

strains, has yet to be unravelled. Herein we measure biofilm progression and dispersal in real-time across the five major

S. aureus

CDC-types (USA100-USA500) revealing adherence patterns that differ markedly amongst strains. To gain insight into this, we performed transcriptomic profiling on these isolates at multiple timepoints, compared to planktonically growing counterparts. Our findings support a model in which eDNA release, followed by increased positive surface charge, perhaps drives initial abiotic attachment. This is seemingly followed by cooperative repression of autolysis and activation of poly-N-acetylglucosamine (PNAG) production, which may indicate a developmental shift in structuring the biofilm matrix. As biofilms mature, diminished translational capacity was apparent, with 53 % of all ribosomal proteins downregulated, followed by upregulation of anaerobic respiration enzymes. These findings are noteworthy because reduced cellular activity and an altered metabolic state have been previously shown to contribute to higher antibiotic tolerance and bacterial persistence. In sum, this work is, to our knowledge, the first study to investigate transcriptional regulation during the early, establishing phase of biofilm formation, and to compare global transcriptional regulation both temporally and across multiple clonal lineages.
Impacts of school closure due to COVID-19 on the mobility trend of Japanese citizens
Authors: Nam Nguyen Hai , Nguyen Anh PN. , Do Le Bao-Tran , Gad Abdelrahman Gamil , Abdelnaeim Abdalla Abdelrahman Sherif Mohamed , Safi Adnan , Pham Anh Gia , Khanh Vo Duc , Huy Nguyen Tien
Published: July 2021

School closure was the only main control measure that Japan took into action from late February to late March in 2020. Accurate evaluation of how Japanese citizens responded to the impact of school closure remains a challenge. Data from the Google COVID-19 Community Mobility Report was used to analyze the mobility trend of Japanese citizens regarding six categories, including retail and recreation, grocery and pharmacy, parks, transit stations, workplace, and residential. The median percentage of mobility in all 47 prefectures of Japan was calculated during five periods of time, including one week before school closure, one week, two weeks, three weeks, and four weeks after school closure. There was a significant decline in the mobility trend of transit stations, grocery and pharmacy, parks, retail and recreation, and workplace at the moment after school closure compared to the prior period. Inversely, the mobility trend in staying at home remarkably increased following the implementation of school closure. Our study determined a significant change in the mobility trend of Japanese citizens before and after school closure. These data reflected the responsibility and the consciousness of Japanese citizens in mitigating COVID-19.
A nationwide study of Chlamydia trachomatis infections in Denmark during the COVID-19 pandemic
Authors: Hedley Paula L. , Hoffmann Steen , Lausten-Thomsen Ulrik , Voldstedlund Marianne , Bjerre Karsten Dalsgaard , Hviid Anders , Krebs Lone , Jensen Jørgen S. , Christiansen Michael
Published: July 2021

Objectives

COVID-19 policies have been employed in Denmark since March 2020. We examined whether COVID-19 restrictions had an impact on Chlamydia trachomatis infections compared with 2018 and 2019.

Methods

This retrospective nation-wide Danish observational study was performed using monthly incidences of laboratory confirmed chlamydia cases and number of tests, obtained from nation-wide surveillance data. Additionally, Oxford COVID-19 Government Response Tracker data, and Google COVID-19 Community Mobility Reports were used to contextualise the behavioural adaptions seen as a result of COVID-19 policies. Testing rates were compared using Poisson regression and test positivity rates were compared using logistic regression.

Results

The crude incidence rate (IR) of laboratory confirmed chlamydia infections was reduced to 66.5 per 105 during the first (March-April 2020) lockdown period as compared to 88.3 per 105 in March-April 2018-2019, but the testing rate was also reduced (Rate ratio 0.72 95% CI 0.71 – 0.73), whereas the odds ratio for a positive test between the two periods was 0.98 (95% CI 0.96 – 1.00). The period of eased COVID 19 restrictions (May – December 2020) and the second lockdown period (December 2020 – March 2021) were characterised by marginally increased crude IRs, while the number of tests performed, and test positivity rates returned very close to the levels seen in 2018-2019. These results were independent of sex, age group, and geographical location.

Conclusion

The first Danish COVID-19 lockdown resulted in a reduction in the number of chlamydia tests performed and a consequent reduction in the number of laboratory-identified cases. This period was followed by a return of testing and test positivity close to the level seen in 2018 – 2019. Altogether the Danish COVID-19 restrictions have had negligible effects on laboratory confirmed C. trachomatis transmission.
SARS-CoV-2 B.1.1.7 lineage rapidly spreads and overwhelms R.1 lineage in Japan: serial and stationary observation in a community
Authors: Hirotsu Yosuke , Omata Masao
Published: July 2021

Background

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) circulates in the world and acquires mutations during evolution. To identify the new emergent variants, the surveillance of the variants of concern (VOC) and variants of interest (VOI) is ongoing. This study aimed to determine how the transition of viral lineage occurred by stationary genome analysis in Yamanashi, Japan.

Methods

We performed the whole genome sequencing using SARS-CoV-2 positive samples (n=325) collected from February 2020 to the end of June 2021. The number of analyzed samples accounted for 15.4% of the total 2,109 samples identified in our community. Viral lineage was defined by the Phylogenetic Assignment of Named Global Outbreak (PANGO) lineages.

Results

We identified 13 types of viral lineages including R.1, P.1, B.1.1.7 (Alpha) and B.1.617.2 (Delta) These virus lineages had distinct periods of expansion and decline. After the emerging of the R.1 lineage harboring E484K variant (designated VOI in Japan), the prevalent B.1.1.214 lineage were no longer identified. The R.1 lineages were temporarily prevalent afterwards, but the influx of B.1.1.7 lineage (designated VOC) led to a decline in R.1. Currently, B.1.1.7 has become dominant after mid-April, 2021.

Conclusion

We clearly elucidated the transition and replacement of viral lineage by the community-based analysis. The virus completely replaced by more infectious lineages, therefore, it will be necessary to continue to monitor the VOC and VOI.
The Ultra Fit Community Mask - Toward Maximal Respiratory Protection via Personalized Face Fit
Authors: Hyun Chulho , Jensen Mark Martin , Yang Kisuk , Weaver James C. , Wang Xiaohong , Kudo Yoshimasa , Gordon Steven J. , Karp Jeffrey M. , Samir Anthony E.
Published: July 2021

Effective masking policies to prevent the spread of airborne infections depend on public access to masks with high filtration efficacy. However, poor face-fit is almost universally present in pleated multilayer disposable face masks, severely limiting both individual and community respiratory protection. We developed a set of simple mask modifications to mass-manufactured disposable masks, the most common type of mask used by the public, that dramatically improves both their personalized fit and performance in a low-cost and scalable manner. These modifications comprise a user-moldable full mask periphery wire, integrated earloop tension adjusters, and an inner flange to trap respiratory droplets. We demonstrate that these simple design changes improves quantitative fit factor by 320%, triples the level of protection against aerosolized droplets, and approaches the model efficacy of N95 respirators in preventing the community spread of COVID-19, for an estimated additional cost of less than 5 cents per mask with automated production.

Teaser

A personalizable, low-cost mask improves facial fit, reduces user exposure, and decreases spread of contagious aerosols.
Persistent HBV replication and serological response during up to fifteen years of tenofovir-based antiretroviral therapy in HIV-hepatitis B coinfected patients: a multicenter prospective cohort study
Authors: Dezanet Lorenza N. C. , Miailhes Patrick , Lascoux-Combe Caroline , Chas Julie , Maylin Sarah , Gabassi Audrey , Rougier Hayette , Delaugerre Constance , Lacombe Karine , Boyd Anders
Published: July 2021

Objectives

To determine the extent of hepatitis B virus (HBV) suppression and its association with hepatitis “e” antigen (HBeAg) and hepatitis B surface antigen (HBsAg)-seroclearance in HIV-HBV-coinfected patients undergoing long-term tenofovir (TDF)-based antiretroviral therapy (ART).

Methods

We prospectively followed 165 HIV-HBV-coinfected patients undergoing TDF-based ART. Serum HBV-DNA viral loads, HBeAg and HBsAg were obtained at TDF-initiation and every 6-12 months. We calculated the proportion achieving virological response (VR, <60 IU/mL) during follow-up. We also calculated rates of HBeAg- and HBsAg-seroclearance, which were compared between those who achieved versus never achieved VR during follow-up using an exact binomial test.

Results

During a median 8.1 years (IQR=4.0-13.2) of TDF-treatment, 152 (92.1%) patients were able to achieve VR and 13 (7.9%) never achieved VR (median HBV-DNA at the end of follow-up=608 IU/mL, range=67-52,400,000). The prevalence of individuals with detectable HBV-DNA (≥60 IU/mL) decreased during TDF-treatment: 15.1% (n=14/93) at 5-years, 3.2% (n=2/62) at 10-years and, 3.2% (n=1/31) at 15-years. 44/96 HBeAg-positive patients (6.15/100 person-years) had HBeAg-seroclearance and 13/165 patients overall (0.87/100 person-years) had HBsAg-seroclearance. No difference in HBeAg-seroclearance was observed between those who achieved versus never achieved VR (7.4 versus 3.7/100 person-years, p=0.33), while HBsAg-seroclearance was only observed in those with VR (1.0 versus 0/100 person-years, p=0.49; respectively). Individuals with VR also had a higher frequency of undetectable HIV-RNA during treatment (p<0.001).

Conclusions

During long-term TDF-based ART for HIV-HBV coinfection, persistent HBV viremia is apparent, but becomes less frequent over time. HBsAg-seroclearance only occurred in those with full HBV and relatively high HIV suppression.
Global Measurement of Physical Intimate Partner Violence to Monitor Sustainable Development Goal 5
Authors: Yount Kathryn M. , Cheong Yuk Fai , Khan Zara , Bergenfeld Irina , Kaslow Nadine , Clark Cari Jo
Published: July 2021

Background

One third of women experience IPV and potential sequelae. Sustainable Development Goal (SDG) 5.2—to eliminate all violence against women, including IPV— compels national governments to monitor such violence. We conducted the first global measurement-invariance assessment of standardized physical IPV items.

Methods

Thirty-six Demographic and Health Surveys (DHS) from 36 Lower-/Middle-Income Countries (LMICs) administering the same 18 IPV items during 2012-2018 were included. We performed exploratory and confirmatory factor analyses (EFA/CFA) with seven physical IPV items, which are the most behaviorally specific and reliable. Datasets meeting EFA/CFA model fit criteria (loadings>.35, RMSEA<.08, CFI/TLI>.95) were included in multiple-group CFA to test strict measurement invariance, and in alignment optimization (AO) to test approximate measurement invariance. We compared national rankings based on AO-derived scores and lifetime physical IPV prevalences, and correlated AO-dervied scores with physical, sexual, and psychological IPV prevalences.

Results

Estimated lifetime physical IPV varied widely (5.6%-50.5%). All loadings and fit statistics met thresholds in country-specific EFA/CFAs. A unidimensional, seven-item physical IPV construct lacked scalar invariance in multiple-group CFA but achieved approximate measurement invariance in AO analysis, as 12.3% (<25%) of model parameters were non-invariant. National rankings of AO-derived scores and estimated physical IPV prevalences were similarly distributed, but national estimates often were not significantly different, so grouped score ranges or prevalence ranges are advised. Three items (slap, twist, choke) warrant cognitive testing to improve their psychometric performance. Correlations of AO-derived scores with IPV prevalences ranged from .48 to .66.

Conclusions

Seven DHS physical-IPV items were approximately invariant across 36 LMICs spanning five regions and are reasonable for cross-national, grouped comparison of physical IPV. Measurement-invariance testing over time will inform their utility to monitor SDG5.2.1; cross-national and cross-time measurement-invariance testing of other IPV item sets is warranted.
Multi-site clinical validation of Isothermal Amplification based SARS-COV-2 detection assays using different sampling strategies
Authors: Desai Kanan T. , Alfaro Karla , Mendoza Laura , Faron Matthew , Mesich Brian , Maza Mauricio , Dominguez Rhina , Valenzuela Adriana , DÍaz Acosta Chyntia , MartÍnez Magaly , Felix Juan C. , Masch Rachel , Gabrilovich Sofia , Plump Michael , Novetsky Akiva P. , Einstein Mark H. , Douglas Nataki C. , Cremer Miriam , Wentzensen Nicolas
Published: July 2021

Background

Isothermal amplification-based tests were developed as rapid, low-cost, and simple alternatives to real-time reverse transcriptase-polymerase chain reaction (RT-PCR) tests for SARS-COV-2 detection.

Methods

Clinical performance of two isothermal amplification-based tests (Atila Biosystems iAMP COVID-19 detection test and OptiGene COVID-19 Direct Plus RT-LAMP test) was compared to clinical RT-PCR assays using different sampling strategies. A total of 1378 participants were tested across four study sites.

Results

Compared to standard of care RT-PCR testing, the overall sensitivity and specificity of the Atila iAMP test for detection of SARS-CoV-2 were 76.2% and 94.9%, respectively, and increased to 88.8% and 89.5%, respectively, after exclusion of an outlier study site. Sensitivity varied based on the anatomic collected site. Sensitivity for nasopharyngeal was 65.4% (range across study sites:52.8%-79.8%), mid-turbinate 88.2%, saliva 55.1% (range across study sites:42.9%-77.8%) and anterior nares 66.7% (range across study sites:63.6%-76.5%). The specificity for these anatomic collection sites ranged from 96.7% to 100%. Sensitivity improved in symptomatic patients (overall 82.7%) and those with a higher viral load (overall 92.4% for ct≤25). Sensitivity and specificity of the OptiGene Direct Plus RT-LAMP test, conducted at a single study-site, were 25.5% and 100%, respectively.

Conclusions

The Atila iAMP COVID test with mid-turbinate sampling is a rapid, low-cost assay for detecting SARS-COV-2, especially in symptomatic patients and those with a high viral load, and could be used to reduce the risk of SARS-COV-2 transmission in clinical settings. Variation of performance between study sites highlights the need for site-specific clinical validation of these assays before clinical adoption.
Colorectal Cancer Disparities Across the Continuum of Cancer Care: A Systematic Review and Meta-Analysis
Authors: Syvyk Solomiya , Roberts Sanford E. , Finn Caitlin B. , Wirtalla Chris , Kelz Rachel
Published: July 2021

Structured Abstract

Background and Objectives

Disparate colorectal cancer outcomes persist in vulnerable populations. We aimed to examine the distribution of research across the colorectal cancer care continuum, and to determine disparities in the use of Surgery among Black patients.

Methods

A systematic review and meta-analysis of colorectal cancer disparities studies was performed. The meta-analysis assessed three utilization measures in Surgery.

Results

Of 1,199 publications, 60% focused on Prevention, Screening, or Diagnosis, 20% on Survivorship, 15% on Treatment, and 1% on End-of-Life Care. A total of 16 studies, including 1,110,674 patients, were applied to three separate meta-analyses regarding utilization of Surgery. Black colorectal cancer patients were less likely to receive surgery, twice as likely to refuse surgery, and less likely to receive laparoscopic surgery when compared to White patients.

Conclusions

Over the past 10 years, the majority of published research remained focused on the prevention, screening, or diagnosis domain. Given the observed treatment disparities and persistently elevated disease-specific mortality among Black patients, future efforts to reduce colorectal cancer disparities should include interventions within Surgery.

Synopsis

In this systematic review on disparities along the colorectal cancer care continuum, we found that 64% of research has been focused on prevention, screening, or diagnosis while only 6% addressed surgical disparities. In the meta-analysis, Black patients were less likely to undergo surgery, more likely to refuse surgery, and less likely to undergo laparoscopic surgery, when compared to White patients. Future research should target treatment differences across populations in order to impact persistent disparities in colorectal cancer survival.
The toll of COVID-19 on African children: A descriptive analysis on the COVID-19-related morbidity and mortality among the pediatric population in Sub-Saharan Africa
Authors: Velásquez Sabina Rodriguez , Jacques Léa , Dalal Jyoti , Sestito Paolo , Habibi Zahra , Venkatasubramanian Akarsh , Nguimbis Benedict , Mesa Sara Botero , Chimbetete Cleophas , Keiser Olivia , Impouma Benido , Mboussou Franck , William George Sie , Ngoy Nsenga , Talisuna Ambrose , Gueye Abdou Salam , Hofer Cristina Barroso , Cabore Joseph Waogodo
Published: July 2021

Introduction

Since the beginning of the COVID-19 pandemic, very little data on the epidemiological characteristics among the pediatric population in Africa has been published. This paper examines the age and sex distribution of the morbidity and mortality rate in children with COVID-19 and compares it to the adult population within 15 Sub-Saharan African countries.

Methods

A merge line listing dataset using a reverse engineering model shared by countries within the Regional Office for Africa was analyzed. Patients diagnosed within 1 March 2020 and 1 September 2020 with confirmed positive RT-PCR test for SARS-CoV-2 were analyzed. Children’s data were stratified into three age groups: 0-4 years, 5-11 years, and 12-17 years, while adults were combined. The cumulative incidence of cases including its medians and 95% confidence intervals were calculated.

Results

9% of the total confirmed cases and 2.4% of the reported deaths were pediatric cases. The 12-17 age group in all 15 countries showed the highest cumulative incidence proportion in children. COVID-19 cases in males and females under the age of 18 were evenly distributed. Among adults, a higher case incidence per 100,000 people was observed compared to children.

Conclusion

The cases and deaths within the children’s population was smaller than the adult population. These differences can reflect biases in COVID-19 testing protocols and reporting implemented by countries, highlighting the need for more extensive investigation and focus on the effects of COVID-19 in children.
Whole-genome sequencing of SARS-COV-2 showed wide spread of B.1.525 in February 2021 in Libya
Authors: Alhudiri Inas M , Ramadan Ahmad M. , Ibrahim Khaled M , Abdalla Adel , Eljilani Mouna , Salem Mohamed Ali , Elgheriani Hajer Mohamed , El Meshri Salah Edin , Elzagheid Adam
Published: July 2021

Alpha (B.1.1.7) SARS-COV-2 variant was detected in September 2020 in minks and humans in Denmark and UK. This variant has several mutations in the spike region (S) which could increase the transmissibility of the virus 43-90% over previously circulating variants. The National Center for Disease Control (NCDC) announced on 24th February 2021 a 25% frequency of B.1.1.7 strain in Libya using a reverse-transcriptase quantitative PCR assay. This assay relies on the specific identification of the H69-V70 deletion in S gene which causes its failure of amplification (SGTF). This deletion is not specific for B.1.1.7; but is also characteristic of two other SARS-COV-2 variants. This study aimed to estimate the frequency of B.1.1.7 and identify other variants circulating in Libya in February 2021. We performed whole genome sequencing of 67 positive SARS-COV-2 samples collected on 25th February 2021 in Libya which were also tested by RT-qPCR for SGTF. Our results showed that 55% of samples had mutations specific to B.1.525 strain and only ∼3% of samples belonged to B.1.1.7. These findings suggested that B.1.525 was spreading widely in Libya. The use of such RT-qPCR assay although useful to track some variants, it cannot discriminate between variants with H69-V70 deletion. RT-qPCR assays could be multiplexed to identify multiple variants and screen samples prior to sequencing. We emphasize on the need for providing whole-genome sequencing to the main COVID-19 diagnostic laboratories in Libya as well as establishing international collaboration for building capacity and advancing research in this time of the pandemic.
Increased Histone-DNA Complexes and Endothelial-Dependent Thrombin Generation in Severe COVID-19
Authors: Bouchard Beth A. , Colovos Christos , Lawson Michael , Osborn Zachary , Sackheim Adrian , Mould Kara J. , Janssen William J. , Cohen Mitchell J. , Majumdar Devdoot , Freeman Kalev
Published: July 2021

Objective

Coagulopathy in severe COVID-19 is common but poorly understood. The purpose of this study was to determine how SARS-CoV-2 infection impacts histone levels, fibrin structure, and endogenous thrombin potential in the presence and absence of endothelial cells.

Approach

We studied individuals with SARS-CoV-2 infection and acute respiratory distress syndrome at the time of initiation of mechanical ventilation compared to healthy controls. Blood samples were assayed for levels of histone-DNA complexes. Confocal microscopy was used to evaluate fibrin structure in clots formed from recalcified plasma samples using fluorescently-labeled fibrinogen. Endogenous thrombin potential was measured by calibrated automated thrombin assays in the presence of tissue factor and phospholipid (PCPS) or cultured human endothelial cells.

Results

Circulating nucleosomes were elevated in the plasma of COVID-19 patients relative to healthy controls (n=6, each group). COVID-19 patient plasma thrombin generation was also altered. Despite having an increased endogenous thrombin potential, patient plasma samples exhibited prolonged lag times and times to peak thrombin in the presence of added tissue factor and PCPS. Strikingly different results were observed when endothelial cells were used in place of tissue factor and PCPS. Control plasma samples did not generate measurable thrombin (lag time >60 min); in contrast, plasma samples from COVID-19+ patients generated thrombin (mean lag time ∼20 min). Consistent with the observed alterations in thrombin generation, clots from COVID-19 subjects exhibited a denser fibrin network, thinner fibers and lower fibrin resolvability.

Conclusions

Elevated histones, aberrant fibrin formation, and increased endothelial-dependent thrombin generation in COVID-19 may contribute to coagulopathy.

HIGHLIGHTS

Histone-DNA complexes are significantly elevated in the plasma of patients with severe SARS-CoV-2 infection.

Measures of thrombin generation by calibrated automated thrombography and fibrin clots formedin situare altered in severe COVID-19.

Plasma from COVID-19 patients promotes thrombin generation on cultured endothelial cells in the absence of added tissue factor or phospholipids.

The additive effects of histones on thrombin generation and endothelial cell function may play a major role in the thrombotic complications observed in severe SARS-CoV-2 infection.
Noradrenergic deficits contribute to apathy in Parkinson’s disease through the precision of expected outcomes
Authors: Hezemans Frank H. , Wolpe Noham , O’Callaghan Claire , Ye Rong , Rua Catarina , Jones P. Simon , Murley Alexander G. , Holland Negin , Regenthal Ralf , Tsvetanov Kamen A. , Barker Roger A. , Williams-Gray Caroline H. , Robbins Trevor W. , Passamonti Luca , Rowe James B.
Published: July 2021

Abstract

Apathy is a debilitating feature of many diseases, including Parkinson’s disease. We tested the hypothesis that degeneration of the locus coeruleus-noradrenaline system contributes to apathy by modulating the relative weighting of prior beliefs about action outcomes. Participants with mild-to-moderate idiopathic Parkinson’s disease (N=17) completed a double-blind, placebo-controlled, crossover study with 40 mg of the noradrenaline reuptake inhibitor atomoxetine. Prior weighting was inferred from psychophysical analysis of performance in an effort-based visuomotor task, and was confirmed as negatively correlated with apathy. Locus coeruleus integrity was assessed in vivo using magnetisation transfer imaging at 7T. The effect of atomoxetine depended on locus coeruleus integrity: participants with a more degenerate locus coeruleus showed a greater increase in prior weighting on atomoxetine versus placebo. The results indicate a contribution of the noradrenergic system to apathy and potential benefit from noradrenergic treatment of people with Parkinson’s disease, subject to stratification according to locus coeruleus integrity.
SARS-CoV-2 environmental contamination from hospitalised COVID-19 patients receiving aerosol generating procedures
Authors: Winslow RL , Zhou J , Windle EF , Nur I , Lall R , Ji C , Millar JE , Dark P , Naisbitt J , Simonds A , Dunning J , Barclay W , Baillie K , Perkins GD , Semple MG , McAuley DF , Green CA
Published: July 2021

Background

Continuous positive airways pressure (CPAP) and high-flow nasal oxygen (HFNO) are considered ‘aerosol-generating procedures’ (AGPs) in the treatment of COVID-19. We aimed to measure air and surface environmental contamination of SARS-CoV-2 virus when CPAP and HFNO were used, compared with supplemental oxygen, to investigate the potential risks of viral transmission to healthcare workers and patients.

Methods

30 hospitalised patients with COVID-19 requiring supplemental oxygen, with a fraction of inspired oxygen ≥0.4 to maintain oxygen saturations ≥94%, were prospectively enrolled into an observational environmental sampling study. Participants received either supplemental oxygen, CPAP or HFNO (n=10 in each group). A nasopharyngeal swab, three air and three surface samples were collected from each participant and the clinical environment. RT qPCR analyses were performed for viral and human RNA, and positive/suspected-positive samples were cultured for the presence of biologically viable virus.

Results

Overall 21/30 (70%) of participants tested positive for SARS-CoV-2 RNA in the nasopharynx. In contrast, only 4/90 (4%) and 6/90 (7%) of all air and surface samples tested positive (positive for E and ORF1a) for viral RNA respectively, although there were an additional 10 suspected-positive samples in both air and surfaces samples (positive for E or ORF1a). CPAP/HFNO use or coughing was not associated with significantly more environmental contamination. Only one nasopharyngeal sample was culture positive.

Conclusions

The use of CPAP and HFNO to treat moderate/severe COVID-19 was not associated with significantly higher levels of air or surface viral contamination in the immediate care environment.
Maternal plasma lipids are involved in the pathogenesis of preterm birth
Authors: Chen Yile , He Bing , Liu Yu , Aung Max T. , Rosario-Pabón Zaira , Vélez-Vega Carmen M. , Alshawabkeh Akram , Cordero José F. , Meeker John D. , Garmire Lana X.
Published: July 2021

Background

Preterm birth is defined by the onset of labor at a gestational age shorter than 37 weeks and it can lead to premature birth and impose a threat to newborns’ health. The Puerto Rico PROTECT cohort is a well-characterized prospective birth cohort that was designed to investigate environmental and social contributors to preterm birth in Puerto Rico, where preterm birth rates have been elevated in recent decades. To elucidate possible relationships between metabolites and preterm birth in this cohort, we conducted a nested case-control study to conduct untargeted metabolomic characterization of maternal plasma of 31 preterm birth women and 69 full-term labor controls at 24-28 gestational weeks.

Results

A total of 333 metabolites were identified and annotated with liquid chromatography/mass spectrometry. Subsequent weighted gene correlation network analysis shows the fatty acid and carene enriched module has a significant positive association (p-value=8e-04) with preterm birth. After controlling for potential clinical confounders, a total of 38 metabolites demonstrated significant changes uniquely associated with preterm birth, where 17 of them were preterm biomarkers. Among seven machine-learning classifiers, application of random forest achieved the highly accurate and specific prediction (AUC = 0.92) for preterm birth in testing data, demonstrating their strong potential as biomarkers for preterm births. The 17 preterm biomarkers are involved in cell signaling, lipid metabolism, and lipid peroxidation functions. Further causality analysis infers that suberic acid upregulates several fatty acids to promote preterm birth.

Conclusions

Altogether, this study demonstrates the involvement of lipids, particularly fatty acids, in the pathogenesis of preterm birth.
Covid-19 Vaccination in Pregnancy: A Systematic Review
Authors: Pratama Nando Reza , Wafa Ifan Ali , Budi David Setyo , Putra Manesha , Wardhana Manggala Pasca , Wungu Citrawati Dyah Kencono
Published: July 2021

Objective

Pregnancy is a risk factor for severe Covid-19. Looking for safe vaccines that evoke protective maternal and fetal antibody response is important.

Methods

We searched from registries (ClinicalTrials.gov, the WHO Clinical Trial Registry, and the EU Clinical Trial Registry) and databases (MEDLINE, ScienceDirect, Cochrane Library, Proquest, and Springer) up until June 20, 2021. Articles were selected based on inclusion and exclusion criteria after duplicates were removed. Infection rate, maternal antibody response, placental antibody transfer, and adverse events were described. This systematic review was performed with quality assessment and semi-quantitative synthesis according to PRISMA guidelines.

Results

Twelve observational studies with a total of 40.509 pregnant women included. The mRNA based vaccines (Pfizer-BioNTech and Moderna) can prevent future SARS-CoV-2 infections (p=0.0004). Both vaccines did not affect pregnancy, delivery, and neonatal outcomes. The most commonly encountered adverse reactions are injection-site pain, fatigue, and headache but only transient. Antibody responses were rapid after the prime dose of vaccines. After booster, antibody responses were higher and associated with better placental antibody transfer. Longer intervals between first vaccination dose and delivery were also associated with higher antibody fetal IgG and better antibody transfer ratio.

Conclusions

The Pfizer-BioNTech and Moderna vaccines are efficacious for preventing future SARS-CoV-2 infections. These vaccines can be considered as a safe option for pregnancy and their fetus. Two doses of vaccines were recommended for more robust maternal and fetal antibody responses. Longer latency was associated with higher fetal antibody responses.

Systematic Review Registration

PROSPERO (CRD42021261684)
Dynamics of SARS-CoV-2 host cell interactions inferred from transcriptome analyses
Authors: Adam Lukas , Stanifer Megan , Springer Fabian , Mathony Jan , Di Ponzio Chiara , Eils Roland , Boulant Steeve , Niopek Dominik , Kallenberger Stefan M.
Published: July 2021

The worldwide spread of severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) caused an urgent need for an in-depth understanding of interactions between the virus and its host. Here, we dissected the dynamics of virus replication and the host cell transcriptional response to SARS-CoV-2 infection at a systems level by combining time-resolved RNA sequencing with mathematical modeling. We observed an immediate transcriptional activation of inflammatory pathways linked to the anti-viral response followed by increased expression of genes involved in ribosome and mitochondria function, thus hinting at rapid alterations in protein production and cellular energy supply. At later stages, metabolic processes, in particular those depending on cytochrome P450 enzymes, were downregulated. To gain a deeper understanding of the underlying transcriptional dynamics, we developed an ODE model of SARS-CoV-2 infection and replication. Iterative model reduction and refinement revealed that a negative feedback from virus proteins on the expression of anti-viral response genes was essential to explain our experimental dataset. Our study provides insights into SARS-CoV-2 virus-host interaction dynamics and facilitates the identification of druggable host pathways supporting virus replication.
Increased frequency of recurrent in-frame deletions in new expanding lineages of SARS CoV-2 reflects immune selective pressure
Authors: Alisoltani Arghavan , Jaroszewski Lukasz , Iyer Mallika , Iranzadeh Arash , Godzik Adam
Published: July 2021

Most of the attention in the surveillance of evolution of SARS-CoV-2 has been centered on single nucleotide substitutions in the spike glycoprotein. We show that in-frame deletions (IFDs) also play a significant role in the evolution of viral genome. The percentage of genomes and lineages with IFDs is growing rapidly and they co-occur independently in multiple lineages, including emerging variants of concerns. IFDs distribution is correlated with spike mutations associated with immune escape and concentrated in proteins involved in interactions with the host immune system. Structural analysis suggests that IFDs remodel viral proteins’ surfaces at common epitopes and interaction interfaces, affecting the virus’ interactions with the immune system. We hypothesize that the increased frequency of IFDs is an adaptive response to elevated global population immunity.

Monitoring of SARS-CoV-2 genome evolution uncovers increased frequency and non-random distribution of in-frame deletions in recently emerged lineages.
Safety and Pharmacokinetics of Intranasally Administered Heparin
Authors: Harris Hannah M. , Boyet Katherine L. , Liu Hao , Dwivedi Rohini , Ashpole Nicole M. , Tandon Ritesh , Bidwell Gene L. , Cheng Zhi , Fassero Lauren A. , Yu Christian S. , Pomin Vitor H. , Mitra Dipanwita , Harrison Kerri A. , Dahl Eric , Gurley Bill J. , Kotha Arun Kumar , Chougule Mahavir Bhupal , Sharp Joshua S.
Published: July 2021

Purpose

Intranasally administered unfractionated heparin (UFH) and other sulfated polysaccharides are potential prophylactics for COVID-19. The purpose of this research was to measure the safety and pharmacokinetics of clearance of intranasally administered UFH solution from the nasal cavity.

Methods

Double-blinded daily intranasal dosing in C57Bl6 mice with four doses (60 ng to 60 μg) of UFH was carried out for fourteen consecutive days, with both blood coagulation measurements and subject adverse event monitoring. The pharmacokinetics of fluorescent-labeled UFH clearance from the nasal cavity were measured in mice by in vivo imaging. Intranasal UFH at 2000 U/day solution with nasal spray device was tested for safety in a small number of healthy human subjects.

Results

UFH showed no evidence of toxicity in mice at any dose measured. No significant changes were observed in activated partial thromboplastin time (aPTT), platelet count, or frequency of minor irritant events over vehicle-only control. Human subjects showed no significant changes in aPTT time, international normalized ratio (INR), or platelet count over baseline measurements.

No serious adverse events were observed. In vivo imaging in a mouse model showed a single phase clearance of UFH from the nasal cavity. After 12 hours, 3.2% of the administered UFH remained in the nasal cavity, decaying to background levels by 48 hours.

Conclusions

UFH showed no toxic effects for extended daily intranasal dosing in mice as well as humans. The clearance kinetics of intranasal heparin solution from the nasal cavity indicates potentially protective levels for up to 12 hours after dosing.
Implementation, adoption and perceptions of telemental health during the COVID-19 pandemic: a systematic review
Authors: Appleton Rebecca , Williams Julie , San Juan Norha Vera , Needle Justin J. , Schlief Merle , Jordan Harriet , Rains Luke Sheridan , Goulding Lucy , Badhan Monika , Roxburgh Emily , Barnett Phoebe , Spyridonidis Spyros , Tomaskova Magdalena , Mo Jiping , Harju-Seppänen Jasmine , Haime Zoë , Casetta Cecilia , Papamichail Alexandra , Lloyd-Evans Brynmor , Simpson Alan , Sevdalis Nick , Gaughran Fiona , Johnson Sonia
Published: July 2021

Background

Early in 2020, mental health services had to rapidly shift from face-to-face models of care to delivering the majority of treatments remotely (by video or phone call or occasionally messaging) due to the COVID-19 pandemic. This resulted in several challenges for staff and patients, but also in benefits such as convenience or increased access for people with impaired mobility or in rural areas. There is a need to understand the extent and impacts of telemental health implementation, and barriers and facilitators to its effective and acceptable use. This is relevant both to future emergency adoption of telemental health, and to debates on its future use in routine mental health care.

Objective

To investigate the adoption and impacts of telemental health approaches during the COVID-19 Pandemic, and facilitators and barriers to optimal implementation.

Methods

Four databases (PubMed, PsycINFO, CINAHL and Web of Science) were searched for primary research relating to remote working, mental health care, and the COVID-19 pandemic. Preprint servers were also searched. Results of studies were synthesised using framework synthesis.

Results

A total of 77 papers met our inclusion criteria. In most studies, the majority of contacts could be transferred to a remote form during the pandemic, and good acceptability to service users and clinicians tended to be reported, at least where the alternative to remote contacts was interrupting care. However, a range of impediments to dealing optimal care by this means were also identified.

Conclusions

Implementation of telemental health allowed some continuing support to the majority of service users during the COVID-19 pandemic and has value in an emergency situation. However, not all service users can be reached by this means, and better evidence is now needed on long-term impacts on therapeutic relationships and quality of care, and on impacts on groups at risk of digital exclusion and how to mitigate these.