bluuebunny/crossref_metadata_2025 huggingface dataset:
Using Epidemiology, Immunology, and Genomics to Study the Biology of Chlamydia trachomatis
Authors: Brunham Robert C.
Published: October 2020

The traditional framework in which to study the biology of human infectious diseases involves characterizing interactions and features of the host, pathogen, and environment. Using the tools of epidemiology, immunology, and genomics allows one to study the biology of infectious disease within this framework. The study of Chlamydia trachomatis biology vividly illustrates the usefulness for the approach. I note key findings from my own studies on C. trachomatis epidemiology, immunology, and genomics to show how important light has been shed on its biology and how this has impacted the Chlamydia field generally. In particular, the epidemiology of C. trachomatis diseases in women shows its impact on reproduction and how public health programs to detect and treat infection has reduced that impact but at the cost of arresting the development of protective immunity and increasing the risk of infection and reinfection. Immunological studies demonstrate the importance of CD4 Th1 cells in protection and that antibiotic treatment interferes with the development of protective immunity when given early in the course of infection. Evaluating the T-cell antigen landscape for C. trachomatis and Chlamydia muridarum demonstrates the role of surface proteins such as the major outer-membrane protein and the polymorphic membrane proteins as major protective CD4 T-cell antigens. Genomic studies reveal that the genome of organism has 3 loci of immunological interest. The antigen loci of the major outer-membrane protein and polymorphic membrane proteins are hotspots for both mutation and recombination, and the plasticity zone contains immune evasion genes that are highly variable from species to species. Interestingly, these 3 loci seem to have entered the Chlamydia phylum at the time of the evolution of the Chlamydiaceae when they became pathogens of vertebrates and encountered the adaptive immune system. In aggregate, these 3 approaches have shed light on human C. trachomatis infections and suggest paths for vaccine development. These approaches are likely to remain useful for the further study of C. trachomatis and for other human pathogens.
Brief Report: Chronic Placental Inflammation Among Women Living With HIV in Uganda
Authors: Bebell Lisa M. , Siedner Mark J. , Ngonzi Joseph , Le Mylinh H. , Adong Julian , Boatin Adeline A. , Bassett Ingrid V. , Roberts Drucilla J.
Published: October 2020

Background:

HIV-exposed, uninfected (HEU) children have poorer early-life outcomes than HIV-unexposed children. The determinants of adverse health outcomes among HEU children are poorly understood but may result from chronic placental inflammation (CPI).

Setting and methods:

We enrolled 176 pregnant women living with HIV (WLWH) taking antiretroviral therapy in southwestern Uganda and 176 HIV-uninfected women to compare CPI prevalence by maternal HIV serostatus. Placentas were evaluated histologically by an expert pathologist for presence of CPI, defined as chronic chorioamnionitis, plasma cell deciduitis, villitis of unknown etiology, or chronic histiocytic intervillositis. Placentas with CPI were additionally immunostained with CD3 (T cell), CD20 (B cell), and CD68 (macrophage) markers to characterize inflammatory cell profiles.

Results:

WLWH and HIV-uninfected women had similar age, parity, and gestational age. Among WLWH, the mean CD4 count was 480 cells/µL, and 74% had an undetectable HIV viral load. We detected CPI in 16 (9%) placentas from WLWH and 24 (14%) from HIV-uninfected women (P = 0.18). Among WLWH, CPI was not associated with the CD4 count or HIV viral load. Villitis of unknown etiology was twice as common among HIV-uninfected women than WLWH (10 vs. 5%, P = 0.04). Among placentas with CPI, more villous inflammatory cells stained for CD3 or CD68 among HIV-uninfected women than WLWH (79% vs. 46%, P = 0.07).

Conclusions:

CPI prevalence did not differ by HIV serostatus. T-cell (CD3) and macrophage (CD68) markers were more prevalent in placental inflammatory cells from HIV-uninfected women. Our results do not support CPI as a leading mechanism for poor outcomes among HEU children in the antiretroviral therapy era.
High Acceptability of Assisted Partner Notification Services Among HIV-Positive Females in Kenya: Results From an Ongoing Implementation Study
Authors: Sharma Monisha , Kariithi Edward , Kemunto Emily , Otieno George , Lagat Harison , Wamuti Beatrice , Obongo Chris , Macharia Paul , Masyuko Sarah , Bosire Rose , Mugambi Mary , Weiner Bryan , Farquhar Carey
Published: October 2020

Background:

Assisted partner services (aPS) involves notification and HIV testing for sexual partners of persons diagnosed HIV-positive (index clients). Because the impact of aPS is contingent on high acceptance, we assessed characteristics and reasons for nonenrollment among female index clients in an ongoing scale-up project.

Methods:

We analyzed data from HIV-positive females offered aPS in 31 facilities from May 2018 to August 2019. We compared sociodemographic characteristics by aPS enrollment (accepted, refused, and ineligible) and used multivariate binomial regression to assess associations between demographics and refusal.

Results:

Twenty-four thousand four hundred eighteen females received HIV testing and 1050 (4.3%) tested HIV-positive; 839 females enrolled in aPS (80%), 59 refused (6%), and 152 were ineligible (14%). APS uptake did not differ by age, testing history, or testing type (provider initiated vs. client initiated). Females refusing aPS were more likely to have completed secondary school [adjusted relative risk (aRR) 2.03, 95% confidence interval (CI): 1.13 to 2.

82] and be divorced/separated (aRR: 3.09, 95% CI: 1.39 to 6.86) or single (aRR: 2.66, 95% CI: 1.31 to 5.42) compared with married/cohabitating. Reasons for refusing aPS included not feeling emotionally ready (31%) and reporting no sexual partners in past 3 years (22%). Reasons for ineligibility included fear or risk of intimate partner violence (9%), previous HIV diagnosis (9%), or insufficient time for aPS provision (3%).

Conclusions:

APS has high acceptability among HIV-positive females regardless of age or testing history. More counseling may be needed to increase uptake among females with higher education and those who are separated/single. Follow-up for females not emotionally ready or who had insufficient time for aPS in their clinic visit can improve coverage.
Association of Kidney Disease With Abnormal Cardiac Structure and Function Among Ugandans With HIV Infection
Authors: Peters Matthew , Margevicius Seunghee , Kityo Cissy , Mirembe Grace , Buggey Jonathan , Brinza Ellen , Schluchter Mark , Yun Chun-Ho , Hung Chung-Lieh , McComsey Grace A. , Longenecker Chris T.
Published: October 2020

Background:

People with HIV (PWH) are at an increased risk of both heart and kidney disease, but the relationship between kidney disease and cardiac structure and function in this population has not been well studied. In particular, whether the relationship between kidney disease and cardiac structure and function is stronger for PWH compared with uninfected controls is unknown.

Methods:

One hundred PWH on antiretroviral therapy were compared with 100 age-matched and sex-matched controls without HIV in Uganda. Multivariable regression models were used to examine associations between creatinine-based and cystatin C-based estimated glomerular filtration rate (eGFR), albumin–creatinine ratio, and echocardiographic measures of cardiac structure and function.

Results:

PWH had lower eGFRcr (β −7.486, 95% confidence interval: −13.868 to −1.104, P = 0.022) and a higher rate of albumin–creatinine ratio ≥30 (odds ratio 2.146, 95% confidence interval: 1.027 to 4.484, P = 0.042) after adjustment for traditional risk factors. eGFR was inversely associated with both left ventricular mass index and diastolic dysfunction in adjusted models but not with systolic function. Albuminuria was associated with more diastolic dysfunction among PWH but not controls (P for interaction = 0.046). The association of HIV with a higher left ventricular mass index (P = 0.005) was not substantially affected by adjusting for eGFRcr.

Conclusion:

Among Ugandans, eGFR is associated with elevated LV mass and diastolic dysfunction. The association between albuminuria and diastolic dysfunction is particularly strong for PWH.
Mind the gaps: challenges in the clinical management of invasive candidiasis in critically ill patients
Authors: Peçanha-Pietrobom Paula M. , Colombo Arnaldo Lopes
Published: October 2020

Purpose of review

Strict adherence to clinical practice guidelines is recognized to improve outcomes but the inconvenient truth is that only a small subset of what is done in medicine has been tested in appropriate, well designed studies. In this article, we aim to review controversial aspects of the clinical management of invasive candidiasis recommended by guidelines.

Recent findings

Despite still being recommended by guidelines, we fail to identify a single randomized clinical trial documenting that the use of antifungal drugs in high-risk critically ill patients without microbiologic documentation of Candida infection decreases mortality. Regarding deep-seated Candida infections, most cohort studies of patients with candidemia found less than 5% of patients developed endophthalmitis and endocarditis. In this scenario, it is reasonable to reconsider routine universal screening of both complications in candidemic patients. Finally, a large number of studies have shown that critically ill patients usually have lower echinocandin exposure when compared with other populations. We need more data on the clinical relevance of this finding.

We need robust studies to validate new strategies for the clinical management of candidemia in ICU, including: the use of fungal biomarkers in the early initiation or interruption of antifungal therapy in high-risk patients to replace the conventional empirical antifungal therapy driven by predictive rules; validation of targeted screening of eye infection and endocarditis with the aid of fungal biomarkers only in high-risk patients; we should clarify if higher doses of candins are necessary to treat invasive candidiasis in critically ill patients, especially in the case of intra-abdominal infections where drug penetration is suboptimal.
Demographic and Clinical Features of ANCA-Associated Vasculitides in a Peruvian Tertiary Center
Authors: Pimentel-Quiroz Victor R. , Sánchez-Torres Alfredo , Acevedo-Vásquez Eduardo , Gamboa-Cárdenas Rocío V. , Reátegui-Sokolova Cristina , Medina-Chinchón Mariela , Zevallos Francisco , Noriega-Zapata Erika , Alfaro-Lozano José , Cucho-Venegas Jorge M. , Sánchez-Schwartz César , Rodríguez-Bellido Zoila , Perich-Campos Risto , Pastor-Asurza César A. , Alarcón Graciela S. , Ugarte-Gil Manuel F.
Published: October 2020

Aim

The aim of this study was to identify the demographic and clinical features of patients with ANCA-associated vasculitides (AAVs) in a Peruvian tertiary referral hospital.

Methods

Medical records of patients with AAV according to classification criteria or diagnosed by an experienced rheumatologist, and covering the period between January 1990 and December 2019, were reviewed. Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and renal-limited vasculitis (RLV) were included. Demographic factors (age at diagnosis, sex), disease duration, clinical manifestations (per organ involvement), creatinine level at diagnosis (milligram per deciliter), ANCA status, diagnosis, 2009 Five Factor Score, disease categorization, and treatment were recorded.

Results

Two hundred twelve patients were included. Their female-to-male ratio was 1.9:1 (139 [65.6%]/73 [34.4%]), and their mean (SD) age at diagnosis was 59.2 (12.5) years. One hundred fifty-eight patients (74.5%) had MPA, 42 (19.8%) GPA, 7 (3.3%) RLV, and 5 (2.4%) EGPA. Neurological, lung, and renal involvements were the most frequently affected systems. Myeloperoxidase preferentially occurred in MPA (82.5%), whereas proteinase 3 did occur in GPA (79.5%). Microscopic polyangiitis patients were older (61.1 [11.5] years). Female sex predominated in MPA and RLV (2.4:1 and 6:1, respectively), but the opposite was the case for EGPA (1:4). Ear-nose-throat and ocular involvement were more frequent in GPA (both p's < 0.001), and neurological and cardiovascular involvement were more frequent in EGPA (p < 0.001 and p = 0.002, respectively).

Conclusions

This is one of the largest series of AAV patients in Latin America. Overall, female sex predominated. Microscopic polyangiitis was the most frequent AAV, and myeloperoxidase-ANCA was the most frequent antibody in Peruvian AAV population.
Beyond the physics and demonstration of ignition
Authors: Dean Stephen O.
Published: October 2020

Fusion holds the promise of providing growing world energy demand with a carbon-free power source having a universally available fuel source and attractive safety and environmental characteristics. A significant global effort has been underway for over 50 years aimed at the achievement of fusion by inertial confinement. The effort to date has necessarily emphasized understanding the physics of compressing and heating a small amount of fusion fuel to the high densities and temperatures required for ignition and energy gain. Though steady progress has been and is still being made to achieve the required physics understanding and energy gain, those goals have not yet quite been met. It is timely to put progress toward fusion power by inertial confinement into perspective by developing an updated roadmap. Preparing a roadmap from present achievements to the ultimate goal of commercial fusion power requires formally identifying and implementing complementary efforts on a number of fronts. These include the choice, development and demonstration of high repetition rate compression drivers (e.g. lasers) to succeed present day single-pulse sources; design, fabrication and testing of high gain targets (gain of order 100); development of mass production, cost-effective, target fabrication and delivery systems capable of inserting targets into the reaction chamber several times per second, and demonstrating ability to accurately hit and efficiently compress those targets to reliably produce the required fusion yields; design and demonstration of reaction chambers capable of handling energy yields and target debris clearing at the levels required for achieving high power plant reliability with low induced radioactivity. A robust ongoing effort on competitive power plant conceptual design is necessary to guide the implementation of a roadmap, including the timing and level of effort on the ‘beyond ignition’ demonstrations.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 1)’.
Modelling burning thermonuclear plasma
Authors: Rose S. J. , Hatfield P. W. , Scott R. H. H.
Published: October 2020

Considerable progress towards the achievement of thermonuclear burn using inertial confinement fusion has been achieved at the National Ignition Facility in the USA in the last few years. Other drivers, such as the Z-machine at Sandia, are also making progress towards this goal. A burning thermonuclear plasma would provide a unique and extreme plasma environment; in this paper we discuss (a) different theoretical challenges involved in modelling burning plasmas not currently considered, (b) the use of novel machine learning-based methods that might help large facilities reach ignition, and (c) the connections that a burning plasma might have to fundamental physics, including quantum electrodynamics studies, and the replication and exploration of conditions that last occurred in the first few minutes after the Big Bang.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 1)’.
Direct drive with the argon fluoride laser as a path to high fusion gain with sub-megajoule laser energy
Authors: Obenschain S. P. , Schmitt A. J. , Bates J. W. , Wolford M. F. , Myers M. C. , McGeoch M. W. , Karasik M. , Weaver J. L.
Published: October 2020

Argon fluoride (ArF) is currently the shortest wavelength laser that can credibly scale to the energy and power required for high gain inertial fusion. ArF's deep ultraviolet light and capability to provide much wider bandwidth than other contemporary inertial confinement fusion (ICF) laser drivers would drastically improve the laser target coupling efficiency and enable substantially higher pressures to drive an implosion. Our radiation hydrodynamics simulations indicate gains greater than 100 are feasible with a sub-megajoule ArF driver. Our laser kinetics simulations indicate that the electron beam-pumped ArF laser can have intrinsic efficiencies of more than 16%, versus about 12% for the next most efficient krypton fluoride excimer laser. We expect at least 10% ‘wall plug' efficiency for delivering ArF light to target should be achievable using solid-state pulsed power and efficient electron beam transport to the laser gas that was demonstrated with the U.S. Naval Research Laboratory's Electra facility. These advantages could enable the development of modest size and lower cost fusion power plant modules. This would drastically change the present view on inertial fusion energy as being too expensive and the power plant size too large.

This article is part of a discussion meeting issue ‘Prospects for high gain inertial fusion energy (part 1)'.
LDL-apheresis as an alternate method for plasma LPS purification in healthy volunteers, dyslipidemic and septic patients
Authors: Dargent Auguste , de Barros Jean-Paul Pais , Saheb Samir , Bittar Randa , Le Goff Wilfried , Carrié Alain , Gautier Thomas , Fournel Isabelle , Rerole Anne Laure , Choubley Hélène , Masson David , Lagrost Laurent , Quenot Jean-Pierre
Published: October 2020

Lipopolysaccharide (LPS) is a key player for innate immunity activation. It is therefore a prime target for sepsis treatment, as antibiotics are not sufficient to improve outcome during septic shock. Extracorporeal removal method by polymyxin B hemoperfusion (PMX-DHP) is used in Japan, but recent trials failed to show a significant lowering of circulating LPS levels after PMX-DHP therapy. PMX-DHP has a direct effect on LPS molecules. However, LPS is not present in a free form in the circulation, as it is mainly carried by lipoproteins, including low density lipoproteins (LDL). Lipoproteins are critical for physiological LPS clearance, as LPS are carried by low density lipoproteins (LDL) to the liver for elimination. We hypothesized that LDL-apheresis can be an alternate method for LPS removal. We demonstrated first in vitro that LDL apheresis microbeads are almost as efficient as PMX beads to reduce LPS concentration in LPS-spiked human plasma, whereas it is not active in phosphate-buffered saline. We found that PMX was also adsorbing lipoproteins, although less specifically. Then, we found that endogenous LPS of patients treated by LDL-apheresis for familial hypercholesterolemia is also removed during their LDL-apheresis sessions, both with electrostatic-based devices and filtration devices. Finally, LPS circulating in the plasma of septic shock and severe sepsis patients with gram-negative bacteremia was also removed in vitro by LDL adsorption. Overall, these results underline the importance of lipoproteins for LPS clearance, making them a prime target to study and treat endotoxemia-related conditions.
Genetic correlation and causality of cancers and Parkinson’s disease
Authors: Senkevich Konstantin , Bandres-Ciga Sara , Yu Eric , Liyanage Upekha E. ,   International Parkinson Disease Genomics Consortium (IPDGC), Noyce Alastair J , Gan-Or Ziv
Published: October 2020

Background and objectives

Most cancers appear with reduced frequency in Parkinson’s disease (PD), but the prevalence of melanoma and brain cancers are often reported to be increased. Shared genetic architecture and causal relationships to explain these associations have not been fully explored.

Methods

Linkage disequilibrium score regression (LDSC) was applied for five cancer studies with available genome-wide association studies (GWAS) summary statistics to examine genetic correlations with PD. Additionally, we used GWAS summary statistics of 15 different types of cancers as exposures and two-sample Mendelian randomization to study the causal relationship with PD (outcome).

Results

LDSC analysis revealed a potential genetic correlation between PD and melanoma, breast cancer and prostate cancer. There was no evidence to support a causal relationship between the studied cancers and PD.

Conclusions

Our results suggest shared genetic architecture between PD and melanoma, breast, and prostate cancers, but no obvious causal relationship between cancers and PD.
Forecasting COVID-19 cases in the Philippines using various mathematical models
Authors: Torres Monica C. , Buhat Christian Alvin H. , Dela Cruz Ben Paul B. , Felix Edd Francis O. , Gemida Eleanor B. , Mamplata Jonathan B.
Published: October 2020

Due to the rapid increase of COVID-19 infection cases in many countries such as the Philippines, many efforts in forecasting the daily infections have been made in order to better manage the pandemic, and respond effectively. In this study, we consider the cumulative COVID-19 infection cases in the Philippines from March 6 to July 31,2020 and forecast the cases from August 1 - 15, 2020 using various mathematical models —weighted moving average, exponential smoothing, Susceptible-Exposed-Infected-Recovered (SEIR) model, Ornstein-Uhlenbeck process, Autoregressive Integrated Moving Average (ARIMA) model, and random forest. We then compare the results to the actual data using traditional error metrics. Our results show that the ARIMA(1,2,1) model has the closest forecast values to the actual data. Policymakers can use our result in determining which forecast method to use for their community in order to have a data-based information for the preparation of their personnel and facilities.
SARS-CoV-2-specific peripheral T follicular helper cells correlate with neutralizing antibodies and increase during convalescence
Authors: Boppana Sushma , Qin Kai , Files Jacob K , Russell Ronnie M. , Stoltz Regina , Bibollet-Ruche Frederic , Bansal Anju , Erdmann Nathan , Hahn Beatrice H. , Goepfert Paul
Published: October 2020

T-cell immunity is likely to play a role in protection against SARS-CoV-2 by helping generate neutralizing antibodies. We longitudinally studied CD4 T-cell responses to the M, N, and S structural proteins of SARS-CoV-2 in 21 convalescent individuals. Within the first two months following symptom onset, a majority of individuals (81%) mount at least one CD4 T-cell response, and 48% of individuals mount detectable SARS-CoV-2-specific peripheral T follicular helper cells (pTfh, defined as CXCR5+PD1+ CD4 T cells). SARS-CoV-2-specific pTfh responses across all three protein specificities correlate with antibody neutralization with the strongest correlation observed for S protein-specific responses. When examined over time, pTfh responses increase in frequency and magnitude in convalescence, and robust responses with magnitudes greater than 5% were detected only at the second convalescent visit, an average of 38 days post-symptom onset. These data deepen our understanding of antigen-specific pTfh responses in SARS-CoV-2 infection, suggesting that M and N protein-specific pTfh may also assist in the development of neutralizing antibodies and that pTfh response formation may be delayed in SARS-CoV-2 infection.

Author Summary

Since December 2019, the Coronavirus Disease 2019 (COVID-19) pandemic has caused significant morbidity and mortality worldwide. Most currently licensed vaccines are understood to protect against infection by inducing neutralizing antibodies. As such, ongoing COVID-19 vaccine trials have focused on antibody neutralization as a primary immunologic endpoint. It is well established that T follicular helper cells are essential to the development of neutralizing antibodies and that a subset of these cells, peripheral T follicular helper cells (pTfh), can be studied in the blood. However, little is known about Tfh responses mounted in SARS-CoV-2 infection. Here, we studied pTfh to three major structural proteins in individuals recovered from COVID-19. We find that SARS-CoV-2-specific pTfh frequencies correlate with neutralizing antibody responses, especially those directed against the spike protein. We also find that pTfh responses to SARS-CoV-2 increase over time. Our findings suggest that pTfh responses against proteins other than the spike protein may contribute to the development of neutralizing antibodies and suggests that formation of pTfh responses in SARS-CoV-2 infection may be delayed.
Variability of Salivary and Nasal Specimens for SARS-CoV-2 Detection
Authors: Manabe Yukari C. , Reuland Carolyn , Yu Tong , Azamfirei Razvan , Church Taylor , Brown Diane M. , Sewell Thelio T. , Hardick Justin P. , Blair Paul W. , Heaney Chris D. , Pekosz Andrew , Thomas David L.
Published: October 2020

In a large cohort of ambulatory confirmed COVID-19 patients with multiple self-collected sample time points, we compared 202 matched nasal-oropharyngeal swabs and oral salivary fluid sample pairs by RT-PCR. Nasal-oropharyngeal swabs were more sensitive than this salivary sample type (oral crevicular fluid) suggesting that not all saliva sample types have equivalent sensitivity. However, all samples that were Vero E6-TMPRSS2 cell culture positive (e.g., infectious virus) were also oral fluid RT-PCR positive suggesting that oral fluid may find the patients most likely to transmit disease to others.
Estimated Seroprevalence of SARS-CoV-2 Antibodies Among Adults in Orange County, California
Authors: Bruckner Tim A. , Parker Daniel M. , Bartell Scott M. , Vieira Veronica M. , Khan Saahir , Noymer Andrew , Drum Emily , Albala Bruce , Zahn Matthew , Boden-Albala Bernadette
Published: October 2020

Background

Clinic-based estimates of SARS-CoV-2 may considerably underestimate the total number of infections. Access to testing in the US has been heterogeneous and symptoms vary widely in infected persons. Public health surveillance efforts and metrics are therefore hampered by underreporting. We set out to provide a minimally biased estimate of SARS-CoV-2 seroprevalence among adults for a large and diverse county (Orange County, CA, population 3.2 million).

Methods

We implemented a surveillance study that minimizes response bias by recruiting adults to answer a survey without knowledge of later being offered a SARS-CoV-2 test. Several methodologies were used to retrieve a population-representative sample. Participants (n=2,979) visited one of 11 drive-thru test sites from July 10thto August 16th, 2020 (or received an in-home visit) to provide a finger pin-prick sample. We applied a robust SARS-CoV-2 Antigen Microarray technology, which has superior measurement validity relative to FDA-approved tests.

Findings

Participants include a broad age, gender, racial/ethnic, and income representation. Adjusted seroprevalence of SARS-CoV-2 infection was 11.5% (95% CI: 10.5% to 12.4%). Formal bias analyses produced similar results. Prevalence was elevated among Hispanics (vs. other non-Hispanic: prevalence ratio [PR]= 1.47, 95% CI: 1.22 to 1.78) and household income <$50,000 (vs. >$100,000: PR= 1.42, 95% CI: 1.14 to 1.79).

Interpretation

Results from a diverse population using a highly specific and sensitive microarray indicate a SARS-CoV-2 seroprevalence of ∼12 percent. This population-based seroprevalence is seven-fold greater than that using official County statistics. In this region, SARS-CoV-2 also disproportionately affects Hispanic and low-income adults.

Funding

Orange County Healthcare Agency
High use of the emergency department shows typical features of complex systems: analysis of multicentre linked data
Authors: Burton Christopher , Stone Tony , Oliver Phillip , Dickson Jon M , Lewis Jen , Mason Suzanne
Published: October 2020

Objective

High use of the ED is a worldwide problem. We hypothesised that high use of the ED could be understood as a feature of a complex system comprising patients, healthcare and society. Complex systems have characteristic statistical properties, with stable patterns at the level of the system emerging from unstable patterns at the level of individuals who make up the system.

Methods

Analysis of a linked dataset of routinely collected health records from all 13 hospital trusts providing ED care in the Yorkshire and Humber region of the UK (population 5.5 million). We analysed the distribution of attendances per person in each of three years and measured the transition of individual patients between high, low and non-attendance. We fitted data to power law distributions typically seen in complex systems using maximum likelihood estimation.

Results

The data included 3.6 million attendances at EDs in 13 hospital trusts. 29/39 (74.3%) analyses showed a statistical fit to a power law; 2 (5.1%) fitted an alternative distribution.. All trusts’ data fitted a power law in at least one year. Differences over time and between hospital trusts were small and partly explained by demographics. In contrast, individual patients’ high use was unstable between years.

Conclusions

ED attendance patterns are stable at the level of the system, but unstable at the level of individual high users. Attendances follow a power law distribution typical of complex systems. Interventions to address ED high use need to consider the whole system and not just the individual high users.
COVID-19 susceptibility and severity risks in a survey of over 500,000 individuals
Authors: Knight Spencer C. , McCurdy Shannon R. , Rhead Brooke , Coignet Marie V. , Park Danny S. , Roberts Genevieve H.L. , Berkowitz Nathan D. , Zhang Miao , Turissini David , Delgado Karen , Pavlovic Milos ,   AncestryDNA Science Team, Haug Baltzell Asher K. , Guturu Harendra , Rand Kristin A. , Girshick Ahna R. , Hong Eurie L. , Ball Catherine A.
Published: October 2020

Background

The enormous toll of the COVID-19 pandemic has heightened the urgency of collecting and analyzing population-scale datasets in real time to monitor and better understand the evolving pandemic.

Methods

The AncestryDNA COVID-19 Study collected self-reported survey data on symptoms, outcomes, risk factors, and exposures for over 563,000 adult individuals in the U.S. in just under four months, including over 4,700 COVID-19 cases as measured by a self-reported positive test.

Results

We replicated previously reported associations between several risk factors and COVID-19 susceptibility and severity outcomes, and additionally found that differences in known exposures accounted for many of the susceptibility associations. A notable exception was elevated susceptibility for males even after adjusting for known exposures and age (adjusted odds ratio [aOR]=1.36, 95% confidence interval [CI] = (1.19, 1.55)). We also demonstrated that self-reported data can be used to build accurate risk models to predict individualized COVID-19 susceptibility (area under the curve [AUC]=0.84) and severity outcomes including hospitalization and critical illness (AUC=0.87 and 0.90, respectively). The risk models achieved robust discriminative performance across different age, sex, and genetic ancestry groups within the study.

Conclusion

The results highlight the value of self-reported epidemiological data to rapidly provide public health insights into the evolving COVID-19 pandemic.

THUMBNAIL

What is already known on this subject

The COVID-19 pandemic has exacted a historic toll on human lives, healthcare systems and global economies, with over 83 million cases and over 1.8 million deaths worldwide as of January 2021.

COVID-19 risk factors for susceptibility and severity have been extensively investigated by clinical and public health researchers.

Several groups have developed risk models to predict COVID-19 illness outcomes based on known risk factors.

What this study adds

We performed association analyses for COVID-19 susceptibility and severity in a large, at-home survey and replicated much of the previous clinical literature.

Associations were further adjusted for known COVID-19 exposures, and we observed elevated positive test odds for males even after adjustment for these known exposures.

We developed risk models and evaluated them across different age, sex, and genetic ancestry cohorts, and showed robust performance across all cohorts in a holdout dataset.

Our results establish large-scale, self-reported surveys as a potential framework for investigating and monitoring rapidly evolving pandemics.
Common physiological processes control mercury reduction during photosynthesis and fermentation
Authors: Grégoire Daniel S. , Janssen Sarah E. , Lavoie Noémie C. , Tate Michael T. , Poulain Alexandre J.
Published: October 2020

Mercury (Hg) is a global pollutant and potent neurotoxin that bioaccumulates in food webs as monomethylmercury (MeHg). The production of MeHg is driven by anaerobic and Hg redox cycling pathways such as Hg reduction, which control the availability of Hg to methylators. Anaerobes play an important role in Hg reduction in methylation hotspots, yet their contributions remain underappreciated due to how challenging these pathways are to study in the absence of dedicated genetic targets and low levels of Hg0in anoxic environments. In this study we used Hg stable isotope fractionation to explore Hg reduction during anoxygenic photosynthesis and fermentation in the model anaerobeHeliobacterium modesticaldumIce1. We show that cells preferentially reduce lighter Hg isotopes in both metabolisms leading to mass-dependent fractionation, but mass-independent fractionation commonly induced by UV-visible light is absent. We show that isotope fractionation is affected by the interplay between pathways controlling Hg recruitment, accessibility, and availability alongside metabolic redox reactions. The combined contributions of these processes lead to isotopic enrichment during anoxygenic photosynthesis that is in between the values reported for anaerobic respiratory microbial Hg reduction and abiotic photoreduction. Isotope enrichment during fermentation is closer to what has been observed in aerobic bacteria that reduce Hg through dedicated detoxification pathways. These results demonstrate that common controls exist at the atomic level for Hg reduction during photosynthesis and fermentation inH. modesticaldum. Our work suggests that similar controls likely underpin diverse microbe-mediated Hg transformations that affect Hg’s fate in oxic and anoxic habitats.

IMPORTANCE

Anaerobic and photosynthetic bacteria that reduce mercury affect mercury delivery to microbes in methylation sites that drive bioaccumulation in food webs. Anaerobic mercury reduction pathways remain underappreciated in the current view of the global mercury cycle because they are challenging to study, bearing no dedicated genetic targets to establish physiological mechanisms. In this study we used stable isotopes to show that common physiological processes control mercury reduction during photosynthesis and fermentation in the model anaerobeHeliobacterium modesticaldumIce1. The sensitivity of isotope analyses highlighted the subtle contribution of mercury uptake towards the isotope signature associated with anaerobic mercury reduction. When considered alongside the isotope signatures associated with microbial pathways for which genetic determinants have been identified, our findings underscore the narrow range of isotope enrichment that is characteristic of microbial mercury transformations. This suggests that there exist common atomic-level controls for biological mercury transformations across a broad range of geochemical conditions.
Expression of Castanea crenata Allene Oxide Synthase in Arabidopsis Improves the Defense to Phytophthora cinnamomi
Authors: Serrazina Susana , Machado Helena , Costa Rita , Duque Paula , Malhó Rui
Published: October 2020

Allene oxide synthase (AOS) is a key enzyme of the jasmonic acid (JA) signaling pathway. The AOS gene was previously found to be upregulated in an Asian chestnut species resistant to infection by the oomycete Phytophthora cinnamomi (Castanea crenata), while lower expression values were detected in the susceptible European chestnut (Castanea sativa). Here, we report a genetic and functional characterization of the C. crenata AOS (CcAOS) upon its heterologous gene expression in a susceptible ecotype of Arabidopsis thaliana, which contains a single AOS gene. It was found that Arabidopsis plants expressing CcAOS delay pathogen progression and exhibit more vigorous growth in its presence. They also show upregulation of jasmonic acid and salicylic acid-related genes. As in its native species, heterologous CcAOS localized to plastids, as revealed by confocal imaging of the CcAOS-eGFP fusion protein in transgenic Arabidopsis roots. This observation was confirmed upon transient expression in Nicotiana benthamiana leaf epidermal cells. To further confirm a specific role of CcAOS in the defense mechanism against the pathogen, we performed crosses between transgenic CcAOS plants and an infertile Arabidopsis AOS knockout mutant line. It was found that plants expressing CcAOS exhibit normal growth, remain infertile but are significantly more tolerant to the pathogen than wild type plants.

Together, our results indicate that CcAOS is an important player in plant defense responses against oomycete infection and that its expression in susceptible varieties may be a valuable tool to mitigate biotic stress responses.

One-sentence summary

Heterologous expression of the Castanea crenata allene oxide synthase gene in Arabidopsis thaliana improves the defense response to the pathogen Phytophthora cinnamomi.
Optical topometry and machine learning to rapidly phenotype stomatal patterning traits for QTL mapping in maize
Authors: Xie Jiayang , Mayfield-Jones Dustin , Erice Gorka , Choi Min , Leakey Andrew D.B.
Published: October 2020

Stomata are adjustable pores on leaf surfaces that regulate the trade-off of CO2uptake with water vapor loss, thus having critical roles in controlling photosynthetic carbon gain and plant water use. The lack of easy, rapid methods for phenotyping epidermal cell traits have limited the use of quantitative, forward and reverse genetics to discover the genetic basis of stomatal patterning. A new high-throughput epidermal cell phenotyping pipeline is presented here and used for quantitative trait loci (QTL) mapping in field-grown maize. The locations and sizes of stomatal complexes and pavement cells on images acquired by an optical topometer from mature leaves were automatically determined. Computer estimated stomatal complex density (SCD; R2= 0.97) and stomatal complex area (SCA; R2= 0.71) were strongly correlated with human measurements. Leaf gas exchange traits correlated with the dimensions and proportion of stomatal complexes but, unexpectedly, did not correlate with SCD. Genetic variation in epidermal traits were consistent across two field seasons. Out of 143 QTLs in total, 36 QTLs were consistently identified for a given trait in both years. 24 hotspots of overlapping QTLs for multiple traits were identified. Orthologs of genes known to regulate stomatal patterning inArabidopsiswere located within some, but not all, of these regions. This study demonstrates how discovery of the genetic basis for stomatal patterning can be accelerated in maize, a model for C4species where these processes are poorly understood.

One sentence summary

Optical topometry and machine learning tools were developed to assess epidermal cell patterning, and applied to analyze its genetic architecture alongside leaf photosynthetic gas exchange in maize.
Transmission of SARS-CoV-2 from Children and Adolescents
Authors: Chu Victoria T. , Yousaf Anna R. , Chang Karen , Schwartz Noah G. , McDaniel Clinton J. , Szablewski Christine M. , Brown Marie , Winglee Kathryn , Lee Scott H. , Cui Zhaohui , Adebayo Adebola , Aholou Tiffiany , Amin Minal M. , Aryee Peter , Castaneda Cindy , Chambers Trudy , Fleshman Amy C. , Goodman Christin , Holmes Tony , Ivey-Stephenson Asha , Kamitani Emiko , Katz Susan , Knapp Jennifer K. , Kolasa Maureen , Lumsden Maranda , Mayweather Erin , Mohammed Asfia , Moorman Anne , Patel-Larson Alpa , Perinet Lara , Pilgard Mark , Pratt Deirdre D. , Railey Shanica , Shah Jaina , Tuckey Dawn , Dirlikov Emilio , Rose Dale A. , Villanueva Julie , Fry Alicia M. , Hall Aron J. , Kirking Hannah L. , Tate Jacqueline E. , Drenzek Cherie L. , Lanzieri Tatiana M. , Stewart Rebekah J.
Published: October 2020

A better understanding of SARS-CoV-2 transmission from children and adolescents is crucial for informing public health mitigation strategies. We conducted a retrospective cohort study among household contacts of primary cases defined as children and adolescents aged 7⍰19 years with laboratory evidence of SARS-CoV-2 infection acquired during an overnight camp outbreak. Among household contacts, we defined secondary cases using the Council of State and Territorial Epidemiologists definition. Among 526 household contacts of 224 primary cases, 48 secondary cases were identified, corresponding to a secondary attack rate of 9% (95% confidence interval [CI], 7%–12%). Our findings show that children and adolescents can transmit SARS-CoV-2 to adult contacts and other children in a household setting.
Identifying Optimal COVID-19 Testing Strategies for Schools and Businesses: Balancing Testing Frequency, Individual Test Technology, and Cost
Authors: Lyng Gregory D. , Sheils Natalie E. , Kennedy Caleb J. , Griffin Daniel , Berke Ethan M.
Published: October 2020

Background

COVID-19 test sensitivity and specificity have been widely examined and discussed yet optimal use of these tests will depend on the goals of testing, the population or setting, and the anticipated underlying disease prevalence. We model various combinations of key variables to identify and compare a range of effective and practical surveillance strategies for schools and businesses.

Methods

We coupled a simulated data set incorporating actual community prevalence and test performance characteristics to a susceptible, infectious, removed (SIR) compartmental model, modeling the impact of base and tunable variables including test sensitivity, testing frequency, results lag, sample pooling, disease prevalence, externally-acquired infections, and test cost on outcomes case reduction.

Results

Increasing testing frequency was associated with a non-linear positive effect on cases averted over 100 days. While precise reductions in cumulative number of infections depended on community disease prevalence, testing every 3 days versus every 14 days (even with a lower sensitivity test) reduces the disease burden substantially. Pooling provided cost savings and made a high-frequency approach practical; one high-performing strategy, testing every 3 days, yielded per person per day costs as low as $1.32.

Conclusions

A range of practically viable testing strategies emerged for schools and businesses. Key characteristics of these strategies include high frequency testing with a moderate or high sensitivity test and minimal results delay. Sample pooling allowed for operational efficiency and cost savings with minimal loss of model performance.
Characterizing the spatial signal of environmental DNA in river systems using a community ecology approach
Authors: Cantera Isabel , Decotte Jean-Baptiste , Dejean Tony , Murienne Jérôme , Vigouroux Régis , Valentini Alice , Brosse Sébastien
Published: October 2020

Environmental DNA (eDNA) is gaining a growing popularity among scientists but its applicability to biodiversity research and management remains limited in river systems by the lack of knowledge about the spatial extent of the downstream transport of eDNA.

Here, we assessed the ability of eDNA inventories to retrieve spatial patterns of fish assemblages along two large and species rich Neotropical rivers. We first examined overall community variation with distance through the distance decay of similarity and compared this pattern to capture-based samples. We then considered previous knowledge on individual species distributions, and compared it to the eDNA inventories for a set of 53 species.

eDNA collected from 28 sites in the Maroni and 25 sites in the Oyapock rivers permitted to retrieve a decline of species similarity with distance between sites. The distance decay of similarity derived from eDNA was similar, and even more pronounced, than that obtained with capture-based methods (gil-nets). In addition, the species upstream-downstream distribution range derived from eDNA matched to the known distribution of most species.

Our results demonstrate that environmental DNA does not represent an integrative measure of biodiversity across the whole upstream river basin but provide a relevant picture of local fish assemblages. Importantly, the spatial signal gathered from eDNA was therefore comparable to that gathered with local capture based methods, which describes fish fauna over a few hundred metres.
A single-cell atlas of Plasmodium falciparum transmission through the mosquito
Authors: Real Eliana , Howick Virginia M. , Dahalan Farah , Witmer Kathrin , Cudini Juliana , Andradi-Brown Clare , Blight Joshua , Davidson Mira S. , Dogga Sunil Kumar , Reid Adam J. , Baum Jake , Lawniczak Mara K. N.
Published: October 2020

Malaria parasites have a complex life cycle featuring diverse developmental strategies, each uniquely adapted to navigate specific host environments. Here we use single-cell transcriptomics to illuminate gene usage across the transmission cycle of the most virulent agent of human malaria – Plasmodium falciparum. We reveal developmental trajectories associated with the colonisation of the mosquito midgut and salivary glands and elucidate the transcriptional signatures of each transmissible stage. Additionally, we identify both conserved and nonconserved gene usage between human and rodent parasites, which point to both essential mechanisms in malaria transmission and species-specific adaptations potentially linked to host tropism. Together, the data presented here, which are made freely available via an interactive website, establish the most complete atlas of the P. falciparum transcriptional journey to date.

One sentence summary

Single-cell transcriptomics of P. falciparum transmission stages highlights developmental trajectories and gene usage.