bluuebunny/crossref_metadata_2025 huggingface dataset:
Orbital Apex Syndrome Secondary to Invasive Aspergillus Infection: A Case Series and Literature Review
Authors: Yuan Melissa , Tandon Anika , Li Anfei , Johnson Editha , Greer Christine , Tooley Andrea , Tran Ann Q. , Godfrey Kyle J. , Dinkin Marc , Oliveira Cristiano
Published: October 2020

Background:

Invasive fungal sinusitis carries high morbidity and mortality and often poses a diagnostic challenge. Orbital apex syndrome (OAS) is not an uncommon presentation in the setting of invasive fungal sinusitis. Delays in diagnosis and appropriate treatment can result in permanent visual dysfunction and, potentially, death. We present 2 cases of OAS secondary to invasive sinus aspergillosis, detailing the diagnostic process, treatment, and outcome for both patients. Subsequently, we present a review of the literature and combined analysis of our 2 patients plus 71 cases from previously published reports.

Methods:

Literature review was performed to identify demographic, diagnostic, clinical, and treatment data of patients with OAS caused by Aspergillus species.

Results:

The review resulted in 52 included articles with 71 patients, plus our 2 reported patients, leading to a total of 73 subjects included in the analysis. The average age of patients at presentation was 59.9 years. A combination of visual disturbance and pain (headache and/or periocular pain) was the most common presentation reported (46 cases; 63%). Diabetes mellitus was reported in 15 cases (21%), with more than half specifically noted to have poorly controlled diabetes. After diabetes, the second most common cause of immunocompromise was chronic steroid use (n = 13; 18%). Empiric antifungal treatment was started in 10 patients (14%), while 25 patients (34%) were first treated with systemic steroids due to a concern for an inflammatory etiology. Time to diagnosis from initial presentation was on average 7.4 weeks (range of 0.3–40 weeks). Approximately 78% of the cases (57 of 73) had biopsies with histology that confirmed Aspergillus fungal morphology, and 30/73 (41%) had diagnostic fungal cultures. The majority of the cases received monotherapy with intravenous (IV) amphotericin B (36 patients; 49%) and IV voriconazole (19 patients; 26%), with a combination of the 2 or more antifungal agents being used in 11 patients (15%). Forty patients (55%) showed signs of clinical improvement with treatment, while 33 (45%) patients did not experience any improvement or continued to deteriorate, and 23 (32%) died in the course of their reported follow-up.

Conclusions:

The present cases illustrate well the challenge in the diagnosis and treatment of OAS due to invasive sinus aspergillosis. Our review and analysis of 73 cases support the notion that a high index of suspicion leading to early biopsy with histology and fungal culture is paramount for diagnosis. Early empiric antifungal treatment and debridement can potentially reduce morbidity and mortality.
Neuro-Ophthalmic Manifestations of Sarcoidosis
Authors: Henderson Amanda D. , Tian Jing , Carey Andrew R.
Published: October 2020

Background:

Sarcoidosis is an idiopathic, multisystem, inflammatory disease that has central nervous system involvement in 5%–15% of cases. The presentation of neurosarcoidosis is highly variable, and the MRI findings often mimic the appearance of other central nervous system diseases. Therefore, the diagnosis can be challenging. About one-third of neurosarcoidosis cases have neuro-ophthalmic manifestations and, thus, may be evaluated by a neuro-ophthalmologist early in the disease course.

Methods:

We performed a retrospective review of 22 cases of biopsy-proven sarcoidosis with neuro-ophthalmic manifestations, seen at the Wilmer Eye Institute from January 2013 to September 2019, in which we described the demographic information, clinical presentations, neuroimaging findings, and diagnostic evaluations.

Results:

Twenty-two patients were included. Fifteen patients identified as black and 7 as white. Fifteen were women, and 7 men. Mean age at sarcoidosis diagnosis was 45.9 years (range 26–66). Neuro-ophthalmic findings included optic neuropathy in 11 (50%); proptosis/orbital inflammation in 5 (23%); abducens palsy in 5 (23%); trochlear palsy, trigeminal distribution numbness, and bitemporal hemianopia in 2 each (9%); and oculomotor palsy, facial palsy, optic perineuritis, dorsal midbrain syndrome, central vestibular nystagmus, and papilledema in 1 each (5%). Eight (36%) had a pre-existing diagnosis of sarcoidosis; however, in 14 (64%), the neuro-ophthalmic presentation led to the sarcoidosis diagnosis. Patients with a pre-existing sarcoidosis diagnosis were younger than those without this diagnosis (38.5 vs 50.1 years, P = 0.035). Brain MRI was abnormal in all but 1 case (95%). In patients without a pre-existing sarcoidosis diagnosis, all 7 tested for angiotensin converting enzyme (ACE) had normal values, and 75% of the 12 who had computed tomography (CT) chest had findings suggestive of sarcoidosis (86% of black patients vs 50% of white patients).

Conclusions:

Patients with neurosarcoidosis may present initially with a neuro-ophthalmic manifestation, and this presentation may be more common in older patients. MRI usually is abnormal, although findings may be nonspecific. Serum testing for ACE is not helpful. Normal CT chest does not rule out underlying sarcoidosis, particularly in white patients.
Prevalence of Adrenal Insufficiency and Glucocorticoid Use in Pediatric Pseudotumor Cerebri Syndrome
Authors: Hoyos-Martinez Alfonso , Horne Vincent E. , Wood Alexis C. , Shah Veeral
Published: October 2020

Background:

The pathophysiology underlying pseudotumor cerebri syndrome (PTCS) is complex and not well understood. There are clear differences between PTCS in adults and pediatrics. Few and isolated case reports have suggested that adrenal function may be involved, yet no large cohort study has examined this relationship.

Methods:

We conducted a retrospective single-center study of children who presented with a diagnosis of PTCS and had cortisol testing measured between January 2010 and September 2019. We included all subjects meeting the revised PTCS diagnostic criteria after the chart review. Based on morning, random or 1-μg cosyntropin stimulated cortisol levels, adrenal functioning was classified as: (1) insufficient (peak cortisol <16 μg/dL and AM cortisol <5 μg/dL), (2) at risk (peak cortisol 16–20 μg/dL, AM cortisol 5–13 μg/dL, or random <13 μg/dL), or (3) sufficient (peak cortisol >20 μg/dL and AM or random cortisol >13 μg/dL).

Results:

A total of 398 individuals were reviewed, and 64 were included for analysis. Of these, 40.6% were men, of mixed race and ethnicity with a mean age of 10.5 (SD 4.7) years. Of these, 23% and 52% had insufficient or at-risk cortisol levels. The majority of those in the insufficient (70%) or at-risk (80%) groups were exposed to topical, nasal, or inhaled glucocorticoids but not systemic. Only 60% and 12% of those with PTCS with insufficient or at-risk cortisol testing, respectively, underwent definitive testing with a stimulation test.

Conclusions:

Glucocorticoid use and hypocortisolism are prevalent in PTCS and need consideration as a potential underlying cause. Most children had insufficient or at-risk cortisol levels, and many did not undergo further testing/workup. Children who present with PTCS, particularly young, males should be evaluated for adrenal insufficiency and its risk factors, including nonsystemic steroids. Prospective studies are necessary to further evaluate the effect of cortisol in relation to pediatric PTCS.
A highly sensitive biosensor with a single-copy evolved sensing cassette for chlorpyrifos pesticide detection
Authors: Chouichit Pakwilai , Whangsuk Wirongrong , Sallabhan Ratiboot , Mongkolsuk Skorn , Loprasert Suvit
Published: October 2020

A formylglycine-generating enzyme (FGE)–sulfatase-based whole-cell biosensor was genetically improved into a single-copy system by integrating the

Sinorhizobium meliloti

transcriptional activator ChpR and the chpA promoter–FGE–sulfatase fusion into the

Escherichia coli

chromosome. The sensitivity was further enhanced through a random mutagenesis of the chpR. The new integrated biosensor offered both a lower detection limit [5 nM chlorpyrifos (CPF)] and fluorescence background. The ready-to-use kit was developed using silica gel for on-field detection. The biosensor kit was stable for 20 days when stored at 4 °C. Moreover, a 1-(1-naphthylmethyl)-piperazine (NMP) efflux pump inhibitor can improve the sensitivity by 57 %.
Fernando de Noronha: how an island controlled the community transmission of COVID-19 in Brazil
Authors: Tabosa Sales Mozart Júlio , Sansigolo Kerr Ligia Regina Franco , Brizolara Regina Vianna , de Holanda Cunha Barreto Ivana Cristina , de Almeida Rosa Lívia Freitas , de Goes Paulo Savio Angeiras , de Andrade Luiz Odorico Monteiro , Torres Leuridan Cavalcante , Alvarenga Pinto Flávia Kelly , Pinheiro Júnior Francisco Marto Leal , Leite Rebeca Valentim , Rego de Carvalho Aline Priscila , Cavalcanti de Abreu Amanda Carolina Felix , Theophilo Rebecca Lucena , Magalhães Fernando Rodrigues , da Silva Susane Lindinalva , Kendall Carl
Published: October 2020

Introduction

Fernando Noronha (FNA) is a small Brazilian archipelago in the Atlantic, part of the state of Pernambuco that COVID-19 has decimated. Anticipating the worst from the pandemic, Island and state authorities implemented a series of public health actions to contain the epidemic. This paper, reporting the results of the first wave of a cohort study, documents the measures and their effects through a cohort study.

Methods

Measures were documented at the time of implementation. A random sample of 904 residents were selected from the health register, interviewed and tested for COVID-19 (RT-PCR and serology). The survey explored socioeconomic variables and adherence to prevention behaviors.

Results

Flights were reduced from 38 to once a week, FNA was closed to tourism, schools were closed, and testing and tracing contacts was mandated along with social distancing and use of masks. A household lockdown was briefly imposed for residents. A prevalence of 5.1% was found, and a total of 158 cases of COVID-19 was estimated, although only 28 had been reported in routine surveillance. Half of the population reported food insecurity and applied for government COVID-19 benefits. Adherence to control measures was high, except for intrahousehold mask use with family and friends.

Conclusion

Despite high levels of COVID-19 in Pernambuco, continued exposure through the provision of essential services from the mainland, and lack of direction from national authorities, FNA was able to implement a series of prevention measures unique in Brazil that contained the epidemic on the island.
Pre-endoscopy SARS-CoV-2 testing strategy during COVID-19 pandemic: The care must go on
Authors: Casper M , Reichert MC , Rissland J , Smola S , Lammert F , Krawczyk M
Published: October 2020

Background

In response to the COVID-19 pandemic, endoscopic societies have recommended reduction of endoscopic procedures. In particular non-urgent endoscopies should be postponed. However, this might lead to unnecessary delay in diagnosing gastrointestinal conditions.

Methods

Retrospectively we analysed the gastrointestinal endoscopies performed at the Central Endoscopy Unit of Saarland University Medical Center during seven weeks from 23 March to 10 May 2020 and present our real-world single-center experience with an individualized rtPCR-based pre-endoscopy SARS-CoV-2 testing (“PECo”) strategy.

Results

Altogether 359 gastrointestinal endoscopies were performed. The PECo strategy enabled us to conservatively handle endoscopy program reduction (44% reduction as compared 2019). The results of COVID-19 rtPCR from nasopharyngeal swabs were available in 89% of patients prior to endoscopies. Apart from six patients with known COVID-19, all other tested patients were negative. The frequencies of endoscopic therapies and clinically significant findings did not differ between patients with or without SARS-CoV-2 tests.

Conclusion

A reasonable reduction of the endoscopy program in the setting of structured SARS-CoV-2 testing is feasible and safe. The PECo strategy allows continuation of endoscopic procedures in a region with intermediate frequency of COVID-19 when hospital capacities are not overwhelmed by the pandemic. Thus, the study might help to develop new strategies during future waves of COVID-19 or local outbreaks.
Economic Benefits of COVID-19 Screening Tests
Authors: Atkeson Andrew , Droste Michael , Mina Michael J. , Stock James H.
Published: October 2020

We assess the economic value of screening testing programs as a policy response to the ongoing COVID-19 pandemic. We find that the fiscal, macroeconomic, and health benefits of rapid SARS-CoV-2 screening testing programs far exceed their costs, with the ratio of economic benefits to costs typically in the range of 2-15 (depending on program details), not counting the monetized value of lives saved. Unless the screening test is highly specific, however, the signal value of the screening test alone is low, leading to concerns about adherence. Confirmatory testing increases the net economic benefits of screening tests by reducing the number of healthy workers in quarantine and by increasing adherence to quarantine measures. The analysis is undertaken using a behavioral SIR model for the United States with 5 age groups, 66 economic sectors, screening and diagnostic testing, and partial adherence to instructions to quarantine or to isolate.
Association between Hydroxyzine Use and Reduced Mortality in Patients Hospitalized for Coronavirus Disease 2019: Results from a multicenter observational study
Authors: Hoertel Nicolas , Sánchez Marina , Vernet Raphaël , Beeker Nathanaël , Neuraz Antoine , Blanco Carlos , Olfson Mark , Lemogne Cédric , Meneton Pierre , Daniel Christel , Paris Nicolas , Gramfort Alexandre , Lemaitre Guillaume , Salamanca Elisa , Bernaux Mélodie , Bellamine Ali , Burgun Anita , Limosin Frédéric
Published: October 2020

Objective

To examine the association between hydroxyzine use and mortality in patients hospitalized for COVID-19, based on its anti-inflammatory and antiviral properties.

Design

Multicenter observational retrospective cohort study.

Setting

Greater Paris University hospitals, France.

Participants

7,345 adults hospitalized for COVID-19 between 24 January and 1 April 2020, including 138 patients (1.9%) who received hydroxyzine during the visit at a mean dose of 49.8 mg (SD=51.5) for an average of 22.4 days (SD=25.9).

Data source

Assistance Publique-Hôpitaux de Paris Health Data Warehouse.

Main outcome measures

The study endpoint was death. We compared this endpoint between patients who received hydroxyzine and those who did not in time-to-event analyses adjusting for patient characteristics (such as age, sex, and comorbidities), clinical and biological markers of disease’s severity, and use of other medications. The primary analysis was a multivariable Cox model with inverse probability weighting. Sensitivity analyses included a multivariable Cox model and a univariate Cox regression model in a matched analytic sample in a 1:1 ratio.

Results

Over a mean follow-up of 20.3 days (SD=27.5), 994 patients (13.5%) had a primary end-point event. The primary multivariable analysis with inverse probability weighting showed a significant association between hydroxyzine use and reduced mortality (HR, 0.42; 95% CI, 0.25 to 0.71; p=0.001) with a significant dose-effect relationship (HR, 0.10; 95% CI, 0.02 to 0.45; p=0.003). This association was similar in sensitivity analyses. In secondary analyses conducted among subsamples of patients, we found a significant association between hydroxyzine use and a faster decrease in biological inflammatory markers associated with COVID-19-related mortality, including neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-C-reactive protein ratio (LCRP), and circulating interleukin 6 levels (IL-6) (all p<0.016), with a significant dose-effect relationship for NLR and LCRP (both p<0.037).

Conclusions

In this retrospective observational study, hydroxyzine use was associated with reduced mortality in patients hospitalized for COVID-19. This association may be partially mediated by specific anti-inflammatory properties of H1 antihistamines. Double-blind controlled randomized clinical trials of hydroxyzine for COVID-19 are needed to confirm these results.
Trigeminal Nerve Blocks In Refractory Trigeminal Neuralgia: About 21 Cases Reported At The Limoges University Hospital
Authors: Jacques Nicolas , Karoutsos Simon , Marais Loïc , Nathan-Denizot Nathalie
Published: October 2020

Introduction

Despite limited scientific evidence, trigeminal nerve blocks are alternative therapies for refractory trigeminal neuralgia (RTN). The duration of analgesia far exceeds the length of the conduction block. This study evaluated the quality of life 15 days after performing this block to treat RTN.

Methods

This retrospective study included all patients who, after informed consent, received iterative trigeminal blocks to treat a RTN between 2014 and 2018 in a university hospital. Patients received 0.5% levobupivacaine in combination with clonidine and a corticosteroid (cortivazol or betamethasone according their availability). Data were obtained from patients medical data files and a telephone questionnaire for the SF-12 score. The main criteria of evaluation was the change in quality of life according SF-12 performed at day 15.

Results

Twenty-one patients aged 62 ±14 years were included. All patients exhibited RTN after many different clinical treatments according ICHD-3 criteria. Seventy-one per cent of RTN occurred after trauma or surgery. Before receiving blocks, SF-12 physical (SF12-PS) and mental (SF-12 MS) scores reached respectively 35 ± 14 and 29 ± 11. A mean time of 4 ± 5 years elapsed between the occurrence of RTN and nerve blockade. At day 15, SF-12 PS increased by a 3 point mean value and SF-12 MS by 5 points. Approximately half of the patients (55%) were considered as non-responders with a cut-off value of less than 10% variation of their initial SF-12 score. When excluding these patients, SF-12 PS and SF-12 MS were increased by 17 and 9 points respectively. The mean duration of blocks lasted 15 ± 59 days and no severe adverse effects were observed. Patient satisfaction was correlated with increased SF-12 PS (r2 = 0.3 p = 0.01) and with the length of analgesia (r2 = 0.51 p = 0.001) but not to SF-12 MS variation (p = 0.12).

Conclusion

Trigeminal nerve blocks are temporarily effective on pain that may increase the quality of life in responder patients. The reason why some patients are unresponsive to this treatment and why durations in efficacy are so variable remain unsolved. However, in responders, trigeminal nerve blocks seem simple, harmless, not excessively cumbersome and without severe adverse effects.
Mendelian randomization integrating GWAS and eQTL data revealed genes pleiotropically associated with major depressive disorder
Authors: Yang Huarong , Liu Di , Zhao Chuntao , Feng Bowen , Lu Wenjin , Yang Xiaohan , Xu Minglu , Zhou Weizhu , Jing Huiquan , Yang Jingyun
Published: October 2020

Objectives

To prioritize genes that are pleiotropically or potentially causally associated with the risk of MDD.

Methods

We applied the summary data-based Mendelian randomization (SMR) method integrating GWAS and expression quantitative trait loci (eQTL) data in 13 brain regions to identify genes that were pleiotropically associated with the risk of MDD. In addition, we repeated the analysis by using the meta-analyzed version of the eQTL summary data in the brain (brain-eMeta).

Results

We identified multiple significant genes across different brain regions that may be involved in the pathogenesis of MDD. The prime-specific geneBTN3A2(corresponding probe: ENSG00000186470.9) was the top hit showing pleotropic association with MDD in 9 of the 13 brain regions and in brain-eMeta, after correction for multiple testing. Many of the identified genes are located in the human major histocompatibility complex (MHC) region on chromosome 6 and are mainly involved in immune response.

Conclusions

Our SMR analysis revealed that multiple genes showed pleiotropic association with MDD across the brain regions. These findings provide important leads to a better understanding of the mechanism of MDD, and reveals potential therapeutic targets for the prevention and effective treatment of MDD.
Economic Losses Associated with COVID-19 Deaths in the United States
Authors: Quast Troy , Andel Ross , Gregory Sean , Storch Eric A.
Published: October 2020

In addition to the overwhelming health effects of COVID-19, the disease has inflicted unprecedented economic damage. Vast resources have been directed at COVID-19 testing and health care while economic activity has been substantially curtailed due to disruptions resulting from individual choices and government policies. This study estimates the economic loss associated with COVID-19 deaths in the U.S. from February 1, 2020 through July 11, 2020. We use estimates of years of life lost that are based on the age and gender of decedents. Using a value of life year estimate of $66,759, we calculate economic losses of roughly $66 billion. The losses are concentrated in New York and New Jersey, which account for 17.5% of the total losses. Our analysis of per capita losses by state indicates that the highest values are located in the northeastern region of the country, while the values in the western states are relatively low. While economic losses associate with COVID-19 deaths is just one aspect of the pandemic, our estimates can provide context to the value of prevention and mitigation efforts.

JEL codes

I12, I18, J17
Staging and typing of chest CT images: A quantitative analysis based on an ambispective observational cohort study of 125 patients with COVID-19 in Xiangyang, China
Authors: Huang Guoxin , Wang Yong , Wu Xiaxia , Qu Gaojing , Chen Junwen , Yu Hui , Zhang Meiling , Wang Lisha , Ai Jinwei , Zhu Haoming , Chen Lei , Pei Bin
Published: October 2020

Background

The stage of CT images was rarely studied and the relationship between the severity of Coronavirus Disease 2019 (COVID-19) and CT images has not been studied based on systematic quantitative analysis currently.

Purpose

To investigate the staging duration and classification of CT images of patients with COVID-19 based on quantitative analysis.

Materials and Methods

This is an ambispective observational cohort study based on 125 patients with COVID-19 from Jan 23 to Feb 28, 2020. The stage of CT and pulmonary lesion size were quantitatively analyzed. The categorical regression analysis based on optimal scale (CATREG) was performed to evaluate the association of CT score, age, and gender with the clinical type.

Results

The CT images of 125 patients with COVID-19 (50.13 ± 16.91 years, 66 women) were analyzed in this study. Except for pre-early stage, the duration of early, progression-consolidation, and dissipation stage of CT images was 3.40 ± 2.31, 10.07 ± 4.91, and 20.60 ± 7.64 days, respectively. The median CT score was 5.00 (2.00-8.50) during the first 30 days, which reached a peak on the 11thday. Significant differences were found between the median CT scores of different clinical types (P<0.05). Besides, the age was correlated with the clinical type (P<0.001), the CT scores of 0.00-11.50, 11.50-16.00, and 16.00-20.00 were separately correlated with the moderate, severe, and critical type with the output accuracy 69.60%.

Conclusion

The four-stage staging method based on quantitative analysis is consistent with the change rules of staging features and COVID-19. Quantitative study by scoring pulmonary lesion sizes accurately revealed the evolvement of pulmonary lesions and differences between different clinical types.

Quantitative study of the stage duration and classification of chest CT images can objectively reveal the relationship between Coronavirus Disease 2019 (COVID-19) and chest CT images.

Key Results

1. A four-stage staging method was proposed. Except for pre-early stage, the duration of early, progression-consolidation, and dissipation stage of CT images was 3.40 ± 2.31, 10.07 ± 4.91, and 20.60 ± 7.64 days, respectively.

2. The severer the disease, the higher the median CT scores and their peak value.

3. The CT scores of 0.00-11.50, 11.50-16.00, and 16.00-20.00 were separately correlated with the moderate, severe, and critical type.
Efficacy and safety of phentermine/topiramate in adults with overweight or obesity: A meta-analysis and systematic review
Authors: Lei Xiang-Guo , Lai Chen , Sun Ziyi , Yang Xi
Published: October 2020

Objective

To examine the association between phentermine/topiramate therapy and weight loss and adverse events in adults with overweight problems or obesity by meta-analysis and systematic review.

Methods

Medical Subject Headings (MeSH) and free-text terms related to phentermine/topiramate were selected to search for eligible trials in PubMed, Cochrane Central Register of Controlled Trials (CENTRAL), and EMBASE up to April 18, 2020. The quality of randomized controlled trials was evaluated by Cochrane risk-of-bias tool. Meta-analysis was performed using random-effect models. Our systematic review protocol, registered on PROSPERO (registration number CRD42020188324).

Results

Phentermine/topiramate therapy resulted in a weight loss of 7.73 kg (95% confidence interval [CI]: 6.60, 8.85) compared to placebo. For phentermine/topiramate subjects in different weight loss subgroups, the weight loss of subjects with ≥5%, ≥10%, and ≥15% baseline weight loss were 3.18 (95% CI: 2.75, 3.67), 5.32 (95% CI: 4.53, 6.25), and 5.65 (95% CI: 3.55, 9.01), respectively. Phentermine/topiramate reduced waist circumference, blood pressure, blood sugar levels, and lipid levels. The adverse effects associated with the treatment mainly included Dysgeusia, Paresthesia, Dry mouth.

Conclusions

Phentermine/topiramate reduced body weight and was well tolerated. However, it increased the risk of nervous system-related adverse events to a certain extent, but the symptoms are not serious. Long-term clinical and pharmacological studies are needed to understand the long-term efficacy and safety of phentermine/topiramate.

Study Importance Questions

Phentermine/topiramate was approved by the FDA as an anti-obesity drug. However, the European Medicines Agency refused marketing authorization for phentermine/topiramate owing to safety concerns.

Phentermine/topiramate reduced body weight and was well tolerated. However, it remarkably increased the risk of nervous system-related adverse events.

In this study, the efficacy and incidence of adverse events of phentermine/topiramate were further evaluated through meta-analysis to provide reference for the clinical use of phentermine/topiramate.
Head-to-head comparison of SARS-CoV-2 antigen-detecting rapid test with self-collected anterior nasal swab versus professional-collected nasopharyngeal swab
Authors: Lindner Andreas K. , Nikolai Olga , Kausch Franka , Wintel Mia , Hommes Franziska , Gertler Maximilian , Krüger Lisa J. , Gaeddert Mary , Tobian Frank , Lainati Federica , Köppel Lisa , Seybold Joachim , Corman Victor M. , Drosten Christian , Hofmann Jörg , Sacks Jilian A. , Mockenhaupt Frank P. , Denkinger Claudia M.
Published: October 2020

Background

Two antigen-detecting rapid diagnostic tests (Ag-RDTs) are now approved through the WHO Emergency Use Listing procedure and can be performed at the point-of-care. However, both tests use nasopharyngeal (NP) swab samples. NP swab samples must be collected by trained healthcare personnel with protective equipment and are frequently perceived as uncomfortable by patients.

Methods

This was a manufacturer-independent, prospective diagnostic accuracy study with comparison of a supervised, self-collected anterior nose (AN) swab sample with a professional-collected NP swab sample, using a WHO-listed SARS-CoV-2 Ag-RDT, STANDARD Q COVID-19 Ag Test (SD Biosensor), which is also being distributed by Roche. The reference standard was RT-PCR from an oro-/nasopharyngeal swab sample. Percent positive and negative agreement as well as sensitivity and specificity were calculated.

Results

Among the 289 participants, 39 (13.5%) tested positive for SARS-CoV-2 by RT-PCR. The positive percent agreement of the two different sampling techniques for the Ag-RDT was 90.6% (CI 75.8-96.8). The negative percent agreement was 99.2% (CI 97.2-99.8). The Ag-RDT with AN sampling showed a sensitivity of 74.4% (29/39 PCR positives detected; CI 58.9-85.4) and specificity of 99.2% (CI 97.1-99.8) compared to RT-PCR. The sensitivity with NP sampling was 79.5% (31/39 PCR positives detected; CI 64.5-89.2) and specificity was 99.6% (CI 97.8-100). In patients with high viral load (>7.0 log 10 RNA SARS-CoV2/swab), the sensitivity of the Ag-RDT with AN sampling was 96% and 100% with NP sampling.

Conclusion

Supervised self-sampling from the anterior nose is a reliable alternative to professional nasopharyngeal sampling using a WHO-listed SARS-CoV-2 Ag-RDT. Considering the ease-of-use of Ag-RDTs, self-sampling and potentially patient self-testing at home may be a future use case.
Who is (Not) Complying with the Social Distancing Directive and Why? Testing a General Framework of Compliance with Multiple Measures of Social Distancing
Authors: Fazio Russell H. , Ruisch Benjamin C. , Moore Courtney A. , Samayoa Javier A. Granados , Boggs Shelby T. , Ladanyi Jesse T.
Published: October 2020

A study involving over 2000 online participants tested a general framework regarding compliance with a directive in the context of the COVID-19 pandemic. The study featured not only a self-report measure of social distancing but also behavioral measures -- simulations that presented participants with graphical depictions mirroring multiple real-world scenarios and asked them to position themselves in relation to others in the scene. The conceptual framework highlights three essential components of a directive: (1) the source, some entity is advocating for a behavioral change; (2) the surrounding context, the directive is in response to some challenge; and (3) the target, the persons to whom the directive is addressed. Belief systems relevant to each of these three components are predicted, and were found, to relate to compliance with the social distancing directive. The implications of the findings for public service campaigns encouraging people to engage in social distancing are discussed.
Implications of the COVID-19 pandemic on eliminating trachoma as a public health problem
Authors: Blumberg Seth , Borlase Anna , Prada Joaquin M , Solomon Anthony W , Emerson Paul , Hooper Pamela J , Deiner Michael S , Amoah Benjamin , Hollingsworth Deirdre , Porco Travis C , Lietman Thomas M
Published: October 2020

Background

Progress towards elimination of trachoma as a public health problem has been substantial, but the COVID-19 pandemic has disrupted community-based control efforts.

Methods

We use a susceptible-infected model to estimate the impact of delayed distribution of azithromycin treatment on the prevalence of active trachoma.

Results

We identify three distinct scenarios for geographic districts depending on whether the basic reproduction number and the treatment-associated reproduction number are above or below a value of one. We find that when the basic reproduction number is below one, no significant delays in disease control will be caused. However, when the basic reproduction number is above one, significant delays can occur. In most districts a year of COVID-related delay can be mitigated by a single extra round of mass drug administration. However, supercritical districts require a new paradigm of infection control because the current strategies will not eliminate disease.

Conclusion

If the pandemic can motivate judicious, community-specific implementation of control strategies, global elimination of trachoma as a public health problem could be accelerated.
The impact of multimodal cognitive rehabilitation on executive functions in older adults with traumatic brain injury (TBI)
Authors: Cisneros Eduardo , Beauséjour Véronique , de Guise Elaine , Belleville Sylvie , McKerral Michelle
Published: October 2020

Abstract

Objectives

This study evaluated the impact of a multimodal cognitive rehabilitation intervention, the Cognitive Enrichment Program (CEP), on executive functioning (EF) and resumption of daily activities following traumatic brain injury (TBI) in older individuals, in comparison to an active control group having received holistic rehabilitation as usual care.

Methods

The CEP’sexecutive function module included planning, problem solving, and goal management training, as well as strategies focusing on self-awareness. Effectiveness was evaluated by psychometric tests (Modified Six Elements Task-adapted – MSET-A, D-KEFSSorting testandStroop four-color version), while generalization was measured through self-reported questionnaires about daily functioning (Dysexecutive Functioning Questionnaire – DEX,Forsaken daily life activities). Measures were obtained before and after intervention, and six months later.

Results

ANCOVA results showed significant group-by-time interactions onTackling the 6 subtasksandAvoiding rule-breakingmeasures of the MSET-A, with moderate effect sizes. Despite improvements in Sorting and Stroop scores, there were no group-by-time interaction on these measures. DEX generalization measure showed a significant reduction in patient/significant other difference on theExecutive Cognitionsubscale. There was a reduction in the number ofForsaken daily life activitiesin the experimental group compared to controls which was not significant immediately after CEP, but that was significant six months later.

Conclusions

Our study shows that older adults with TBI can improve their executive functioning with a positive impact on everyday activities after receiving multimodal cognitive training compared to an active control group.
Association between vitamin D deficiency and exercise capacity in patients with CKD, a cross-sectional analysis
Authors: Watson Emma L , Wilkinson Thomas J , O’Sullivan Tom F , Baker Luke A , Gould Douglas W , Xenophontos Soteris , Graham-Brown Matthew PM , Major Rupert W , Jenkinson Carl , Hewison Martin , Philp Andrew , Smith Alice C
Published: October 2020

Evidence is growing for a role of vitamin D in regulating skeletal muscle mass, strength and functional capacity. Given the role the kidneys play in activating total vitamin D, and the high prevalence of vitamin D deficiency in Chronic Kidney Disease (CKD), it is possible that deficiency contributes to the low levels of physical function and muscle mass in these patients. This is a secondary cross-sectional analysis of previously published interventional study, withex vivofollow up work. 34 CKD patients at stages G3b-5 (eGFR 25.5 ± 8.3ml/min/1.73m2; age 61 ± 12 years) were recruited, with a sub-group (n=20) also donating a muscle biopsy. Vitamin D and associated metabolites were analysed in plasma by liquid chromatography tandem-mass spectroscopy and correlated to a range of physiological tests of muscle size, function, exercise capacity and body composition. The effects of 1α,25(OH)2D3 supplementation on myogenesis and myotube size was investigated in primary skeletal muscle cells from vitamin D deficient donors.In vivo, there was no association between total or active vitamin D and muscle size or strength, but a significant correlation withwas seen with the total form.Ex vivo, 1α,25(OH)2D3 supplementation reduced IL-6 mRNA expression, but had no effect upon proliferation, differentiation or myotube diameter. This early preliminary work suggests that vitamin D deficiency is not a prominent factor driving the loss of muscle mass in CKD, but may play a role in reduced exercise capacity.
ZeBraInspector, a platform for the automated segmentation and analysis of body and brain volumes in whole 5 dpf zebrafish following simultaneous visualization with identical orientations
Authors: Lempereur Sylvain , Simion Matthieu , Machado Elodie , Licata Fabrice , Buzer Lilian , Robineau Isabelle , Hémon Julien , Banerjee Payel , De Crozé Noémie , Léonard Marc , Affaticati Pierre , Jenett Arnim , Talbot Hugues , Joly Jean-Stéphane
Published: October 2020

In recent years, the zebrafish has become a well-established laboratory model. We describe here the ZeBraInspector (ZBI) platform for high-content 3D imaging (HCI) of 5 dpf zebrafish eleuthero-embryos (EEs). This platform includes a mounting method based on 3D-printed stamps to create a grid of wells in an agarose cast, facilitating batch acquisitions with a fast-confocal laser scanning microscope. We describe reference labeling in cleared fish with a fluorescent lipophilic dye.

Based on this labeling, the ZBI software registers EE 3D images, making it possible to visualize numerous identically oriented EEs on a single screen, and to compare their morphologies and any fluorescent patterns at a glance. High-resolution 2D snapshots can be extracted. ZBI software is therefore useful for diverse high-content analyses (HCAs).

Following automated segmentation of the lipophilic dye signal, the ZBI software performs volumetric analyses on whole EEs and their nervous system white matter. Through two examples, we illustrate the power of these analyses for obtaining statistically significant results from a small number of samples: the characterization of a phenotype associated with a neurodevelopmental mutation, and of the defects caused by treatments with a toxic anti-cancer compound.
Allantoin induces pruritus by activating MrgprD in chronic kidney disease
Authors: Yang Yan , Sun Yulin , Guan Donglang , Chen Dan , Wang Dijun , Liu Tongtong , Sheng Meixiao , Jing Tao , Jun Shi , Zhu Chan , Yu Guang , Dong Xinzhong , Tang Zongxiang
Published: October 2020

Chronic kidney disease is a disease with decreased, irreversible renal function. Pruritus is the most common skin symptom in patients with chronic kidney disease, especially in end-stage renal disease (AKA chronic kidney disease-associated pruritus [CKD-aP]); however, the underlying molecular and neural mechanism of the CKD-aP in patients remains obscure. Our data show that the level of allantoin increases in the serum of CKD-aP and CKD model mice. Allantoin could induce scratching behavior in mice and active DRG neurons; the calcium influx and the action potential were significantly reduced in DRG neurons of MrgprD KO or TRPV1 KO mice. U73122, an antagonist of PLC, could also block calcium influx in DRG neurons induced by allantoin. Thus, our results concluded that allantoin plays an important role in CKD-aP, mediated by MrgprD and TrpV1, in CKD patients.
The selfish nature in interpersonal exchange among adolescents: imposing the kind and submitting to the exploitative
Authors: Wu Xiaoyan , Feng Chunliang , Zhang Shen , Liang Zilu , Dong Wenshan , Qin Shaozheng , Luo Yue-Jia , Liu Chao
Published: October 2020

Bullying events during adolescence are common, yet it remains largely unclear which kinds of behavioral patterns are more likely to result in being exploited. Leveraging recent advances in computational modeling and experimental economics, this study examines whether being nice or tough during early social interactions will impact future interactions. Adolescents were randomly assigned to play a cooperation game with two different simulated partners. We found that participants were more likely to cooperate with the initially tough partner than with the initially nice partner. Computational modeling revealed that behavioral changes were driven by changes in perceived social rewards from reciprocity. Perceived social rewards mediated the effects of different partners on the participants’ cooperative behaviors. The results indicate that being nice is not a good strategy for building social cooperation, and advance our knowledge of how adolescents form sustained social relationships with peers and may have implications for the education field.

Statement of Relevance

Bullying events in high school have been extremely common across cultures. Most studies focus on the modulations of adolescent’s behaviors by a specific factor, e.g., education, parenting style or psychological distorter. Our study examines a more general question: whether and how the way of adolescents exhibit themselves would dynamically influence the way that other people treat them. Our findings suggest that being nice initially is not a good strategy for building social cooperation. Being nice early in a relationship will weaken the value of reciprocity perceived by others, which in turn results in being exploited. We regard our work as being of significance for the fields of psychological science, education and human morality. This study advances our knowledge of how adolescents form sustained social relationships with their peers, and it may have implications for the education field.
Cellular and genomic properties ofHaloferax gibbonsiiLR2-5, the host of euryarchaeal virus HFTV1
Authors: Tittes Colin , Schwarzer Sabine , Pfeiffer Friedhelm , Dyall-Smith Mike , Rodriguez-Franco Marta , Oksanen Hanna M. , Quax Tessa E.F.
Published: October 2020

Hypersaline environments are the source of many viruses infecting different species of halophilic euryarchaea. Information on infection mechanisms of archaeal viruses is scarce, due to the lack of genetically accessible virus-host models. Recently a new archaeal siphovirus, Haloferax tailed virus 1 (HFTV1), was isolated together with its host belonging to the genusHaloferax,but it is not infectious on the widely used model euryarcheonHfx. volcanii.To gain more insight into the biology of HFTV1 host strain LR2-5, we studied characteristics that might play a role in its virus susceptibility: growth-dependent motility, surface layer, filamentous surface structures and cell shape. Its genome sequence showed that LR2-5 is a new strain ofHfx. gibbonsii.LR2-5 lacks obvious viral defense systems, such as CRISPR-Cas, and the composition of its cell surface is different fromHfx. volcanii,which might explain the different viral host range. This work provides first deep insights into the relationship between the host of halovirus HFTV1 and other members of the genusHaloferax. Given the close relationship to the genetically accessibleHfx. volcanii, LR2-5 has high potential as a new model for virus-host studies in euryarchaea.
Functional genomic analyses highlights a shift inGpr17-regulated cellular processes in oligodendrocyte progenitor cells (OPC) and underlying myelin dysregulation in the aged forebrain
Authors: Rivera Andrea D. , Pieropan Francesca , De La Rocha Irene Chacon , Lecca Davide , Abbracchio Maria P. , Azim Kasum , Butt Arthur M
Published: October 2020

Brain aging is characterised by a decline in neuronal function and associated cognitive deficits. There is increasing evidence that myelin disruption is an important factor that contributes to the age-related loss of brain plasticity and repair responses. In the brain, myelin is produced by oligodendrocytes, which are generated throughout life by oligodendrocyte progenitor cells (OPCs). Currently, a leading hypothesis points to aging as a major reason for the ultimate breakdown of remyelination in Multiple Sclerosis (MS). However, an incomplete understanding of the cellular and molecular processes underlying brain aging hinders the development of regenerative strategies. Here, our combined systems biology and neurobiological approach demonstrates that oligodendroglial and myelin genes are amongst the most altered in the aging mouse cortex. This was underscored by the identification of causal links between signaling pathways and their downstream transcriptional networks that define oligodendroglial disruption in aging. The results highlighted that the G-protein coupled receptor GPR17 is central to the disruption of OPC in aging and this was confirmed by genetic fate mapping and cellular analyses. Finally, we used systems biology strategies to identify therapeutic agents that rejuvenate OPC and restore myelination in age-related neuropathological contexts.
Machine learning models for predicting protein condensate formation from sequence determinants and embeddings
Authors: Saar Kadi L. , Morgunov Alexey S. , Qi Runzhang , Arter William E. , Krainer Georg , Lee Alpha A. , Knowles Tuomas P. J.
Published: October 2020

Intracellular phase separation of proteins into biomolecular condensates is increasingly recognised as an important phenomenon for cellular compartmentalisation and regulation of biological function. Different hypotheses about the parameters that determine the tendency of proteins to form condensates have been proposed with some of them probed experimentally through the use of constructs generated by sequence alterations. To broaden the scope of these observations, here, we established anin silicostrategy for understanding on a global level the associations between protein sequence and condensate formation, and used this information to construct machine learning classifiers for predicting liquid–liquid phase separation (LLPS) from protein sequence. Our analysis highlighted that LLPS–prone sequences are more disordered, hydrophobic and of lower Shannon entropy than sequences in the Protein Data Bank or the Swiss-Prot database, and have their disordered regions enriched in polar, aromatic and charged residues. Using these determining features together with neural network based word2vec sequence embeddings, we developed machine learning classifiers for predicting protein condensate formation. Our model, trained to distinguish LLPS-prone sequences from structured proteins, achieved high accuracy (93%; 25-fold cross-validation) and identified condensate forming sequences from external independent test data at 97% sensitivity. Moreover, in combination with a classifier that had developed a nuanced insight into the features governing protein phase behaviour by learning to distinguish between sequences of varying LLPS propensity, the sensitivity was supplemented with high specificity (approximated ROC–AUC of 0.85). These results provide a platform rooted in molecular principles for understanding protein phase behaviour. The predictor is accessible fromhttps://deephase.ch.cam.ac.uk/.

Significance Statement

The tendency of many cellular proteins to form protein-rich biomolecular condensates underlies the formation of subcellular compartments and has been linked to various physiological functions. Understanding the molecular basis of this fundamental process and predicting protein phase behaviour have therefore become important objectives. To develop a global understanding of how protein sequence determines its phase behaviour, here, we constructed bespoke datasets of proteins of varying phase separation propensity and identified explicit biophysical and sequence-specific features common to phase separating proteins. Moreover, by combining this insight with neural network based sequence embeddings, we trained machine learning classifiers that identified phase separating sequences with high accuracy, including from independent external test data. The predictor is available fromhttps://deephase.ch.cam.ac.uk/.