bluuebunny/crossref_metadata_2025 huggingface dataset:
Brief Report: Lower Socioeconomic Status Associates With Greater Systemic and Arterial Inflammation in HIV
Authors: Zhang Lili , Abohashem Shady , Osborne Michael T. , Naddaf Nicki , Park Rebecca , Moore Kelvin , Patrich Tomas , Deeks Steven G. , Hsue Priscilla Y. , Tawakol Ahmed A.
Published: January 2021

Objectives:

In the general population, the lower socioeconomic status (SES) associates with greater systemic and arterial inflammation and a greater risk of cardiovascular disease. Because arterial inflammation is heightened in individuals living with HIV, we tested the hypothesis that SES associates with arterial inflammation in this population.

Settings:

Prospective cohort study.

Methods:

Men living with HIV were recruited. Arterial inflammation and leukopoietic activity (ie, bone marrow activity) were measured using 18F-fluorodeoxyglucose positron emission tomography/computed tomography. Zip code-level SES measures were derived from the US Census Bureau. Linear regression and mediation analyses were used to assess associations between SES, arterial inflammation, leukopoietic activity, C-reactive protein (CRP), and interleukin-6.

Results:

Thirty-nine virologically suppressed men living with HIV were studied (mean ± SD age 50.5 ± 11.1 years). The median CD4 count was 663 cells/mm3 (interquartile range: 399–922); 82% were receiving antiretroviral therapies. Local median income inversely associated with arterial inflammation [standardized β (95% confidence interval): −0.42 (−0.76 to −0.08)] after adjusting for age, Framingham risk score, statin use, antiretroviral use, and nadir CD4 count. The high-school graduation rate independently associated with arterial inflammation [−0.45 (−0.78 to −0.12)] and CRP [−0.49 (−0.86 to −0.012)]. Mediation analysis demonstrated the impact of SES on arterial inflammation was partially mediated by heightened circulating inflammatory levels: ↓SES (as high school graduation rate) →↑CRP →↑arterial inflammation accounting for 44% of the total effect (P < 0.05).

Conclusion:

In individuals living with HIV, lower SES independently associated with higher leukopoietic activity, circulating markers of inflammation, and arterial inflammation. Furthermore, the link between SES and arterial inflammation was mediated by increased systemic inflammation.
FDG PET/CT of an Advanced Case of Malignant Nerve Sheath Tumor of Pleura
Authors: Saidi Bahare , Fallahi Babak , Abdi Anahid , Rakhshani Nasser , Eftekhari Mohammad
Published: January 2021

We present a rare case of malignant nerve sheath tumor of pleura referred for the evaluation of metastases and local invasion. FDG PET/CT demonstrated a hypermetabolic tumoral lesion extensively involving the right pleura with no involvement of mediastinal structures or pulmonary parenchyma and no clear evidence of distant metastasis. Malignant nerve sheath tumor of pleura is an extremely rare entity, and FDG PET/CT is valuable in demonstrating the extent of disease and can have potential role for postsurgical as well as postchemotherapy assessment of possible residual disease.
Quantitative Assessment of Myocardial Ischemia With Positron Emission Tomography
Authors: Sohn Jae Ho , Behr Spencer C. , Hernandez Pampaloni Miguel , Seo Youngho
Published: January 2021

Recent advances in positron emission tomography (PET) technology and reconstruction techniques have now made quantitative assessment using cardiac PET readily available in most cardiac PET imaging centers. Multiple PET myocardial perfusion imaging (MPI) radiopharmaceuticals are available for quantitative examination of myocardial ischemia, with each having distinct convenience and accuracy profile. Important properties of these radiopharmaceuticals (15O-water, 13N-ammonia, 82Rb, 11C-acetate, and 18F-flurpiridaz) including radionuclide half-life, mean positron range in tissue, and the relationship between kinetic parameters and myocardial blood flow (MBF) are presented. Absolute quantification of MBF requires PET MPI to be performed with protocols that allow the generation of dynamic multiframes of reconstructed data. Using a tissue compartment model, the rate constant that governs the rate of PET MPI radiopharmaceutical extraction from the blood plasma to myocardial tissue is calculated. Then, this rate constant (K
1) is converted to MBF using an established extraction formula for each radiopharmaceutical. As most of the modern PET scanners acquire the data only in list mode, techniques of processing the list-mode data into dynamic multiframes are also reviewed. Finally, the impact of modern PET technologies such as PET/CT, PET/MR, total-body PET, machine learning/deep learning on comprehensive and quantitative assessment of myocardial ischemia is briefly described in this review.
Oncologic Outcomes Associated With MRI-detected Extramural Venous Invasion (mrEMVI) in Rectal Cancer
Authors: Rouleau Fournier François , Motamedi Mohammad Ali K. , Brown Carl J. , Phang Terry , Raval Manoj J. , Hague Cameron J. , Karimuddin Ahmer A.
Published: January 2021

Background:

The role of MRI-detected EMVI (mrEMVI) as a reliable prognostic factor in rectal cancer has been emphasized in recent years but this finding remains underreported by many institutions.

Objective:

This review aimed to demonstrate the importance of pre- and post-treatment MRI-detected EMVI as independent prognostic factors of adverse oncologic outcomes in patients undergoing neoadjuvant therapy followed by total mesorectal excision.

Methods:

This review was designed using the PRISMA guidelines. The following electronic databases were searched from January 2002 to January 2020: CENTRAL, Ovid MEDLINE, PubMed, and Ovid Embase. Main outcomes included DFS and overall survival (OS). Other outcomes of interest comprised positive resection margin and synchronous metastases.

Results:

Seventeen studies involving a total of 3821 patients were included for data synthesis. For preneoadjuvant treatment mrEMVI, pooled hazard ratio (HR) estimate for DFS was 2.30 (95% confidence intervals (CI) 1.54–3.44) for higher recurrence in mrEMVI-positive patients. mrEMVI-positive patients were found to have a lower OS with a pooled HR of 1.68 (95%CI 1.27–2.22). Pooled risk ratio for synchronous metastasis was 4.11 (95%CI 2.80–6.02) for mrEMVI-positivity. For postneoadjuvant treatment EMVI (ymrEMVI), positive status showed a lower DFS with a pooled HR of 2.04 (95%CI 1.55–2.69). Risk ratio of having a positive resection margin status was 2.95 (95%CI 1.75–4.98) for ymrEMVI-positive patients.

Conclusions:

This review showed that oncologic outcomes are significantly worse for both pre- and post-neoadjuvant treatment mrEMVI-positive patients. MRI-detected EMVI should be consistently reported in rectal cancer staging and may provide guidance for the targeted use of additional systemic therapy.
Valuing what happens: a biogenic approach to valence and (potentially) affect
Authors: Lyon Pamela , Kuchling Franz
Published: January 2021

Valence is half of the pair of properties that constitute core affect, the foundation of emotion. But what is valence, and where is it found in the natural world? Currently, this question cannot be answered. The idea that emotion is the body's way of driving the organism to secure its survival, thriving and reproduction runs like a leitmotif from the pathfinding work of Antonio Damasio through four book-length neuroscientific accounts of emotion recently published by the field's leading practitioners. Yet while Damasio concluded 20 years ago that the homeostasis–affect linkage is rooted in unicellular life, no agreement exists about whether even non-human animals with brains experience emotions. Simple neural animals—those less brainy than bees, fruit flies and other charismatic invertebrates—are not even on the radar of contemporary affective research, to say nothing of aneural organisms. This near-sightedness has effectively denied the most productive method available for getting a grip on highly complex biological processes to a scientific domain whose importance for understanding biological decision-making cannot be underestimated. Valence arguably is the fulcrum around which the dance of life revolves. Without the ability to discriminate advantage from harm, life very quickly comes to an end. In this paper, we review the concept of valence, where it came from, the work it does in current leading theories of emotion, and some of the odd features revealed via experiment. We present a biologically grounded framework for investigating valence in any organism and sketch a preliminary pathway to a computational model.

This article is part of the theme issue ‘Basal cognition: conceptual tools and the view from the single cell’.
From environmental sensing to developmental control: cognitive evolution in dictyostelid social amoebas
Authors: Schaap Pauline
Published: January 2021

Dictyostelid social amoebas respond to starvation by self-organizing into multicellular slugs that migrate towards light to construct spore-bearing structures. These behaviours depend on excitable networks that enable amoebas to produce propagating waves of the chemoattractant cAMP, and to respond by directional movement. cAMP additionally regulates cell differentiation throughout development, with differentiation and cell movement being coordinated by interaction of the stalk inducer c-di-GMP with the adenylate cyclase that generates cAMP oscillations. Evolutionary studies indicate how the manifold roles of cAMP in multicellular development evolved from a role as intermediate for starvation-induced encystation in the unicellular ancestor. A merger of this stress response with the chemotaxis excitable networks yielded the developmental complexity and cognitive capabilities of extant Dictyostelia.

This article is part of the theme issue ‘Basal cognition: conceptual tools and the view from the single cell’.
Adaptive behaviour and learning in slime moulds: the role of oscillations
Authors: Boussard Aurèle , Fessel Adrian , Oettmeier Christina , Briard Léa , Döbereiner Hans-Günther , Dussutour Audrey
Published: January 2021

The slime mouldPhysarum polycephalum, an aneural organism, uses information from previous experiences to adjust its behaviour, but the mechanisms by which this is accomplished remain unknown. This article examines the possible role of oscillations in learning and memory in slime moulds. Slime moulds share surprising similarities with the network of synaptic connections in animal brains. First, their topology derives from a network of interconnected, vein-like tubes in which signalling molecules are transported. Second, network motility, which generates slime mould behaviour, is driven by distinct oscillations that organize into spatio-temporal wave patterns. Likewise, neural activity in the brain is organized in a variety of oscillations characterized by different frequencies. Interestingly, the oscillating networks of slime moulds are not precursors of nervous systems but, rather, an alternative architecture. Here, we argue that comparable information-processing operations can be realized on different architectures sharing similar oscillatory properties. After describing learning abilities and oscillatory activities ofP. polycephalum, we explore the relation between network oscillations and learning, and evaluate the organism's global architecture with respect to information-processing potential. We hypothesize that, as in the brain, modulation of spontaneous oscillations may sustain learning in slime mould.

This article is part of the theme issue ‘Basal cognition: conceptual tools and the view from the single cell’.
Comparison of chlorogenic acid and rutin contents and antioxidant
activity of Dendropanax morbiferus extracts according to
ethanol concentration
Authors: Hwang Chung Eun , Kim Su Cheol , Cho Chang Soo , Song Won Yeong , Joo Ok Soo , Cho Kye Man
Published: January 2021

This study investigated the phenolics (TP) and phytochemical contents and
radical-scavenging activity of ethanol extracts of Dendropanax
morbiferus parts (leaf, stem, and root). The contents of
chlorogenic acid (CA) and rutin (RT) and radical-scavenging activity of all
extracts by parts were in the order of leaf, stem and root. In the case of leaf,
the TP contents were 2.15-2.52 mg/g when extracted with hot water and ethanol
concentration (30-70%), and there was no difference depending on
extraction solvents and times. However, 95% alcohol extracts showed the
lowest content of TP (extraction time: 2-4 h). Particularly, CA and RT contents
of 70% ethanolic extract for 2 h were the highest as 12.33 mg/g and 14.01
mg/g, respectively, in which DPPH and ABTS radical scavenging activities were
also highest (85% and 110%), respectively.
The “throwaways”. Conflicts of interest in dermatology publications
Authors: Roman Jorge , Elpern David J.
Published: January 2021

Importance

Conflict of interest as it relates to medical education is a topic of concern. Dermatology journals, periodicals, editorials, and news magazines are influential resources that are not uniformly regulated and subject to influence from the pharmaceutical industry.

Objective

This study evaluates industry payments to physician editorial board members of common dermatology publications, including “throwaway” publications.

Design

A list of editorial board members was compiled from a collection of clinical dermatology publications received over a 3-month period. To analyze the nature and extent of industry payments to this cohort, payments data from the Open Payments database from 2013 to 2019 were collected. Analysis of the total payments, number of transactions, categories of payments, payment sources, and physician specific characteristics was performed.

Results

Ten publications were evaluated, and payments data for 466 physicians were analyzed. The total compensation across all years was $75,622,369.64. Services other than consulting, consulting, and travel/lodging payments comprised most of the payments. A faction of dermatologists received the majority of payments. The top payers were manufacturers of biologic medications. Payment amounts were higher for throwaway publications compared to peer-reviewed journals.

Conclusions

Editorial board members of dermatology publications received substantial payments from the pharmaceutical industry. A minority of physicians receive the lion’s share of payments from industry. “Throwaway” publications have more financial conflict of interest than peer-reviewed journals. The impact of these conflicts of interest on patient care, physicians practice patterns, and patient perception of physicians is noteworthy.
Validation of the new pathology staging system for progressive supranuclear palsy
Authors: Briggs Mayen , Allinson Kieren SJ , Malpetti Maura , Spillantini Maria Grazia , Rowe James Benedict , Kaalund Sanne Simone
Published: January 2021

Progressive supranuclear palsy (PSP) is a neurodegenerative disorder associated with neuroglial accumulation of 4-repeat tau protein. Kovacs et al. have recently proposed a new semi-quantitative staging system to categorise the severity of PSP pathology, using the distribution of tau aggregates as it progresses from subcortical to cerebellar and cortical regions. Here, we test the new PSP pathology staging system in an independent series of PSP, and test the potential association between pathology stage and clinical severity at death. We include tissue from 35 people with a clinical diagnosis of PSP (including N=25 with Richardson’s syndrome and N=10 with other phenotypes). Donors had attended longitudinal clinical studies at the Cambridge Centre Parkinson-plus including assessment of clinical severity by the PSP rating scale (PSPRS) and cognitive performance by the revised Addenbrooke’s Cognitive Examination (ACE-R). We rated tau pathology from none-to-severe in six regions. We focused on (I) astrocytic tau inclusions in striatum, frontal and occipital regions, and (II) neuronal and oligodendroglia tau inclusions in globus pallidus, subthalamic nucleus, and cerebellum. Thirty-two cases (91%) readily conformed to the new staging system, ranging from stage 2 to 6. Staging system applied to brains from people with different clinical phenotypes of PSP. Neuropathology stages correlated with clinical severity at death using both PSPRS and ACE-R, weighted for the interval between last assessment and donation. Our study supports the proposed sequential distribution of tau aggregates in PSP pathology, and the hypothesised relationship between clinical and neuropathological severity. For future studies, in order to standardise rating between centres, we propose a set of operational criteria for region-specific thresholds or tau burden, and a visual guide.
Diagnosing pulmonary tuberculosis using sequence-specific purification of urine cell-free DNA
Authors: Oreskovic Amy , Panpradist Nuttada , Marangu Diana , Ngwane M. William , Magcaba Zanele P. , Ngcobo Sindiswa , Ngcobo Zinhle , Horne David J. , Wilson Douglas P.K. , Shapiro Adrienne E. , Drain Paul K. , Lutz Barry R.
Published: January 2021

Transrenal urine cell-free DNA (cfDNA) is a promising tuberculosis (TB) biomarker, but is challenging to detect because of the short length (<100 bp) and low concentration of TB-specific fragments. We aimed to improve the diagnostic sensitivity of TB urine cfDNA by increasing recovery of short fragments during sample preparation. We developed a highly sensitive sequence-specific purification method that uses hybridization probes immobilized on magnetic beads to capture short TB cfDNA (50 bp) with 91.8% average efficiency. Combined with short-target PCR, the assay limit of detection was ≤5 copies of cfDNA in 10 mL urine. In a clinical cohort study in South Africa, our urine cfDNA assay had 83.7% sensitivity (95% CI: 71.0– 91.5%) and 100% specificity (95% CI: 86.2–100%) for diagnosis of active pulmonary TB when using sputum Xpert MTB/RIF as the reference standard. The detected cfDNA concentration was 0.14–2804 copies/mL (median 14.6 copies/mL) and was inversely correlated with CD4 count and days to culture positivity. Sensitivity was non-significantly higher in HIV-positive (88.2%) compared to HIV-negative patients (73.3%), and was not dependent on CD4 count. Sensitivity remained high in sputum smear-negative (76.0%) and urine LAM-negative (76.5%) patients. With improved sample preparation, urine cfDNA is a viable biomarker for TB diagnosis. Our assay has the highest reported accuracy of any TB urine cfDNA test to date and has the potential to enable rapid non-sputum-based TB diagnosis across key underserved patient populations.
Gene-level analysis of rare variants in 363,977 whole exome sequences identifies an association of GIGYF1 loss of function with type 2 diabetes
Authors: Deaton Aimee M. , Parker Margaret M. , Ward Lucas D. , Flynn-Carroll Alexander O. , BonDurant Lucas , Hinkle Gregory , Akbari Parsa , Lotta Luca A. ,   Regeneron Genetics Center,   DiscovEHR Collaboration, Baras Aris , Nioi Paul
Published: January 2021

Sequencing of large cohorts offers an unprecedented opportunity to identify rare genetic variants and to find novel contributors to human disease. We used gene-based collapsing tests to identify genes associated with glucose, HbA1c and type 2 diabetes (T2D) diagnosis in 363,977 exome-sequenced participants in the UK Biobank. We identified associations for variants in GCK, HNF1A and PDX1, which are known to be involved in Mendelian forms of diabetes. Notably, we uncovered novel associations for GIGYF1, a gene not previously implicated by human genetics, in diabetes. GIGYF1 predicted loss of function (pLOF) variants associated with increased levels of glucose (0.77 mmol/L increase, p = 4.42 × 10-12) and HbA1c (4.33 mmol/mol, p = 1.28 × 10-14) as well as T2D diagnosis (OR = 4.15, p= 6.14 ×10-11). Multiple rare variants contributed to these associations, including singleton variants. GIGYF1 pLOF also associated with decreased cholesterol levels as well as an increased risk of hypothyroidism. The association of GIGYF1 pLOF with T2D diagnosis replicated in an independent cohort from the Geisinger Health System. In addition, a common variant association for glucose and T2D was identified at the GIGYF1 locus. Our results highlight the role of GIGYF1 in regulating insulin signaling and protecting from diabetes.

Author Summary

Genetic studies focused on high impact variants in protein-coding regions of the genome can provide valuable insight into the biology of human disease. As these variants tend to be rare, studying them requires large cohort sizes and methods to aggregate variants that are likely to have a similar biological impact. We studied how rare genetic variants contribute to type 2 diabetes (T2D) using sequencing data from 363,977 participants in the UK Biobank, employing methods to aggregate variants at the level of individual genes. As well as identifying genes known to be involved in inherited forms of diabetes, we uncovered a novel association for GIGYF1. GIGYF1 loss of function associated with increased risk of T2D and increased levels of the diabetes biomarkers glucose and HbA1c. This association was also seen in an independent dataset. GIGYF1 encodes a protein that binds a negative regulator of the insulin receptor that has not been well-characterized in the literature. By highlighting the importance of GIGYF1 in modulating insulin signaling these results may lead to new therapeutic approaches for diabetes as well as a new appreciation for GIGYF1 loss of function as a genetic risk factor for T2D.
Mental health and wellbeing amongst people with informal caring responsibilities across different time points during the COVID-19 pandemic: A population-based propensity score matching analysis
Authors: Mak Hei Wan , Bu Feifei , Fancourt Daisy
Published: January 2021

Aims

Due to a prolonged period of national and regional lockdown measures during the coronavirus (COVID-19) pandemic, there has been an increase reliance on informal care and a consequent increase in care intensity for informal carers. In light of this, the current study compared the experiences of carers and non-carers on various mental health and wellbeing measures across 5 key time points during the pandemic.

Methods

Data analysed were from the UCL COVID -19 Social Study. Our study focused on 5 time points in England: (i) the first national lockdown (March-April 2020; N=12,053); (ii) the beginning of lockdown rules easing (May 2020; N=24,374); (iii) further easing (July 2020; N=21,395); (iv) new COVID-19 restrictions (September 2020; N=4,792); and (v) the three-tier system restrictions (October 2020; N=4,526). We considered 5 mental health and wellbeing measures-depression, anxiety, loneliness, life satisfaction and sense of worthwhile. Propensity score matching were applied for the analyses.

Results

We found that informal carers experienced higher levels of depressive symptoms and anxiety than non-carers across all time points. During the first national lockdown, carers also experienced a higher sense of life being worthwhile. No association was found between informal caring responsibilities and levels of loneliness and life satisfaction.

Conclusion

Given that carers are an essential national health care support, especially during a pandemic, it is crucial to integrate carers’ needs into healthcare planning and delivery. These results highlight there is a pressing need to provide adequate and targeted mental health support for carers during and following this pandemic.
A phase IV, multi-centre, randomized clinical trial comparing two pertussis-containing vaccines in pregnant women in England and vaccine responses in their infants
Authors: Jones Christine Elizabeth , Calvert Anna , Southern Jo , Matheson Mary , Andrews Nick , Khalil Asma , Cuthbertson Hannah , Hallis Bassam , England Anna , Heath Paul T , Miller Elizabeth
Published: January 2021

Background

Pertussis vaccines containing three or five pertussis antigens are recommended in pregnancy in many countries, but no studies have compared the effect on infants’ antigen-specific immunoglobulin G (IgG) concentrations. The aim of this study was to compare anti-pertussis IgG responses following primary immunization in infants of mothers vaccinated with TdaP5-IPV (low dose diphtheria toxoid, tetanus toxoid, acellular pertussis [five antigens] and inactivated polio) or TdaP3-IPV in pregnancy (three pertussis antigens).

Methods

This multi-centre phase IV randomized clinical trial was conducted in a tertiary referral centre and primary care sites in England from 2014-2016. Women were randomized to receive TdaP5-IPV (n=77) or TdaP3-IPV (n=77) at 28-32 gestational weeks. A non-randomized control group of 44 women who had not received a pertussis-containing vaccine in pregnancy and their 47 infants were enrolled postpartum.

Results

Following infant primary immunization, there was no difference in the geometric mean concentrations (GMCs) of anti-pertussis toxin, filamentous haemagglutinin or pertactin IgG between infants born to women vaccinated with TdaP5-IPV (n=67) or TdaP3-IPV (n=63). However, the GMC of anti-pertussis toxin IgG was lower in infants born to TdaP5-IPV and TdaP3-IPV vaccinated mothers compared to infants born to unvaccinated mothers (n=45) (geometric mean ratio: 0.71 [0.56-0.90] and 0.78 [0.61-0.98], respectively); by 13 months of age, this difference was no longer observed.

Conclusion

Blunting of anti-pertussis toxin IgG response following primary immunization occurs in infants born to women vaccinated with TdaP5-IPV and TdaP3-IPV, with no difference between maternal vaccines. The blunting effect had resolved by 13 months of age. These results may be helpful for countries considering which pertussis-containing vaccine to recommend for use in pregnancy.

Clinical Trials identifier

ClinicalTrials.gov: NCT02145624
An interactive COVID-19 virus Mutation Tracker (CovMT) with a particular focus on critical mutations in the Receptor Binding Domain (RBD) region of the Spike protein
Authors: Alam Intikhab , Radovanovic Aleksandar , Incitti Roberto , Kamau Allan , Alarawi Muhammad , Azhar Esam I. , Gojobori Takashi
Published: January 2021

Almost one year has passed since the appearance of SARS-CoV-2, causing the COVID-19 pandemic. The number of confirmed SARS-Cov-2 cases worldwide has now reached ∼92 million, with 2 million reported deaths (https://covid19.who.int). Nearly 400,000 SARS-Cov-2 genomes were sequenced from COVID-19 samples and added to public resources such as GISAID (https://gisaid.org). With the vaccines becoming available or entering trials (https://covid19.trackvaccines.org), it is vital to keep track of mutations in the genome of SARS-CoV-2, especially in the Spike protein’s Receptor Binding Domain (RBD) region, which could have a potential impact on disease severity and treatment strategies.1–3 In the wake of a recent increase in cases with a potentially more infective RBD mutation (N501Y) in the United Kingdom, countries worldwide are concerned about the spread of this or similar variants. Impressive sampling and timely increase in sequencing efforts related to COVID-19 in the United Kingdom (UK) helped detect and monitor the spread of the new N501Y variant. Similar sequencing efforts are needed in other countries for timely tracking of this or different variants. To track geographic sequencing efforts and mutations, with a particular focus on RBD region of the Spike protein, we present our daily updated COVID-19 virus Mutation Tracker system, see https://www.cbrc.kaust.edu.sa/covmt.
High-altitude is associated with better short-term survival in critically ill COVID-19 patients admitted to the ICU
Authors: Jaramillo Pablo R. Morocho , Simbaña-Rivera Katherine , Silva Javier V. Velastegui , Gómez-Barreno Lenin , Campoverde Ana B. Ventimilla , Cevallos Juan F. Novillo , Guanoquiza Washington E. Almache , Cedeño Guevara Silvio L. , Castro Luis G. Imba , Puerta Nelson A. Moran , Valladares Alex W. Guayta , Lister Alex , Ortiz-Prado Esteban
Published: January 2021

Background

The novel human coronavirus, SARS-CoV-2, has affected at least 218 countries worldwide. Some geographical and environmental factors are positively associated with a better or worse prognosis concerning COVID-19 disease and with lower or higher SARS-CoV-2 transmission. High altitude exposure has been associated with lower SARS-CoV-2 attack rates; nevertheless, the role of chronic high-altitude exposure on the clinical outcome of critically ill COVID-19 patients has not been studied.

Objective

To compare the clinical course and outcomes of critically ill patients with COVID-19 hospitalized in two intensive care units (ICU) located at low and high altitude.

Exposure and Outcome

To explore the effect of two different elevations (10 m vs 2,850 m above sea level) on COVID-19 clinical outcome and survival.

Methods

A prospective cohort, two-center study in confirmed COVID-19 adult patients admitted to a low altitude (Sea level) and high altitude (2,850 m) ICU units in Ecuador was conducted. Two hundred and thirty confirmed COVID-19 patients were enrolled from March 15thto July 15th, 2020. Sociodemographic, clinical, laboratory and imaging parameters including supportive therapies, pharmacological treatments and medical complications were reported and compared between the low and high-altitude groups.

Results

The median age of all the patients was 60 years, 64.8% were men and 35.2% were women. A total of 105 (45.7%) patients had at least one underlying comorbidity, the most frequent being chronic diseases, such as hypertension (33.5%), diabetes (16.5%), and chronic kidney failure (5.7%). The APACHE II scale at 72 hours was especially higher in the low-altitude group with a median of 18 points (IQR: 9.5-24.0), compared to 9 points (IQR: 5.0-22.0) obtained in the group of high altitude. There is evidence of a difference in survival in favor of the high-altitude group (p = 0.006), the median survival being 39 days, compared to 21 days in the low altitude group.

Conclusion

There has been a substantial improvement in survival amongst people admitted to the high-altitude critical care unit. High altitude living was associated with improved survival, especially among patients with no comorbidities. COVID-19 patients admitted to the high-altitude ICU unit have improved severity-of-disease classification system scores at 72 hours and reported better respiratory and ventilatory profiles than the low altitude group.
Acute and persistent symptoms in non-hospitalized PCR-confirmed COVID-19 patients
Authors: Bliddal Sofie , Banasik Karina , Pedersen Ole Birger , Nissen Ioanna , Cantwell Lisa , Schwinn Michael , Tulstrup Morten , Westergaard David , Ullum Henrik , Brunak Søren , Tommerup Niels , Feenstra Bjarke , Geller Frank , Ostrowski Sisse Rye , Grønbæk Kirsten , Nielsen Claus Henrik , Nielsen Susanne Dam , Feldt-Rasmussen Ulla
Published: January 2021

Background

Reports of persistent symptoms after hospitalization with COVID-19 have raised concern of a “long COVID” syndrome. This study aimed at characterizing acute and persistent symptoms in non- hospitalized patients with polymerase chain reaction (PCR) confirmed COVID-19.

Methods

Cohort study of 445 non-hospitalized participants identified via the Danish Civil Registration System with a SARS-CoV-2-positive PCR-test and available biobank samples for genetic analyses. Participants received a digital questionnaire on demographics and COVID-19-related symptoms. Persistent symptoms: symptoms >four weeks (in sensitivity analyses >12 weeks).

Results

445 participants were included, of whom 34% were asymptomatic. Most common acute symptoms were fatigue, headache, and sneezing, while fatigue and reduced smell and taste were reported as most severe. Persistent symptoms, most commonly fatigue and memory and concentration difficulties, were reported by 36% of 198 symptomatic participants with follow-up >four weeks. Risk factors for persistent symptoms included female sex (women 44% vs. men 24%, odds ratio 2.7, 95%CI:1.4-5.1, p=0.003) and BMI (odds ratio 1.1, 95%CI:1.0-1.2, p=0.001).

Conclusion

Among non-hospitalized PCR-confirmed COVID-19 patients one third were asymptomatic while one third of symptomatic participants had persistent symptoms illustrating the heterogeneity of disease presentation. These findings should be considered in future health care planning and policy making related to COVID-19.
An Online Risk Calculator for Rapid Prediction of In-hospital Mortality from COVID-19 Infection
Authors: Evans Daniel S. , Kim Kyoung Min , Jiang Xiaqing , Jacobson Jessica , Browner Warren , Cummings Steven R.
Published: January 2021

Prediction of mortality from COVID-19 infection might help triage patients to hospitalization and intensive care. To estimate the risk of inpatient mortality, we analyzed the data of 13,190 adult patients in the New York City Health + Hospitals system admitted for COVID-19 infection from March 1 to June 30, 2020. They had a mean age 58 years, 40% were Latinx, 29% Black, 9% White and 22% of other races/ethnicities and 2,875 died. We used Machine learning (Gradient Boosted Decision Trees; XGBoost) to select predictors of inpatient mortality from demographics, vital signs and lab tests results from initial encounters. XGBoost identified O2 saturation, systolic and diastolic blood pressure, pulse rate, respiratory rate, age, and BUN with an Area Under the Receiver Operating Characteristics Curve = 94%. We applied CART to find cut-points in these variables, logistic regression to calculate odds-ratios for those categories, and assigned points to the categories to develop a score. A score = 0 indicates a 0.8% (95% confidence interval, 0.5 – 1.0%) risk of dying and ≥ 12 points indicates a 98% (97-99%) risk, and other scores have intermediate risks. We translated the models into an online calculator for the probability of mortality with 95% confidence intervals (as pictured):

Abstract Figure

danielevanslab.shinyapps.io/COVID_mortality/
Local adaptations of Mediterranean sheep and goats through an integrative approach
Authors: Serranito Bruno , Cavalazzi Marco , Vidal Pablo , Taurisson-Mouret Dominique , Ciani Elena , Bal Marie , Rouvellac Eric , Servin Bertrand , Moreno-Romieux Carole , Tosser-Klopp Gwenola , Hall Stephen J. G. , Lenstra Johannes A. , Pompanon François , Benjelloun Badr , Da Silva Anne
Published: January 2021

In a context of climate change, identifying the genes underlying adaptations to extreme environments is essential. Small ruminants are adapted to a wide variety of habitats and thus, are promising study models. Here, we considered 17 goat and 25 sheep local Mediterranean breeds, in Italy, France and Spain. We proposed, and empirically tested a new methodology to highlight selection signatures in relation to the environments. Based on historical archives, we selected the breeds potentially most linked to a territory and defined their original geographical cradle, including transhumant pastoral areas. For both species, the cradles were arranged along latitudinal gradient of aridity and altitude. Then we used the programs PCAdapt and LFMM. Considering cradles, instead of current GPS coordinates, markedly improved the sensitivity of the LFMM analyses. All the results combined with a systematic literature review, revealed a set of genes with potentially key adaptive roles. Some of these genes, have been found implicated in lipid metabolism (SUCLG2, BMP2), hypoxia/heat stress (UBE2R2/UBAP2), lung function (BMPR2), seasonal patterns (SOX2, DPH6) or neuronal function (TRPC4, TRPC6). For the intergenic region between PCDH9 and KLH1, as well as NBEA, identified in both species, the adaptive role could be strong. We found for RXFP2, associated with sheep horn development, and MSRB3 and SLC26A4, both associated with hearing of sheep, a strong association with the environment gradient. We conclude that our new methodology, which considers breeds in their historical, environmental and anthropological context, provides novel and essential information on local breeds and their unique adaptations.
Separable pupillary signatures of perception and action during perceptual multistability
Authors: Brascamp Jan W. , de Hollander Gilles , Wertheimer Michael D. , DePew Ashley N. , Knapen Tomas
Published: January 2021

The pupil provides a rich, non-invasive measure of the neural bases of perception and cognition, and has been of particular value in uncovering the role of arousal-linked neuromodulation, which alters cortical processing as well as pupil size. But pupil size is subject to a multitude of influences, which complicates unique interpretation. We measured pupils of observers experiencing perceptual multistability -- an ever-changing subjective percept in the face of unchanging but inconclusive sensory input. In separate conditions the endogenously generated perceptual changes were either task-relevant or not, allowing a separation between perception-related and task-related pupil signals. Perceptual changes were marked by a complex pupil response that could be decomposed into two components: a dilation tied to task execution and plausibly indicative of an arousal-linked noradrenaline surge, and an overlapping constriction tied to the perceptual transient and plausibly a marker of altered visual cortical representation. Constriction, but not dilation, amplitude systematically depended on the time interval between perceptual changes, possibly providing an overt index of neural adaptation. These results show that the pupil provides a simultaneous reading on interacting but dissociable neural processes during perceptual multistability, and suggest that arousal-linked neuromodulation shapes action but not perception in these circumstances.
The unique role of parietal cortex in action observation: Functional organization for communicative and manipulative actions
Authors: Urgen Burcu A. , Orban Guy A.
Published: January 2021

Action observation is supported by a network of regions in occipito-temporal, parietal, and premotor cortex in primates. Recent research suggests that the parietal node has regions dedicated to different action classes including manipulation, interpersonal, skin-displacing, locomotion, and climbing. The goals of the current study consist of: 1) extending this work with new classes of actions that are communicative and specific to humans, 2) investigating how parietal cortex differs from the occipito-temporal and premotor cortex in representing action classes. Human subjects underwent fMRI scanning while observing three action classes: indirect communication, direct communication, and manipulation, plus two types of control stimuli, static controls which were static frames from the video clips, and dynamic controls consisting of temporally-scrambled optic flow information. Using univariate analysis, MVPA, and representational similarity analysis, our study presents several novel findings. First, we provide further evidence for the anatomical segregation in parietal cortex of different action classes: We have found a new region that is specific for representing human-specific indirect communicative actions in cytoarchitectonic parietal area PFt. Second, we found that the discriminability between action classes was higher in parietal cortex than the other two levels suggesting the coding of action identity information at this level. Finally, our results advocate the use of the control stimuli not just for univariate analysis of complex action videos but also when using multivariate techniques.
CropMetaPop : a population genetics program to simulate the evolution of crop metapopulations
Authors: Thomas Mathieu , Miramon Anne , Naino Jika Abdel Kader , Rouger Baptiste , Hospital Frédéric , Noûs Camille , Goldringer Isabelle
Published: January 2021

Stochastic simulation programs are useful to study the evolution of crop populations in changing environments. These programs require to take into account some specific features characterizing farmers’ practices such as seed circulation or seed mixing. However such human-mediated evolutionary processes are different from the classical colonization or migration models used in most existing stochastic simulation programs for quantitative population genetics.

To fill this gap, CropMetaPop is an individual based forward-time simulation program for quantitative population genetics developed to represent a diversity of socially established rules underlying seed circulation between farmers. For instance, one farmer can give seeds to neighbours according to his stock and receive from them according to his needs. Crop-Metapop also takes into account other important evolutionary forces encountered in crop diversity management systems, such as different population sizes and selection modalities for different populations.

CropMetaPop makes it possible to study the impacts of different crop biodiversity management strategies. For this purpose, it simulates the genetic evolution over time of several crop populations submitted to genetic drift and selection and linked by explicitly modeled seed circulation and mixtures.
Cancer Hallmarks Define a Continuum of Plastic Cell States between Small Cell Lung Cancer Archetypes
Authors: Groves Sarah Maddox , Ireland Abbie , Liu Qi , Simmons Alan J. , Lau Ken , Iams Wade T. , Tyson Darren , Lovly Christine M. , Oliver Trudy G. , Quaranta Vito
Published: January 2021

Small Cell Lung Cancer (SCLC) tumors are heterogeneous mixtures of transcriptional subtypes. Understanding subtype dynamics could be key to explaining the aggressive properties that make SCLC a recalcitrant cancer. Applying archetype analysis and evolutionary theory to bulk and single-cell transcriptomics, we show that SCLC cells reside within a cell-state continuum rather than in discrete subtype clusters. Gene expression signatures and ontologies indicate each vertex of the continuum corresponds to a functional phenotype optimized for a cancer hallmark task: three neuroendocrine archetypes specialize in proliferation/survival, inflammation and immune evasion, and two non-neuroendocrine archetypes in angiogenesis and metabolic dysregulation. Single cells can trade-off between these defined tasks to increase fitness and survival. SCLC cells can easily transition from specialists that optimize a single task to generalists that fall within the continuum, suggesting that phenotypic plasticity may be a mechanism by which SCLC cells become recalcitrant to treatment and adaptable to diverse microenvironments. We show that plasticity is uncoupled from the phenotype of single cells using a novel RNA-velocity-based metric, suggesting both specialist and generalist cells have the capability of becoming destabilized and transitioning to other phenotypes. We use network simulations to identify transcription factors such as MYC that promote plasticity and resistance to treatment. Our analysis pipeline is suitable to elucidate the role of phenotypic plasticity in any cancer type, and positions SCLC as a prime candidate for treatments that target plasticity.
Genome-wide analysis of mobile element insertions in human genomes
Authors: Niu Yiwei , Teng Xueyi , Shi Yirong , Li Yanyan , Tang Yiheng , Zhang Peng , Luo Huaxia , Kang Quan ,   The Han100K Initiative, Xu Tao , He Shunmin
Published: January 2021

Mobile element insertions (MEIs) are a major class of structural variants (SVs) and have been linked to many human genetic disorders, including hemophilia, neurofibromatosis, and various cancers. However, human MEI resources from large-scale genome sequencing are still lacking compared to those for SNPs and SVs. Here, we report a comprehensive map of 36,699 non-reference MEIs constructed from 5,675 genomes, comprising 2,998 Chinese samples (∼26.2X, NyuWa) and 2,677 samples from the 1000 Genomes Project (∼7.4X, 1KGP). We discovered that LINE-1 insertions were highly enriched at centromere regions, implying the role of chromosome context in retroelement insertion. After functional annotation, we estimated that MEIs are responsible for about 9.3% of all protein-truncating events per genome. Finally, we built a companion database named HMEID for public use. This resource represents the latest and largest genomewide study on MEIs and will have broad utility for exploration of human MEI findings.
Do Not Attempt Resuscitation (DNAR) status in people with suspected COVID-19: Secondary analysis of the PRIEST observational cohort study
Authors: Sutton Laura , Goodacre Steve , Thomas Ben , Connelly Sarah
Published: January 2021

Background

Cardiac arrest is common in people admitted with suspected COVID-19 and has a poor prognosis. Do Not Attempt Resuscitation (DNAR) orders can reduce the risk of futile resuscitation attempts but have raised ethical concerns.

Objectives

We aimed to describe the characteristics and outcomes of adults admitted to hospital with suspected COVID-19 according to their DNAR status and identify factors associated with an early DNAR decision.

Methods

We undertook a secondary analysis of 13977 adults admitted to hospital with suspected COVID-19 and included in the Pandemic Respiratory Infection Emergency System Triage (PRIEST) study. We recorded presenting characteristics and outcomes (death or organ support) up to 30 days. We categorised patients as early DNAR (occurring before or on the day of admission) or late/no DNAR (no DNAR or occurring after the day of admission). We undertook descriptive analysis comparing these groups and multivariable analysis to identify independent predictors of early DNAR.

Results

We excluded 1249 with missing DNAR data, and identified 3929/12748 (31%) with an early DNAR decision. They had higher mortality (40.7% v 13.1%) and lower use of any organ support (11.6% v 15.7%), but received a range of organ support interventions, with some being used at rates comparable to those with late or no DNAR (e.g. non-invasive ventilation 4.4% v 3.5%). On multivariable analysis, older age (p<0.001), active malignancy (p<0.001), chronic lung disease (p<0.001), limited performance status (p<0.001), and abnormal physiological variables were associated with increased recording of early DNAR. Asian ethnicity was associated with reduced recording of early DNAR (p=0.001).

Conclusions

Early DNAR decisions were associated with recognised predictors of adverse outcome, and were inversely associated with Asian ethnicity. Most people with an early DNAR decision survived to 30 days and many received potentially life-saving interventions.

Registration

ISRCTN registry, ISRCTN28342533, http://www.isrctn.com/ISRCTN28342533
Predictive power of SARS-CoV-2 wastewater surveillance for diverse populations across a large geographical range
Authors: Melvin Richard G. , Chaudhry Nabiha , Georgewill Onimitein , Freese Rebecca , Simmons Glenn E.
Published: January 2021

The COVID-19 pandemic has exacerbated the disparities in healthcare delivery in the US. Many communities had, and continue to have, limited access to COVID-19 testing, making it difficult to track the spread and impact of COVID-19 in early days of the outbreak. To address this issue we monitored severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA at the population-level using municipal wastewater influent from 19 cities across the state of Minnesota during the COVID-19 outbreak in Summer 2020. Viral RNA was detected in wastewater continually for 20-weeks for cities ranging in populations from 500 to >1, 000, 000. Using a novel indexing method, we were able to compare the relative levels of SARS-CoV-2 RNA for each city during this sampling period. Our data showed that viral RNA trends appeared to precede clinically confirmed cases across the state by several days. Lag analysis of statewide trends confirmed that wastewater SARS-CoV-2 RNA levels preceded new clinical cases by 15-17 days. At the regional level, new clinical cases lagged behind wastewater viral RNA anywhere from 4-20 days. Our data illustrates the advantages of monitoring at the population-level to detect outbreaks. Additionally, by tracking infections with this unbiased approach, resources can be directed to the most impacted communities before the need outpaces the capacity of local healthcare systems.