bluuebunny/crossref_metadata_2025 huggingface dataset:
A Novel Method to Treat Progressive Desmoid Tumors Involving Neurovascular Bundles: A Retrospective Cohort Study
Authors: Yin Jun-Qiang , Fu Yi-Wei , Gao Zhen-Hua , Zou Chang-Ye , Xie Xian-Biao , Wang Bo , Zhong Zhi-Hai , Huang Gang , Shen Jing-Nan
Published: December 2020

BACKGROUND

More effective therapies are needed to treat progressive desmoid tumors when active surveillance and systemic therapy fail.

OBJECTIVE

To assess the efficacy and safety of sandwich isolation surgery on the local control of progressive desmoid tumors involving neurovascular bundles.

METHODS

A total of 27 patients with progressive desmoid tumors at extremities involving neurovascular bundles who received surgery at our hospital between August 2014 and August 2018 were identified. A total of 13 patients received sandwich isolation surgery, in which R2 resection was performed in neurovasculature-involving regions, and a biomaterial patch was used to envelop involved neurovascular structures and isolate residual tumors. In non-neurovasculature-involving regions, wide resection was performed without isolation. A total of 14 patients received traditional surgery, which included tumor resection without isolation procedure.

RESULTS

In sandwich isolation group, tumor progressions and local recurrences occurred in 3 patients outside the isolated neurovasculature-involving regions. However, no progressions or recurrences occurred in any patients in the isolated neurovasculature-involving regions where R2 resection was performed. Sandwich isolation surgery group and traditional surgery group shared similar baseline clinical characteristics. The estimated 3-yr event-free survival rate was 76.9% after sandwich isolation surgery, and 32.7% after traditional surgery (P = .025). Patients who received sandwich isolation surgery were less likely to have local recurrence (hazard ratio: 0.257, P = .040). No complications were noted except intermittent mild pain in operative regions (2 cases).

CONCLUSION

Sandwich isolation surgery is effective and safe for local control of desmoid tumors involving neurovascular bundles.
The impact of climate change on neglected tropical diseases: a systematic review
Authors: Tidman Rachel , Abela-Ridder Bernadette , de Castañeda Rafael Ruiz
Published: December 2020

Neglected tropical diseases (NTDs) are a diverse group of diseases that continue to affect >1 billion people, with these diseases disproportionately impacting vulnerable populations and territories. Climate change is having an increasing impact on public health in tropical and subtropical areas and across the world and can affect disease distribution and transmission in potentially diverse ways. Improving our understanding of how climate change influences NTDs can help identify populations at risk to include in future public health interventions. Articles were identified by searching electronic databases for reports of climate change and NTDs between 1 January 2010 and 1 March 2020. Climate change may influence the emergence and re-emergence of multiple NTDs, particularly those that involve a vector or intermediate host for transmission. Although specific predictions are conflicting depending on the geographic area, the type of NTD and associated vectors and hosts, it is anticipated that multiple NTDs will have changes in their transmission period and geographic range and will likely encroach on regions and populations that have been previously unaffected. There is a need for improved surveillance and monitoring to identify areas of NTD incursion and emergence and include these in future public health interventions.
CE: Back to Basics: The Complete Blood Count
Authors: Bertschi Lydia A.
Published: December 2020

In this latest article in the AJN series Back to Basics—developed to improve nurses' understanding and application of common laboratory diagnostic tests—the author delineates the meaning and function of complete blood count components, highlighting the important pathophysiological evidence they provide and using composite patient scenarios to assist nurses in recognizing findings that can inform their plan of care and produce the best patient outcomes.
Hydroxychloroquine is associated with slower viral clearance in clinical COVID-19 patients with mild to moderate disease
Authors: Mallat Jihad , Hamed Fadi , Balkis Maher , Mohamed Mohamed A. , Mooty Mohamad , Malik Asim , Nusair Ahmad , Bonilla Maria-Fernanda
Published: December 2020

There are conflicting data regarding the use of hydroxychloroquine (HCQ) in COVID-19 hospitalized patients. The objective of this study was to assess the efficacy of HCQ in increasing SARS-CoV-2 viral clearance.

Hospitalized adult patients with confirmed SARS-CoV-2 infection were retrospectively included in the study. The primary outcome was the time from a confirmed positive nasopharyngeal swab to turn negative. A negative nasopharyngeal swab conversion was defined as a confirmed SARS-CoV-2 case followed by 2 negative results using RT-PCR assay with samples obtained 24 hours apart. Multiple linear regression analysis was used to adjust for potential confounders.

Thirty-four confirmed COVID-19 patients completed the study. Nineteen (55.9%) patients presented with symptoms, and 14 (41.2%) had pneumonia. Only 21 (61.8%) patients received HCQ. The time to SARS-CoV-2 negativity nasopharyngeal test was significantly longer in patients who received HCQ than those who did not receive HCQ [17 (13–21) vs 10 (4–13) days, P = .023]. HCQ was independently associated with time to negativity test after adjustment for potential confounders (symptoms, comorbidities, antiviral drugs, pneumonia, or oxygen therapy) in multivariable Cox proportional hazards regression analysis (hazard ratio = 0.33, 95% confidence interval: 0.13–0.9, P = .024). On day 14, 47.8% (14/23) patients tested negative in the HCQ group compared with 90.9% (10/11) patients who did not receive HCQ (P = .016).

HCQ was associated with a slower viral clearance in COVID-19 patients with mild to moderate disease. Data from ongoing randomized clinical trials with HCQ should provide a definitive answer regarding the efficacy and safety of this treatment.
The Missing Chapter: The Education of Surgery and Anesthesiology Trainees as Civic Advocates
Authors: Chawla Kashmira S. , Jayaram Anusha , McClain Craig D.
Published: December 2020

The SARS-CoV-2 pandemic has highlighted existing systemic inequities that adversely affect a variety of communities in the United States. These inequities have a direct and adverse impact on the healthcare of our patient population. While civic engagement has not been cultivated in surgical and anesthesia training, we maintain that it is inherent to the core role of the role of a physician. This is supported by moral imperative, professional responsibility, and a legal obligation. We propose that such civic engagement and social justice activism is a neglected, but necessary aspect of physician training. We propose the implementation of a civic advocacy education agenda across department, community and national platforms. Surgical and anesthesiology residency training needs to evolve to the meet these increasing demands.
Crowdsourced feature tagging for scalable and privacy-preserved autism diagnosis
Authors: Washington Peter , Tariq Qandeel , Leblanc Emilie , Chrisman Brianna , Dunlap Kaitlyn , Kline Aaron , Kalantarian Haik , Penev Yordan , Paskov Kelley , Voss Catalin , Stockham Nathaniel , Varma Maya , Husic Arman , Kent Jack , Haber Nick , Winograd Terry , Wall Dennis P.
Published: December 2020

Standard medical diagnosis of mental health conditions often requires licensed experts who are increasingly outnumbered by those at risk, limiting reach. We test the hypothesis that a trustworthy crowd of non-experts can efficiently label features needed for accurate machine learning detection of the common childhood developmental disorder autism. We implement a novel process for creating a trustworthy distributed workforce for video feature extraction, selecting a workforce of 102 workers from a pool of 1,107. Two previously validated binary autism logistic regression classifiers were used to evaluate the quality of the curated crowd’s ratings on unstructured home videos. A clinically representative balanced sample (N=50 videos) of videos were evaluated with and without face box and pitch shift privacy alterations, with AUROC and AUPRC scores >0.98. With both privacy-preserving modifications, sensitivity is preserved (96.0%) while maintaining specificity (80.0%) and accuracy (88.0%) at levels that exceed classification methods without alterations. We find that machine learning classification from features extracted by a curated nonexpert crowd achieves clinical performance for pediatric autism videos and maintains acceptable performance when privacy-preserving mechanisms are applied. These results suggest that privacy-based crowdsourcing of short videos can be leveraged for rapid and mobile assessment of behavioral health.
Adaptive combination of interventions required to reach population immunity due to stochastic community dynamics and limited vaccination
Authors: Goldenbogen Björn , Adler Stephan O , Bodeit Oliver , Wodke Judith AH , Escalera-Fanjul Ximena , Korman Aviv , Krantz Maria , Bonn Lasse , Morán-Torres Rafael , Haffner Johanna EL , Karnetzki Maxim , Maintz Ivo , Mallis Lisa , Prawitz Hannah , Segelitz Patrick S , Seeger Martin , Linding Rune , Klipp Edda
Published: December 2020

Reaching population immunity against COVID-19 is proving difficult even in countries with high vaccination levels. We demonstrate that this in part is due to heterogeneity and stochasticity resulting from community-specific human-human interaction and infection networks. We address this challenge by community-specific simulation of adaptive strategies. Analyzing the predicted effect of vaccination into an ongoing COVID-19 outbreak, we find that adaptive combinations of targeted vaccination and non-pharmaceutical interventions (NPIs) are required to reach population immunity. Importantly, the threshold for population immunity is not a unique number but strategy and community dependent. Furthermore, the dynamics of COVID-19 outbreaks is highly community-specific: in some communities vaccinating highly interactive people diminishes the risk for an infection wave, while vaccinating the elderly reduces fatalities when vaccinations are low due to supply or hesitancy. Similarly, while risk groups should be vaccinated first to minimize fatalities, optimality branching is observed with increasing population immunity. Bimodality emerges as the infection network gains complexity over time, which entails that NPIs generally need to be longer and stricter. Thus, we analyze and quantify the requirement for NPIs dependent on the chosen vaccination strategy. We validate our simulation platform on real-world epidemiological data and demonstrate that it can predict pathways to population immunity for diverse communities world-wide challenged by limited vaccination.
Hematological and biochemical predictors of bone marrow metastases in non-hematological malignancies: a clinico-pathological analysis
Authors: Agrawal Shruti , Bhandari Rekha , Gowda Vinay N , Gupta Amit , Singh Neha , Chowdhury Nilotpal , Rao Shalinee , Kishore Sanjeev , Gupta Arvind Kumar , Chandra Harish
Published: December 2020

Background

Bone marrow metastasis is a significant presentation of many non-hematological malignancies. The present study was conducted with the aim of analysing the clinical, hematological and biochemical parameters of the patients with bone marrow metastases and to determine the parameters which could be possible indicators of bone marrow metastases.

Material and methods

Bone marrow aspirate, imprint and biopsy slides of 22 cases with bone marrow metastases were reviewed and the hematological and biochemical data of all these cases was compared with that of 20 controls who had no evidence of metastases.

Results

The mean values of mean platelet volume (MPV), neutrophil to lymphocyte ratio (NLR) and serum lactate dehydrogenase (LDH) were found to be significantly different (p<0.001) between the cases and controls. A MPV<8.1 fL, NLR>3.5 and LDH>452 U/L showed high likelihood ratio in predicting bone marrow metastases.

Conclusion

Parameters such as MPV, NLR and LDH can be used as efficient and easily available means to predict bone marrow metastasis for an early diagnosis.
Increased visual and cognitive demands emphasize the importance of meeting visual needs at all distances while driving
Authors: Patoine Amigale , Mikula Laura , Romero Sergio Mejía , Michaels Jesse , Keruzore Océane , Chaumillon Romain , Bernardin Delphine , Faubert Jocelyn
Published: December 2020

Having an optimal quality of vision as well as adequate cognitive capacities is known to be essential for driving safety. However, the interaction between vision and cognitive mechanisms while driving remains unclear. We hypothesized that, in a context of high cognitive load, reduced visual acuity would have a negative impact on driving behavior, even when the acuity corresponds to the legal threshold for obtaining a driving license in Canada, and that the impact observed on driving performance would be greater with the increase in the threshold of degradation of visual acuity. In order to investigate this relationship, we examined driving behavior in a driving simulator under optimal and reduced vision conditions through two scenarios involving different levels of cognitive demand. These were: 1. a simple rural driving scenario with some pre-programmed events and 2. a highway driving scenario accompanied by a concurrent task involving the use of a navigation device. Two groups of visual quality degradation (lower/ higher) were evaluated according to their driving behavior. The results support the hypothesis: A dual task effect was indeed observed provoking less stable driving behavior, but in addition to this, by statistically controlling the impact of cognitive load, the effect of visual load emerged in this dual task context. These results support the idea that visual quality degradation impacts driving behavior when combined with a high mental workload driving environment while specifying that this impact is not present in the context of low cognitive load driving condition.
Hypoxia Regulation ofndrgs
Authors: Le Nguyet , Hufford Timothy , Brewster Rachel
Published: December 2020

Many organisms rely on oxygen to generate energy in the form of adenosine triphosphate (ATP). During severe hypoxia, the production of ATP decreases due to diminished activity of the electron transport chain, leading to cell damage or death. Conversely, excessive oxygen causes oxidative stress that is equally damaging to cells. To mitigate pathological outcomes, organisms have evolved mechanisms to adapt to fluctuations in oxygen levels. Zebrafish embryos are remarkably hypoxia-tolerant, surviving anoxia (zero oxygen) for hours in a hypometabolic, energy-conserving state. To begin to unravel underlying mechanisms, we analyze here the distribution and hypoxia-dependent regulation of members of the N-myc Downstream Regulated Gene (Ndrg) family, Ndrg 1-4. These genes have primarily been studied in cancer cells, and hence little is understood about their normal function. We show here usingin situhybridization that, under normoxic conditions,ndrgsare expressed in metabolically-demanding organs of the zebrafish embryo, such as the brain, kidney, and heart. Following exposure of embryos to different severity and durations of hypoxia, we observed thatndrgsare differentially regulated and thatndrg1ais the most responsive member of this family, with nine-fold upregulation following prolonged anoxia. We further show that this treatment resulted inde novoexpression ofndrg1ain tissues where it is not observed under normoxia, such as head vasculature, the inner ear, and somites. These findings provide an entry point into understanding the role of this conserved gene family in hypoxia adaptation of normal cells.
Causal effect of atrial fibrillation on brain white or grey matter volume: A Mendelian randomization study
Authors: Park Sehoon , Lee Soojin , Kim Yaerim , Cho Semin , Kim Kwangsoo , Kim Yong Chul , Han Seung Seok , Lee Hajeong , Lee Jung Pyo , Lee Soryoung , Choi Eue-Keun , Joo Kwon Wook , Lim Chun Soo , Kim Yon Su , Kim Dong Ki
Published: December 2020

Background

Atrial fibrillation (AF) and brain volume loss are prevalent in older individuals. Further study investigating the causal effect of AF on brain volume is warranted.

Methods

This study was a Mendelian randomization (MR) analysis. The genetic instrument for AF was constructed from a previous genome-wide association study (GWAS) meta-analysis and included 537,409 individuals of European ancestry. The outcome summary statistics for quantile-normalized white or grey matter volume measured by magnetic resonance imaging were provided by the previous GWAS of 8426 white British UK Biobank participants. The main MR method was the inverse variance weighted method, supported by sensitivity MR analysis including MR-Egger regression and the weighted median method. The causal estimates from AF to white or grey matter volume were further adjusted for effects of any stroke or ischemic stroke by multivariable MR analysis.

Results

A higher genetic predisposition for AF (one standard deviation increase) was significantly associated with lower white matter volume [beta −0.128 (−0.208, −0.048)] but not grey matter volume [beta −0.041 (−0.101, 0.018)], supported by all utilized sensitivity MR analyses. The multivariable MR analysis indicated that AF is causally linked to lower white matter volume independent of the stroke effect.

Conclusions

AF is a causative factor for white matter volume loss. The effect of AF on grey matter volume was inapparent in this study. A future trial is necessary to confirm whether appropriate AF management can be helpful in preventing cerebral white matter volume loss or related brain disorders in AF patients.
Negative vaccine attitudes and intentions to vaccinate against Covid-19 in relation to smoking status: a population survey of UK adults
Authors: Jackson Sarah E. , Paul Elise , Brown Jamie , Steptoe Andrew , Fancourt Daisy
Published: December 2020

Introduction

We examined differences in negative attitudes towards vaccines in general, and intentions to vaccinate against Covid-19 specifically, by smoking status in a large sample of adults in the UK.

Method

Data were from 29,148 adults participating in the Covid-19 Social Study in September-October 2020. Linear regression analyses examined associations between smoking status (current/former/never) and four types of general negative vaccine attitudes: mistrust of vaccine benefit, worries about unforeseen effects, concerns about commercial profiteering, and preference for natural immunity. Multinomial logistic regression examined associations between smoking status and uncertainty and unwillingness to be vaccinated for Covid-19. Covariates included sociodemographic characteristics and diagnosed health conditions.

Results

Relative to never and former smokers, current smokers reported significantly greater mistrust of vaccine benefit, were more worried about unforeseen future effects, had greater concerns about commercial profiteering, and had a stronger preference for natural immunity (Badjs 0.16-0.36, p<0.001). Current smokers were more likely to be uncertain (27.6% vs. 22.7% of never smokers: RRadj 1.43 [95%CI 1.31-1.56]; vs. 19.3% of former smokers: RRadj 1.55 [1.41-1.73]) or unwilling (21.5% vs. 11.6% of never smokers: RRadj 2.12 [1.91-2.34]; vs. 14.7% of former smokers: RRadj 1.53 [1.37-1.71]) to receive a Covid-19 vaccine.

Conclusions

Current smokers hold more negative attitudes towards vaccines in general, and are more likely to be undecided or unwilling to vaccinate against Covid-19, compared with never and former smokers. With a disproportionately high number of smokers belonging to socially clustered and disadvantaged socioeconomic groups, lower vaccine uptake in this group could also exacerbate health inequalities.

Implications

These results suggest that without intervention, smokers will be less likely than non-smokers to take up the offer of a Covid-19 vaccine when offered. Targeted policy action may be required to ensure low uptake of Covid-19 vaccination programmes does not compound health inequalities between smokers and non-smokers.
Immune Cell Profiles and Cytokine Levels of Patients with Interstitial Cystitis/Bladder Pain Syndrome
Authors: Moldwin Robert M. , Nursey Vishaan , Yaskiv Oksana , Dalvi Siddhartha , Funaro Michael , DeGouveia William , Ruzimovsky Marina , Rilo Horacio R. , Miller Edmund J. , Najjar Souhel , Tabansky Inna , Stern Joel N.H.
Published: December 2020

Aims

To quantify the number of immune cells in the bladder urothelium and concentrations of urinary cytokines in patients with Interstitial Cystitis/Bladder Pain Syndrome (IC/BPS). To identify differences in these measures in IC/BPS patients with Hunner’s lesions (IC/BPS-HL) and without Hunner’s lesions (IC/BPS-NHL).

Methods

Bladder tissue biopsies were obtained from 48 patients with IC/BPS-HL and unaffected controls (UC) and stained with antibodies for various immune cell markers such as CD138, CD20 and CD56. Levels of cytokines (Interferon (IFN)-γ, Interleukin (IL)-1β, IL-2, IL- 4, IL-6, IL-8, IL12P70, IL-13, and TNF-α) were measured from normalized urine obtained from 18 IC/BPS-HL, 18 IC/BPS-NHL, and 4 UC.

Results

Numbers of CD138+ plasma cells, CD20+ B cells, and CD3+ T cells were significantly increased (50 fold, 30 fold, and an almost 3 fold increase, respectively; p-values: 1.34E-06, 3.26E-04, and 2.52E-6) in the bladders of IC/BPS-HL patients compared to UC. Patients with IC/BPS-HL had significantly elevated urinary levels of IL-6 (p=0.0028) and TNF-α (p=0.009) compared to patients with IC/BPS-NHL and UC. In contrast, IL-12p70 levels were significantly higher in the patients with IC/BPS-NHL than in HL patients (p=0.033). No significant difference in IL-12p70 levels were observed between IC/BPS-HL and UC.

Conclusion

Different cytokines were elevated in the urine of IC/BPS patients with and without HL, suggesting differences in underlying disease processes. Elevated levels of CD138+, CD20+, and CD3+ cells in HL indicate B and T-cell involvement in lesion formation. Determining which cytokines and immunological pathways are present in IC/BPS-HL could elucidate the disease mechanism.
Suppression of miR-155 attenuates lung cytokine storm induced by SARS-CoV-2 infection in human ACE2-transgenic mice
Authors: Soni Dharmendra Kumar , Cabrera-Luque Juan , Kar Swagata , Sen Chaitali , Devaney Joseph , Biswas Roopa
Published: December 2020

Coronavirus disease 2019 (COVID-19) is a recent global pandemic. It is a deadly human viral disease, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), with a high rate of infection, morbidity and mortality. Therefore, there is a great urgency to develop new therapies to control, treat and prevent this disease. Endogenous microRNAs (miRNAs, miRs) of the viral host are key molecules in preventing viral entry and replication, and building an antiviral cellular defense. Here, we have analyzed the role of miR-155, one of the most powerful drivers of host antiviral responses including immune and inflammatory responses, in the pathogenicity of SARS-CoV-2 infection. Subsequently, we have analyzed the potency of anti-miR-155 therapy in a COVID-19 mouse model (mice transgenic for human angiotensin I-converting enzyme 2 receptor (tg-mice hACE2)). We report for the first time that miR-155 expression is elevated in COVID-19 patients. Further, our data indicate that the viral load as well as miR-155 levels are higher in male relative to female patients. Moreover, we find that the delivery of anti-miR-155 to SARS-CoV-2-infected tg-mice hACE2 effectively suppresses miR-155 expression, and leads to improved survival and clinical scores. Importantly, anti-miR-155-treated tg-mice hACE2 infected with SARS-CoV-2 not only exhibit reduced levels of pro-inflammatory cytokines, but also have increased anti-viral and anti-inflammatory cytokine responses in the lungs. Thus, our study suggests anti-miR-155 as a novel therapy for mitigating the lung cytokine storm induced by SARS-CoV-2 infection.
Cohesin regulates homology search during recombinational DNA repair
Authors: Piazza Aurèle , Bordelet Hélène , Dumont Agnès , Thierry Agnès , Savocco Jérôme , Girard Fabien , Koszul Romain
Published: December 2020

Homologous recombination (HR) is a ubiquitous DNA double-strand break (DSB) repair mechanism that promotes cell survival. It entails a potentially genome-wide homology search step, carried out along a conserved RecA/Rad51-ssDNA nucleoprotein filament (NPF) assembled on each DSB ends1–3. This search is subdued to NPF-dsDNA collision probability, dictated in part by chromatin conformation2,4. In contrast to the extensive knowledge about chromatin composition and mobility changes elicited by the DNA damage checkpoint (DDC)5–7, whether, how, and to which extent a DSB impacts spatial chromatin organization, and whether this organization in turns influences the homology search process, remains ill-defined8,9. Here we characterize two layers of spatial chromatin reorganization following DSB formation inS. cerevisiae.While cohesin folds chromosomes into cohesive arrays of 10-20 kb long chromatin loops as cells arrest in G2/M10,11, the DSB-flanking regions locally interact in a resection- and 9-1-1 clamp-dependent manner, independently of cohesin and HR proteins. This local structure blocks cohesin progression, constraining the extending NPF at loop base. Functionally this organization promotes side-specificcisDSB-dsDNA interactions that scales with loop expansion span, and provides a kinetic advantage for identification of intra- over inter-chromosomal homologies. We propose that cohesins regulate homology search by promotingcisdsDNA over-sampling, both upon loop expansion-coupled unidimensional dsDNA scanning, NPF trapping, and chromosome individualization, largely independent of their role in sister chromatid cohesion.
Identification of a novel conserved signaling motif in CD200 Receptor required for its inhibitory function
Authors: Timmerman Laura M. , de Graaf Fréderique , Satravelas Nikolaos , Kesmir Çan , Meyaard Linde , van der Vlist Michiel
Published: December 2020

The inhibitory signaling of CD200 receptor 1 (CD200R) has been attributed to its NPxY signaling motif. However, NPxY-motifs are present in multiple protein families and are mostly known to mediate protein trafficking between subcellular locations rather than signaling. Therefore, we investigated whether additional motifs specify the inhibitory function of CD200R. We performed phylogenetic analysis of the intracellular domain of CD200R in mammals, birds, bony fish, amphibians and reptiles. Indeed, the tyrosine of the NPxY-motif is fully conserved across species, in line with its central role in CD200R signaling. In contrast, P295 of the NPxY-motif is not conserved. Instead, a conserved stretch of negatively charged amino acids, EEDE279, and two conserved residues P285 and K292 in the flanking region prior to the NPxY-motif are required for CD200R mediated inhibition of p-Erk, p-Akt308, p-Akt473, p-rpS6 and LPS-induced IL-8 secretion. Altogether, we show that instead of the more common NPxY-motif, CD200R signaling can be assigned to a unique signaling motif in mammals defined by: EEDExxPYxxYxxKxNxxY.
Genotype-phenotype map of an RNA-ligand complex
Authors: Puchta Olga , Sobczyk Grzegorz , Smer-Barreto Vanessa , Ireland Hollie , Vendrell Marc , Oyarzún Diego A. , Bujnicki Janusz M. , Whyte Graeme , Kudla Grzegorz
Published: December 2020

RNA-ligand interactions play important roles in biology and biotechnology, but they often involve complex three-dimensional folding of RNA and are difficult to predict. To systematically explore the phenotypic landscape of an RNA-ligand complex, we used microarrays to investigate all possible single and double mutants of the 49-nt RNA aptamer Broccoli bound to the fluorophore DFHBI-1T. We collected more than seven million fluorescence measurements in varying conditions, and inferred dissociation rate constants, spectral shifts, and intragenic epistasis. Our results reveal an unexpectedly complex phenotypic landscape, in which mutations near the fluorophore binding pocket modulated magnesium-, potassium- and fluorophore-binding and fluorescence spectra, while distal mutations influenced structural stability and fluorescence intensity. We trained a machine learning model that accurately predicted RNA secondary structure from local epistatic interactions, despite the presence of G-quadruplexes and other noncanonical structures. Our experimental platform will facilitate the discovery and analysis of new RNA-ligand interactions.
Seasonal niche differentiation between evolutionary closely related marine bacteria
Authors: Auladell Adrià , Barberán Albert , Logares Ramiro , Garcés Esther , Gasol Josep M. , Ferrera Isabel
Published: December 2020

Bacteria are highly dynamic in marine environments, where they play key biogeochemical roles. Here, we tested how similar the niche of closely related marine bacteria is and what are the environmental parameters modulating their ecological responses in a coastal oligotrophic time series. We further explored how conserved the niche is at broader taxonomic levels. We found that, for certain genera, niche similarity decreases as nucleotide divergence increases between closely related amplicon sequence variants, a pattern compatible with selection of similar taxa through habitat filtering. Additionally, we observed evidence of niche partitioning within various genera shown by the distinct seasonal patterns of closely related taxa. At broader levels, we did not observe coherent seasonal trends at the class level, with the order and family ranks conditioned to the patterns that exist at the genus level. This study explores the coexistence of niche overlap and niche partitioning in a coastal marine environment.
Redistribution of FLAgellar Member 8 during the trypanosome life cycle: consequences for cell fate prediction
Authors: Alvarez Estefanía Calvo , Bonnefoy Serge , Salles Audrey , Benson Fiona E. , McKean Paul G. , Bastin Philippe , Rotureau Brice
Published: December 2020

The single flagellum of African trypanosomes is essential in multiple aspects of the parasite development. The FLAgellar Member 8 protein (FLAM8), localised to the tip of the flagellum in cultured insect forms, was identified as a marker of the locking event that controls flagellum length. Here, we investigated whether FLAM8 could also reflect the flagellum maturation state in other stages. We observed that FLAM8 distribution extended along the entire flagellar cytoskeleton in mammalian infective forms. Then, a rapid FLAM8 concentration to the distal tip occurs during differentiation into early insect forms, illustrating for the first time the remodeling of an existing flagellum in trypanosomes. In the tsetse cardia, FLAM8 further localizes to the entire length of the new flagellum during an asymmetric division. Strikingly, in parasites dividing in the tsetse midgut and in the salivary glands, the amount and distribution of FLAM8 in the new flagellum was seen to predict the daughter cell fate. We propose and discuss how FLAM8 could be considered as a meta-marker of the flagellum stage and maturation state in trypanosomes.

Summary statement

The trypanosome protein FLAM8 displays a dynamic and stage-specific distribution during the entire parasite cycle, representing a novel marker of the flagellum stage and maturation state.
Genetic correlations between COVID-19 and a variety of traits and diseases
Authors: Chang Xiao , Li Yun , Nguyen Kenny , Qu Huiqi , Liu Yichuan , Glessner Joseph , Sleiman Patrick M A , Hakonarson Hakon
Published: December 2020

We analyzed GWAS results released by COVID-19 Host Genetics Initiative, UK biobank and GWAS Catalog to explore the genetic overlap between COVID-19 and a broad spectrum of traits and diseases. We validate previously reported medical conditions and risk factors based on epidemiological studies, including but not limited to hypertension, type 2 diabetes and obesity. We also report novel traits associated with COVID-19, which have not been previously reported from epidemiological data, such as opioid use and educational attainment. Taken together, this study extends our understanding of the genetic basis of COVID-19, and provides target traits for further epidemiological studies.
Taranto’s long shadow? Cancer mortality shows alarming peaks for specific types in the most polluted city of Italy but also in surrounding towns
Authors: Roberto Cazzolla Gatti R. , Velichevskaya Alena
Published: December 2020

A national-scale study in Italy showed an incidence of cancer higher in the territories indicated as highly polluted compared to the regional average. One of them, the city of Taranto in Apulia (Italy), which is considered one of the most polluted cities in Europe, has numerous industrial activities that impact population health. We studied the epidemiological effects of a high level of pollution produced by the industrial area of Taranto in increasing the mortality rate for some specific cancer types in the city and towns of the two provinces located downwind. We analysed 10-year mortality rates for 14 major types of tumours reported among the residents of Taranto, of 6 surrounding towns, randomly placed within an imaginary cone in the main wind direction from the vertex of the industrial zone of Taranto. Our results confirm our hypothesis that the mortality rate for some specific types of cancer (namely, Hodgkin and non-Hodgkin lymphomas, leukaemia, liver and bladder tumours) are higher than the norm in the municipality of Taranto and we have evidence that other local causes may be implicated in the excess of mortality besides the potential dispersal of pollutants from the industrial area of Taranto. The proximity to the industrial area of Taranto cannot, therefore, explain alone the anomalies detected in some populations. It is likely that other site-specific sources of heavy pollution are playing a role in worsening the death toll of these towns and this must be taken into serious consideration by environmental policy-makers and local authorities.
Face covering adherence is positively associated with better mental health and wellbeing: a longitudinal analysis of the CovidLife surveys
Authors: Altschul Drew , Fawns-Ritchie Chloe , Kwong Alex , Hartley Louise , Nangle Clifford , Edwards Rachel , Dawson Rebecca , Levein Christie , Campbell Archie , Flaig Robin , McIntosh Andrew , Deary Ian , Marioni Riccardo , Hayward Caroline , Sudlow Cathie , Douglas Elaine , Bell David , Porteous David
Published: December 2020

Face masks or coverings are effective at reducing airborne infection rates, yet pandemic mitigation measures, including wearing face coverings, have been suggested to contribute to reductions in quality of life and poorer mental health. Longitudinal analyses of more than 11,000 participants across the UK found no association between lower adherence to face covering guidelines and poorer mental health. The opposite appears to be true. Even after controlling for behavioral, social, and psychological confounds, including measures of pre-pandemic mental health, individuals who wore face coverings “most of the time” or “always” had better mental health and wellbeing than those who did not. These results suggest that wearing face coverings more often will not negatively impact mental health.
Mental Disorder Prevalence Among Populations Impacted by Coronavirus Pandemics: A Multilevel Meta-Analytic Study of COVID-19, MERS & SARS
Authors: Boden Matt , Cohen Nichole , Froelich Jessilyn M. , Hoggatt Katherine J. , Magid Hoda S. Abdel , Mushiana Swapandeep S.
Published: December 2020

Objective

Through a systematic review and meta-analysis of research on COVID-19, severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS) pandemics, we investigated whether mental disorder prevalence: (a) was elevated among populations impacted by coronavirus pandemics (relative to unselected populations reported in the literature), and (b) varied by disorder (undifferentiated psychiatric morbidity, anxiety, depressive, posttraumatic stress disorders [PTSD]) and impacted population (community, infected/recovered, healthcare provider, quarantined).

Method

From 68 publications (N=87,586 participants), 808 estimates were included in a series of multilevel meta-analyses/regressions including random effects to account for estimates nested within studies.

Results

Median summary point prevalence estimates varied by disorder and population. Psychiatric morbidity (20%-56%), PTSD (10-26%) and depression (9-27%) were most prevalent in most populations. The highest prevalence of each disorder was found among infected/recovered adults (18-56%), followed by healthcare providers (11-28%) and community adults (11-20%). Prevalence estimates were often notably higher than reported for unselected samples. Sensitivity analyses demonstrated that overall prevalence estimates moderately varied by pandemic, study location, and mental disorder measure type.

Conclusion

Coronavirus pandemics are associated with multiple mental disorders in several impacted populations. Needed are investigations of causal links between specific pandemic-related stressors, threats, and traumas and mental disorders.
Criteria-based curation of a therapy-focused compendium to support treatment recommendations in precision oncology
Authors: Lin Frank P. , Thavaneswaran Subotheni , Grady John P. , Ballinger Mandy , Kansara Maya , Oakes Samantha R. , Desai Jayesh , Lee Chee Khoon , Simes John , Thomas David M.
Published: December 2020

BACKGROUND

While several key resources exist that interpret therapeutic significance of genomic alterations in cancer, many regional real-world issues limit access to drugs. There is a need for a pragmatic, evidence-based, context-adapted tool to guide clinical management based on molecular biomarkers.

METHODS

A compendium of approved and experimental therapies with associated biomarkers was built following a survey of drug regulatory databases, existing knowledge bases, and published literature. Each biomarker-disease-therapy triplet was then categorized using a tiering system reflective of key therapeutic considerations: approved and reimbursed standard-of-care therapies with respect to a jurisdiction (Tier 1), evidence of efficacy or approval in another jurisdiction (Tier 2), evidence of antitumour activity (Tier 3), and plausible biological rationale (Tier 4). Two resistance categories were defined: lack of efficacy (Tier R1), and lack of antitumor activity (Tier R2).

RESULTS

Following comprehensive literature review and appraisal, we developed a curated knowledge base focused on drugs relevant and accessible in the Australian healthcare system (TOPOGRAPH: Therapy Oriented Precision Oncology Guidelines for Recommending Anticancer Pharmaceuticals). As of November 2020, TOPOGRAPH comprised 2810 biomarker-disease-therapy triplets in 989 expert-appraised entries, including 373 therapies, 199 predictive biomarkers, and 106 cancer types. In the 345 biomarker-linked therapies catalogued, 84 (24%) and 65 (19%) therapies in contexts of different cancer types have Tier 1 and 2 designations respectively, while 271 (79%) therapies were supported by preclinical studies, early clinical trials, retrospective studies, or case series (Tiers 3 and 4). A total of 119 of 373 (33%) therapies associated with biomarkers of resistance were also catalogued. A clinical algorithm was also developed to support therapeutic decision-making using predictive biomarkers. This resource is accessible online at https://topograph.info/.

CONCLUSION

TOPOGRAPH is intended to support oncologists with context-appropriate clinical decision-making– optimising selection and accessibility of the most appropriate targeted therapy for any given genomic biomarker. Our approach can be readily adapted to build jurisdiction-specific resources to standardise decision-making in precision oncology.
Resolving the transcriptional transitions associated with oligodendrocyte generation from adult neural stem cells by single cell sequencing
Authors: Azim Kasum , Calzolari Filippo , Cantone Martina , Akkermann Rainer , Vera Julio , Hartung Hans-Peter , Basak Onur , Butt Arthur Morgan , Küry Patrick
Published: December 2020

The subventricular zone (SVZ) is the largest neurogenic niche in the adult forebrain. Notably, neural stem cells (NSCs) of the SVZ generate not only neurons, but also oligodendrocytes, the myelin-forming cells of the central nervous system. Transcriptomic studies have provided detailed knowledge of the molecular events that regulate neurogenesis, but little is understood about adult oligodendrogenesis from SVZ-NSCs. To address this, we performed in-depth single-cell transcriptomic analyses to resolve the major differences in neuronal and oligodendroglial lineages derived from the adult SVZ. A hallmark of adult oligodendrogenesis was the stage-specific expression of transcriptional modulators that regulate developmental oligodendrogenesis. Notably, divergence of the oligodendroglial lineage was distinguished by Wnt-Notch and angiogenesis-related signaling, whereas G-protein-coupled receptor signaling pathways were the major signature observed in the neurogenic lineage. Moreover, in-depth gene regulatory network analysis identified key stage-specific master regulators of the oligodendrocyte lineage and revealed new mechanisms by which signaling pathways interact with transcriptional networks to control lineage progression. Our work provides an integrated view of the multi-step differentiation process leading from NSCs to mature oligodendrocytes, by linking environmental signals to known and novel transcriptional mechanisms orchestrating oligodendrogenesis.

Main points

Distinct adult NSC populations giving rise to either oligodendrocytes or neurons can be identified by the expression of transcription factors.

Gene regulatory control of oligodendrogenesis is a major fate-determinant for their generation.
Sugarcane Nitrogen and Irrigation Level Prediction Based on UAV-Captured Multispectral Images at the Elongation Stage
Authors: Li Xiuhua , Ba Yuxuan , Zhang Shimin , Nong Mengling , Zhang Muqing , Wang Ce
Published: December 2020

Introduction

Sugarcane is the main industrial crop for sugar production; its growth status is closely related to fertilizer, water, and light input. Unmanned aerial vehicle (UAV)-based multispectral imagery is widely used for high-throughput phenotyping because it can rapidly predict crop vigor. This paper mainly studied the potential of multispectral images obtained by low-altitude UAV systems in predicting canopy nitrogen (N) content and irrigation level for sugarcane.

Methods

An experiment was carried out on sugarcane fields with three irrigation levels and five nitrogen levels. A multispectral image at a height of 40 m was acquired during the elongation stage, and the canopy nitrogen content was determined as the ground truth. N prediction models, including partial least square (PLS), backpropagation neural network (BPNN), and extreme learning machine (ELM) models, were established based on different variables. A support vector machine (SVM) model was used to recognize the irrigation level.

Results

The PLS model based on band reflectance and five vegetation indices had better accuracy (R=0.7693, root mean square error (RMSE)=0.1109) than the BPNN and ELM models. Some spectral information from the multispectral image had obviously different features among the different irrigation levels, and the SVM algorithm was used for irrigation level classification. The classification accuracy reached 77.8%.

Conclusion

Low-altitude multispectral images could provide effective information for N prediction and water irrigation level recognition.
A new concept on anti-SARS-CoV-2 vaccines: strong CD8+ T-cell immune response in both spleen and lung induced in mice by endogenously engineered extracellular vesicles
Authors: Ferrantelli Flavia , Chiozzini Chiara , Manfredi Francesco , Leone Patrizia , Federico Maurizio
Published: December 2020

Severe acute respiratory syndrome coronavirus (SARS-CoV)-2 is spreading rapidly in the absence of validated tools to control the growing epidemic besides social distancing and masks. Many efforts are ongoing for the development of vaccines against SARS-CoV-2 since there is an imminent need to develop effective interventions for controlling and preventing SARS-CoV-2 spread. Essentially all vaccines in most advanced phases are based on the induction of antibody response against either whole or part of spike (S) protein. Differently, we developed an original strategy to induce CD8+ T cytotoxic lymphocyte (CTL) immunity based on in vivo engineering of extracellular vesicles (EVs). We exploited this technology with the aim to identify a clinical candidate defined as DNA vectors expressing SARS-CoV-2 antigens inducing a robust CD8+ T-cell response. This is a new vaccination approach employing a DNA expression vector encoding a biologically inactive HIV-1 Nef protein (Nefmut) showing an unusually high efficiency of incorporation into EVs even when foreign polypeptides are fused to its C-terminus. Nanovesicles containing Nefmut-fused antigens released by muscle cells are internalized by antigen-presenting cells leading to cross-presentation of the associated antigens thereby priming of antigen-specific CD8+ T-cells. To apply this technology to a design of anti-SARS-CoV-2 vaccine, we recovered DNA vectors expressing the products of fusion between Nefmut and four viral antigens, namely N- and C-terminal moieties of S (referred to as S1 and S2), M, and N. All fusion products are efficiently uploaded in EVs. When the respective DNA vectors were injected in mice, a strong antigen-specific CD8+ T cell immunity was generated. Most important, high levels of virus-specific CD8+ T cells were found in bronchoalveolar lavages of immunized mice. Co-injection of DNA vectors expressing the diverse SARS-CoV-2 antigens resulted in additive immune responses in both spleen and lung. EVs engineered with SARS-CoV-2 antigens proved immunogenic also in the human system through cross-priming assays carried out with ex vivo human cells. Hence, DNA vectors expressing Nefmut-based fusion proteins can be proposed as anti-SARS-CoV-2 vaccine candidates.
QTL Mapping in Outbred Tetraploid (and Diploid) Diallel Populations
Authors: Amadeu Rodrigo R. , Munoz Patricio R. , Zheng Chaozhi , Endelman Jeffrey B.
Published: December 2020

Over the last decade, multiparental populations have become a mainstay of genetics research in diploid species. Our goal was to extend this paradigm to autotetraploids by developing software for quantitative trait locus (QTL) mapping in connected F1 populations derived from a set of shared parents. For QTL discovery, phenotypes are regressed on the dosage of parental haplotypes to estimate additive effects. Statistical properties of the model were explored by simulating half-diallel diploid and tetraploid populations with different population sizes and numbers of parents. Across scenarios, the number of progeny per parental haplotype (pph) largely determined the statistical power for QTL detection and accuracy of the estimated haplotype effects. Multi-allelic QTL with heritability 0.2 were detected with 90% probability at 25 pph and genome-wide significance level 0.05, and the additive haplotype effects were estimated with over 90% accuracy. Following QTL discovery, the software enables a comparison of models with multiple QTL and non-additive effects. To illustrate, we analyzed potato tuber shape in a half-diallel population with 3 tetraploid parents. A well-known QTL on chromosome 10 was detected, for which the inclusion of digenic dominance lowered the Deviance Information Criterion (DIC) by 17 points compared to the additive model. The final model also contained a minor QTL on chromosome 1, but higher order dominance and epistatic effects were excluded based on the DIC. In terms of practical impacts, the software is already being used to select offspring based on the effect and dosage of particular haplotypes in breeding programs.