bluuebunny/crossref_metadata_2025 huggingface dataset:
Pediatric Calvarial Tumors: 10 Years of Clinical Experience and Differences From the Literature
Authors: Sahinoglu Mert , Gundogdu Derya Karaoglu , Karabagli Pinar , Koktekir Ender , Karabagli Hakan
Published: November 2020

Very few studies have focused exclusively on pediatric calvarial tumors. These studies have primarily addressed the similarities of the cases with those reported in the literature, as opposed to their distinctive features. In contrast, the present study is the most detailed study conducted in the last 10 years that includes only pediatric calvarial tumors and highlights their differences according to the literature. A total of 31 patients with pediatric calvarial tumor surgically treated in our center between 2010 and 2020 were included in the study. The patients’ files were analyzed retrospectively and 17 different preoperative, intraoperative, and postoperative parameters were determined and compared with previous studies. Except for the tumors causing lytic or sclerotic lesions, there was at least one distinguishing aspect of our series in all parameters. Despite the many distinctive features, the consensus in the treatment of calvarial tumors is to perform complete resection of the tumor and, if possible, remove some of the adjacent healthy bone. Considering the age factor, however, closure of the resulting bone defects with cranioplasty to address issues of cosmesis and intracranial pressure is yet another aspect of pediatric calvarial tumors, because pediatric cranioplasty has its own specific complications. Using intraoperative neuronavigation and performing tumor resection alone without additional craniectomy are also methods the authors use to prevent major bone defects.
An Experimental Simulation of Heat Effects on Cognition and Workload of Surgical Team Members
Authors: Ward Mary K. , Yam Cheryl M. H. , Palejwala Zehra , Wallman Karen , Taggart Sarah M. , Wood Fiona M. , Parker Sharon K.
Published: November 2020

Objective:

To isolate heat exposure as a cause of cognitive impairment and increased subjective workload in burns surgical teams.

Summary of Background Data:

Raising ambient temperature of the operating room can improve burns patient outcomes, but risks increased cognitive impairment and workload of surgical team members. Prior research indicates ambient heat exposure depletes physiological and cognitive resources, but these findings have not been studied in the context of burns surgical teams.

Methods:

Seventeen surgical team members completed 2 surgery simulations of similar complexities in a hot and in a normothermic operating room. During each simulation, participants completed multiple cognitive tests to assess cognitive functioning and the SURG-TLX to self-assess workload. Order effects, core body temperature changes due to menstruation, and circadian rhythms were controlled for in the experimental design. Descriptive statistics, correlations, and mixed ANOVAs were performed to assess relationships between ambient heat exposure with cognitive functioning and perceived workload.

Results:

Heat had a main effect on executive functioning and verbal reasoning. Duration of heat exposure (heat ∗ time) increased response times and negatively impacted executive functioning, spatial planning, and mental rotation. Perceived workload was higher in the hot condition.

Conclusions:

We provide causal evidence that over time, heat exposure impairs cognitive speed and accuracy, and increases subjective workload. We recommend building on this study to drive best-practices for acute burns surgery and design work to enable burns teams to maintain their cognitive stamina, lower their workload, and improve outcomes for patients and surgeons.
Isovaline efficacy in a rat pup model of infantile spasms
Authors: Manzoor Rohaan , Malek Farah , Malek Sohail , Shin Damian S.
Published: November 2020

Infantile spasms, also known as epileptic spasms during infancy, is an epileptic disorder of infancy and early childhood that is associated with developmental delay or regression, high mortality rate and is difficult to treat with conventional antiseizure medication. Previously, we reported that a unique amino acid called isovaline had potent anticonvulsive efficacy in the 4-aminopyridine and pilocarpine rat models of seizures. In this study, we examined whether isovaline possess therapeutic utility in a well-established rat model of infantile spasms which involves the pretreatment of a pregnant dam with betamethasone and subsequent induction of spasms with N-methyl-D-asparate (NMDA), a glutamate receptor agonist, in 15-day old pups. We treated seven of these pups with saline prior to administering NMDA and eight of these pups with isovaline (300 mg/kg) intraperitoneal (i.p.) prior to NMDA. Isovaline significantly reduced the number of full-body jumps from 18.1 ± 5.0 to 6.3 ± 1.8 and leg/arm/tail strains from 4.4 ± 1.6 to 1.1 ± 0.5. A trend in a reduction of body twitch was noted in rat pups administered isovaline (P = 0.05), but no significant difference was seen in NMDA-induced head nods (P = 0.221). In conclusion, our data demonstrate a potential for isovaline to attenuate an aggressive form of epilepsy that typically requires highly toxic medications to treat in children.
Two new species of Euplotes with cirrotype-9, Euplotes foissneri sp. nov. and Euplotes warreni sp. nov. (Ciliophora, Spirotrichea, Euplotida), from the coasts of Patagonia: implications from their distant, early and late branching in the Euplotes phylogenetic tree
Authors: Valbonesi Alessandro , Di Giuseppe Graziano , Vallesi Adriana , Luporini Pierangelo
Published: November 2020

Two new Euplotes species have been isolated from cold shallow sandy sediments of the extreme Southern Chilean coasts: Euplotes foissneri sp. nov., from a low-salinity site at Puerto Natales on the Pacific coast, and Euplotes warreni sp. nov., from a marine site at Punta Arenas on the Atlantic coast. Euplotes foissneri has a medium body size (53×36 µm in vivo), a dorsal surface marked by six prominent ridges, a double dargyrome, six dorsal and two ventrolateral kineties, a buccal field extending to about 3/4 of the body length, an adoral zone composed of 28–32 membranelles, and nine fronto-ventral, five transverse and two or three caudal cirri. The bulky, hook-, horseshoe- or 3-shaped macronucleus is associated with one sub-spherical micronucleus. The central body region hosts taxonomically unidentified endosymbiotic eubacteria. Euplotes warreni has a small body size (39×27 µm in vivo), a smooth dorsal surface marked by three deep grooves, a double dargyrome, four dorsal and two ventrolateral kineties, a buccal field extending to about 2/3 of the body length, an adoral zone composed of 23–25 adoral membranelles, and nine fronto-ventral, five transverse and three caudal cirri. The macronucleus is hook- or C-shaped and associated with one spherical micronucleus. Endosymbiotic bacteria belonging to the genus

Francisella

reside preferentially in the anterior cell region. Both species lack the fronto-ventral cirrus numbered ‘V/2’, whereby their cirrotype-9 conforms to the so-called ‘pattern I’, which is the basic distinctive trait of the genus Euplotopsis Borror and Hill, 1995. Phylogenetic analyses of small subunit rRNA gene sequences, however, classify E. warreni into its own early branching clade and E. foissneri into a late branching clade. This indicates a polyphyletic nature and taxonomic inconsistency of the genus Euplotopsis, which was erected to include Euplotes species with cirrotype-9 pattern I.
Hematopoietic mosaic chromosomal alterations and risk for infection among 767,891 individuals without blood cancer
Authors: Zekavat Seyedeh M. , Lin Shu-Hong , Bick Alexander G. , Liu Aoxing , Paruchuri Kaavya , Uddin Md Mesbah , Ye Yixuan , Yu Zhaolong , Liu Xiaoxi , Kamatani Yoichiro , Pirruccello James P. , Pampana Akhil , Loh Po-Ru , Kohli Puja , McCarroll Steven A. , Neale Benjamin , Engels Eric A. , Brown Derek W. , Smoller Jordan W. , Green Robert , Karlson Elizabeth W. , Lebo Matthew , Ellinor Patrick T. , Weiss Scott T. , Daly Mark J. ,   The Biobank Japan Project,   FinnGen Consortium, Terao Chikashi , Zhao Hongyu , Ebert Benjamin L. ,   COVID-19 Host Genetics Initiative, Ganna Andrea , Machiela Mitchell J. , Genovese Giulio , Natarajan Pradeep
Published: November 2020

Summary Paragraph

Age is the dominant risk factor for infectious diseases, but the mechanisms linking the two are incompletely understood1,2. Age-related mosaic chromosomal alterations (mCAs) detected from blood-derived DNA genotyping, are structural somatic variants associated with aberrant leukocyte cell counts, hematological malignancy, and mortality3-11. Whether mCAs represent independent risk factors for infection is unknown. Here we use genome-wide genotyping of blood DNA to show that mCAs predispose to diverse infectious diseases. We analyzed mCAs from 767,891 individuals without hematological cancer at DNA acquisition across four countries. Expanded mCA (cell fraction >10%) prevalence approached 4% by 60 years of age and was associated with diverse incident infections, including sepsis, pneumonia, and coronavirus disease 2019 (COVID-19) hospitalization. A genome-wide association study of expanded mCAs identified 63 significant loci. Germline genetic alleles associated with expanded mCAs were enriched at transcriptional regulatory sites for immune cells. Our results link mCAs with impaired immunity and predisposition to infections. Furthermore, these findings may also have important implications for the ongoing COVID-19 pandemic, particularly in prioritizing individual preventive strategies and evaluating immunization responses.
Far-red fluorescent genetically encoded calcium ion indicators
Authors: Dalangin Rochelin , Drobizhev Mikhail , Molina Rosana S. , Aggarwal Abhi , Patel Ronak , Abdelfattah Ahmed S. , Zhao Yufeng , Wu Jiahui , Podgorski Kaspar , Schreiter Eric R. , Hughes Thomas E. , Campbell Robert E. , Shen Yi
Published: November 2020

Genetically encoded calcium ion (Ca2+) indicators (GECIs) are widely-used molecular tools for functional imaging of Ca2+dynamics and neuronal activities on a single cell level. Here we report the design and development of two new far-red fluorescent GECIs, FR-GECO1a and FR-GECO1c, based on the monomeric far-red fluorescent protein mKelly. We characterized these far-red GECIs as purified proteins and assessed their performance when expressed in cultured neurons. FR-GECOs have excitation and emission maxima at ~ 596 nm and ~ 644 nm, respectively, display large responses to Ca2+(ΔF/F0= 6 for FR-GECO1a, 18 for FR-GECO1c), and are bright under both one-photon and two-photon illumination. FR-GECOs also have high affinities (apparentKd= 29 nM for FR-GECO1a, 83 nM for FR-GECO1c) for Ca2+, and they enable sensitive and fast detection of single action potentials in neurons.
Performance of SARS-CoV-2 Serology tests: Are they good enough?
Authors: Piec Isabelle , English Emma , Thomas M Annette , Dervisevic Samir , Fraser William D , John W Garry
Published: November 2020

Background

In the emergency of the SARS-CoV-2 pandemic, great efforts were made to quickly provide serology testing to the medical community however, these methods have been introduced into clinical practice without the complete validation usually required by the regulatory organizations.

Methods

SARS-CoV-2 patient samples (n=43) were analysed alongside pre-pandemic control specimen (n=50), confirmed respiratory infections (n=50), inflammatory polyarthritis (n=22) and positive for thyroid stimulating immunoglobulin (n=30). Imprecision, diagnostic sensitivity and specificity and concordance were evaluated on IgG serologic assays from EuroImmun, Epitope Diagnostics (EDI), Abbott Diagnostics and DiaSorin and a rapid IgG/IgM test from Healgen.

Results

EDI and EuroImmun imprecision was 0.02-14.0% CV. Abbott and DiaSorin imprecision (CV) ranged from 5.2% - 8.1% and 8.2% - 9.6% respectively. Diagnostic sensitivity of the assays were 100% (CI: 80-100%) for Abbott, EDI and EuroImmun and 95% (CI: 73-100%) for DiaSorin at ≥14 days post PCR. Only the Abbott assay had a diagnostic specificity of 100% (CI: 91-100%). EuroImmun cross-reacted in 3 non-SARS-CoV-2 respiratory infections and 2 controls. The DiaSorin displayed more false negative results and cross-reacted in six cases across all conditions tested. EDI had one cross-reactive sample. The Healgen rapid test showed excellent sensitivity and specificity. Overall, concordance of the assays ranged from 76.1% to 97.9%.

Conclusions

Serological tests for SARS-CoV-2 showed good analytical performance. The head-to-head analysis of samples revealed differences in results that may be linked to the use of nucleocapsid or spike proteins. The point of care device tested demonstrated adequate performance for antibody detection.
ELIPSE-COL: A novel ELISA test based on rational envisioned synthetic peptides for detection of SARS-CoV-2 infection in Colombia
Authors: Arévalo Adriana , Franco-Muñoz Carlos , Duque-Beltrán Sofía , Muñoz-Galindo Lyda , Herrera-Sepulveda María , Lozano José Manuel , Salazar Luz Mary , Ospina-Martinez Martha L. , Mercado-Reyes Marcela
Published: November 2020

Background

COVID-19 pandemic caused by infection with the betacoronavirus SARS-CoV-2 is the greatest public health defiant on a global scale in the last 100 years. Governments and health Institutes face challenges during the pandemic, related to the diagnosis, mitigation, treatment, and timely detection after the epidemic peak for the prevention of new infections and the evaluation of the real impact of the COVID-19 disease in different geographic areas. To develop a valuable tool to study the seroprevalence of SARS-CoV-2 infection in Colombia, an “in-house” ELISA was achieved for the detection of IgG anti-SARS-CoV-2 antibodies in serum.

Methods

The test was standardized using an antigenic epitope “Pool” of the synthetic peptide as antigen derived from antigenic regions of the spike, nucleocapsid, envelope, and membrane structural proteins, which were designed, based on the genomic information of SARS-CoV-2 circulating in Colombia. In the ELISA standardization process, 94 positive sera were used, including sera from asymptomatic and symptomatic patients (mild and severe) and 123 negative sera, including pre-pandemic historical negatives originating from patients living in arbovirus endemic areas or patients with a history of respiratory diseases and sera from patients with a negative rRT-PCR test for SARS-CoV-2.

Results

The in-house peptide ELIPSE-COL test showed promising performance, being able to detect reactivity in sera from asymptomatic and symptomatic patients. The sensitivity and specificity of the assay were 91.4% and 83.7% respectively.

Conclusion

ELIPSE-COL assay was developed as an ELISA test using synthetic peptides for the study of the seroprevalence of SARS-CoV-2 infection in Colombia.

SUMMARY BOX

Detection of IgG anti-SARS-CoV-2 antibodies is required for the evaluation of the pandemic impact and vaccination strategies.

ELIPSE-COL is an in-house test based on synthetic peptides as antigen derived from antigenic regions of the spike, nucleocapsid, envelope, and membrane structural proteins.

The sensitivity and specificity of the assay were 91.4% and 83.7% respectively suggesting a promising performance.

ELIPSE-COL test is a valuable tool for the study of seroprevalence in Colombia.
UKCTOCS Update: Applying insights of delayed effects in cancer screening trials to the long-term follow-up mortality analysis
Authors: Burnell Matthew , Gentry-Maharaj Aleksandra , Skates Steven J , Ryan Andy , Karpinskyj Chloe , Kalsi Jatinderpal , Apostolidou Sophia , Singh Naveena , Dawnay Anne , Woolas Robert , Fallowfield Lesley , Campbell Stuart , McGuire Alistair , Jacobs Ian J , Parmar Mahesh , Menon Usha
Published: November 2020

Background

During trials that span decades, new evidence including progress in statistical methodology, may require revision of original assumptions. An example is the continued use of a constant-effect approach to analyse the mortality reduction which is often delayed in cancer-screening trials. The latter led us to re-examine our approach for the upcoming primary mortality analysis(2020) of long-term follow-up of the United Kingdom Collaborative Trial of Ovarian Cancer Screening (LTFU UKCTOCS), having initially(2014) used the proportional hazards(PH) Cox-model.

Methods

We wrote to 12 experts in statistics/epidemiology/screening-trials, setting out current evidence, importance of pre-specification, previous mortality analysis (2014) and three possible choices for the follow-up analysis (2020) of the mortality outcome - (A)all data(2001-2020) using the Cox-model(2014) (B)new data(2015-2020) only (C)all data(2001-2020) using a test that allows for delayed effects.

Results

Of 11 respondents, eight supported changing the 2014-approach to allow for a potential delayed effect (optionC), suggesting various tests while three favoured retaining the Cox-model (optionA). Consequently, we opted for the Versatile test introduced in 2016 which maintains good power for early, constant or delayed effects. We retained the Royston-Parmar model to estimate absolute differences in disease-specific mortality at 5,10,15 and 18 years.

Conclusions

The decision to alter the follow-up analysis for the primary outcome on the basis of new evidence and using new statistical methodology for long-term follow-up is novel and has implications beyond UKCTOCS. There is an urgent need for consensus building on how best to design, test, estimate and report mortality outcomes from long-term randomised cancer screening trials.

Trial registration: (ISRCTN22488978, Registration date: 6/4/2000)
Automated Segmentation of Amyloid-βStained Whole Slide Images of Brain Tissue
Authors: Lai Zhengfeng , Guo Runlin , Xu Wenda , Hu Zin , Mifflin Kelsey , DeCarli Charles , Dugger Brittany N. , Cheung Sen-ching , Chuah Chen-Nee
Published: November 2020

Neurodegenerative disease pathologies have been reported in both grey matter (GM) and white matter (WM) with different density distributions, an automated separation of GM/WM would be extremely advantageous for aiding in neuropathologic deep phenotyping. Standard segmentation methods typically involve manual annotations, where a trained researcher traces the delineation of GM/WM in ultra-high-resolution Whole Slide Images (WSIs). This method can be time-consuming and subjective, preventing the analysis of large amounts of WSIs at scale. This paper proposes an automated segmentation pipeline combining a Convolutional Neural Network (CNN) module for segmenting GM/WM regions and a post-processing module to remove artifacts/residues of tissues as well as generate XML annotations that can be visualized via Aperio ImageScope. First, we investigate two baseline models for medical image segmentation: FCN, and U-Net. Then we propose a patch-based approach, ResNet-Patch, to classify the GM/WM/background regions. In addition, we integrate a Neural Conditional Random Field (NCRF) module, ResNet-NCRF, to model and incorporate the spatial correlations among neighboring patches. Although their mechanisms are greatly different, both U-Net and ResNet-Patch/ResNet-NCRF achieve Intersection over Union (IoU) of more than 90% in GM and more than 80% in WM, while ResNet-Patch achieves 1% superior to U-Net with lower variance among various WSIs. ResNet-NCRF further improves the IoU by 3% for WM compared to ResNet-Patch before post-processing. We also apply gradient-weighted class activation mapping (Grad-CAM) to interpret the segmentation masks and provide relevant explanations and insights.
Dissociation Between Individual Differences in Self-Reported Pain Intensity and Underlying Brain Activation
Authors: Hoeppli M.E. , Nahman-Averbuch H. , Hinkle W.A. , Leon E. , Peugh J. , Lopez-Sola M. , King C.D. , Goldschneider K.R. , Coghill R.C.
Published: November 2020

Pain is a uniquely individual experience. Previous studies have highlighted changes in brain activation and morphology associated with inter- and intra-individual pain perception. In this study we sought to characterize brain mechanisms associated with individual differences in pain in a large sample of healthy participants (N = 101). Pain ratings varied widely across individuals. Moreover, individuals reported changes in pain evoked by small differences in stimulus intensity in a manner congruent with their pain sensitivity, further supporting the utility of subjective reporting as a measure of the true individual experience. However, brain activation related to inter-individual differences in pain was not detected, despite clear sensitivity of the BOLD signal to small differences in noxious stimulus intensities within individuals. These findings raise questions about the utility of fMRI as an objective measure to infer reported pain intensity.
Noradrenergic Regulation of Two-Armed Bandit Performance
Authors: Swanson Kyra , Averbeck Bruno B. , Laubach Mark
Published: November 2020

Reversal learning depends on cognitive flexibility. Many reversal learning studies assess cognitive flexibility based on the number of reversals that occur over a test session. Reversals occur when an option is repeatedly chosen, e.g. eight times in a row. This design feature encourages win-stay behavior and thus makes it difficult to understand how win-stay decisions influence reversal performance. We used an alternative design, reversals over blocks of trials independent of performance, to study how perturbations of the medial orbital cortex and the noradrenergic system influence reversal learning. We found that choice accuracy varies independently of win-stay behavior and the noradrenergic system controls sensitivity to positive feedback during reversal learning.
Comparing global and regional maps of intactness in the boreal region of North America: Implications for conservation planning in one of the world’s remaining wilderness areas
Authors: Vernier Pierre , Leroux Shawn , Cumming Steve , Lisgo Kim , Esteban Alberto Suarez , Krawchuck Meg , Schmiegelow Fiona
Published: November 2020

Though North America’s boreal forest contains some of the largest remaining intact and wild ecosystems in the world, human activities are systematically reducing its extent. Consequently, forest intactness and human influence maps are increasingly used for monitoring and conservation planning in the boreal region. We compare eight forest intactness and human impact maps to provide a multi-model assessment of intactness in the boreal region. All maps are global in extent except for Global Forest Watch Canada’s Human Access (2000) and Intact Forest Landscapes (2000, 2013) maps, although some global maps are restricted to areas that were at least 20% treed. As a function of each map’s spatial coverage in North America, the area identified as intact ranged from 55% to 79% in Canada and from 32% to 96% in Alaska. Likewise, the similarity between pairs of datasets in the Canadian boreal ranged from 0.58 to 0.86 on a scale of 0-1. In total, 45% of the region was identified as intact by the seven most recent datasets. There was also variation in the ability of the datasets to account for anthropogenic disturbances that are increasingly common in the boreal region, such as those associated with resource extraction. In comparison to a recently developed high resolution regional disturbance dataset, the four human influence datasets (Human Footprint, Global Human Modification, Large Intact Areas, and Anthropogenic Biomes), in particular, omitted 59-85% of all linear disturbances and 54-89% of all polygonal disturbances. In contrast, the global IFL, Canadian IFL, and Human Access maps omitted 2-7% of linear disturbances and 0.1-5% of polygonal disturbances. Several differences in map characteristics, including input datasets and methods used to develop the maps may help explain these differences. Ultimately, the decision on which dataset to use will depend on the objectives of each specific conservation planning project, but we recommend using datasets that 1) incorporate regional anthropogenic activities, 2) are updated regularly, 3) provide detailed information of the methods and input data used, and 4) can be replicated and adapted for local use. This is especially important in landscapes that are undergoing rapid change due to development, such as the boreal forest of North America.
Impact of the COVID-19 pandemic on Older Adults Mental Health Services: a mixed methods study
Authors: Bhome Rohan , Huntley Jonathan , Dalton- Locke Christian , Vera San Juan Norha , Oram Sian , Foye Una , Livingston Gill
Published: November 2020

Purpose

The Covid-19 pandemic is likely to have a significant impact on older adults mental health care. Our study aimed to explore staff perspectives on key challenges and innovations, to help inform the delivery of older adults mental health care in subsequent waves of the pandemic.

Methods

A mixed methods online questionnaire developed by NIHR Mental Health Policy Research Unit (MHPRU) was used to gather staff perspectives on their challenges at work, problems faced by service users and their carers, and sources of help and support. Descriptive statistics were used for quantitative analysis and descriptive content analysis for qualitative analysis.

Results

158 participants, working in either community or inpatient settings, and from a range of professional disciplines, were included. For inpatient staff, a significant challenge was infection control. In the community, staff identified a lack of access to physical and social care as well as reduced contact with friends and families as being challenges for patients. Remote working was seen as a positive innovation along with Covid-19 related guidance from various sources and peer support.

Conclusion

Our study, with a focus on staff and patient well-being, helps to inform service development for future waves of the pandemic. We discuss measures to improve infection control in inpatient settings, the role of voluntary organisations in supporting socially isolated community patients, the need for better integration of physical and mental health services at an organisational level, and the importance of training staff to support patients and their families with end of life planning.
Occurrence of cardiovascular complications associated with SARS-CoV-2 infection: a systematic review
Authors: Sardinha Daniele Melo , Lima Karla VB , Ueno Thalyta MRL , Rodrigues Yan Correa , Garcez Juliana CD , Santos Anderson LS , Ferreira Ana LS , Guimaraes Ricardo JPS , Lima Luana NGC
Published: November 2020

Cardiovascular Diseases represent the main cause of death in the world, and are associated with risk factors that cause serious complications in cases of infections, such as those of the respiratory tract. In March 2020 the World Health Organization declared a pandemic for SARS-CoV-2, a new coronavirus causing severe pneumonia, which emerged in December 2019 in Wuhan, China. The objective is to investigate the occurrence of cardiovascular complications associated with SARS-CoV-2 infection. It is a systematic review, quantitative, in the databases, PubMed and Science direct, including primary studies with hospitalized patients confirmed for COVID-19 and who presented cardiovascular complications, the form used tools for evaluation of quality and evidence, following the PRISMA recommendations. Results: 12 studies were included. The occurrence of cardiovascular complications was: 27.35% of the sample of 3,316 patients. Types: Acute cardiac injury 17.09%; Thromboembolism 4.73%; Heart failure 3.43%; Arrhythmias 1.77%; stroke 0.33%. Mean age 61 years. Conclusions: This study showed that there are several cardiovascular complications associated with SARS-CoV-2, that the main one is acute cardiac injury, which causes several instabilities in the cardiopulmonary system, and that it is associated with mortality.
Detection of the SARS-CoV-2 spike protein in saliva with Shrinky-Dink© electrodes
Authors: Zakashansky Julia A. , Imamura Amanda H. , Salgado Darwin F. , Romero Mercieca Heather C. , Aguas Raphael F.L. , Lao Angelou M. , Pariser Joseph , Arroyo-Currás Netzahualcóyotl , Khine Michelle
Published: November 2020

Using the children’s toy, Shrinky-Dink ©, we present an aptamer-based electrochemical (E-AB) assay that recognizes the spike protein of SARS-CoV-2 in saliva for viral infection detection. The low-cost electrodes are implementable at population scale and demonstrate detection down to 0.1 fg mL−1 of the S1 subunit of the spike protein.
SARS-CoV-2 causes a different cytokine response compared to other cytokine storm-causing respiratory viruses in severely ill patients
Authors: Olbei Marton , Hautefort Isabelle , Modos Dezso , Treveil Agatha , Poletti Martina , Gul Lejla , Shannon-Lowe Claire D , Korcsmaros Tamas
Published: November 2020

Hyper-induction of pro-inflammatory cytokines, also known as a cytokine storm or cytokine release syndrome (CRS) is one of the key aspects of the currently ongoing SARS-CoV-2 pandemic. This process occurs when a large number of innate and adaptive immune cells are activated, and start producing pro-inflammatory cytokines, establishing an exacerbated feedback loop of inflammation. It is one of the factors contributing to the mortality observed with COVID-19 for a subgroup of patients. CRS is not unique to SARS-CoV-2 infection; it was prevalent in most of the major human coronavirus and influenza A subtype outbreaks of the past two decades (H5N1, SARS-CoV, MERS-CoV, H7N9). Here, we collected changing cytokine levels upon infection with the aforementioned viral pathogens through a comprehensive literature search. We analysed published patient data to highlight the conserved and unique cytokine responses caused by these viruses. A map of such responses could help specialists identify interventions that successfully alleviated CRS in different diseases and evaluate whether they could be used in COVID-19 cases.
Phe2vec: Automated Disease Phenotyping based on Unsupervised Embeddings from Electronic Health Records
Authors: De Freitas Jessica K. , Johnson Kipp W. , Golden Eddye , Nadkarni Girish N. , Dudley Joel T. , Bottinger Erwin P. , Glicksberg Benjamin S. , Miotto Riccardo
Published: November 2020

Objective

Robust phenotyping of patient data from electronic health records (EHRs) at scale is a current challenge in the field of clinical informatics. We introduce Phe2vec, an automated framework for disease phenotyping from EHRs based on unsupervised learning, and we assess its effectiveness against standard rule-based algorithms from the Phenotype KnowledgeBase (PheKB).

Materials and Methods

Phe2vec is based on pre-computing embeddings of medical concepts and patients’ longitudinal clinical history. Disease phenotypes are then derived from a seed concept and its neighbors in the embedding space. Patients are similarly linked to a disease if their embedded representation is close to the phenotype. We implemented Phe2vec using 49,234 medical concepts from structured EHRs and clinical notes from 1,908,741 patients in the Mount Sinai Health System. We assessed performance on ten diverse diseases that have a PheKB algorithm.

Results

Phe2vec phenotypes derived using Word2vec, GloVe, and Fasttext embeddings led to promising performance in disease definition and patient cohort identification with respect to phenotypes and cohorts obtained by PheKB. When comparing Phe2vec and PheKB disease patient cohorts head-to-head using chart review, Phe2vec performed on par or better in nine out of ten diseases in terms of positive predictive values.

Discussion

Phe2vec offers a solution to improve time-consuming phenotyping pipelines. Differently from other approaches in the literature, it is data-driven and unsupervised, can easily scale to any disease and was validated against widely adopted expert-based standards.

Conclusion

Phe2vec aims to optimize clinical informatics research by augmenting current frameworks to characterize patients by condition and derive reliable disease cohorts.
Sediment Selection: Range Expanding Fiddler Crabs are Better Burrowers Than Their Historic Range Counterparts
Authors: Wong Richard J , Roy Michael S. , Byrnes Jarrett E. K.
Published: November 2020

Species ranges are shifting in response to climate change. In New England saltmarshes, the mud fiddler crab,Minuca pugnax, is expanding north of Cape Cod, MA into the Gulf of Maine (GoM) due to warming waters. The burrowing lifestyle ofM. pugnaxmeans sediment compaction in saltmarshes may influence the ability for crabs to dig, with more compact soils being resilient to burrowing. Previous studies indicate that saltmarshes along the GoM have higher soil strength (i.e., compaction) relative to marshes south of Cape Cod. Together, physical characteristics and temperature of this habitat may be influencing the burrowing performance ofM. pugnax, and therefore the continuation of their northward range expansion into the GoM. To determine if compaction affects burrowing activity ofM. pugnaxin historical and range expanded populations, we conducted a controlled laboratory experiment. We manipulated soil compaction in standardized lab assays and measured crab burrowing performance with individuals collected from Nantucket (i.e., historical range) and the Plum Island Estuary (PIE, i.e., expanded range). We determined compaction negatively affected burrowing ability in crabs from both sites; however, crabs from PIE burrowed in higher soil compactions than Nantucket crabs. In addition, PIE crabs were more likely to burrow overall. We conclude that site level differences in compaction are likely altering burrowing behavior in the crab’s expanded range territory by way of phenotypic plasticity or rapid evolution. Our study demonstrates that non-temperature physical habitat traits can be as important as temperature in influencing climate driven range expansions.
Machine learning aided top-down proteomics on a microfluidic platform
Authors: Zhang Yuewen , Wright Maya A. , Saar Kadi L. , Challa Pavankumar , Morgunov Alexey S. , Peter Quentin A. E. , Devenish Sean , Dobson Christopher M. , Knowles Tuomas P.J.
Published: November 2020

The ability to determine the identity of specific proteins is a critical challenge in many areas of cellular and molecular biology, and in medical diagnostics. Here, we present a microfluidic protein characterisation strategy that within a few minutes generates a three-dimensional fingerprint of a protein sample indicative of its amino acid composition and size and, thereby, creates a unique signature for the protein. By acquiring such multidimensional fingerprints for a set of ten proteins and using machine learning approaches to classify the fingerprints, we demonstrate that this strategy allows proteins to be classified at a high accuracy, even though classification using a single dimension is not possible. Moreover, we show that the acquired fingerprints correlate with the amino acid content of the samples, which makes it is possible to identify proteins directly from their sequence without requiring any prior knowledge about the fingerprints. These findings suggest that such a multidimensional profiling strategy can lead to the development of novel method for protein identification in a microfluidic format.
The Network Analysis Profiler (NAP v2.0): A web tool for visual topological comparison between multiple networks
Authors: Koutrouli Mikaela , Theodosiou Theodosios , Iliopoulos Ioannis , Pavlopoulos Georgios A.
Published: November 2020

In this article we present the Network Analysis Profiler (NAP v2.0), a web tool to directly compare the topological features of multiple networks simultaneously. NAP is written in R and Shiny and currently offers both 2D and 3D network visualization as well as simultaneous visual comparisons of node- and edge-based topological features both as bar charts or as a scatterplot matrix. NAP is fully interactive and users can easily export and visualize the intersection between any pair of networks using Venn diagrams or a 2D and a 3D multi-layer graph-based visualization. NAP supports weighted, unweighted, directed, undirected and bipartite graphs and is available at:http://bib.fleming.gr:3838/NAP/. Its code can be found at:https://github.com/PavlopoulosLab/NAP
Data-driven streamflow modelling in ungauged basins: regionalizing random forest (RF) models
Authors: Araza Arnan , Hein Lars , Duku Confidence , Rawlins Maurice Andres , Lomboy Richard
Published: November 2020

Streamflow predictions in ungauged basins (PUB) has been geared towards data-driven methods, including the use of machine learning methods such as random forest (RF). Such methods are applied in PUB regionalization or the transfer of a streamflow model from gauged to ungauged (sub) basins or watersheds after grouping watersheds on similarity rules. Regionalized streamflow models are needed for tropical-mountainous regions like Luzon, Philippines - where gauged data is limited - but demands on streamflow modelling for water resources accounting and management are high. In 21 watersheds in Luzon, we “regionalize” RF streamflow models after grouping watersheds based on: a principal components analysis (PCA-clustered), by major river basins (basin-clustered), whole study area scale (one-clustered). Another method without watershed grouping (watershed-level) was also included and inter-compared. Among the four methods, goodness-of-fit evaluations revealed that PCA-clustered method was higher by at most 0.35 coefficient of determinationR2and 0.31 nash-sutcliffe efficiencyNSE, and the least bias in 8 of 12 monthly flows. These are attributed to the added-value of homogeneous watershed grouping, reflected by higher importance (to RF models), of static covariates from open and high-resolution data. Normalized errors from monthly streamflow showed a clear bias (least with the PCA-clustered metohd), linked to season and water management practices in the study area. Ungauged watersheds in the Philippines can effectively use streamflow models from gauged watersheds if they belong to the same cluster.

Key Points

Ungauged sub-basins (watersheds) can effectively use RF streamflow models from gauged watersheds if both belong to the same cluster.

Biophysical data from high-resolution open data are valuable: as basis for watershed clustering and as streamflow predictors to RF models.

The predicted streamflow from the RF models reflects seasonal deviations in streamflow caused by natural and man-made water regulation
Gene Expression Meta-Analysis Reveals Interferon-induced Genes
Authors: Park Amber , Harris Laura K.
Published: November 2020

Background

Severe Acute Respiratory Syndrome (SARS) corona virus (CoV) infections are a serious public health threat because of their pandemic-causing potential. This work analyzes mRNA expression data from SARS infections through meta-analysis of gene signatures, possibly identifying therapeutic targets associated with major SARS infections.

Methods

This work defines 37 gene signatures representing SARS-CoV, Middle East Respiratory Syndrome (MERS)-CoV, and SARS-CoV2 infections in human lung cultures and/or mouse lung cultures or samples and compares them through Gene Set Enrichment Analysis (GSEA). To do this, positive and negative infectious clone SARS (icSARS) gene panels are defined from GSEA-identified leading-edge genes between two icSARS-CoV derived signatures, both from human cultures. GSEA then is used to assess enrichment and identify leading-edge icSARS panel genes between icSARS gene panels and 27 other SARS-CoV gene signatures. The meta-analysis is expanded to include five MERS-CoV and three SARS-CoV2 gene signatures. Genes associated with SARS infection are predicted by examining the intersecting membership of GSEA-identified leading-edges across gene signatures.

Results

Significant enrichment (GSEA p<0.001) is observed between two icSARS-CoV derived signatures, and those leading-edge genes defined the positive (233 genes) and negative (114 genes) icSARS panels. Non-random significant enrichment (null distribution p<0.001) is observed between icSARS panels and all verification icSARSvsmock signatures derived from human cultures, from which 51 over- and 22 under-expressed genes are shared across leading-edges with 10 over-expressed genes already associated with icSARS infection. For the icSARSvsmock mouse signature, significant, non-random significant enrichment held for only the positive icSARS panel, from which nine genes are shared with icSARS infection in human cultures. Considering other SARS strains, significant, non-random enrichment (p<0.05) is observed across signatures derived from other SARS strains for the positive icSARS panel. Five positive icSARS panel genes, CXCL10, OAS3, OASL, IFIT3, and XAF1, are found across mice and human signatures regardless of SARS strains.

Conclusion

The GSEA-based meta-analysis approach used here identifies genes with and without reported associations with SARS-CoV infections, highlighting this approach’s predictability and usefulness in identifying genes that have potential as therapeutic targets to preclude or overcome SARS infections.
Mimicking the Human Tympanic Membrane: the Significance of Geometry
Authors: Anand Shivesh , Stoppe Thomas , Lucena Mónica , Rademakers Timo , Neudert Marcus , Danti Serena , Moroni Lorenzo , Mota Carlos
Published: November 2020

The human tympanic membrane (TM) captures sound waves reaching the outer ear from the environment and transforms them into mechanical motion. The successful transmission of these acoustic vibrations in varying frequency ranges is attributed to the structural architecture of the TM. However, a limited knowledge is available on the contribution of its discrete anatomical features, which is important to fabricate functional biomimetic TM replacements. This work synergizes theoretical and experimental approaches toward understanding the significance of geometry in tissue engineered TM scaffolds. Three test designs along with a plain control were chosen to decouple some of the dominant structural attributes, such as, the radial and circumferential alignment of the collagen fibrils.In silicomodels suggested a geometrical dependency of their mechanical and acoustical responses, where the presence of radially aligned fibers was observed to have a more prominent effect compared to their circumferential counterparts. Following which, a hybrid fabrication strategy combining electrospinning and additive manufacturing was optimized to manufacture hierarchical scaffolds within the dimensions of the native TM. The experimental characterizations conducted using macro-indentation and laser Doppler vibrometry were in line with the computational models. Finally, biological studies performed with human dermal fibroblasts and human mesenchymal stromal cells, revealed a favorable influence of scaffold hierarchy on cellular alignment and subsequent collagen deposition.

Abstract Figure

Graphical abstract.

Schematic diagram illustrating the overall flowchart of the work. 3D: three-dimensional; ES: electrospinning; FDM: fused deposition modeling; TM: tympanic membrane.
Non-coding variants upstream ofMEF2Ccause severe developmental disorder through three distinct loss-of-function mechanisms
Authors: Wright Caroline F , Quaife Nicholas M , Ramos-Hernández Laura , Danecek Petr , Ferla Matteo P , Samocha Kaitlin E , Kaplanis Joanna , Gardner Eugene J , Eberhardt Ruth Y , Chao Katherine R , Karczewski Konrad J , Morales Joannella , Balasubramanian Meena , Banka Siddharth , Gompertz Lianne , Kerr Bronwyn , Kirby Amelia , Lynch Sally A , Morton Jenny EV , Pinz Hailey , Sansbury Francis H , Stewart Helen , Zuccarelli Britton D ,   Genomics England Research Consortium, Cook Stuart A , Taylor Jenny C , Juusola Jane , Retterer Kyle , Firth Helen V , Hurles Matthew E , Lara-Pezzi Enrique , Barton Paul JR , Whiffin Nicola
Published: November 2020

Clinical genetic testing of protein-coding regions identifies a likely causative variant in only ∼35% of severe developmental disorder (DD) cases. We screened 9,858 patients from the Deciphering Developmental Disorders (DDD) study forde novomutations in the 5’untranslated regions (5’UTRs) of dominant haploinsufficient DD genes. We identify four single nucleotide variants and two copy number variants upstream ofMEF2Cthat cause DD through three distinct loss-of-function mechanisms, disrupting transcription, translation, and/or protein function. These non-coding variants represent 23% of disease-causing variants identified inMEF2Cin the DDD cohort. Our analyses show that non-coding variants upstream of known disease-causing genes are an important cause of severe disease and demonstrate that analysing 5’UTRs can increase diagnostic yield, even using existing exome sequencing datasets. We also show how non-coding variants can help inform both the disease-causing mechanism underlying protein-coding variants, and dosage tolerance of the gene.
ToRQuEMaDA: Tool for Retrieving Queried Eubacteria, Metadata and Dereplicating Assemblies
Authors: Léonard Raphaël R. , Leleu Marie , Van Vlierberghe Mick , Kerff Frédéric , Baurain Denis
Published: November 2020

TQMD is a tool which downloads, stores and produces lists of dereplicated prokaryotic genomes. It has been developed to counter the ever-growing number of prokaryotic genomes and their uneven taxonomic distribution. It is based on word-based alignment-free methods (k-mers), an iterative single-linkage approach and a divide-and-conquer strategy to remain both efficient and scalable. We studied the performance of TQMD by verifying the influence of its parameters and heuristics on the clustering outcome. We further compared TQMD to two other dereplication tools (dRep and Assembly-Dereplicator). Our results showed that TQMD is optimized to dereplicate at high taxonomic levels (phylum/class), whereas the other dereplication tools are optimized for lower taxonomic levels (species/strain), making TQMD complementary to the existing dereplicating tools. TQMD is available at .
A novel human fetal liver-derived model reveals that MLL-AF4 drives a distinct fetal gene expression program in infant ALL
Authors: Rice Siobhan , Jackson Thomas , Crump Nicholas T , Fordham Nicholas , Elliott Natalina , O’Byrne Sorcha , Inglott Sarah , Ladon Dariusz , Wright Gary , Bartram Jack , Ancliff Philip , Mead Adam J , Halsey Christina , Roberts Irene , Milne Thomas A , Roy Anindita
Published: November 2020

Although 90% of children with acute lymphoblastic leukemia (ALL) are now cured1, the prognosis of infant-ALL (diagnosis within the first year of life) remains dismal2. Infant-ALL is usually caused by a single genetic hit that arisesin utero: rearrangement of theMLL/KMT2Agene (MLL-r). This is sufficient to give rise to a uniquely aggressive and treatment-refractory leukemia compared to older children with the sameMLL-r3–5. The reasons for disparate outcomes in patients of different ages with identical driver mutations are unknown. This paper addresses the hypothesis that fetal-specific gene expression programs co-operate with MLL-AF4 to initiate and maintain infant-ALL. Using direct comparison of fetal and adult HSC and progenitor transcriptomes we identify fetal-specific gene expression programs in primary human cells. We show thatMLL-AF4-driven infant-ALL, but notMLL-AF4childhood-ALL, displays expression of fetal-specific genes. In a direct test of this observation, we find that CRISPR-Cas9 gene editing of primary human fetal liver cells to produce a t(4;11)/MLL-AF4translocation replicates the clinical features of infant-ALL and drives infant-ALL-specific and fetal-specific gene expression programs. These data strongly support the hypothesis that fetal-specific gene expression programs co-operate with MLL-AF4 to initiate and maintain the distinct biology of infant-ALL.