bluuebunny/crossref_metadata_2025 huggingface dataset:
Features of tumor texture influence surgery and outcome in intracranial meningioma
Authors: Sauvigny Thomas , Ricklefs Franz L , Hoffmann Lena , Schwarz Raphael , Westphal Manfred , Schmidt Nils Ole
Published: September 2020

Background

Texture-related factors such as consistency, vascularity, and adherence vary considerably in meningioma and are thought to be linked with surgical resectability and morbidity. However, data analyzing the true impact of meningioma texture on the surgical management is sparse.

Methods

Patients with intracranial meningioma treated between 08/2014 and 04/2018 at our institution were prospectively collected for demographics, clinical presentation, histology, and surgical treatment with related morbidity and extend of resection. Tumor characteristics were reported by the surgeon using a standardized questionnaire including items such as tumor consistency, homogeneity, vascularization, and adherence to surrounding neurovascular structure and analyzed for their impact surgical outcome parameters using univariate and logistic regression analyses.

Results

Tumor texture-related parameters of 300 patients (72.3% female) with meningioma were analyzed. Meningioma localizations were grouped into 3 different cohorts namely convexity, skull base, and posterior. Postoperative occurrence of a neurological deficit (transient 23.0%; permanent 6.1%) was associated with the duration of surgery (P = .001), size of tumor (P = .046), tumor vascularization (P = .015), and adherence to neurovascular structures (P = .002). Coherently, the duration of surgery (mean 230.99 ± 101.33 min) was associated with size of tumor (P < .0001), vascularization (P < .0001), and adherence (P < .0001). Similar associations were recapitulated in subgroup analyses of different tumor localizations. Noteworthy, tumor rigidity had no significant impact on time of surgery and neurological outcome.

Conclusions

Our analysis demonstrates that tumor texture has an impact on the surgical management of meningioma and provides data that tumor vascularization and adherence are significant factors influencing surgical outcome whereas the influence of tumor consistency has less impact than previously thought.
Asymmetric incentives and the new politics of monetary policy
Authors: Park Gene , Cheung Gabrielle , Katada Saori N
Published: September 2020

This article develops and tests a theory of asymmetric incentives to explain why politicians might be less motivated to confront deflation than inflation. Leveraging Japan as a least-likely crucial case, we analyze the conditions that lead legislators to take advantage of their power to summon central bankers for questioning. We find that even moderate inflation makes it more likely that legislators will summon central bankers compared to periods when the inflation rate is near zero. By contrast, deflation has either no effect or reduces the likelihood of summonses. We also find some evidence that unconventional monetary policies to combat deflation, specifically quantitative easing, are likely to invite greater legislative scrutiny. These findings have important policy implications. While deflation is widely viewed as pernicious and more difficult to exit than inflation, there are weaker incentives for politicians to address it.
New 2013 incidence peak in childhood narcolepsy: more than vaccination?
Authors: Zhang Zhongxing , Gool Jari K , Fronczek Rolf , Dauvilliers Yves , Bassetti Claudio L A , Mayer Geert , Plazzi Giuseppe , Pizza Fabio , Santamaria Joan , Partinen Markku , Overeem Sebastiaan , Peraita-Adrados Rosa , da Silva Antonio Martins , Sonka Karel , del Rio-Villegas Rafael , Heinzer Raphael , Wierzbicka Aleksandra , Young Peter , Högl Birgit , Manconi Mauro , Feketeova Eva , Mathis Johannes , Paiva Teresa , Canellas Francesca , Lecendreux Michel , Baumann Christian R , Lammers Gert Jan , Khatami Ramin
Published: September 2020

Increased incidence rates of narcolepsy type-1 (NT1) have been reported worldwide after the 2009–2010 H1N1 influenza pandemic (pH1N1). While some European countries found an association between the NT1 incidence increase and the H1N1 vaccination Pandemrix, reports from Asian countries suggested the H1N1 virus itself to be linked to the increased NT1 incidence. Using robust data-driven modeling approaches, that is, locally estimated scatterplot smoothing methods, we analyzed the number of de novo NT1 cases (n = 508) in the last two decades using the European Narcolepsy Network database. We confirmed the peak of NT1 incidence in 2010, that is, 2.54-fold (95% confidence interval [CI]: [2.11, 3.19]) increase in NT1 onset following 2009–2010 pH1N1. This peak in 2010 was found in both childhood NT1 (2.75-fold increase, 95% CI: [1.95, 4.69]) and adulthood NT1 (2.43-fold increase, 95% CI: [2.05, 2.97]). In addition, we identified a new peak in 2013 that is age-specific for children/adolescents (i.e. 2.09-fold increase, 95% CI: [1.52, 3.32]). Most of these children/adolescents were HLA DQB1*06:02 positive and showed a subacute disease onset consistent with an immune-mediated type of narcolepsy. The new 2013 incidence peak is likely not related to Pandemrix as it was not used after 2010. Our results suggest that the increased NT1 incidence after 2009–2010 pH1N1 is not unique and our study provides an opportunity to develop new hypotheses, for example, considering other (influenza) viruses or epidemiological events to further investigate the pathophysiology of immune-mediated narcolepsy.
COVID-19 conspiracy beliefs, health behaviors, and policy support
Authors: Earnshaw Valerie A , Eaton Lisa A , Kalichman Seth C , Brousseau Natalie M , Hill E Carly , Fox Annie B
Published: September 2020

Conspiracy theories have been proliferating during the COVID-19 pandemic. Evidence suggests that belief in conspiracy theories undermines engagement in pro-health behaviors and support for public health policies. Moreover, previous work suggests that inoculating messages from opinion leaders that expose conspiracy theories as false before people are exposed to them can help to prevent belief in new conspiracies. Goals of this study were to: (a) explore associations between COVID-19 conspiracy beliefs with SARS-CoV-2 vaccine intentions, cooperation with public health recommendations, and support for public health policies among U.S. adults and (b) investigate trusted sources of COVID-19 information to inform strategies to address conspiracy beliefs. A cross-sectional, online survey was conducted with 845 U.S. adults in April 2020. Data were analyzed using analyses of variance and multivariable regressions. One-third (33%) of participants believed one or more conspiracies about COVID-19. Participants who believed conspiracies reported that their intentions to vaccinate were 3.9 times lower and indicated less support for COVID-19 public health policies than participants who disbelieved conspiracies. There were no differences in cooperation with public health recommendations by conspiracy belief endorsement in the multivariable regression analysis. Although there were some key differences in trusted sources of COVID-19 information, doctor(s) were the most trusted source of information about COVID-19 overall with 90% of participants trusting doctor(s). Doctor(s) may play a role in addressing COVID-19 conspiracy theories before people are exposed to them to promote COVID-19 prevention efforts.
Outcomes of Severe Seronegative Hepatitis‐associated Aplastic Anemia
Authors: Kemme Sarah , Stahl Marisa , Brigham Dania , Lovell Mark A. , Nakano Taizo , Feldman Amy G. , Mack Cara
Published: September 2020

Objectives:

Hepatitis‐associated aplastic anemia (HAAA) is a potentially life‐threatening diagnosis without clear treatment guidelines. The goal of the study was to characterize the presentation, evaluation, histopathology, and outcomes of therapy in children with HAAA to guide future research and to develop standardized care guidelines for this rare disease.

Methods:

Retrospective chart review of 4 patients with HAAA who presented to Children's Hospital Colorado between 2016 and 2019 was conducted. Patient presentation, evaluation, bone marrow and liver pathology, interventions, and clinical course were collected. Immunohistochemistry of liver biopsies was performed.

Results:

We treated 4 patients with HAAA without liver failure. All had evidence of systemic hyperinflammation and CD8+ T cell predominant liver tissue infiltration. One had a genetic mutation predisposing him to immune‐mediated disease, but all other genetic testing was negative. In 3 of the 4 patients, hepatitis was poorly responsive to standard therapy with steroids, azathioprine, or tacrolimus; however, sustained biochemical remission of hepatitis was induced after more aggressive immunosuppressive therapies including Anti‐Thymocyte Globulin (ATG) at standard immunosuppressive therapy (IST) dosing for severe Aplastic Anemia (sAA). Two patients underwent hematopoietic stem cell transplant (HSCT); 1 as first line therapy and 1 for refractory sAA.

Conclusions:

We found that ATG‐based IST induced remission of hepatitis in patients with steroid‐refractory HAAA. This is also an appropriate initial treatment for severe Aplastic Anemia, though may not prevent the need for HSCT. We propose that equine ATG based IST at standard dosing regimen for sAA is a therapy that in select cases can be considered early on in the treatment course and could lead to a sustained remission of both hepatitis and sAA. This should be considered in collaboration with a pediatric hematologist.
Two‐step Testing for Clostridioides Difficile is Inadequate in Differentiating Infection From Colonization in Children
Authors: Parnell Jacob M. , Fazili Irtiqa , Bloch Sarah C. , Lacy D. Borden , Garcia‐Lopez Valeria A. , Bernard Rachel , Skaar Eric P. , Edwards Kathryn M. , Nicholson Maribeth R.
Published: September 2020

Objectives:

Recent Infectious Disease Society of America guidelines recommend multistep testing algorithms to diagnose Clostridioides difficile infection (CDI), including a combination of nucleic acid amplification‐based testing (NAAT) and toxin enzyme immunoassay (EIA). The use of these algorithms in children, including the ability to differentiate between C. difficile colonization and CDI, however, has not been evaluated.

Methods:

We prospectively enrolled asymptomatic pediatric patients with cancer, cystic fibrosis (CF), or inflammatory bowel disease (IBD) and obtained a stool sample for NAAT testing. If positive by NAAT (colonized), EIA was performed. In addition, children with symptomatic CDI who tested positive by NAAT via the clinical laboratory were enrolled, and EIA was performed on residual stool. A functional cell cytotoxicity neutralization assay (CCNA) was also applied to stool samples from both the colonized and symptomatic cohorts.

Results:

Of the 225 asymptomatic children enrolled in the study, 47 (21%) were colonized with C. difficile including 9/59 (15.5%) with cancer, 30/92 (32.6%) with CF, and 8/74 (10.8%) with IBD. An additional 41 children with symptomatic CDI were enrolled. When symptomatic and colonized children were compared, neither EIA positivity (44% vs 26%, P = 0.07) nor CCNA positivity (49% vs 45%, P = 0.70) differed significantly or were able to predict disease severity in the symptomatic cohort.

Conclusions:

Use of a multistep testing algorithm with NAAT followed by EIA failed to differentiate symptomatic CDI from asymptomatic colonization in our pediatric cohort. As multistep algorithms are moved into clinical care, the pediatric provider will need to be aware of their limitations.
A Novel Interdisciplinary Iterative Approach for Optimizing the Electronic Health Record to Improve Perioperative Efficiency
Authors: Franceschi Dido , Suarez Maritza M. , Ruiz Jose W. , Seo David , Merchant Nipun B.
Published: September 2020

Objective:

We present a holistic perioperative optimization approach led by a CI team with the goal to optimize the workflow within our EHR, improve operative room metrics and user satisfaction.

Summary of Background Data:

The EHR has become integral to perioperative care. Many approaches are utilized to improve performance including systems-based approaches, process redesign, lean methodology, checklists, root cause analysis, and parallel processing. Although most reports describe strategies improving day or surgery productivity, few include perioperative interventions to improve efficiencies.

Methods:

An interdisciplinary CI team consisting of clinicians, informatics specialists, and analysts spent 6 weeks assessing users and optimizing all perioperative areas (scheduling, day of surgery, postop discharge/admission). Elbow-to-elbow retraining and simultaneous content development was performed utilizing an Agile workflow process optimization with the Scrum framework. This iterative approach averaged 1 week from build to change implementation. Pre/post optimization surveys were sent.

Results:

Two hundred forty-two perioperative enhancements were completed. While most impacted documentation, all areas were enhanced including billing, reporting, registration, device integration, scheduling, central supply, and so on. FCOTS improved from <70% to >85% and total delay was halved. These parameters were consistently sustained for over 1 year after the 6-week optimization. While only 5% of pre-optimization users agreed to proficiency in the EHR system, this improved to 70% post-optimization. Furthermore, EHR confidence and acceptance improved from 40% to 90%.

Conclusions:

To improve workflow efficiency, all who contribute to the perioperative process must be assessed. This IT driven initiative resulted in improved FCOTS, perioperative workflows, and user satisfaction.
Shewanella algae and Microbulbifer elongatus from marine macro-algae – isolation and characterization of agar-hydrolysing bacteria
Authors: Kandasamy Keerthana Ponni , Subramanian Radhesh Krishnan , Srinivasan Radhakrishnan , Ragunath Sengali , Balaji G. , Gracy M. , Latha K.
Published: September 2020

Macro-algae are a good source of agar oligosaccharides, which can be obtained through bacterial enzymatic hydrolysis. The agarase enzyme secreted by the micro-organisms cleaves the cell wall of the algae and releases agar oligosaccharides as degradation products with various applications. Agarolytic bacteria were isolated from the marine algae Kappaphycus sp., and Sargassum sp., and studied for their agar-degrading properties. Among the 70 isolates, 2 isolates (A13 and Sg8) showed agarase activity in in vitro assays. The maximum agarolytic index was recorded in the isolate Sg8 (3.75 mm and 4.29 µg ml−1 agarase activity), followed by the isolate A13 (2.53 mm and 2.6 µg ml−1 agarase activity). Optimum agarase production of isolate Sg8 was observed at pH7 and at a temperature of 25 °C in 24–48 h, whereas for isolate A13 the optimum production was at pH7 and at a temperature of 37 °C in 48 h. The identities of the agarolytic isolates (Sg8 and A13) were confirmed based on microscopy, morphological, biochemical and molecular analysis as

Shewanella algae

[National Center for Biotechnology Information (NCBI) GenBank accession number MK121204.1] and

Microbulbifer elongatus

[NCBI GenBank accession number MK825484.1], respectively.
Methylococcus geothermalis sp. nov., a methanotroph isolated from a geothermal field in the Republic of Korea
Authors: Awala Samuel Imisi , Bellosillo Lorraine Araza , Gwak Joo-Han , Nguyen Ngoc-Loi , Kim So-Jeong , Lee Byoung-Hee , Rhee Sung-Keun
Published: September 2020

A Gram-stain-negative, aerobic, non-motile and coccoid methanotroph, strain IM1T, was isolated from hot spring soil. Cells of strain IM1Twere catalase-negative, oxidase-positive and displayed a characteristic intracytoplasmic membrane arrangement of type I methanotrophs. The strain possessed genes encoding both membrane-bound and soluble methane monooxygenases and grew only on methane or methanol. The strain was capable of growth at temperatures between 15 and 48 °C (optimum, 30–45 °C) and pH values between pH 4.8 and 8.2 (optimum, pH 6.2–7.0). Based on phylogenetic analysis of 16S rRNA gene and PmoA sequences, strain IM1Twas demonstrated to be affiliated to the genusMethylococcus. The 16S rRNA gene sequence of this strain was most closely related to the sequences of an uncultured bacterium clone FD09 (100 %) and a partially described culturedMethylococcussp. GDS2.4 (99.78 %). The most closely related taxonomically described strains wereMethylococcus capsulatusTexasT(97.92 %),Methylococcus capsulatusBath (97.86 %) andMethyloterricola oryzae73aT(94.21 %). Strain IM1Tshared average nucleotide identity values of 85.93 and 85.62 % withMethylococcus capsulatusstrains TexasTand Bath, respectively. The digital DNA–DNA hybridization value with the closest type strain was 29.90 %. The DNA G+C content of strain IM1Twas 63.3 mol% and the major cellular fatty acids were C16 : 0(39.0 %), C16 : 1 ω7c(24.0 %), C16 : 1 ω6c(13.6 %) and C16 : 1 ω5c(12.0 %). The major ubiquinone was methylene-ubiquinone-8. On the basis of phenotypic, genetic and phylogenetic data, strain IM1Trepresents a novel species of the genusMethylococcusfor which the nameMethylococcus geothermalissp. nov. is proposed, with strain IM1T(=JCM 33941T=KCTC 72677T) as the type strain.
Antrihabitans stalactiti gen. nov., sp. nov., a new member of the family Nocardiaceae isolated from a cave
Authors: Dong Lee Soon , Kim In Seop , Verbarg Susanne , Joung Yochan
Published: September 2020

Two Gram-stain-positive, strictly aerobic, non-spore-forming actinobacterial strains, designated YC2-7T and YC5-17, were isolated from the Yongcheondonggul (larva cave) in Jeju, Republic of Korea and their taxonomic ranks were examined by a polyphasic approach. The 16S rRNA gene tree showed that the novel isolates occupied an independent position separated from recognized genera of the family

Nocardiaceae

. In the 92 core gene-based phylogenomic analysis, strain YC2-7T was loosely associated with the type strain of Aldersonia kummingensis with 66.2 % average amino acid identity. The 16S rRNA gene sequence simairity between the isolate and members of the family

Nocardiaceae

was below 96.7 %. The cell-wall peptidoglycan was meso-diaminopimelic acid as a diagnostic diamino acid. Whole-cell sugars consisted of arabinose, galactose and glucose. The predominant menaquinone was MK-8(H4, ω-cycl). The major polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The cellular fatty acids consisted mainly of saturated and unsaturated components with small amounts of tuberculostearic acid. Mycolic acids of 52–58 carbon atoms were present. The DNA G+C content of the genome was 63.8 mol%. On the basis of combination of morphological and chemotaxonomic differences, in addition to phylogenetic distinctness, the novel isolates are considered to constitute members of a novel species of a new genus in the family

Nocardiaceae

, for which the name Antrihabitans stalactiti gen. nov., sp. nov. is proposed. The type strain is YC2-7T (=KACC 19965T=DSM 108733T).
CancerSiamese: one-shot learning for predicting primary and metastatic tumor types unseen during model training
Authors: Mostav Milad , Chiu Yu-Chiao , Chen Yidong , Huang Yufei
Published: September 2020

We consider cancer classification based on one single gene expression profile. We proposed CancerSiamese, a new one-shot learning model, to predict the cancer type of a query primary or metastatic tumor sample based on a support set that contains only one known sample for each cancer type. CancerSiamese receives pairs of gene expression profiles and learns a representation of similar or dissimilar cancer types through two parallel Convolutional Neural Networks joined by a similarity function. We trained CancerSiamese for both primary and metastatic cancer type predictions using samples from TCGA and MET500. Test results for differentN-way predictions yielded an average accuracy improvement of 8% and 4% over the benchmark 1-Nearest Neighbor (1-NN) classifier for primary and metastatic tumors, respectively. Moreover, we applied the guided gradient saliency map and feature selection to CancerSiamese to identify and analyze the marker-gene candidates for primary and metastatic cancers. Our work demonstrated, for the first time, the feasibility of applying one-shot learning for expression-based cancer type prediction when gene expression data of cancer types are limited and could inspire new and ingenious applications of one-shot and few-shot learning solutions for improving cancer diagnosis, treatment planning, and our understanding of cancer.
Inhibition of guanosine monophosphate synthetase (GMPS) blocks glutamine metabolism and prostate cancer growthin vitroandin vivo
Authors: Wang Qian , Guan Yi F. , Hancock Sarah E. , Wahi Kanu , van Geldermalsen Michelle , Zhang Blake K. , Pang Angel , Nagarajah Rajini , Mak Blossom , Horvath Lisa G. , Turner Nigel , Holst Jeff
Published: September 2020

Cancer cells increase their uptake of nutrients and metabolize them to provide the necessary building blocks for new cancer cells. Glutamine is a critical nutrient in cancer, however its contribution to purine metabolism in prostate cancer has not previously been determined. Guanosine monophosphate synthetase (GMPS) acts in thede novopurine biosynthesis pathway, utilizing a glutamine amide to synthesize the guanine nucleotide and replenish the purine pool in proliferative cancer cells. This study demonstrates that GMPS mRNA expression correlates with Gleason score in prostate cancer samples, while high GMPS expression was associated with decreased rates of overall and disease/progression-free survival. Pharmacological inhibition or knockdown of GMPS significantly decreased cell growth in both LNCaP and PC-3 prostate cancer cells. GMPS knockdown was rescued by addition of extracellular guanosine to the media, suggesting a direct effect on nucleotide synthesis. We utilized15N-(amide)-glutamine and U-13C5-glutamine metabolomics to dissect the pathways involved, and intriguingly, despite similar growth inhibition by GMPS knockdown, we show unique metabolic effects across each cell line. PC-3 cells showed a build-up of purine precursors, as well as activation of purine salvage pathways highlighted by significant increases in guanine, adenosine, inosine and cytosine. Both cell lines exhibited increased levels of pyrimidines and prioritized TCA cycle in distinct ways to produce increased aspartate, another important purine precursor. Using a PC-3 xenograft mouse model, tumor growth was also significantly decreased after GMPS knockdown. These data further highlight the importance of glutamine metabolism for prostate cancer cell growth and provide support for GMPS as a new therapeutic target in prostate cancer.
Massachusetts General Hospital Covid-19 Registry reveals two distinct populations of hospitalized patients by race and ethnicity
Authors: Bassett Ingrid V. , Triant Virginia A. , Bunda Bridget A. , Selvaggi Caitlin A. , Shinnick Daniel J. , He Wei , Lu Frances , Porneala Bianca C. , Cao Tingyi , Lubitz Steven A. , Meigs James B. , Hsu John , Foulkes Andrea S.
Published: September 2020

Objective

To evaluate differences by race/ethnicity in clinical characteristics and outcomes among hospitalized patients with Covid-19 at Massachusetts General Hospital (MGH).

Methods

The MGH Covid-19 Registry includes confirmed SARS-CoV-2-infected patients hospitalized at MGH and is based on manual chart reviews and data extraction from electronic health records (EHRs). We evaluated differences between White/Non-Hispanic and Hispanic patients in demographics, complications and 14-day outcomes among the N=866 patients hospitalized with Covid-19 from March 11, 2020 – May 4, 2020.

Results

Overall, 43% of patients hospitalized with Covid-19 were women, median age was 60.4 [IQR=(48.2, 75)], 11.3% were Black/non-Hispanic and 35.2% were Hispanic. Hispanic patients, representing 35.2% of patients, were younger than White/non-Hispanic patients [median age 51y; IQR=(40.6, 61.6) versus 72y; (58.0, 81.7) (p< 0.001)]. Hispanic patients were symptomatic longer before presenting to care (median 5 vs 3d, p=0.039) but were more likely to be sent home with self-quarantine than be admitted to hospital (29% vs 16%, p< 0.001). Hispanic patients had fewer comorbidities yet comparable rates of ICU or death (34% vs 36%). Nonetheless, a greater proportion of Hispanic patients recovered by 14 days after presentation (62% vs 45%, p< 0.001; OR=1.99, p=0.011 in multivariable adjusted model) and fewer died (2% versus 18%, p< 0.001).

Conclusions

Hospitalized Hispanic patients were younger and had fewer comorbidities compared to White/non-Hispanic patients; despite comparable rates of ICU care or death, a greater proportion recovered. These results have implications for public health policy and the design and conduct of clinical trials.
Sleep Disturbances, Anxiety, and Burnout during the COVID-19 Pandemic: a nationwide cross-sectional study in Brazilian Healthcare Professionals
Authors: Drager Luciano F. , Pachito Daniela V. , Moreno Claudia R.C. , Tavares Almir R. , Conway Silvia G. , Assis Márcia , Sguillar Danilo A. , Moreira Gustavo A. , Bacelar Andrea , Genta Pedro R.
Published: September 2020

Study objectives

To evaluate the impact of COVID-19 pandemic on sleep, anxiety, and Burnout in healthcare professionals.

Methods

A survey was distributed using social media and organizational emails to Brazilian active healthcare professionals during the COVID-19 outbreak. We explored potential associated factors including age, gender, occupation, workplace, work hours, income, previous infection with COVID-19, recent/current contact with COVID-19 patients, regional number of incident deaths due to COVID-19, anxiety, and burnout. We evaluated new-onset or previous insomnia worsening (primary outcome), sleep quality, and duration (secondary outcomes).

Results

A total of 4,384 health professionals from all regions of the country were included in the analysis (mean age: 44±12 years, 76% females, 53.8% physicians). Overall, 55.7% were assisting patients with COVID-19, and 9.2% had a previous COVID-19 infection. New-onset insomnia symptoms or previous insomnia worsening occurred in 41.4% of respondents in parallel to 13% (n=572) new pharmacological treatments for insomnia. Prevalent anxiety and burnout during the pandemic were observed in 44.2% and 21% of participants, respectively. Multivariate analyses showed that females (OR:1.756; 95% CI 1.487-2.075), weight change (decrease: OR:1.852; 95% CI 1.531-2.240; increase: OR:1.542; 95% CI 1.323-1.799), prevalent anxiety(OR:3.209; 95% CI 2.796-3.684), new-onset burnout (OR:1.986; 95% CI 1.677-2.352), family income reduction >30% (OR:1.366; 95% CI 1.140-1.636) and assisting patients with COVID-19 (OR:1.293; 95% CI 1.104-1.514) were independently associated with new-onset or worsening of previous insomnia.

Conclusions

We observed a huge burden of insomnia in healthcare professionals during the COVID-19 pandemic. In this scenario, dedicated approaches for sleep health are highly desirable.

Statement of Significance

Considering the stressful routine and risk of infection by COVID-19 among healthcare professionals, it is conceivable that sleep disturbances are significantly impaired during the pandemic. This nationwide survey conducted in Brazil found that 41.4% developed new-onset or worsening of previous insomnia symptoms. Moreover, 572 (13%) of respondents initiated pharmacological treatments for insomnia. Females, weight change, anxiety, Burnout development, family income reduction >30%, and recent/current care of patients with COVID-19 were independently associated with the development of insomnia or exacerbated previous insomnia symptoms. Considering the potential impact of insomnia on work performance/healthcare decisions as well as the potential long-term dependence of pharmacological treatments for insomnia, this study underscores the need for dedicated sleep and mental health programs for healthcare professionals.
LongGeneDB: a data hub for long genes
Authors: Moon Sohyun , Kim Yura , Naghavi Mariam , Zhao Jerry Yingtao
Published: September 2020

The human genome contains more than 4000 genes that are longer than 100 kb. These long genes require more time and resources to make a transcript than shorter genes do. Long genes have also been linked to various human diseases. Specific mechanisms are utilized by long genes to facilitate their transcription and co-transcriptional processes. This results in unique features in their multi-omics profiles. Although these unique profiles are important to understand long genes, a database that provides an integrated view and easy access to the multi-omics profiles of long genes does not exist. We leveraged the publicly accessible multi-omics data and systematically analyzed the genomic conservation, histone modifications, chromatin organization, tissue-specific transcriptome, and single cell transcriptome of 992 protein-coding genes that are longer than 200 kb in the mouse genome. We also examined the evolution history of their gene lengths in 15 species that belong to six Classes and 11 Orders. To share the multi-omics profiles of long genes, we developed a user-friendly and easy-to-use database, LongGeneDB (https://longgenedb.org), for users to search, browse, and download these profiles. LongGeneDB will be a useful data hub for the biomedical research community to understand long genes.
Tumors widely express hundreds of embryonic germline genes
Authors: Bruggeman Jan Willem , Irie Naoko , Lodder Paul , van Pelt Ans M.M. , Koster Jan , Hamer Geert
Published: September 2020

We have recently described a class of 756 genes that are widely expressed in cancer, while normally restricted to adult germ cells, referred to as germ cell cancer genes (GC-genes). We hypothesized that carcinogenesis involves reactivation of biomolecular processes and regulatory mechanisms that, under normal circumstances, are restricted to germline development. This would imply that cancer cells share gene expression profiles with primordial germ cells (PGCs). We therefore compared the transcriptomes of human PGCs (hPGCs) and PGC-like cells (PGCLCs) with 17 382 samples from 54 healthy somatic tissues (GTEx) and 11 003 samples from 33 tumor types (TCGA), and identified 672 GC-genes, expanding the known GC-gene pool by 387 genes (51%). Because GC-genes specific to the embryonic germline are not expressed in any adult tissue, targeting these in cancer treatment may result in fewer side effects than targeting conventional cancer/testis (CT) or GC-genes and may preserve fertility. We anticipate that our extended GC-dataset enables improved understanding of tumor development and may provide multiple novel targets for cancer treatment development.
Regeneration of lung epithelial cells by Fullerene C60nanoformulation: A possible treatment strategy for acute respiratory distress syndrome (ARDS)
Authors: Sinha Nabodita , Thakur Ashwani Kumar
Published: September 2020

Acute respiratory distress syndrome (ARDS) involves death of lung epithelial cells. ARDS is a leading reason behind mortality in respiratory infections. Here we show a proof-of-concept that a Fullerene nanoformulation can be used for the regeneration of cells treated with apoptosis-inducing molecules, suggeting its potential for ARDS therapy.
EEG Source Identification through Phase Space Reconstruction and Complex Networks
Authors: Soroush Morteza Zangeneh
Published: September 2020

Artifact elimination has become an inseparable part while processing electroencephalogram (EEG) in most brain computer interface (BCI) applications. Scientists have tried to introduce effective and efficient methods which can remove artifacts and also reserve desire information pertaining to brain activity. Blind source separation (BSS) methods have been receiving a great deal of attention in recent decades since they are considered routine and standard signal processing tools and are commonly used to eliminate artifacts and noise. Most studies, mainly EEG-related ones, apply BSS methods in preprocessing sections to achieve better results. On the other hand, BSS methods should be followed by a classifier in order to identify artifactual sources and remove them in next steps. Therefore, artifact identification is always a challenging problem while employing BSS methods. Additionally, removing all detected artifactual components leads to loss of information since some desire information related to neural activity leaks to these sources. So, an approach should be employed to suppress the artifacts and reserve neural activity. In this study, a new hybrid method is proposed to automatically separate and identify electroencephalogram (EEG) sources with the aim of classifying and removing artifacts. Automated source identification is still a challenge. Researchers have always made efforts to propose precise, fast and automated source verification methods. Reliable source identification has always been of great importance. This paper addresses blind source separation based on second order blind identification (SOBI) as it is reportedly one of the most effective methods in EEG source separation problems. Then a new method for source verification is introduced which takes advantage of components phase spaces and their dynamics. A new state space called angle space (AS) is introduced and features are extracted based on the angle plot (AP) and Poincare planes. Identified artifactual sources are eliminated using stationary wavelet transform (SWT). Simulated, semi-simulated and real EEG signals are employed to evaluate the proposed method. Different simulations are performed and performance indices are reported. Results show that the proposed method outperforms most recent studies in this subject.
Comprehensive interrogation of the ADAR2 deaminase domain for engineering enhanced RNA base-editing activity, functionality and specificity
Authors: Katrekar Dhruva , Palmer Nathan , Xiang Yichen , Saha Anushka , Meluzzi Dario , Mali Prashant
Published: September 2020

Adenosine deaminases acting on RNA (ADARs) can be repurposed to enable programmable RNA editing, however their exogenous delivery leads to transcriptome-wide off-targeting, and additionally, enzymatic activity on certain RNA motifs, especially those flanked by a 5’ guanosine is very low thus limiting their utility as a transcriptome engineering toolset. To address this, we explored comprehensive ADAR2 protein engineering via three approaches: First, we performed a novel deep mutational scan of the deaminase domain that enabled direct coupling of variants to corresponding RNA editing activity. Experimentally measuring the impact of every amino acid substitution across 261 residues, i.e. ~5000 variants, on RNA editing, revealed intrinsic domain properties, and also several mutations that greatly enhanced RNA editing. Second, we performed a domain-wide mutagenesis screen to identify variants that increased activity at5’-GA-3’ motifs, and discovered novel mutants that enabled robust RNA editing. Third, we engineered the domain at the fragment level to create split deaminases. Notably, compared to full-length deaminase overexpression, split-deaminases resulted in >1000 fold more specific RNA editing. Taken together, we anticipate this comprehensive deaminase engineering will enable broader utility of the ADAR toolset for RNA biotechnology and therapeutic applications.
Regarding theF-word: the effects of dataFilteringon inferred genotype-environment associations
Authors: Ahrens Collin W , Jordan Rebecca , Bragg Jason , Harrison Peter A , Hopley Tara , Bothwell Helen , Murray Kevin , Steane Dorothy A , Whale John W , Byrne Margaret , Andrew Rose , Rymer Paul D.
Published: September 2020

Genotype-environment association (GEA) methods have become part of the standard landscape genomics toolkit, yet, we know little about how to filter genotype-by-sequencing data to provide robust inferences for environmental adaptation. In many cases, default filtering thresholds for minor allele frequency and missing data are applied regardless of sample size, having unknown impacts on the results. These effects could be amplified in downstream predictions, including management strategies. Here, we investigate the effects of filtering on GEA results and the potential implications for adaptation to environment. Using empirical and simulated datasets derived from two widespread tree species to assess the effects of filtering on GEA outputs. Critically, we find that the level of filtering of missing data and minor allele frequency affect the identification of true positives. Even slight adjustments to these thresholds can change the rate of true positive detection. Using conservative thresholds for missing data and minor allele frequency substantially reduces the size of the dataset, lessening the power to detect adaptive variants (i.e. simulated true positives) with strong and weak strength of selections. Regardless, strength of selection was a good predictor for GEA detection, but even SNPs under strong selection went undetected. We further show that filtering can significantly impact the predictions of adaptive capacity of species in downstream analyses. We make several recommendations regarding filtering for GEA methods. Ultimately, there is no filtering panacea, but some choices are better than others, depending largely on the study system, availability of genomic resources, and desired objectives of the study.
Quantifying proximity, confinement, and interventions in disease outbreaks: a decision support framework for air-transported pathogens
Authors: Bond Tami C. , Bosco-Lauth Angela , Farmer Delphine K. , Francisco Paul W. , Pierce Jeffrey R. , Fedak Kristen M. , Ham Jay M. , Jathar Shantanu H. , VandeWoude Sue
Published: September 2020

The inability to communicate how infectious diseases are transmitted in human environments has triggered avoidance of interactions during the COVID-19 pandemic. We define a metric, Effective ReBreathed Volume (ERBV), that encapsulates how infectious pathogens transport in air. This measure distinguishes environmental transport from other factors in the chain of infection, thus allowing quantitative comparisons of the riskiness of different situations for any pathogens transported in air, including SARS-CoV-2. Particle size is a key factor in transport, removal onto surfaces, and elimination by mitigation measures, so ERBV is presented for a range of exhaled particle diameters: 1 μm, 10 μm, and 100 μm. Pathogen transport is enhanced by two separate but interacting effects: proximity and confinement. Confinement in enclosed spaces overwhelms proximity after 10–15 minutes for all but the largest particles. Therefore, we review plausible strategies to reduce the confinement effect. Changes in standard ventilation and filtration can reduce person-to-person transport of 1-μm particles (ERBV1) by 13-85% in residential and commercial situations. Deposition to surfaces competes with intentional removal for 10-μm and 100-μm particles, so the same interventions reduce ERBV10 by only 3-50%, and ERBV100 is unaffected. Determining transmission modes is critical to identify intervention effectiveness, and would be accelerated with prior knowledge of ERBV. When judiciously selected, the interventions examined can provide substantial reduction in risk, and the conditions for selection are identified. The framework of size-dependent ERBV supports analysis and mitigation decisions in an emerging situation, even before other infectious parameters are well known.
Protecting synapses from amyloid β-associated degeneration by manipulations of Wnt/planar cell polarity signaling
Authors: Feng Bo , Freitas Andiara E. , Tian Runyi , Lee Yeo Rang , Grewal Akumbir S. , Wang Jingyi , Zou Yimin
Published: September 2020

Synapse loss is an early event in Alzheimer’s disease and is thought to be associated with amyloid pathology and caused by Amyloid β (Aβ) oligomers. Whether and how Aβ oligomers directly target signaling pathways for glutamatergic synapse maintenance is unknown. Glutamatergic synapse development is controlled by the opposing functions of Celsr3 and Vangl2, core components of the Wnt/planar cell polarity (PCP) signaling pathway, functioning directly in the synapses. Celsr3 promotes synapse formation, whereas Vangl2 inhibits synapse formation. Here we show that oligomeric Aβ binds to Celsr3 and assists Vangl2 in disassembling synapses by disrupting the intercellular Celsr3/Frizzled3-Celsr3 complex, essential for PCP signaling. Together with Vangl2, a Wnt receptor, Ryk, is also required for Aβ oligomer-induced synapse loss in a mouse model of Alzheimer’s disease, 5XFAD, where conditionalRykknockout protected synapses and preserved cognitive function. Our study reveals a fine balance of Wnt/PCP signaling components in glutamatergic synapse maintenance and suggests that overproduced Aβ oligomers may lead to excessive synapse loss by tipping this balance. Together with previous reports that an inhibitor of Wnt/Ryk signaling, WIF1, is found reduced in Alzheimer’s disease patients, our results suggest that the imbalance of PCP signaling in these patients may contribute to synapse loss in Alzheimer’s disease and manipulating Wnt/PCP signaling may preserve synapses and cognitive function.
Near-Physiological-Temperature Serial Femtosecond X-ray Crystallography Reveals Novel Conformations of SARS-CoV-2 Main Protease Active Site for Improved Drug Repurposing
Authors: Durdagi Serdar , Dag Cagdas , Dogan Berna , Yigin Merve , Avsar Timucin , Buyukdag Cengizhan , Erol Ismail , Ertem Betul , Calis Seyma , Yildirim Gunseli , Orhan Muge D. , Guven Omur , Aksoydan Busecan , Destan Ebru , Sahin Kader , Besler Sabri O. , Oktay Lalehan , Shafiei Alaleh , Tolu Ilayda , Ayan Esra , Yuksel Busra , Peksen Ayse B. , Gocenler Oktay , Yucel Ali D. , Can Ozgur , Ozabrahamyan Serena , Olkan Alpsu , Erdemoglu Ece , Aksit Fulya , Tanisali Gokhan , Yefanov Oleksandr M. , Barty Anton , Tolstikova Alexandra , Ketawala Gihan K. , Botha Sabine , Dao E. Han , Hayes Brandon , Liang Mengning , Seaberg Matthew H. , Hunter Mark S. , Batyuk Alex , Mariani Valerio , Su Zhen , Poitevin Frederic , Yoon Chun Hong , Kupitz Christopher , Sierra Raymond G. , Snell Edward , DeMirci Hasan
Published: September 2020

The COVID19 pandemic has resulted in 25+ million reported infections and nearly 850.000 deaths. Research to identify effective therapies for COVID19 includes: i) designing a vaccine as future protection; ii) structure-based drug design; and iii) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determined two apo structures of Severe Acute Respiratory Syndrome CoronaVirus-2 main protease at ambienttemperature by Serial Femtosecond X-ray crystallography. We employed detailed molecular simulations of selected known main protease inhibitors with the structures and compared binding modes and energies. The combined structural biology and molecular modeling studies not only reveal the dynamics of small molecules targeting main protease but will also provide invaluable opportunities for drug repurposing and structure-based drug design studies against SARS-CoV-2.

One Sentence Summary

Radiation-damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological-temperature offer invaluable information for immediate drug-repurposing studies for the treatment of COVID19.
Untangling mechanisms of crude oil toxicity: linking gene expression, morphology and PAHs at two developmental stages in a cold-water fish
Authors: Sørhus Elin , Donald Carey E. , da Silva Denis , Thorsen Anders , Karlsen Ørjan , Meier Sonnich
Published: September 2020

Early life stages of fish are highly sensitive to crude oil exposure and thus, short term exposures during critical developmental periods could have detrimental consequences for juvenile survival. Here we administered crude oil to Atlantic haddock (Melanogrammus aeglefinus) in short term (3-day) exposures at two developmental time periods: before first heartbeat, from gastrulation to cardiac cone stage (early), and from first heartbeat to one day before hatching (late). A frequent sampling regime enabled us to determine immediate PAH uptake, metabolite formation and gene expression changes. In general, the embryotoxic consequences of an oil exposure were more severe in theearlyexposure animals. Oil droplet fouling in the highest doses resulted in severe cardiac and craniofacial abnormalities. Gene expression changes of Cytochrome 1 a,b,c and d (cyp1a,b,c,d), Bone morphogenetic protein 10 (bmp10), ABC transporter b1 (abcb1) and Rh-associated G-protein (rhag) were linked to PAH uptake, occurrence of metabolites of phenanthrene and developmental and functional abnormalities. We detected circulation-independent, oil-induced gene expression changes and separated phenotypes linked to proliferation, growth and disruption of formation events at early and late developmental stages. Our study gives an increased knowledge about developmentally dependent effects of crude oil toxicity. Thus, providing more knowledge and detail to new and several existing adverse outcome pathways of crude oil toxicity.

Graphical abstract

Highlights

Oil droplet fouling occurred in the whole water column and increased the oil toxicity.

Early exposure resulted in higher PAH uptake due to lower metabolism resulting in more severe abnormalities.

A rapid and circulation-indepenent regulation ofbmp10suggested a direct oil-induced effect on calcium homeostasis.

Expression ofrhagindicated a direct oil-induced effect on osmoregulatory cells and osmoregulation.

Severe eye abnormalities especially in the late exposure was linked to inappropriate overexpression ofcyp1bin the eyes.