bluuebunny/crossref_metadata_2025 huggingface dataset:
Improved Computed Tomography Contrast Injection Rates Through Implantable Chest Power Ports
Authors: Fielding James C. , Wagner-Bartak Nicolaus A. , Javadi Sanaz , Morani Ajaykumar C. , Ganeshan Dhakshinamoorthy , Ibarra-Rovira Juan J. , Liu Xinming , Jensen Corey T.
Published: September 2020

Objective

The aim of this study was to optimize chest port contrast injections using stepwise improvements.

Methods

Ex vivo injections were tested. Two hundred scans using power port injections were then evaluated.

Results

The highest flow rate was achieved using a 19G access needle, larger diameter tubing, and warmed contrast.

The mean injection rates in baseline and postimprovement groups were 2.7 ± 0.4 and 4.8 ± 0.4 mL/s, respectively (P < .0001).

Conclusion

Component optimization of the port apparatus can maximize contrast flow rates.
Differentiation of Multiple Myeloma and Lytic Bone Metastases: Histogram Analysis
Authors: Yildirim Mustafa , Baykara Murat
Published: September 2020

Objective

Metastasis and multiple myeloma are common malignant bone marrow lesions. It may be difficult to distinguish because of similar imaging findings. The purpose of this study was to determine the value of histogram analysis on the computed tomography imaging.

Methods

Twenty-three patients with primary tumor and 23 patients with multiple myeloma were included in the study. All patients had lytic bone lesions on the thorax and abdominal computed tomography scan with contrast. Multiple bone lesions of patients with primary tumor were accepted as metastasis. Multiple bone lesions of patients with multiple myeloma were accepted as multiple myeloma involvement. Histogram analysis was performed from lytic bone metastases and bone involvement of multiple myeloma. Results of both groups were compared.

Results

In histogram analysis, minimum, median, and maximum gray level parameters were found to be significantly higher in lytic bone metastases (P < 0.001).

Conclusion

Computed tomography histogram analysis can be considered as a method to be used in the differentiation of multiple myeloma and lytic bone metastases.
Do Not Judge an Ossicle by Its Size: Type 1 Ossicles Associated With Posterior Tibial Tendon Dysfunction
Authors: Gonzalez Felix M. , Singer Adam D. , Robertson Douglas D. , Chamieh Jad , Umpierrez Monica , Labib Sameh A.
Published: September 2020

Introduction

Patients with type II navicular ossicles have traditionally been considered to be symptomatic, whereas patients with type I and III bones are considered asymptomatic without additional relevant imaging findings. The main objective of this study is to investigate the association of type I os naviculare with clinical symptomology and magnetic resonance imaging findings in comparison to types II and III ossicles.

Methods

Three hundred nine subjects with accessory navicular bone types were identified, and their associations with focal navicular pain, pes planus alignment, ossicle or proximal navicular bone marrow edema pattern presence (BMEP), and posterior tibial tendon (PTT) sheath fluid distension were assessed. Fisher's exact test was used for categorical data and unpaired t tests for continuous data. Intraobserver and interobserver agreement was calculated.

Results

Overall, 28% (85/309) of type I, 57% (176/309) of type II, and 16% (48/309) of type III accessory bones had focal navicular pain (type I vs type II, P = 0.17; type III vs type II, P = 0.001). Thirty-two percent of type I, 38% type II, and 8% type III accessory bones had pes planus (type I vs II, P = 0.3; type III vs type II, P = 0.001). Nine percent of type I, 48% of type II, and 6% of type III accessory bones had BMEP (type I vs II, P < 0.0001; type III vs type II, P = 0.001). Thirty-three percent of type I, 42% of type II, and 6% of type III accessory bones had PTT intrasheath fluid (type I vs II, P = 0.16; type III vs type II, P = 0.001).

Conclusions

Symptomatic type I navicular ossicle patients demonstrate an increased tendency to present with early findings of PTT dysfunction and morphologic pes planus to a greater degree than previously recognized.

Level of Clinical Evidence: 3
Early Achievement of Enteral Nutrition Protein Goals by Intensive Care Unit Day 4 is Associated With Fewer Complications in Critically Injured Adults
Authors: Hartwell Jennifer L. , Cotton Ann , Wenos Chelsea D. , Timsina Lava , Zarzaur Ben L. , Rozycki Grace
Published: September 2020

Objective: We hypothesized that failure to achieve protein goals early in the critical care course via enteral nutrition is associated with increased complications.

Background:

Although robust randomized controlled trials are lacking, present data suggest that early, adequate nutrition is associated with improved outcomes in critically ill patients. Injured patients are at risk of accumulating significant protein debt due to interrupted feedings and intolerance.

Methods:

Critically injured adults who were unable to be volitionally fed were included in this retrospective review. Data collected included demographics, injury characteristics, number and types of operations, total prescribed and delivered protein and calories during the first 7 days of critical care admission, complications, and outcomes. Group-based trajectory modeling was applied to identify subgroups with similar feeding trajectories in the cohort.

Results:

There were 274 patients included (71.2% male). Mean age was 50.56  ± 19.76 years. Group-based trajectory modeling revealed 5 Groups with varying trajectories of protein goal achievement. Group 5 fails to achieve protein goals, includes more patients with digestive tract injuries (33%, P = 0.0002), and the highest mean number of complications (1.52, P = 0.0086). Group 2, who achieves protein goals within 4 days, has the lowest mean number of complications (0.62, P = 0.0086) and operations (0.74, P = 0.001).

Conclusions:

There is heterogeneity in the trajectory of protein goal achievement among various injury pattern Groups. There is a sharp decline in complication rates when protein goals are reached within 4 days of critical care admission, calling into question the application of current guidelines to healthy trauma patients to tolerate up to 7 days of nil per os status and further reinforcing recommendations for early enteral nutrition when feasible.
Taxonomic resolution of Stylonychia notophora (Alveolata, Ciliophora, Hypotricha) sensu Sapra and Dass 1970 using an integrative approach
Authors: Kaur Harpreet , Shashi  , Warren Alan , Negi Ram Krishan , Kamra Komal
Published: September 2020

The spirotrichean ciliate Stylonychia notophora has previously been recorded in India although the descriptions are lacking in detail. It has been suggested several times that the Indian population, S. notophora sensu Sapra and Dass, 1970 collected along the Delhi stretch of the River Yamuna, is identical to Tetmemena pustulata, but this has never been confirmed due to insufficient data for the former. The present study includes detailed descriptions (classical and molecular) of populations of Tetmemena isolated from six locations along the River Yamuna, India. These include four from the Delhi stretch including that from which Sapra and Dass, 1970 isolated their population of S. notophora. Due to the lack of a sufficiently detailed description, the taxonomic status of S. notophora sensu Sapra and Dass, 1970 was not clear. Comparisons among the populations isolated in the present study with previous descriptions of T. pustulata and S. notophora sensu Sapra and Dass, 1970 show only minor differences in morphometry, morphogenesis and in 18S rDNA sequences. The 18S rDNA sequences of all six populations had 99% similarity to both T. pustulata and S. notophora. These findings support the contention that S. notophora sensu Sapra and Dass, 1970 was misidentified and is a population of T. pustulata. This study supports the need for adopting an integrative approach based on morphological, morphogenetic and molecular data in order to understand species delimitation in ciliated protists.
Phylogenetic and genomic analysis reveals high genomic openness and genetic diversity of Clostridium perfringens
Authors: Feng Yuqing , Fan Xuezheng , Zhu Liangquan , Yang Xinyue , Liu Yan , Gao Shiguang , Jin Xiaolu , Liu Dan , Ding Jiabo , Guo Yuming , Hu Yongfei
Published: September 2020

Clostridium perfringens

is associated with a variety of diseases in both humans and animals. Recent advances in genomic sequencing make it timely to re-visit this important pathogen. Although the genome sequence of

C. perfringens

was first determined in 2002, large-scale comparative genomics with isolates of different origins is still lacking. In this study, we used whole-genome sequencing of 45

C

.

perfringens

isolates with isolation time spanning an 80‐year period and performed comparative analysis of 173 genomes from worldwide strains. We also conducted phylogenetic lineage analysis and introduced an openness index (OI) to evaluate the openness of bacterial genomes. We classified all these genomes into five lineages and hypothesized that the origin of

C. perfringens

dates back to ~80 000 years ago. We showed that the pangenome of the 173

C

.

perfringens

strains contained a total of 26 954 genes, while the core genome comprised 1020 genes, accounting for about a third of the genome of each isolate. We demonstrated that

C. perfringens

had the highest OI compared with 51 other bacterial species. Intact prophage sequences were found in nearly 70.0 % of

C. perfringens

genomes, while CRISPR sequences were found only in ~40.0 %. Plasmids were prevalent in

C. perfringens

isolates, and half of the virulence genes and antibiotic resistance genes (ARGs) identified in all the isolates could be found in plasmids. ARG-sharing network analysis showed that

C. perfringens

shared its 11 ARGs with 55 different bacterial species, and a high frequency of ARG transfer may have occurred between

C. perfringens

and species in the genera

Streptococcus

and

Staphylococcus

. Correlation analysis showed that the ARG number in

C. perfringens

strains increased with time, while the virulence gene number was relative stable. Our results, taken together with previous studies, revealed the high genome openness and genetic diversity of

C. perfringens

and provide a comprehensive view of the phylogeny, genomic features, virulence gene and ARG profiles of worldwide strains.
Chitin biosynthesis genes inDiaphorina citri, Asian citrus psyllid
Authors: Miller Sherry , Shippy Teresa D. , Tamayo Blessy , Hosmani Prashant S , Flores-Gonzalez Mirella , Mueller Lukas A , Hunter Wayne B , Brown Susan J , D’elia Tom , Saha Surya
Published: September 2020

The polysaccharide chitin is critical for the formation of many insect structures, including the exoskeleton, and is required for normal development. Here we report the annotation of three genes from the chitin synthesis pathway in the Asian citrus psyllid,Diaphorina citri(Hemiptera: Liviidae), the vector of Huanglongbing (citrus greening disease). Most insects have two chitin synthase (CHS) genes but, like other hemipterans,D. citrihas only one. In contrast,D. citriis unusual among insects in having two UDP-N-acetylglucosamine pyrophosphorylase (UAP) genes. One of theD. citriUAP genes is broadly expressed, while the other is expressed predominantly in males. Our work helps pave the way for potential utilization of these genes as pest control targets to reduce the spread of Huanglongbing.
First phylogenetic analysis of Malian SARS-CoV-2 sequences provide molecular insights into the genomic diversity of the Sahel region
Authors: Kouriba B , Dürr A , Rehn A , Sangaré AK , Traoré BY , Bestehorn-Willmann MS , Ouedraogo WLJ , Heitzer A , Sogodogo E , Maiga A , Walter MC , Zimmermann F , Wölfel R , Antwerpen MH
Published: September 2020

We are currently facing a pandemic of COVID-19, caused by a spillover from an animal-originating coronavirus to humans occuring in the Wuhan region, China, in December 2019. From China the virus has spread to 188 countries and regions worldwide, reaching the Sahel region on the 2nd of March 2020. Since whole genome sequencing (WGS) data is very crucial to understand the spreading dynamics of the ongoing pandemic, but only limited sequence data is available from the Sahel region to date, we have focused our efforts on generating the first Malian sequencing data available. Screening of 217 Malian patient samples for the presence of SARS-CoV-2 resulted in 38 positive isolates from which 21 whole genome sequences were generated. Our analysis shows that both, the early A (19B) and the fast evolving B (20A/C) clade, are present in Mali indicating multiple and independent introductions of the SARS-CoV-2 to the Sahel region.
Genetic Associations with Age at Dementia Onset in thePSEN1 E280AColombian Kindred
Authors: Cochran J. Nicholas , Acosta-Uribe Juliana , Esposito Bianca T. , Madrigal Lucia , Aguillón David , Giraldo Margarita M. , Taylor Jared W. , Bradley Joseph , Fulton-Howard Brian , Andrews Shea J. , Acosta-Baena Natalia , Alzate Diana , Garcia Gloria P. , Piedrahita Francisco , Lopez Hugo E. , Anderson Ashlyn G. , Rodriguez-Nunez Ivan , Roberts Kevin ,   Dominantly Inherited Alzheimer Network, Absher Devin , Myers Richard M. , Beecham Gary W. , Reitz Christiane , Rizzardi Lindsay F. , Fernandez Maria Victoria , Goate Alison M. , Cruchaga Carlos , Renton Alan E. , Lopera Francisco , Kosik Kenneth S.
Published: September 2020

INTRODUCTION

Genetic associations with Alzheimer’s disease (AD) age at onset (AAO) could reveal genetic variants with therapeutic applications. We present a large Colombian kindred with autosomal dominant AD (ADAD) as a unique opportunity to discover AAO genetic associations.

METHODS

A genetic association study was conducted for ADAD dementia AAO in 340 individuals with thePSEN1 E280Amutation via TOPMed array imputation. Replication was assessed in two ADAD cohorts, one sporadic EOAD study, and four late onset AD studies.

RESULTS

13 variants hadp<1×10−7orp<1×10−5with replication including three independent loci with candidate associations with clusterin including nearCLU. Other suggestive associations were identified in or nearHS3ST1, HSPG2, ACE, LRP1B, TSPAN10, andTSPAN14.

DISCUSSION

Variants with suggestive associations with AAO were associated with biological processes including clusterin, heparin sulfate and amyloid processing. The detection of these effects in the presence of a strong mutation for ADAD reinforce their potentially impactful role.
Suitability of Two Rapid Lateral Flow Immunochromatographic Assays for Predicting SARS-CoV-2 Neutralizing Activity of Sera
Authors: Valdivia Arantxa , Torres Ignacio , Latorre Víctor , Francés-Gómez Clara , Ferrer Josep , Forqué Lorena , Costa Rosa , de la Asunción Carlos Solano , Huntley Dixie , Gozalbo-Rovira Roberto , Buesa Javier , Giménez Estela , Rodríguez-Díaz Jesús , Geller Ron , Navarro David
Published: September 2020

Purpose

Assessment of commercial SARS-CoV-2 immunoassays for their capacity to provide reliable information on sera neutralizing activity is an emerging need. We evaluated the performance of two commercially-available lateral flow immunochromatographic assays (LFIC) (Wondfo SARS-CoV-2 Antibody test and the INNOVITA 2019-nCoV Ab test) in comparison with a SARS-CoV-2 neutralization pseudotyped assay for COVID-19 diagnosis in hospitalized patients, and investigate whether the intensity of the test band in LFIC associates with neutralizing antibody (NtAb) titers.

Patients and Methods

Ninety sera were included from 51 patients with moderate to severe COVID-19. A green fluorescent protein (GFP) reporter-based pseudotyped neutralization assay (vesicular stomatitis virus coated with SARS-CoV-2 spike protein) was used. Test line intensity was scored using a 4-level scale (0 to 3+).

Results

Overall sensitivity of LFIC assays was 91.1% for the Wondfo SARS-CoV-2 Antibody test, 72.2% for the INNOVITA 2019-nCoV IgG, 85.6% for the INNOVITA 2019-nCoV IgM and 92.2% for the NtAb assay. Sensitivity increased for all assays in sera collected beyond day 14 after symptoms onset (93.9%, 79.6%,93.9% and 93.9%, respectively). Reactivities equal to or more intense than the positive control line (≥2+) in the Wondfo assay had a negative predictive value of 100% and a positive predictive value of 96.4% for high NtAb50titers (≥1/160).

Conclusions

Our findings support the use of LFIC assays evaluated herein, particularly the Wondfo test, for COVID-19 diagnosis. We also find evidence that these rapid immunoassays can be used to predict high SARS-CoV-2-S NtAb50titers.
Dysbiosis in metabolic genes of the gut microbiomes of patients with an ileo-anal pouch resembles that observed in Crohn’s Disease
Authors: Dubinsky Vadim , Reshef Leah , Rabinowitz Keren , Yadgar Karin , Godny Lihi , Zonensain Keren , Wasserberg Nir , Dotan Iris , Gophna Uri
Published: September 2020

Background

Crohn’s disease (CD), ulcerative colitis (UC) and pouchitis are multifactorial and chronic inflammatory diseases of the gastrointestinal tract, termed together as inflammatory bowel diseases (IBD). Pouchitis develops in former patients with UC after total proctocolectomy and ileal pouch-anal anastomosis (“pouch surgery”) and is characterized by inflammation of the previously normal small intestine comprising the pouch. It has been extensively shown that broad taxonomic and functional alterations (“dysbiosis”) occur in the gut microbiome of patients with IBD. However, the extent to which microbial dysbiosis in pouchitis resembles that of CD or UC has not been investigated in-depth, and the pathogenesis of pouchitis largely remains unknown.

Results

In this study we collected 250 fecal metagenomes from 75 patients with a pouch, including both non-inflamed (normal pouch) and inflamed (pouchitis) phenotypes, and compared them to publicly available metagenomes of patients with CD (n=88), and UC (n=76), as well as healthy controls (n=56). Patients with pouchitis presented the highest level of dysbiosis compared to other IBD phenotypes based on species, metabolic pathways and enzyme profiles, and their level of dysbiosis was correlated with intestinal inflammation. In patients with pouchitis, the microbiome mucin degradation potential was lower, but was accompanied by an enrichment of Ruminococcus gnavus strains encoding specific mucin-degrading glycoside hydrolases, which might be pro-inflammatory. Butyrate and secondary bile acids producers were decreased in all IBD phenotypes and were especially low in pouchitis. Butyrate synthesis genes were positively correlated with total dietary fiber intake. Patients with pouchitis harbored more facultative anaerobic bacteria encoding enzymes involved in oxidative stress response, suggesting high oxidative stress during pouch inflammation. Finally, we have developed enzymes-based classifiers that can distinguish between patients with a normal pouch and pouchitis with an area under the curve of 0.91.

Conclusions

We propose that the non-inflamed pouch is already dysbiotic (function- and species-wise) and microbially is more similar to CD than to UC. Our study reveals microbial functions that underlie the pathogenesis of pouchitis and suggests bacterial groups and functions that could be targeted for nutritional intervention to attenuate or prevent small intestinal inflammation present in pouchitis and CD.
More than words: Extra-Sylvian neuroanatomic networks support indirect speech act discourse comprehension in behavioral variant frontotemporal dementia
Authors: Healey Meghan , Howard Erica , Ungrady Molly , Olm Christopher , Nevler Naomi , Irwin David J. , Grossman Murray
Published: September 2020

Indirect speech acts— responding “I forgot to wear my watch today” to someone who asked for the time — are ubiquitous in daily conversation, but are understudied in current neurobiological models of language. To comprehend an indirect speech act like this one, listeners must not only decode the lexical-semantic content of the utterance, but also make a pragmatic, bridging inference. This inference allows listeners to derive the speaker’s true, intended meaning—in the above dialogue, for example, that the speaker cannot provide the time. In the present work, we address this major gap by asking non-aphasic patients with behavioral variant frontotemporal dementia (bvFTD, n=21) and brain-damaged controls with amnestic mild cognitive impairment (MCI, n=17) to judge simple question-answer dialogues of the form: “Do you want some cake for dessert?” “I’m on a very strict diet right now”, and relate the results to structural and diffusion MRI. Accuracy and reaction time results demonstrate that subjects with bvFTD, but not MCI, are selectively impaired in indirect relative to direct speech act comprehension, due in part to their social and executive limitations, and performance is related to caregivers’ judgment of communication efficacy. MRI imaging associates the observed impairment in bvFTD to cortical thinning not only in traditional language-associated regions, but also in fronto-parietal regions implicated in social and executive cerebral networks. Finally, diffusion tensor imaging analyses implicate white matter tracts in both dorsal and ventral projection streams, including superior longitudinal fasciculus, frontal aslant, and uncinate fasciculus. These results have strong implications for updated neurobiological models of language, and emphasize a core, language-mediated social disorder in patients with bvFTD.
Epidemiological characterization of symptomatic and asymptomatic COVID-19 cases and positivity in subsequent RT-PCR tests in the United Arab Emirates
Authors: Al-Rifai Rami H. , Acuna Juan , Al Hossany Farida Ismail , Aden Bashir , Al Memari Shamma Abdullah , Al Mazrouei Shereena Khamis , Ahmed Luai A.
Published: September 2020

Background

The COVID-19 RT-PCR confirmed cases could be symptomatic or asymptomatic. In the United Arab Emirates (UAE), the identified COVID-19 RT-PCR confirmed cases are yet to be characterized. In this study, wecharacterized the first cohort of COVID-19 RT-PCR confirmed cases reported in the Abu Dhabi Emirate, UAE, according to symptomatic state, and identified factors associated with the symptomatic state. Also, the strength of association between the symptomatic state and testing positive in three subsequent RT-PCR testing rounds was examined and quantified.

Method

We analyzed data collected from the first cohort of the RT-PCR confirmed COVID-19 cases reported to the health authorities in the Abu Dhabi Emirate – UAE between February 28 and April 08, 2020. Self-reported sociodemographic, working status, travel history, and chronic comorbidities of 1,249 COVID-19 cases were analyzed according to symptomatic state (symptomatic and asymptomatic). After the first RT-PCR confirmatory test, the results of three subsequent testing rounds were also analyzed.

Results

A total of 791 confirmed cases with a mean age of 35.6 years±12.7 (range: 1-81 years) and information on symptomatic state were analyzed. Nearly, 56.0% were asymptomatic cases. The most frequent two symptoms were fever (58.0%) and cough (41.0%). The mean age of symptomatic (36.3 year ±12.6SD) was significantly higher than that of asymptomatic cases (34.5 year ±12.7SD). Compared to non-working populations, working in public places (aOR, 1.76, 95% CI: 1.11–2.80), healthcare settings (aOR, 2.09, 95% CI: 1.01–4.31), or in aviation and tourism sector (aOR, 2.24, 95% CI: 1.14–4.40), were independently associated with symptomatic state. Reporting at least one chronic comorbidity was also associated with symptomatic cases (aOR, 1.76, 5% CI: 1.03-3.01). Compared to asymptomatic, symptomatic COVID-19 cases had consistent odds of two or more of testing positive to COVID-19 in three subsequent testing rounds.

Conclusions

A substantial proportion of the diagnosed COVID-19 cases in the Abu Dhabi Emirate was asymptomatic. Quarantine of asymptomatic cases along with prevention measures and raising awareness of populations working in high-risk settings is warranted. Further follow up research is needed to understand viral clearance and clinical outcomes according to the symptomatic state of the COVID-19 cases.
Combinations of PCR and isothermal amplification techniques are suitable for fast and sensitive detection of SARS-CoV-2 viral RNA
Authors: Varlamov Dmitriy A. , Blagodatskikh Konstantin A. , Smirnova Evgenia V. , Kramarov Vladimir M. , Ignatov Konstantin B.
Published: September 2020

The newly identified coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), causes coronavirus disease 2019 (COVID-19) and has affected over 25 million people worldwide as of 31 August 2020. To aid in the development of diagnostic kits for rapid and sensitive detection of the virus, we evaluated a combination of polymerase chain reaction (PCR) and isothermal nucleic acid amplification techniques. Here, we compared conventional PCR and loop-mediated isothermal amplification (LAMP) methods with hybrid techniques such as polymerase chain displacement reaction (PCDR) and a newly developed PCR-LAMP method. We found that the hybrid methods demonstrated higher sensitivity and assay reaction rates than those of the classic LAMP and PCR techniques and can be used to for SARS-CoV-2 detection. The proposed methods based on the modern hybrid amplification techniques markedly improve virus detection and, therefore, can be extremely useful in the development of new diagnostic kits.
Body mass index and heart failure risk: a cohort study in 1.5 million individuals and Mendelian randomisation analysis
Authors: Lumbers R. Thomas , Katsoulis Michail , Henry Albert , Mordi Ify , Lang Chim , Hemingway Harry , Langenberg Claudia , Holmes Michael V. , Sattar Naveed
Published: September 2020

Aims

Elevated body mass index (BMI) is a known risk factor for heart failure (HF), however, the underlying mechanisms are incompletely understood. The aim of this study was to investigate the role of common HF risk factors as potential mediators.

Methods and Results

Electronic health record data from primary care, hospital admissions and death registrations in England were used to perform an observational analysis. Data for 1.5 million individuals aged 18 years or older, with BMI measurements and free from heart failure at baseline, were included between 1998 and 2016. Cox models were used to estimate the association between BMI and HF with and without adjustment for atrial fibrillation (AF), diabetes mellitus (DM), coronary heart disease (CHD), and hypertension (HTN). Univariable and multivariable two-sample Mendelian randomisation was performed to estimate causal effects.

Among non-underweight individuals, BMI was positively associated with HF with a 1-SD (∼ 4.8kg/m2) higher BMI associated with a hazard ratio (HR) of 1.31 (95% confidence interval [CI] 1.30, 1.32). Genetically predicted BMI yielded a causal odds ratio (OR) of 1.64 per 4.8 kg/m2BMI (95% CI 1.58, 1.70) which attenuated by 41% (to OR of 1.38 (95% CI 1.31 - 1.45), when simultaneously accounting for AF, DM, CHD and SBP.

Conclusion

About 40% of the excess risk of HF due to adiposity is driven by SBP, AF, DM and CHD. These findings highlight the importance of the prevention and treatment of excess adiposity and downstream HF risk factors to prevent HF, even in people in whom the above risk factors are well managed.

One-sentence summary

This study of the role of excess adiposity as a risk factor for HF, including an observational analysis of measured BMI 1.5 million individuals and multivariable MR analysis of genetically elevated BMI, provides evidence that adiposity is causally associated with HF, with approximately 40% of the effect being mediated by conventional risk pathways.

Graphical abstract
Coarse Raman and optical diffraction tomographic imaging enable label-free phenotyping of isogenic breast cancer cells of varying metastatic potential
Authors: Paidi Santosh Kumar , Shah Vaani , Raj Piyush , Glunde Kristine , Pandey Rishikesh , Barman Ishan
Published: September 2020

Identification of the metastatic potential represents one of the most important tasks for molecular imaging of cancer. While molecular imaging of metastases has witnessed substantial progress as an area of clinical inquiry, determining precisely what differentiates the metastatic phenotype has proven to be more elusive underscoring the need to marry emerging imaging techniques with tumor biology. In this study, we utilize both the morphological and molecular information provided by 3D optical diffraction tomography and Raman spectroscopy, respectively, to propose a label-free route for optical phenotyping of cancer cells at single-cell resolution. By using an isogenic panel of cell lines derived from MDA-MB-231 breast cancer cells that vary in their metastatic potential, we show that 3D refractive index tomograms can capture subtle morphological differences among the parental, circulating tumor cells, and lung metastatic cells. By leveraging the molecular specificity of Raman spectroscopy, we demonstrate that coarse Raman microscopy is capable of rapidly mapping a sufficient number of cells for training a random forest classifier that can accurately predict the metastatic potential of cells at a single-cell level. We also leverage multivariate curve resolution – alternating least squares decomposition of the spectral dataset to demarcate spectra from cytoplasm and nucleus, and test the feasibility of identifying metastatic phenotypes using the spectra only from the cytoplasmic and nuclear regions. Overall, our study provides a rationale for employing coarse Raman mapping to substantially reduce measurement time thereby enabling the acquisition of reasonably large training datasets that hold the key for label-free single-cell analysis and, consequently, for differentiation of indolent from aggressive phenotypes.
Stretching of the retinal pigment epithelium contributes to zebrafish optic cup morphogenesis
Authors: Moreno-Mármol Tania , Ledesma-Terrón Mario , Tabanera Noemí , Martin-Bermejo María Jesús , Cardozo Marcos J , Cavodeassi Florencia , Bovolenta Paola
Published: September 2020

The vertebrate eye primordium consists of a pseudostratified neuroepithelium, the optic vesicle (OV), in which cells acquire neural retina or retinal pigment epithelium (RPE) fates. As these fates arise, the OV assumes a cup-shape, influenced by mechanical forces generated within the neural retina. Whether the RPE passively adapts to retinal changes or actively contributes to OV morphogenesis remains unexplored. Here, we generated a zebrafish Tg(E1-bhlhe40:GFP) line to track RPE morphogenesis and interrogate its participation in OV folding. We show that, in virtual absence of proliferation, RPE cells stretch into a squamous configuration, thereby matching the curvature of the underlying retina. Forced proliferation and localized interference with the RPE cytoskeleton disrupt its stretching and OV folding. Thus, extreme RPE flattening and accelerated differentiation are efficient solutions adopted by fast-developing species to enable timely optic cup formation. This mechanism differs in amniotes, in which proliferation largely drives RPE expansion with a much-reduced need of cell flattening.
Effects of a 50-Hz electric field on sleep quality and life span mediated by ultraviolet (UV)-A/blue light photoreceptor CRYPTOCHROME inDrosophila melanogaster
Authors: Kawasaki Haruhisa , Okano Hideyuki , Nedachi Takaki , Nakagawa-Yagi Yuzo , Hara Akikuni , Ishida Norio
Published: September 2020

Although electric fields (EF) exert beneficial effects on animal wound healing and differentiation, the molecular mechanisms of these effects have remained unclear for years. Therefore, we aimed to elucidate the molecular mechanisms underlying these effects inDrosophila melanogasteras a genetic animal model. The sleep quality of wild-type (WT) flies was improved by exposure to a 50-Hz (35 kv/m) constant electric field during the daytime, but not during the night. This effect was undetectable inCryptochromemutant (Cryb) flies. Exposure to a 50-Hz electric field under low nutrient conditions elongated the lifespan of male and female WT flies by ~18%, but not of three diferrentCrymutants andCryRNAi strains. Metabolome analysis indicated that the adenosine triphosphate (ATP) content was 5-fold higher in intact WT thanCrygene mutant strains exposed to an electric field.

A putative magnetoreceptor protein and UV-A/blue light photoreceptor, CRYPTOCHROME (CRY) is involved in electric field receptors in animals. The present findings constitute hitherto unknown genetic evidence of a CRY-based system that is electric-field sensitive in animals.
NANOS2 suppresses the cell cycle by repressing mTORC1 activators in embryonic male germ cells
Authors: Shimada Ryuki , Koike Hiroko , Hirano Takamasa , Saga Yumiko
Published: September 2020

During murine germ cell development, male germ cells enter the mitotically arrested G0 stage, which is an initial step of sexually dimorphic differentiation. The male specific RNA-binding protein NANOS2 has a key role in suppressing the cell cycle in germ cells. However, the detailed mechanism of how NANOS2 regulates the cell cycle remains unclear. Using single-cell RNA sequencing (scRNA-seq), we extracted the cell cycle state of each germ cell in wild-type andNanos2-KO testes, and revealed thatNanos2expression starts in mitotic cells and induces mitotic arrest. We also found that NANOS2 and p38 MAPK work in parallel to regulate the cell cycle, suggesting that several different cascades are involved in the induction of cell cycle arrest. Furthermore, we identifiedRheb, a regulator of mTORC1, andPtmaas possible targets of NANOS2. We propose that the repression of the cell cycle is a primary function of NANOS2 and that it is mediated via the suppression of mTORC1 activity by repressingRhebin a post-transcriptional manner.
ATPIF1 inactivation promotes antitumor immunity through metabolic reprogramming of CD8+T cells
Authors: Zhong Genshen , Wang Ying , Zhang Jiaojiao , Wang Yichun , Li Yuan , Guan Yaya , Shen Shuang , Zhang Xiaoying , Cao Xinyu , Wu Minna , Zhang Zhongxin , Shi Ming , Lou Yunwei , Liang Yinming , Wang Hui , Ye Jianping
Published: September 2020

Induction of CD8+T cell activity is a promising strategy in the cancer immunotherapy. In this study, we identified ATP synthase inhibitory factor 1 (ATPIF1) as a potential target in the induction of CD8+T cell immunity against tumor. Inactivation of ATPIF1 gene in mice promoted the antitumor activity of CD8+T cells leading to suppression of tumor growth of B16 melanoma and Lewis lung cancer. The phenotype was abolished by deletion of CD8+T cells in the ATPIF1-KO mice. The tumor infiltrating CD8+T cells exhibited strong activities in the proliferation, effector and memory as revealed by the single cell RNA sequencing results of CD45+tumor infiltrating lymphocytes (TILs) isolated from the tumors. The CD8+T cells expressed more antitumor makers in the tumor microenvironment and in coculture with the tumor cells. The cells had a higher level of glycolysis after the T cell receptor-mediated activation as revealed by the targeted metabolomics assay. The cells exhibited an extra activity of oxidative phosphorylation before the activation as indicated by the oxygen consumption rate. The cells gained capacities in the proliferation, apoptosis resistance and mitophagy in the glucose-limiting environment. These data suggest that inhibition of ATPIF1 activity by gene inactivation rewired the energy metabolism of CD8+T cells to enhance their immune activities to the tumors. ATPIF1 is a potential molecular target in the induction of antitumor immunity through metabolic reprogramming of CD8+T cells for the cancer immunotherapy.
Persistence of the T12 Vibrio cholerae O1 lineage in West Africa: Insights from a Regional Sequencing Workshop
Authors: Ekeng Eme , Tchatchouang Serges , Akenji Blaise , Issaka Bassira Boubacar , Akintayo Ifeoluwa , Chukwu Christopher , Dan Dano Ibrahim , Melingui Sylvie , Sani Ousmane , Popoola Michael Oladotun , Nzouankeu Ariane , Boum Yap , Luquero Francisco J , Ahumibe Anthony , Naidoo Dhamari , Azman Andrew S , Lessler Justin , Wohl Shirlee
Published: September 2020

We sequenced 46 Vibrio cholerae isolates from Cameroon, Niger, and Nigeria, 37 of which were from 2018–2019. These sequences belong to the T12 lineage observed in the region since 2009, suggesting continuous transmission. Data were generated during a workshop in Nigeria, providing a model for future regionally coordinated surveillance efforts.
Impact of COVID-19 on the mortality rates for the resident population of the Umbria region in Italy
Authors: Bietta Carla , Morini Mattia , Zaidi Asiya Kamber , Cozzolino Francesco , Dehgani-Mobaraki Puya
Published: September 2020

The mortality figures related to the coronavirus pandemic has been the topic of debate lately. Several hypothesis are made regarding the expected number of deaths in a region but there are various factors governing the same. In this paper, we have discussed the mortality figures in the Umbria region after analyzing the data from the national Health registry between December 2019 to April 2020; the period of infection and its comparison with the data from previous five years. The factors governing these figures were studied including temperature, standard mortality rates, territorial distribution, death due to all cases as well as the non-COVID deaths. A sharp increase in mortality figures was observed for the month of march and low temperature also had a role to play. However the difference when compared to previous 5 years was not significant as was expected at the start of the study. A single factor cannot be responsible for the total mortality figures in a region as is frequently predicted.
On the Analysis of Mortality Risk Factors for Hospitalized COVID-19 Patients: a Data-driven Study Using the Major Brazilian Database
Authors: de Souza Fernanda Sumika Hojo , Hojo-Souza Natália Satchiko , de Oliveira Batista Ben Dêivide , da Silva Cristiano Maciel , Guidoni Daniel Ludovico
Published: September 2020

Background

Brazil became the epicenter of the COVID-19 epidemic in a brief period of a few months after the first officially registered case. The knowledge of the epidemiological/clinical profile and the risk factors of Brazilian COVID-19 patients can assist in the decision making of physicians in the implementation of early and most appropriate measures for poor prognosis patients. However, these reports are missing. Here we present a comprehensive study that addresses this demand.

Methods

This data-driven study was based on the Brazilian Ministry of Health Database (SIVEP-Gripe, 2020) regarding notified cases of hospitalized COVID-19 patients during the period from February 26 to August 10, 2020. Demographic data, clinical symptoms, comorbidities and other additional information of patients were analyzed.

Results

The hospitalization rate was higher for male gender (56.56%) and for older age patients of both sexes. Overall, the mortality rate was quite high (41.28%) among hospitalized patients, especially those over 60 years of age. Most prevalent symptoms were cough, dyspnoea, fever, low oxygen saturation and respiratory distress. Heart disease, diabetes, obesity, kidney disease, neurological disease, and pneumopathy were the most prevalent comorbidities. A high prevalence of hospitalized COVID-19 patients with heart disease (65.7%) and diabetes (53.55%) and with a high mortality rate of around 50% was observed. The ICU admission rate was 39.37% and of these 62.4% died. 24.4% of patients required invasive mechanical ventilation (IMV), with high mortality among them (82.98%). The main mortality risk predictors were older age and IMV requirement. In addition, socioeconomic conditions have been shown to significantly influence the disease outcome, regardless of age and comorbidities.

Conclusion

Our study provides a comprehensive overview of the hospitalized Brazilian COVID-19 patients profile and the mortality risk factors. The analysis also evidenced that the disease outcome is influenced by multiple factors, as unequally affects different segments of population.
What have we learned about positive changes experienced during COVID-19 lockdown? Evidence of the social patterning of change
Authors: Williams Lynn , Rollins Lesley , Young David , Fleming Leanne , Grealy Madeleine , Janssen Xanne , Kirk Alison , MacDonald Bradley , Flowers Paul
Published: September 2020

Background

Multiple studies have highlighted the negative impact of COVID-19 and its particular effects on vulnerable sub-populations. Complementing this work, here, we report on the social patterning of self-reported positive changes experienced during COVID-19 national lockdown in Scotland.

Methods

The CATALYST study collected data from 3342 adults in Scotland during weeks 9-12 of a national lockdown. Participants completed an online questionnaire providing data on key sociodemographic and health variables, and completed a measure of positive change. The positive change measure spanned diverse domains (e.g., more quality time with family, developing new hobbies, more physical activity, and better quality of sleep). We used univariate analysis and stepwise regression to examine the contribution of a range of sociodemographic factors (e.g., age, gender, ethnicity, educational attainment, and employment status) in explaining positive change.

Results

There were clear sociodemographic differences across positive change scores. Those reporting higher levels of positive change were female, from younger age groups, married or living with their partner, employed, and in better health.

Conclusion

Overall our results highlight the social patterning of positive changes during lockdown in Scotland. These findings begin to illuminate the complexity of the unanticipated effects of national lockdown and will be used to support future intervention development work sharing lessons learned from lockdown to increase positive health change amongst those who may benefit.
Cognitive impairment is differentially associated with depression and anxiety at six-months post-stroke
Authors: Williams Owen A , Demeyere Nele
Published: September 2020

Objective

This study investigated the associations between general cognitive impairment and domain specific cognitive impairment with post-stroke depression and anxiety at six-months post-stroke.

Methods

Participants were a subset of 437 stroke patients from the OCS-CARE study who were followed up at a 6 months post-stroke assessment. Depression and anxiety symptoms were assessed by the Hospital Anxiety and Depression Scale sub-scales. General cognitive impairment was assessed using the Montreal Cognitive Assessment and stroke-specific cognitive domain impairments was assessed using the Oxford Cognitive Screen. Multivariable linear regression was used to examine the associations between cognition and depression/anxiety symptoms, controlling for acute stroke severity and ADL impairment, age, sex, education, and co-occurring post-stroke depression/anxiety.

Results

Six-month post-stroke depression was associated with six-month impairment on the MoCA (beta [b] =0.96, standard error [SE] =0.31, p=0.006), and all individual domains assessed by the OCS including spatial attention (b=0.67, SE=0.33, p =0.041), executive function (b=1.37, SE=0.47, p=0.004), language processing (b=0.87, SE=0.38, p=0.028), memory (b=0.76, SE=0.37, p=0.040), number processing (b=1.13, SE=0.40, p=0.005), and praxis (b=1.16, SE =0.49, p=0.028). Post-stroke anxiety was associated with impairment on the MoCA (b=1.47, SE=0.42, p=0.001), and spatial attention (b=1.25, SE=0.45, p=0.006), but these associations did not remain significant after controlling for co-occurring post-stroke depression.

Conclusion

The different profiles of associations between cognitive impairment and post-stroke depression and anxiety suggest that cognitive impairment is highly related to depressive symptomatology, but associations observed between cognitive impairment and anxiety may actually be the result of co-morbid post stroke depression.
Psychopathology in mothers of children with pathogenic Copy Number Variants
Authors: Niarchou Maria , Cunningham Adam C. , Chawner Samuel J.R.A. , Moulding Hayley , Sopp Matthew ,   IMAGINE-ID, Hall Jeremy , Owen Michael J. , van den Bree Marianne
Published: September 2020

Caring for children with pathogenic neurodevelopmental Copy Number Variants (CNVs) (i.e., deletions and duplications of genetic material) can place a considerable burden on parents, and their quality of life. Our study is the first to examine the frequency of psychiatric diagnoses in mothers of children with CNVs compared to the frequency of psychiatric problems in age-matched mothers from a large community study. 268 mothers of children with CNVs had higher frequency of depression compared to the 2,680 age-matched mothers (p<0.001). Mothers of children with CNVs reported higher frequency of anorexia, bulimia, alcohol abuse and drug addiction compared to the age-matched mothers from the community sample. The frequency of depression arising after the birth of the index child was similar between the two groups (48% in mothers of children with CNVs vs. 44% in mothers of the community sample, p=0.43), but mothers of children with CNVs had higher frequency of anxiety (55%) compared to mothers from the community sample (30%, p=0.03). Our study highlights the need for health-care providers to devise treatment plans that not only focus on meeting the child’s needs, but also assessing and if needed, addressing the mental health needs of the parent.
Face Masks, Public Policies and Slowing the Spread of COVID-19: Evidence from Canada
Authors: Karaivanov Alexander , Lu Shih En , Shigeoka Hitoshi , Chen Cong , Pamplona Stephanie
Published: September 2020

We estimate the impact of indoor face mask mandates and other non-pharmaceutical interventions (NPI) on COVID-19 case growth in Canada. Mask mandate introduction was staggered from mid-June to mid-August 2020 in the 34 public health regions in Ontario, Canada’s largest province by population. Using this variation, we find that mask mandates are associated with a 22 percent weekly reduction in new COVID-19 cases, relative to the trend in absence of mandate. Province-level data provide corroborating evidence. We control for mobility behaviour using Google geo-location data and for lagged case totals and case growth as information variables. Our analysis of additional survey data shows that mask mandates led to an increase of about 27 percentage points in self-reported mask wearing in public. Counterfactual policy simulations suggest that adopting a nationwide mask mandate in June could have reduced the total number of diagnosed COVID-19 cases in Canada by over 50,000 over the period July–November 2020. Jointly, our results indicate that mandating mask wearing in indoor public places can be a powerful policy tool to slow the spread of COVID-19.

JEL codes

I18, I12, C23