bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spindle Orientation-Independent Control of Cell Fate Determination by RGS3 and KIF20A
Authors: Qiu Runxiang , Murai Kiyohito , Lu Qiang 
Published: February 2020

Abstract
It was proposed that similar to its role in the invertebrate nervous system, mitotic spindle orientation (or cell cleavage plane orientation) of a dividing neural progenitor cell specifies the fate of daughter cells in the mammalian brain, modulating the production of neurons via symmetric versus asymmetric cell divisions during the course of neurogenesis. Experimental tests of the sufficiency of spindle/cleavage plane orientation in mammalian cell fate determination have yielded conflicting results. On the other hand, the necessity of spindle/cleavage plane orientation in mammalian cell fate determination has not yet been addressed. Here we examined the necessity of spindle/cleavage plane orientation during cortical neurogenesis in mice with loss-of-function of the RGS3-KIF20A interaction axis. We present evidence that while inactivation of RGS3 or KIF20A was linked to a shift in neural progenitor cells from proliferative to differentiative divisions in the developing cortex, these genetic mutations did not lead to anticipated alteration in the orientation of spindle/cleavage plane. Our results indicate that the RGS3-KIF20A axis regulates the balance between proliferation and differentiation in the mammalian cortex employing a mechanism independent of spindle/cleavage plane orientation. These data also caution against using spindle/cleavage plane orientation as the synonym for cell fate determination.
Candidate targets for immune responses to 2019-Novel Coronavirus (nCoV): sequence homology- and bioinformatic-based predictions
Authors: Grifoni Alba , Sidney John , Zhang Yun , Scheuermann Richard H , Peters Bjoern , Sette Alessandro 
Published: February 2020

ABSTRACTEffective countermeasures against the recent emergence and rapid expansion of the 2019-Novel Coronavirus (2019-nCoV) require the development of data and tools to understand and monitor viral spread and immune responses. However, little information about the targets of immune responses to 2019-nCoV is available. We used the Immune Epitope Database and Analysis Resource (IEDB) resource to catalog available data related to other coronaviruses, including SARS-CoV, which has high sequence similarity to 2019-nCoV, and is the best-characterized coronavirus in terms of epitope responses. We identified multiple specific regions in 2019-nCoV that have high homology to SARS virus. Parallel bionformatic predictions identifieda prioripotential B and T cell epitopes for 2019-nCoV. The independent identification of the same regions using two approaches reflects the high probability that these regions are targets for immune recognition of 2019-nCoV.ONE SENTENCE SUMMARYWe identified potential targets for immune responses to 2019-nCoV and provide essential information for understanding human immune responses to this virus and evaluation of diagnostic and vaccine candidates.
Application of n-of-1 clinical trials in personalized nutrition research: a trial protocol for Westlake N-of-1 Trials for Macronutrient Intake (WE-MACNUTR)
Authors: Tian Yunyi , Ma Yue , Fu Yuanqing , Zheng Ju-Sheng 
Published: February 2020

AbstractPersonalized dietary recommendations can help with more effective disease prevention. This study aims to investigate the individual postprandial glucose response to diets with diverse macronutrient proportions at both individual level and population level and explore the potential of the novel single-patient (n-of-1) trial for the personalization of diet. Secondary outcomes include individual phenotypic response and the effects of dietary ingredients on the composition and structure of gut microbiota. Westlake N-of-1 Trials for Macronutrient Intake (WE-MACNUTR) is a multiple crossover feeding trial consisting of three successive 12-day dietary intervention pairs including a 6-day wash-out period before each 6-day isocaloric dietary intervention (a 6-day high-fat, low-carbohydrate (HF-LC) diet and a 6-day low-fat, high-carbohydrate (LF-HC) diet). The results will help provide personalized dietary recommendation on macronutrients in terms of postprandial blood glucose response. Well-designed n-of-1 trial is likely to become an effective method of optimizing individual health and advancing health care. This trial is registered at clinicaltrials.gov (NCT04125602).
Short-term versus 6-week prednisone in the treatment of subacute thyroiditis: a randomized controlled trial
Authors: Duan Lian , Feng Xiaoli , Zhang Rui , Tan Xiaojuan , Xiang Xiaoyan , Shen Rufei , Zheng Hongting 
Published: February 2020

AbstractBackgroundModerate-to-severe subacute thyroiditis is commonly treated with 6-8 weeks glucocorticoids; however, no studies have described short-term prednisone treatment for subacute thyroiditis. We evaluated the efficacy of this treatment for subacute thyroiditis.MethodsThis was a 24-week, prospective, single-blind, randomized controlled study. Patients aged 18-70 years with subacute thyroiditis were hospitalized from August 2013 to December 2014. Patients with moderate-to-severe symptoms were randomized to receive either 30 mg/d prednisone for 1 week and then switched to 1 week of nonsteroidal anti-inflammatory drugs or 6 weeks of prednisone. The primary endpoints were the differences in efficacy at the end of treatment between two groups. Secondary endpoints included differences between the two groups in parameters of side effects at withdrawal and thyroid function at weeks 6, 12, 24.ResultsOf 96 patients screened, 52 subjects were randomized and 50 completed the study. Efficacy and recurrence rates were not significantly different at withdrawal in both groups (P=0.65). Parathyroid hormone (28.8 vs 38.9 pg/ml, p=0.011) and mean systolic blood pressure (113.9 vs 122.4 mmHg, p=0.023) were significantly lower in the experimental group than in the control group at discontinuation. No significant differences were observed in other secondary endpoints at withdrawal and in thyroid function at the 6th, 12th and 24th week during the follow-up time between the two groups.ConclusionsFewer side effects of glucocorticoids and similar efficacy and recurrence rates were observed with short-term prednisone compared with those with 6-week treatment for subacute thyroiditis. Short-term prednisone with a better safety profile may be as one alternative strategy for ameliorating moderate-to-severe symptoms of subacute thyroiditis.Trial registrationTrial registration number NCT01837433. Registered with Clinicaltrials.gov on 23 April 2013
Refractive errors, ocular biometry and diabetic retinopathy: a systematic review
Authors: He Miao , Chen Haiying , Wang Wei 
Published: February 2020

ABSTRACTDiabetic retinopathy (DR) is one of the major causes of visual impairment and blindness worldwide. The onset and progression of DR are influenced by systemic factors such as hyperglycemia and hypertension as well as ocular parameters. A better knowledge of the risk factors for DR is vital to improving the outcome of patients with DR and risk stratification. More recently, there has been increasing focus on the influence of myopia on DR development. Some observational studies have reported myopia being a protective factor for the development of DR, however the findings were inconsistent. In addition, it remains unclear whether it was myopia, axial length (AL), or other refractive factors that play the protective role. The protective mechanism against DR may be related to ocular elongation, posterior vitreous detachment, low perfusion in the retina and the abnormal cytokine profile. This systematic review will summarize the association of DR with refractory status as well as different refractive components including anterior chamber depth, refractory power of the lens, AL, and axial length-to-corneal radius ratio.
Estimating number of global importations of COVID-19 from Wuhan, risk of transmission outside mainland China and COVID-19 introduction index between countries outside mainland China
Authors: Sun Haoyang , Dickens Borame L , Chen Mark I. C. , Cook Alex R , Clapham Hannah E 
Published: February 2020

AbstractBackgroundThe emergence of a novel coronavirus (SARS-CoV-2) in Wuhan, China in early December 2019 has caused widespread transmission within the country, with over 1,000 deaths reported to date. Other countries have since reported coronavirus disease 2019 (COVID-19) importation from China, with some experiencing local transmission and even case importation from countries outside China. We aim to estimate the number of cases imported from Wuhan to each country or territory outside mainland China, and with these estimates assess the risk of onward local transmission and the relative potential of case importation between countries outside China.MethodsWe used the reported number of cases imported from Wuhan and flight data to generate an uncertainty distribution for the estimated number of imported cases from Wuhan to each location outside mainland China. This uncertainty was propagated to quantify the local outbreak risk using a branching process model. A COVID-19 introduction index was derived for each pair of donor and recipient countries, accounting for the local outbreak risk in the donor country and the between- country connectivity.ResultsWe identified 13 countries or territories outside mainland China that may have under-detected COVID-19 importation from Wuhan, such as Thailand and Indonesia. In addition, 16 countries had a local outbreak risk estimate exceeding 50%, including four outside Asia. The COVID-19 introduction index highlights potential locations outside mainland China from which cases may be imported to each recipient country.ConclusionsAs SARS-CoV-2 continues to spread globally, more epicentres may emerge outside China. Hence, it is important for countries to remain alert for the possibilities of viral introduction from other countries outside China, even before local transmission in a source country becomes known.
Clinical features and progression of acute respiratory distress syndrome in coronavirus disease 2019
Authors: Liu Yanli , Sun Wenwu , Li Jia , Chen Liangkai , Wang Yujun , Zhang Lijuan , Yu Li 
Published: February 2020

SummaryBackgroundThe outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) results in a cluster of coronavirus disease 2019 (COVID-19). We reported the clinical characteristics of COVID-19 patients with acute respiratory distress syndrome (ARDS), and further investigated the treatment and progression of ARDS in COVID-19.MethodsThis study enrolled 109 patients with COVID-19 admitted to the Central Hospital of Wuhan, a designated hospital in Wuhan, China, from January 2 to February 1, 2020. Patients were followed up to February 12, 2020. The clinical data were collected from the electronic medical records. The differences in the treatment and progression with the time and the severity of ARDS were determined.FindingsAmong 109 patients, mean age was 55 years, and 59 patients were male. With a median 15 days (range, 4 to 30 days) follow-up period, 31 patients (28.4%) died, while 78 (71.6%) survived and discharged. Of all patients, 53 (48.6%) developed ARDS. Compared to non-ARDS patients, ARDS patients were elder (mean age, 61 years vs. 49 years), and more likely to have the coexistent conditions, including diabetes (20.8% vs. 1.8%), cerebrovascular disease (11.3% vs. 0%), and chronic kidney disease (15.1% vs. 3.6%). Compared to mild ARDS patients, those with moderate and severe ARDS had higher mortality rates. No significant effect of antivirus, glucocorticoid, or immunoglobulin treatment on survival was observed in patients with ARDS.InterpretationThe mortality rate increased with the severity of ARDS in COVID-19, and the effects of current therapies on the survival for these patients were not satisfactory, which needs more attention from clinicians.FundingHealth and Family Planning Commission of Wuhan Municipality.
Integratedin silicoand 3Din vitromodel of macrophage migration in response to physical and chemical factors in the tumor microenvironment
Authors: Lee Sharon Wei Ling , Seager R.J. , Litvak Felix , Spill Fabian , Sieow Je Lin , Penny Hweixian Leong , Kumar Dillip , Tan Alrina Shin Min , Wong Siew Cheng , Adriani Giulia , Zaman Muhammad H , Kamm Roger Dale 
Published: February 2020

AbstractMacrophages are abundant in the tumor microenvironment (TME), serving as accomplices to cancer cells for their invasion. Studies have explored the biochemical mechanisms that drive pro-tumor macrophage functions, however the role of TME interstitial flow (IF) is often disregarded. Therefore, we developed a three-dimensional microfluidic-based model with tumor cells and macrophages to study how IF affects macrophage migration and its potential contribution to cancer invasion. The presence of either tumor cells or IF individually increased macrophage migration directedness and speed. Interestingly, there was no additive effect on macrophage migration directedness and speed under the simultaneous presence of tumor cells and IF. Further, we present anin silicomodel that couples chemokine-mediated signaling with mechanosensing networks to explain ourin vitroobservations. The model proposes IL-8, CCL2 and β-integrin as key pathways that commonly regulate various Rho GTPases. In agreement,in vitromacrophage migration remained elevated when exposed to a saturating concentration of recombinant IL-8 or CCL2, or to the co-addition of a sub-optimal concentration of both cytokines. Moreover, antibody blockade against IL-8 and/or CCL2 inhibited migration that could be restored by IF, indicating cytokine-independent mechanisms of migration induction. Importantly, we demonstrate the utility of an integratedin silicoand 3Din vitroapproach to aid the design of tumor-associated macrophage-based immunotherapeutic strategies.
Elongation Index as a Sensitive Measure of Cell Deformation in High-Throughput Microfluidic Systems
Authors: Hymel S. J. , Lan H. , Khismatullin D. B. 
Published: February 2020

AbstractOne of the promising approaches for high-throughput screening of cell mechanotype is microfluidic deformability cytometry (mDC) in which the apparent deformation index (DI) of the cells stretched by extensional flow at the stagnation point of a cross-slot microchannel is measured. The DI is subject to substantial measurement errors due to cell offset from the flow centerline and velocity fluctuations in inlet channels, leading to artificial widening of DI vs. cell size plots. Here, we simulated an mDC experiment using a custom computational algorithm for viscoelastic cell migration. Cell motion and deformation in a cross-slot channel was modeled for fixed or randomized values of cellular mechanical properties (diameter, shear elasticity, cortical tension) and initial cell placement, with or without sinusoidal fluctuations between the inlet velocities. Our numerical simulation indicates that mDC loses sensitivity to changes in shear elasticity when the offset distance exceeds 5 μm, and just 1% velocity fluctuation causes an 11.7% drop in the DI. The obtained relationships between the cell diameter, shear elasticity, and offset distance were used to establish a new measure of cell deformation, referred to as “Elongation Index” (EI). In the randomized study, the EI scatter plots were visibly separated for the low and high elasticity populations of cells, with a mean of 300 and 3,500 Pa, while the standard DI output was unable to distinguish between these two groups of cells. The successful suppression of the offset artefacts with a narrower data distribution was shown for the EI output of MCF-7 cells.Statement ofSignificanceThis study establishes a new measure of high-throughput microfluidic deformability cytometry, referred to as “elongation index”, that is not subject to cell offset artefacts and can sensibly and reliably detect disease-induced changes in mechanical properties of living cells.
Genetic, Cellular, and Connectomic Characterization of the Adult Human Brain Regions Commonly Plagued by Glioma
Authors: Mandal Ayan S. , Romero-Garcia Rafael , Hart Michael G. , Suckling John 
Published: February 2020

AbstractA better understanding of the nonrandom localization patterns of gliomas across the brain could lend clues to the origins of these types of tumors. Following hypotheses derived from prior research into neuropsychiatric disease and cancer, gliomas may be expected to localize to brain regions characterized by hubness, stem-like cells, and transcription of genetic drivers of gliomagenesis. We combined neuroimaging data from 335 adult patients with high- and low-grade glioma to form a replicable tumor frequency map. Using this map, we demonstrated that glioma frequency is elevated in association cortex and correlated with multiple graph-theoretical metrics of high functional connectedness. Brain regions populated with stem-like cells also exhibited a high glioma frequency. Furthermore, gliomas were localized to brain regions enriched with the expression of genes associated with chromatin organization and synaptic signaling. Finally, a regression model incorporating connectomic, cellular, and genetic factors explained 58% of the variance in glioma frequency. Our findings illustrate how factors of diverse scale, from genetic to connectomic, can independently influence the anatomic localization of oncogenesis.
A novel cortical biomarker signature for predicting pain sensitivity: protocol for the PREDICT longitudinal analytical validation study
Authors: Seminowicz David A , Bilska Katarzyna , Chowdhury Nahian S , Skippen Patrick , Millard Samantha K , Chiang Alan KI , Chen Shuo , Furman Andrew J , Schabrun Siobhan M 
Published: February 2020

ABSTRACTIntroductionTemporomandibular disorder (TMD) is a common musculoskeletal pain condition with development of chronic symptoms in 49% of patients. Although a number of biological factors have shown an association with chronic TMD in cross-sectional and case control studies, there are currently no biomarkers that can predict the development of chronic symptoms. The PREDICT study aims to undertake analytical validation of a novel peak alpha frequency (PAF) and corticomotor excitability (CME) biomarker signature using a human model of the transition to sustained myofascial temporomandibular pain (masseter intramuscular injection of nerve growth factor [NGF]). This paper describes, a-priori, the methods and analysis plan.Methods and analysisThis study uses a multi-site longitudinal, experimental study to follow individuals for a period of 30 days as they progressively develop and experience complete resolution of NGF-induced muscle pain. 150 healthy participants will be recruited. Participants will complete twice daily electronic pain dairies from Day 0 to Day 30 and undergo assessment of pressure pain thresholds, and recording of PAF and CME on Days 0, 2 and 5. Intramuscular injection of NGF will be given into the right masseter muscle on Days 0 and 2. The primary outcome is pain sensitivity.Ethics and disseminationEthical approval has been obtained from The University of New South Wales (HC190206) and the University of Maryland Baltimore (HP-00085371). Dissemination will occur through presentations at National and International conferences and publications in international peer-reviewed journals.Registration detailsClinicalTrials.gov: NCT04241562 (prospective)STRENGTHS AND LIMITATIONS OF THIS STUDYPREDICT is the first study to undertake analytical validation of a peak alpha frequency and corticomotor excitability biomarker signature. The study will determine the sensitivity, specificity and accuracy of this biomarker signature at predicting pain sensitivity.PREDICT will establish the reportable range of test results and determine automation and simplification of methods for biomarker detection in the clinic.The methods and statistical analysis plan are pre-specified to ensure reporting transparency.Future patient studies will be required for clinical validation.
A whole-genome sequenced control population in northern Sweden reveals subregional genetic differences
Authors: Svensson Daniel , Rentoft Matilda , Dahlin Anna M. , Lundholm Emma , Olason Pall I. , Sjödin Andreas , Nylander Carin , Melin Beatrice S. , Trygg Johan , Johansson Erik 
Published: February 2020

AbstractThe number of national reference populations that are whole-genome sequenced are rapidly increasing. Partly driving this development is the fact that genetic disease studies benefit from knowing the genetic variation typical for the geographical area of interest. A whole-genome sequenced Swedish national reference population (n=1000) has been recently published but with few samples from northern Sweden. In the present study we have whole-genome sequenced a control population (n=300) (ACpop) from Västerbotten County, a sparsely populated region in northern Sweden previously shown to be genetically different from southern Sweden. The aggregated variant frequencies within ACpop are publicly available (DOI 10.17044/NBIS/G000005) to function as a basic resource in clinical genetics and for genetic studies. Our analysis of ACpop, representing approximately 0.11% of the population in Västerbotten, indicates the presence of a genetic substructure within the county. Furthermore, a demographic analysis showed that the population from which samples were drawn was to a large extent geographically stationary, a finding that was corroborated in the genetic analysis down to the level of municipalities. Including ACpop in the reference population when imputing unknown variants in a Västerbotten cohort resulted in a strong increase in the number of high-confidence imputed variants (up to 81% for variants with minor allele frequency < 5%). ACpop was initially designed for cancer disease studies, but the genetic structure within the cohort will be of general interest for all genetic disease studies in northern Sweden.
Gut eukaryotic communities in pigs: diversity, composition and host genetics contribution
Authors: Ramayo-Caldas Yuliaxis , Prenafeta Francesc , Zingaretti Laura M , Gonzales Olga , Dalmau Antoni , Quintanilla Raquel , Ballester Maria 
Published: February 2020

AbstractThis study aims to characterize commensal fungi and protists inhabiting the gut of healthy pigs, and explore the putative host genetic control over diversity and composition of pig gut eukaryotes. Fecal fungi and protists communities from 514 Duroc pigs of two sexes and two different ages were characterized by 18S and ITS ribosomal RNA gene sequencing. The gut mycobiota was dominated by yeasts, with a high prevalence ofKazachstaniaspp. Regarding protists, representatives of four genera (Blastocystis, Neobalantidium, Tetratrichomonas and Trichomitus) persisted through more than the 80% of the pigs. Heritabilities for the diversity and abundance of gut eukaryotic communities were estimated with the subset of 60 days aged piglets (N=405). Obtained heritabilities ranged from 0.15 to 0.28, indicating a rather limited host-genetic control. A genome wide association study reported genetic variants associated with the fungal α-diversity (SSC6) and with the abundance ofBlastocystisspp. (SSC6, SSC17 and SSC18). Annotated candidate genes (IL23R, IL12RB2, PIK3C3, PIK3CD,HNF4AandTNFRSF9) were mainly related to immunity, gut homeostasis and metabolic processes. Our results point towards a minor and taxa specific genetic control over the diversity and composition of the pig gut eukaryotic communities.