bluuebunny/crossref_metadata_2025 huggingface dataset:
Hypertriglyceridemia Induced Pancreatitis
Authors: Ippisch Holly M. , Alfaro-Cruz Ligia , Fei Lin , Zou Yuanshu , Thompson Tyler , Abu-El-Haija Maisam
Published: March 2020

Objectives

Hypertriglyceridemia-induced pancreatitis is an important cause of acute pancreatitis (AP) in children, which lacks established guidelines. The aim of this study was to review management approaches at a single pediatric center.

Methods

This retrospective study included all inpatients younger than 21 years with AP and triglycerides (TG) of 1000 mg/dL or greater. A linear mixed effect model was used to calculate drop in TGs. The patient's diet, intravenous fluid (IVF) rate, insulin, and plasmapheresis were included in the model.

Results

Seventeen admissions were identified among 8 patients, average age 15 years (range, 6–19 years). Fifty percent had recurrent AP and 29% of admissions had complications including 1 death. The population was primarily female (75%), white (75%), and overweight, and 63% had diabetes. The median stay was 5.4 days. There were 14 approaches used with variations in IVF rates, insulin, plasmapheresis, and nill per os (NPO) versus feeds. Variables that reduced TG's were NPO, higher IVF rates, plasmapheresis, and insulin (P < 0.05). Importantly, NPO reduced TGs faster than those who started early nutrition.

Conclusions

Hypertriglyceridemia is an important cause of pancreatitis in children. This study shares a management algorithm from a single institution. Larger studies are needed for more evidence-based guidelines.
Coexistent Dedifferentiated Endometrioid Carcinoma of the Uterus and Adenocarcinoma of the Bladder in Lynch Syndrome: Case Report and Review of the Literature
Authors: Groth John V. , Prabhu Sanjiv , Periakaruppan Ramayee , Ohlander Samuel , Emmadi Rajyasree , Kothari Rajul
Published: March 2020

Lynch syndrome is an autosomal dominant disorder, caused by an abnormality in DNA mismatch repair genes and characterized by the development of a variety of cancers. Upper urinary tract urothelial carcinoma is well characterized in Lynch syndrome; however, support for the inclusion of bladder urothelial carcinoma is limited, except for MSH2 mutation carriers. Urologic adenocarcinoma has not been documented in Lynch syndrome. Here we report, to the best of our knowledge, the first case of bladder adenocarcinoma, synchronous with uterine endometrioid dedifferentiated endometrioid adenocarcinoma in a patient with Lynch syndrome. We present a 47-year-old woman with an MLH1 gene mutation (G133X 397G>T) who presented with menorrhagia. Eleven family members have this mutation, 6 with carcinoma: 5 colorectal and 1 with a gynecologic primary of unknown type. Colonoscopy and endoscopy were unremarkable. Positron emission and computed tomography revealed a 3 cm anterior dome bladder mass without additional extrauterine disease or uterine connection. She underwent partial cystectomy, laparoscopic hysterectomy, bilateral salpingo-oophorectomy, and lymphadenectomy. The uterus demonstrated a dedifferentiated endometrioid adenocarcinoma, immunohistochemically positive for vimentin, ER, CK7, MSH2, MSH6, and p53 (focally) and negative for CEA, CDX2, CK20, β-catenin, MLH1, and PMS2. The bladder demonstrated a well-differentiated, enteric-type adenocarcinoma without muscularis propria invasion, positive for CEA, CDX2, CK20, p53, MSH2, and MSH6 and negative for vimentin, ER, CK7, MLH1, and PMS2. Eleven nodes were negative for carcinoma. The morphologic, immunohistochemical, and clinical findings support synchronous bladder adenocarcinoma, enteric type, and uterine dedifferentiated endometrioid adenocarcinoma, in a patient with Lynch syndrome.
Ki-67 Proliferation Index in Breast Cancer as a Function of Assessment Method: A NordiQC Experience
Authors: Røge Rasmus , Nielsen Søren , Riber-Hansen Rikke , Vyberg Mogens
Published: March 2020

Immunohistochemical staining for Ki-67 is used to calculate a Ki-67 proliferation index (PI) that carries prognostic and predictive information in various cancers including breast carcinomas. Studies have documented challenges for observers to reproducibly estimate the Ki-67 PI. At present, no international consensus exists concerning scoring method (eg, hotspots vs. overall average, digital vs. manual counting) or even the definition of a Ki-67-positive cell. To clarify the approach to Ki-67 scoring and evaluation of the interobserver agreement among participants in the Nordic Immunohistochemical Quality Control (NordiQC) Breast Cancer Module, a study was set up on the basis of an online web module containing 15 digitized tissue microarray cores of breast carcinomas stained for Ki-67 in the NordiQC reference laboratory. All participants were invited to attend the study. In addition to Ki-67 scoring, they were asked to disclose their preferred method for Ki-67 estimation and their job title. For comparison, slides were analyzed using a Digital Image Analysis algorithm based on Virtual Double Staining. In total, 199 participants enrolled for the study. Overall, there was a good correlation in Ki-67 PIs among the participants, although results for some cores varied significantly. However, when applying a cutoff of 20%, a relatively low κ value of 0.52 was observed. Participants scoring in hotspots reported higher Ki-67 PIs than participants estimating an overall average, and, not surprisingly, participants who considered weak Ki-67 nuclear staining positive obtained higher Ki-67 PIs than those who did not. Ki-67 PI was not correlated to job title. The Virtual Double Staining algorithm obtained Ki-67 values close to the mean value of the human observers. Our study underlines the need for international standardization and guidelines in estimation of Ki-67 PI. Digital Image Analysis may be a useful tool in this process.
Brief Report: High Accuracy of a Real-Time Urine Antibody-Based Tenofovir Point-of-Care Test Compared With Laboratory-Based ELISA in Diverse Populations
Authors: Spinelli Matthew A. , Rodrigues Warren C. , Wang Guohong , Vincent Michael , Glidden David V. , Okochi Hideaki , Stalter Randy , Defechereux Patricia , Deutsch Madeline , Grant Robert M. , Ngure Kenneth , Mugo Nelly R. , Baeten Jared M. , Gandhi Monica ,   for the Partners PrEP Study Team
Published: March 2020

Background:

Therapeutic drug monitoring measures antiretroviral adherence more accurately than self-report but has not been available at the point-of-care (POC) until now. We compare a novel POC test for urine tenofovir to laboratory-based enzyme-linked immunosorbent assay (ELISA) testing in diverse patient populations urine pre-exposure prophylaxis (PrEP).

Setting:

Urine samples were analyzed using ELISA and the POC lateral flow immunoassay (LFA) test from 2 cohorts of PrEP users taking tenofovir disoproxil fumarate/emtricitabine: the Partners PrEP Study, which recruited Kenyan and Ugandan heterosexual men and women, and the IBrEATHe Study, which recruited US transgender women and men using gender-affirming hormone therapy.

Methods:

We calculated the sensitivity, specificity, and accuracy of the POC test compared with ELISA at a cutoff of 1500 ng/mL.

Results:

Overall, 684 urine samples were tested from 324 participants in the 2 cohorts. In Partners PrEP, 454 samples from 278 participants (41% women) were tested with a median age of 33 years. In IBrEATHe, 231 samples from 46 individuals (50% transwomen) were tested with a median age of 31 years. Comparison of the LFA read-out to ELISA yielded 100% sensitivity [97.5% one-sided confidence interval (CI) = 99.3%], 98.3% specificity (95% CI = 95.2% to 99.7%), and 99.6% accuracy (95% CI = 98.7% to 99.9%).

Conclusion:

The sensitivity, specificity, and accuracy of a novel POC test for urine tenofovir all exceeded 98% when compared with a laboratory-based ELISA method when tested in diverse patient populations. Given the LFA's high accuracy and expected low cost, this POC test is a promising tool to support antiretroviral adherence that could be widely scalable to real-world clinical settings.
Experimental vacancies do not induce settlement despite habitat saturation in a cooperative breeder
Authors: Brouwer Lyanne , Cockburn Andrew
Published: March 2020

The paradox of cooperative breeding, whereby individuals assist others instead of reproducing independently, is generally explained through ecological constraints, but experimental evidence is scant. Here we performed the crucial test of the role of habitat saturation through the experimental creation of vacancies and found that, despite abundant presence of potential mates, subordinates are reluctant to disperse into suitable vacant habitat where conspecifics are absent. We argue that sudden disappearance of multiple group members might indicate a heightened risk of predation. Thereby the results of this study are consistent with the ‘perceptual trap’ hypothesis: the avoidance of habitats because cues do not accurately reflect their quality. Interestingly, this hypothesis can also explain previous findings, which were widely interpreted as evidence for ecological constraints as a driver of cooperative breeding. Our results can have considerable implications for conservation as they mean that opportunities for colonization might go unexploited.
Beauty in artistic expressions through the eyes of networks and physics
Authors: Perc Matjaž
Published: March 2020

Beauty is subjective, and as such it, of course, cannot be defined in absolute terms. But we all know or feel when something is beautiful to us personally. And in such instances, methods of statistical physics and network science can be used to quantify and to better understand what it is that evokes that pleasant feeling, be it when reading a book or looking at a painting. Indeed, recent large-scale explorations of digital data have lifted the veil on many aspects of our artistic expressions that would remain forever hidden in smaller samples. From the determination of complexity and entropy of art paintings to the creation of the flavour network and the principles of food pairing, fascinating research at the interface of art, physics and network science abounds. We here review the existing literature, focusing in particular on culinary, visual, musical and literary arts. We also touch upon cultural history and culturomics, as well as on the connections between physics and the social sciences in general. The review shows that the synergies between these fields yield highly entertaining results that can often be enjoyed by layman and experts alike. In addition to its wider appeal, the reviewed research also has many applications, ranging from improved recommendation to the detection of plagiarism.
Mechanical basis for thermonastic movements of cold-hardy
Rhododendron
leaves
Authors: Wang Hailong , Nilsen Erik T. , Upmanyu Moneesh
Published: March 2020

The profusion of rhododendrons in cold climates is as remarkable as the beauty of their blooms. The cold-hardiness of some of the montane species is in part due to reversible leaf movements triggered under frigid conditions wherein the leaves droop at the leaf stalks (petioles) and their margins roll up around the midrib. We probe the mechanics of these movements using leaf dissection studies that reveal that the through-thickness differential expansion necessary for leaf rolling is anisotropically distributed transverse to and along the midrib. Numerical simulations and theoretical analyses of bilayer laminae show that the longitudinal expansion amplifies the transverse rolling extent. The curvature diversion scales with the in-plane Poisson’s ratio, suitably aided by the stiff midrib that serves as a symmetry breaking constraint that controls the competition between the longitudinal and transverse rolling. Comparison of leaf rolling with and without the petiole indicates that the petiole flexibility and leaf rolling are in part mechanically coupled responses, implicating the hydraulic pathways that maintain the critical level of midrib stiffness necessary to support the longitudinal expansion. The study highlights the importance of curvature diversion for efficient nastic and tropic leaf movements that enhance cold-hardiness and drought resistance, and for morphing more general hinged laminae.
Three-dimensional wing structure attenuates aerodynamic efficiency in flapping fly wings
Authors: Engels Thomas , Wehmann Henja-Niniane , Lehmann Fritz-Olaf
Published: March 2020

The aerial performance of flying insects ultimately depends on how flapping wings interact with the surrounding air. It has previously been suggested that the wing's three-dimensional camber and corrugation help to stiffen the wing against aerodynamic and inertial loading during flapping motion. Their contribution to aerodynamic force production, however, is under debate. Here, we investigated the potential benefit of three-dimensional wing shape in three different-sized species of flies using models of micro-computed tomography-scanned natural wings and models in which we removed either the wing's camber, corrugation, or both properties. Forces and aerodynamic power requirements during root flapping were derived from three-dimensional computational fluid dynamics modelling. Our data show that three-dimensional camber has no benefit for lift production and attenuates Rankine–Froude flight efficiency by up to approximately 12% compared to a flat wing. Moreover, we did not find evidence for lift-enhancing trapped vortices in corrugation valleys at Reynolds numbers between 137 and 1623. We found, however, that in all tested insect species, aerodynamic pressure distribution during flapping is closely aligned to the wing's venation pattern. Altogether, our study strongly supports the assumption that the wing's three-dimensional structure provides mechanical support against external forces rather than improving lift or saving energetic costs associated with active wing flapping.
Biosynthesis and biology of mammalian GPI-anchored proteins
Authors: Kinoshita Taroh
Published: March 2020

At least 150 human proteins are glycosylphosphatidylinositol-anchored proteins (GPI-APs). The protein moiety of GPI-APs lacking transmembrane domains is anchored to the plasma membrane with GPI covalently attached to the C-terminus. The GPI consists of the conserved core glycan, phosphatidylinositol and glycan side chains. The entire GPI-AP is anchored to the outer leaflet of the lipid bilayer by insertion of fatty chains of phosphatidylinositol. Because of GPI-dependent membrane anchoring, GPI-APs have some unique characteristics. The most prominent feature of GPI-APs is their association with membrane microdomains or membrane rafts. In the polarized cells such as epithelial cells, many GPI-APs are exclusively expressed in the apical surfaces, whereas some GPI-APs are preferentially expressed in the basolateral surfaces. Several GPI-APs act as transcytotic transporters carrying their ligands from one compartment to another. Some GPI-APs are shed from the membrane after cleavage within the GPI by a GPI-specific phospholipase or a glycosidase. In this review, I will summarize the current understanding of GPI-AP biosynthesis in mammalian cells and discuss examples of GPI-dependent functions of mammalian GPI-APs.
Characterization of the hemolytic activity of Riemerella anatipestifer
Authors: Gong Yanshan , Yang Yongsheng , Chen Yan , Sun Bingqing , Xue Yafei , Xu Xinxin , Wang Xi , Islam Nazrul , Du Xiaoli , Hu Qinghai
Published: March 2020

Riemerella anatipestifer

infection causes serious economic losses in the duck industry worldwide. Acute septicemia and high blood bacterial loading in

R. anatipestifer

infected ducks indicate that

R. anatipestifer

may be able to obtain iron and other nutrients by lysing duck erythrocytes to support its rapid growth and proliferation in the blood. However, so far, little is known about the hemolytic activity of

R. anatipestifer

to duck erythrocytes. In this study, 29 of 52

R

.

anatipestifer

strains showed hemolytic activity on duck blood agar, whereas all the tested dba+ (with hemolytic activity on duck blood agar) and dba− strains created pores in the duck red blood cells, with 4.35–9.03% hemolytic activity in a liquid hemolysis assay after incubation for 24 h. The concentrated culture supernatants of all the tested

R. anatipestifer

strains and the extracted outer membrane proteins (OMPs) from dba+

R. anatipestifer

strains showed hemolytic activity on duck blood agar. These results, together with the median lethal dose (LD50) of some dba+ and dba-

R. anatipestifer

strains in ducklings, suggested that there was no direct relationship between the hemolytic capacity of

R. anatipestifer

on duck blood agar and its virulence.
Temporal Dynamics of the Adult Female Lower Urinary Tract Microbiota
Authors: Price Travis K. , Wolff Birte , Halverson Thomas , Limeira Roberto , Brubaker Linda , Dong Qunfeng , Mueller Elizabeth R. , Wolfe Alan J.
Published: March 2020

Temporal dynamics of certain human microbiotas have been described in longitudinal studies; variability often relates to modifiable factors or behaviors. Early studies of the urinary microbiota preferentially used samples obtained by transurethral catheterization to minimize vulvo-vaginal microbial contributions. Whereas voided specimens are preferred for longitudinal studies, the few studies that reported longitudinal data were limited to women with lower urinary tract (LUT) symptoms, due to ease of accessing a clinical population for sampling and the impracticality and risk of collecting repeated catheterized urine specimens in a non-clinical population. Here, we studied the microbiota of the LUT of non-symptomatic, pre-menopausal women using mid-stream voided urine (MSU) specimens to investigate relationships between microbial dynamics and personal factors. Using 16S rRNA gene sequencing and a metaculturomics method called Expanded Quantitative Urine Culture (EQUC), we characterized the microbiotas of MSU and peri-urethral swab specimens collected daily for approximately three months from a small cohort of adult women. Participants were screened for eligibility, including ability to self-collect paired urogenital specimens prior to enrollment. In this population, we found that measures of microbial dynamics related to specific participant-reported factors, particularly menstruation and vaginal intercourse. Further investigation of the trends revealed differences in composition and diversity of LUT microbiotas within and across participants. These data, in combination with previous studies showing relationships between the LUT microbiota and LUT symptoms, suggest that personal factors relating to the genitourinary system may be an important consideration in the etiology, prevention, and/or treatment of LUT disorders.

IMPORTANCE

Following the discovery of the collective human urinary microbiota, important knowledge gaps remain, including the stability and variability of this microbial niche over time. Initial urinary studies preferentially utilized samples obtained by transurethral catheterization to minimize contribution from vulvo-vaginal microbes. However, catheterization has the potential to alter the urinary microbiota; therefore, voided specimens are preferred for longitudinal studies. In this report, we describe the microbial findings obtained by daily assessment over three months in a small cohort of adult women. Similar to vaginal microbiotas, we found that lower urinary tract (LUT) microbiotas are dynamic with changes relating to several factors, particularly menstruation and vaginal intercourse. Our study shows that LUT microbiotas are both dynamic and resilient. It also offers novel opportunities to target LUT microbiotas for preventative or therapeutic means, through risk and/or protective factor modification.
Prevalence and Risk Factors for Acute Posttraumatic Stress Disorder during the COVID-19 Outbreak
Authors: Sun Luna , Sun Zhuoer , Wu Lili , Zhu Zhenwen , Zhang Fan , Shang Zhilei , Jia Yanpu , Gu Jingwen , Zhou Yaoguang , Wang Yan , Liu Nianqi , Liu Weizhi
Published: March 2020

Background

To exam the prevalence of and risk factors for acute posttraumatic stress disorder (PTSD) in Chinese people shortly after the COVID-19 outbreak.

Methods

An online questionnaire survey was conducted between 30 January and 3 February, 2020. The survey included two self-administered questionnaires: one was designed to require participants’ personal information (gender, age, education background), current location, recent epidemic area contact history, the classification of population, and subjective sleep quality; the other was the PTSD Checklist for DSM-5 (PCL-5).

Results

A total of 2091 Chinese participated in this study. The prevalence of PTSD among the Chinese public one month after the COVID-19 outbreak was 4.6%. Multiple linear regression analysis revealed that gender (p< 0.001), epidemic area contact history (p= 0.047), classification of population (p< 0.001), and subjective sleep quality (p< 0.001) could be regarded as predictor factors for PTSD.

Limitations

First, the majority of participants in this study were the general public, and confirmed or suspected patients being a small part. Second, the measurement of PTSD might be vulnerable to selection bias because of an online self-report study, such as participants’ recruitment. Third, the prevalence of PTSD in this study was estimated by an online questionnaire rather than a clinical interview.

Conclusions

The results revealed that some Chinese showed acute PTSD during the COVID-19 outbreak. Therefore, comprehensive psychological intervention needs further implementation. Furthermore, females, people who having recent epidemic area contact history, those at high risk of infection or with poor sleep quality deserve special attention.
Prognostic value of NT-proBNP in patients with severe COVID-19
Authors: Gao Lei , Jiang Dan , Wen Xue-song , Cheng Xiao-cheng , Sun Min , He Bin , You Lin-na , Lei Peng , Tan Wei-xiao , Qin Shu , Cai Guo-qiang , Zhang Dong-ying
Published: March 2020

The outbreak of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China has been declared a public health emergency of international concern. The cardiac injury was dominate in the process. However, whether N terminal pro B type natriuretic peptide (NT-proBNP) predicted outcome of COVID-19 patients was unknown. The study initially enrolled 102 patients with severe COVID-19 pneumonia from a continuous sample. After screening out the ineligible cases, 54 patients were analyzed in this study. Results found that patients with higher NT-proBNP (above 88.64 pg/mL) level had more risks of in-hospital death. After adjusting for potential cofounders in separate modes, NT-proBNP presented as an independent risk factor of in-hospital death in patients with severe COVID-19.
Detecting heterogeneity of intervention effects using analysis and meta-analysis of differences in variance between arms of a trial
Authors: Mills Harriet L , Higgins Julian PT , Morris Richard W , Kessler David , Heron Jon , Wiles Nicola , Smith George Davey , Tilling Kate
Published: March 2020

Background

Randomised controlled trials (RCTs) with continuous outcomes usually only examine mean differences in response between trial arms. If the intervention has heterogeneous effects, then outcome variances will also differ between arms. Power of an individual trial to assess heterogeneity is lower than the power to detect the same size of main effect.

Methods

Several methods for assessing differences in variance in trial arms were described and applied to a single trial with individual patient data (IPD) and to meta-analyses using summary data. Where IPD were available, regression-based methods were used to examine the effects of covariates on variation. An additional method to meta-analyse differences in variances with summary data was presented.

Results

In the single trial there was agreement between methods, and the difference in variance was largely due to differences in depression at baseline. In two meta-analyses, most individual trials did not show strong evidence of a difference in variance between arms, with wide confidence intervals. However, both meta-analyses showed evidence of greater variance in the control arm, and in one example this was perhaps because mean outcome in the control arm was higher.

Conclusions

Low power of individual trials to examine differences in variance can be overcome using meta-analysis. Evidence of differences in variance should be followed-up to identify potential effect modifiers and explore other possible causes such as varying compliance.
A retrospective study of the clinical characteristics of COVID-19 infection in 26 children
Authors: Tang Anjue , Xu Wenhui , Shen Min , Chen Peifen , Li Guobao , Liu Yingxia , Liu Lei
Published: March 2020

Background

The outbreak of novel coronavirus pneumonia in China began in December 2019. Studies on novel coronavirus disease (COVID-19) were less based on pediatric patients. This study aimed to reveal the clinical characteristics of COVID-19 in children.

Method

This study retrospectively analyzed the clinical symptoms, laboratory results, chest CT, and treatment of children with laboratory-confirmed COVID-19(ie, with samples that were positive for 2019 novel coronavirus[2019-nCoV]) who were admitted to Shenzhen Center of National Infectious Disease Clinical Medical Research from January 16 to February 8, 2020.

Result

Nine patients had no obvious clinical symptom. 11 patients developed fever. Other symptoms, including cough(in eleven of seventeen patients), rhinorrhea(in two), diarrhea(in two), vomiting(in two), were also observed. A small minority of patients had lymphocytopenia. Alanine transaminase or transaminase increased in three cases. According to chest CT scan, 11 patients showed unilateral pneumonia, 8 patients had no pulmonary infiltration. No serious complications such as acute respiratory syndrome and acute lung injury occurred in all patients.

Conclusion

The clinical characteristics of 2019-nCoV infection in children were different from adult. The overall condition of children were mild and have a good prognosis.

Mainpoint

COVID-19 is a kind of new infectious disease.The clinical characteristics of 2019-nCoV infection in children may different from adult. Myocardium likely less affected by 2019-nCoV in children.
Clinical Characteristics of Two Human to Human Transmitted Coronaviruses: Corona Virus Disease 2019 versus Middle East Respiratory Syndrome Coronavirus
Authors: Xu Ping , Sun Guo-Dong , Li Zhi-Zhong
Published: March 2020

After the outbreak of the middle east respiratory syndrome (MERS) worldwide in 2012. Currently, a novel human coronavirus has caused a major disease outbreak, and named corona virus disease 2019 (COVID-19). The emergency of MRES-COV and COVID-19 has caused global panic and threatened health security. Unfortunately, the similarities and differences between the two coronavirus diseases remain to be unknown. The aim of this study, therefore, is to perform a systematic review to compare epidemiological, clinical and laboratory features of COVID-19 and MERS-COV population. We searched PubMed, EMBASE and Cochrane Register of Controlled Trials database to identify potential studies reported COVID-19 or MERS-COV. Epidemiological, clinical and laboratory outcomes, the admission rate of intensive cure unit (ICU), discharge rate and fatality rate were evaluated using GraphPad Prism software. Thirty-two studies involving 3770 patients (COVID-19 = 1062, MERS-COV = 2708) were included in this study. The present study revealed that compared with COVID-19 population, MERS-COV population had a higher rate of ICU admission, discharge and fatality and longer incubation time. It pointed out that fever, cough and generalised weakness and myalgia were main clinical manifestations of both COVID-19 and MERS-COV, whereas ARDS was main complication. The most effective drug for MERS-COV is ribavirin and interferon.
Prediction of COVID-19 Spreading Profiles in South Korea, Italy and Iran by Data-Driven Coding
Authors: Zhan Choujun , Tse Chi K. , Lai Zhikang , Hao Tianyong , Su Jingjing
Published: March 2020

This work applies a data-driven coding method for prediction of the COVID-19 spreading profile in any given population that shows an initial phase of epidemic progression. Based on the historical data collected for COVID-19 spreading in 367 cities in China and the set of parameters of the augmented Susceptible-Exposed-Infected-Removed (SEIR) model obtained for each city, a set of profile codes representing a variety of transmission mechanisms and contact topologies is formed. By comparing the data of an early outbreak of a given population with the complete set of historical profiles, the best fit profiles are selected and the corresponding sets of profile codes are used for prediction of the future progression of the epidemic in that population. Application of the method to the data collected for South Korea, Italy and Iran shows that peaks of infection cases are expected to occur before the end of March 2020, and that the percentage of population infected in each city will be less than 0.01%, 0.05% and 0.02%, for South Korea, Italy and Iran, respectively.
Effects-sizes of deletions and duplications on autism risk across the genome
Authors: Douard Elise , Zeribi Abderrahim , Schramm Catherine , Tamer Petra , Loum Mor Absa , Nowak Sabrina , Saci Zohra , Lord Marie-Pier , Rodríguez-Herreros Borja , Jean-Louis Martineau , Moreau Clara , Loth Eva , Schumann Gunter , Pausova Zdenka , Elsabbagh Mayada , Almasy Laura , Glahn David C. , Bourgeron Thomas , Labbe Aurélie , Paus Tomas , Mottron Laurent , Greenwood Célia M. T. , Huguet Guillaume , Jacquemont Sébastien
Published: March 2020

Objective

Deleterious copy number variants (CNVs) are identified in up to 20% of individuals with autism. However, only 13 genomic loci have been formally associated with autism because the majority of CNVs are too rare to perform individual association studies. To investigate the implication of undocumented CNVs in neurodevelopmental disorders, we recently developed a new framework to estimate their effect-size on intelligence quotient (IQ) and sought to extend this approach to autism susceptibility and multiple cognitive domains.

Methods

We identified CNVs in two autism samples (Simons Simplex Collection and MSSNG) and two unselected populations (IMAGEN and Saguenay Youth Study). Statistical models integrating scores of genes encompassed in CNVs were used to explain their effect on autism susceptibility and multiple cognitive domains.

Results

Among 9 scores of genes, the “probability-of-being loss-of-function intolerant” (pLI) best explains the effect of CNVs on IQ and autism risk. Deletions decrease IQ by a mean of 2.6 points per point of pLI. The effect of duplications on IQ is three-fold smaller. The odd ratios for autism increases when deleting or duplicating any point of pLI. This increased autism risk is similar in subgroups of individuals below or above median IQ. Once CNV effects on IQ are accounted for, autism susceptibility remains mostly unchanged for duplications but decreases for deletions. Model estimates for autism risk overlap with previously published observations. Deletions and duplications differentially affect social communication, behaviour, and phonological memory, whereas both equally affect motor skills.

Conclusions

Autism risk conferred by duplications is less influenced by IQ compared to deletions. CNVs increase autism risk similarly in individuals with high and low IQ. Our model, trained on CNVs encompassing >4,500 genes, suggests highly polygenic properties of gene dosage with respect to autism risk. These models will help interpreting CNVs identified in the clinic.
Narrowband multivariate source separation for semi-blind discovery of experiment contrasts
Authors: Zuure Marrit B. , Cohen Michael X
Published: March 2020

Background

Electrophysiological recordings contain mixtures of signals from distinct neural sources, impeding a straightforward interpretation of the sensor-level data. This mixing is particularly detrimental when distinct sources resonate in overlapping frequencies. Fortunately, the mixing is linear and instantaneous. Multivariate source separation methods may therefore successfully separate statistical sources, even with overlapping spatial distributions.

New Method

We demonstrate a feature-guided multivariate source separation method that is tuned to narrowband frequency content as well as binary condition differences. This method — comparison scanning generalized eigendecomposition, csGED — harnesses the covariance structure of multichannel data to find directions (i.e., eigenvectors) that maximally separate two subsets of data. To drive condition specificity and frequency specificity, our data subsets were taken from different task conditions and narrowband-filtered prior to applying GED.

Results

To validate the method, we simulated MEG data in two conditions with shared noise characteristics and unique signal. csGED outperformed the best sensor at reconstructing the ground truth signals, even in the presence of large amounts of noise. We next applied csGED to a published empirical MEG dataset on visual perception vs. imagery. csGED identified sources in alpha, beta, and gamma bands, and successfully separated distinct networks in the same frequency band.

Comparison with Existing Method(s)

GED is a flexible feature-guided decomposition method that has previously successfully been applied. Our combined frequency- and condition-tuning is a novel adaptation that extends the power of GED in cognitive electrophysiology.

Conclusions

We demonstrate successful condition-specific source separation by applying csGED to simulated and empirical data.
Structural Basis for Ca2+-Dependent Activation of a Plant Metacaspase
Authors: Zhu Ping , Yu Xiao-Hong , Wang Cheng , Zhang Qingfang , Liu Wu , McSweeney Sean , Shanklin John , Lam Eric , Liu Qun
Published: March 2020

Plants metacaspases mediate programmed cell death in development1,2, biotic and abiotic stresses3, damage-induced immune response4, and resistance to pathogen attack5. Most metacaspases require Ca2+for their activation and substrate processing6–8. However, the Ca2+-dependent activation mechanism remains elusive9–11. Here we report the crystal structure of Metacaspase 4 fromArabidopsis thaliana(AtMC4) that modulates Ca2+-dependent, damage-induced plant immune defense. TheAtMC4 structure exhibits an inhibitory conformation in which a large linker domain blocks activation and substrate access. In addition, the side chain of Lys225 in the linker domain blocks the active site by sitting directly between two catalytic residues. We show that the activation ofAtMC4 and cleavage of its physiological substrate involve multiple cleavages in the linker domain upon activation by Ca2+. Our analysis provides insight into the Ca2+-dependent activation ofAtMC4 and lays the basis for tuning its activity in response to stresses that may help engineer more sustainable crops for production of food and biofuel.
Anatomy and activity patterns in a multifunctional motor neuron and its surrounding circuits
Authors: Ashaber Mária , Tomina Yusuke , Kassraian Pegah , Bushong Eric A. , Kristan William B. , Ellisman Mark H. , Wagenaar Daniel A.
Published: March 2020

Dorsal Excitor motor neuron DE-3 in the medicinal leech plays three very different dynamical roles in three different behaviors. Without rewiring its anatomical connectivity, how can a motor neuron dynamically switch roles to play appropriate roles in various behaviors? We previously used voltage-sensitive dye imaging to record from DE-3 and most other neurons in the leech segmental ganglion during (fictive) swimming, crawling, and local-bend escape (Tomina and Wagenaar, 2017). Here, we repeated that experiment, then re-imaged the same ganglion using serial blockface electron microscopy and traced all of DE-3’s processes. Further, we traced back the processes of all of DE-3’s presynaptic partners to their respective somata. This allowed us to analyze the relationship between circuit anatomy and the activity patterns it sustains. We found that input synapses important for all of the behaviors were widely distributed over DE-3’s branches, yet that functional clusters were different during (fictive) swimming vs. crawling.
CM93, a novel covalent small molecule inhibitor targeting lung cancer with mutant EGFR
Authors: Wang Qiwei , Ni Jing , Jiang Tao , Choi Hwan Geun , Zhang Tinghu , Gray Nathanael , Zhao Jean J.
Published: March 2020

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) have provided successful targeted therapies for patients with EGFR-mutant non-small-cell lung cancer (NSCLC). Osimertinib (AZD9291) is a third-generation irreversible EGFR TKI that has received regulatory approval for overcoming resistance mediated by the EGFR T790M mutation as well as a first-line treatment targeting EGFR activating mutations. However, a significant fraction of patients cannot tolerate the adverse effect associated with AZD9291. In addition, brain metastases are common in patients with NSCLN and remain a major clinical challenge. Here, we report the development of a novel third-generation EGFR TKI, CM93. Compared to AZD9291, CM93 exhibits improved lung cancer targeting and brain penetration and has demonstrated promising antitumor efficacy in mouse models of both EGFR-mutant NSCLC orthotopic and brain metastases. In addition, we find that CM93 confers superior safety benefits in mice. Our results demonstrate that further evaluations of CM93 in clinical studies for patients with EGFR-mutant NSCLC and brain metastases are warranted.
Engineered IL-10 variants elicit potent immuno-modulatory activities at therapeutic low ligand doses
Authors: Gorby C. , Sotolongo Bellón J. , Wilmes S. , Warda W. , Pohler E. , Fyfe P.K. , Cozzani A. , Ferrand C. , Walter M.R. , Mitra S. , Piehler J. , Moraga I.
Published: March 2020

Interleukin-10 is a dimeric cytokine with both immune-suppressive and immune-stimulatory activities. Despite its immuno-modulatory potential, IL-10-based therapies have shown only marginal benefits in the clinic. Here we have explored whether the stability of the IL-10-receptor complex contributes to IL-10 immuno-modulatory potency. For that, we have generated an IL-10 mutant with greatly enhanced affinity for its IL-10Rβ receptor via yeast surface display. The affinity enhanced IL-10 variants recruited IL-10Rβ more efficiently into active cell surface signaling complexes than the wild-type cytokine and triggered more potent STAT1 and STAT3 activation in human monocytes and CD8 T cells. This in turn led to more robust induction of IL-10-mediated gene expression programs at a wide range of ligand concentrations in both human cell subsets. IL-10 regulated genes are involved in monocyte energy homeostasis, migration and trafficking, and genes involved in CD8 T cell exhaustion. Interestingly, at non-saturating doses, IL-10 lost key components of its gene-expression program, which may explain its lack of efficacy in clinical settings. Remarkably, our engineered IL-10 variant exhibited a more robust bioactivity profile than IL-10 wt at all the doses tested in monocytes and CD8 T cells. Moreover, CAR-modified T cells expanded with the engineered IL-10 variant displayed superior cytolytic activity than those expanded with IL-10 wt. Our study provides unique insights into how IL-10-receptor complex stability fine-tunes IL-10 biology, and opens new opportunities to revitalize failed IL-10 therapies.
Inequality in tax evasion: the case of the Spanish income tax
Authors: Torregrosa-Hetland Sara
Published: March 2020

Purpose

The purpose of this paper is to estimate tax evasion and its impact on progressivity, redistribution and the measurement of inequality, using microdata from the Spanish income tax for 2001-2004.

Design/methodology/approach

The approach follows Feldman and Slemrod (2007) by exploiting the relation of charitable donations with the composition of income but introduces two methodological innovations, which could be useful for further studies: correction for sample selection with a Heckman two-step setting and the calculation of different evasion rates for top incomes with an interaction term.

Findings

Evasion in capital incomes was significant throughout these years. Financial incomes were reported at around 50-70 per cent of their real value, with the lowest estimates corresponding to the top decile. Revenues from fixed capital display similarly low compliance rates for the top 10 per cent. Tax evasion in self-employment incomes (direct assessment) is estimated at 20 per cent for 2001. Mostly because of a composition effect, this means that fraud was higher at the top of the income distribution, thus having a regressive impact. Inequality statistics and top income concentration estimates should, therefore, be revised upwards.

Originality/value

This is the first paper to estimate the distributive impacts of tax evasion in Spain, and one of very few internationally.
A review on the applications of the chemical reactor network approach on the prediction of pollutant emissions
Authors: Khodayari Hamidreza , Ommi Fathollah , Saboohi Zoheir
Published: March 2020

Purpose

The purpose of this paper is to review the applications of the chemical reactor network (CRN) approach for modeling the combustion in gas turbine combustors and classify the CRN construction methods that have been frequently used by researchers.

Design/methodology/approach

This paper initiates with introducing the CRN approach as a practical tool for precisely predicting the species concentrations in the combustion process with lower computational costs. The structure of the CRN and its elements as the ideal reactors are reviewed in recent studies. Flow field modeling has been identified as the most important input for constructing the CRNs; thus, the flow field modeling methods have been extensively reviewed in previous studies. Network approach, component modeling approach and computational fluid dynamics (CFD), as the main flow field modeling methods, are investigated with a focus on the CRN applications. Then, the CRN construction approaches are reviewed and categorized based on extracting the flow field required data. Finally, the most used kinetics and CRN solvers are reviewed and reported in this paper.

Findings

It is concluded that the CRN approach can be a useful tool in the entire process of combustion chamber design. One-dimensional and quasi-dimensional methods of flow field modeling are used in the construction of the simple CRNs without detailed geometry data. This approach requires fewer requirements and is used in the initial combustor designing process. In recent years, using the CFD approach in the construction of CRNs has been increased. The flow field results of the CFD codes processed to create the homogeneous regions based on construction criteria. Over the past years, several practical algorithms have been proposed to automatically extract reactor networks from CFD results. These algorithms have been developed to identify homogeneous regions with a high resolution based on the splitting criteria.

Originality/value

This paper reviews the various flow modeling methods used in the construction of the CRNs, along with an overview of the studies carried out in this field. Also, the usual approaches for creating a CRN and the most significant achievements in this field are addressed in detail.
Explaining consumers' intention to use menu labels: a structural equation modeling analysis
Authors: Lee Yee Ming , Sozen Erol
Published: March 2020

Purpose

This study investigated whether consumers have reasonable estimates of the calorie content of Americans' top 10 favorite foods, explored the effects of calorie disclosure on United States consumers' future consumption frequency of these food items, and examined the effects of health consciousness, food calorie knowledge, and attitudes toward menu labels on intention to use menu labels.

Design/methodology/approach

An online survey was developed, pilot tested, and distributed through Amazon Mechanical Turk (AMT). The overall model fit and hypotheses were tested using structural equation modeling (SEM).

Findings

The results from 1,005 completed surveys showed that the accuracy of calorie estimations varied across food items. Most consumers could not estimate the calories of steak, hamburgers, chocolate chip cookies, and vanilla ice cream within the acceptable range. Disclosure of calorie information did affect future consumption frequency of the food items. The SEM results showed that health consciousness, food calorie knowledge, and attitudes toward menu labels positively affected consumers' future intention to use menu labels.

Originality/value

This study points to a need to educate consumers about food calories and suggests plausible ways to encourage consumers' intention to use of menu labels.
Boundary spanners in crisis management
Authors: Kalkman Jori Pascal
Published: March 2020

Purpose

Crisis management increasingly requires coordination and collaboration between multiple organizations. This means that inter-organizational boundaries have to be spanned by dedicated organizational members (i.e. boundary spanners). This paper aims to describe which features facilitate the work of boundary spanners in crisis management.

Design/methodology/approach

A case study, consisting of 26 interviews, has been conducted in the Netherlands to explore how civilian and military representatives effectively spanned inter-organizational boundaries.

Findings

Five features are identified that enable boundary spanners to improve crisis management coordination and collaboration. Boundary spanners are likely to be successful when they (1) serve long terms, (2) are sensitive to partners' concerns, (3) have considerable discretion, (4) are politically skilled and (5) prove influential in their own organization.

Practical implications

Crisis organizations can extend boundary spanners' term length, broaden their discretionary space and give them more influence to facilitate their work. Additionally, in the selection process, it would be well to choose organizational members who display a sensitivity to the interests of crisis partners and possess political skill.

Originality/value

Multiple studies have reiterated the key role of boundary spanners in enabling crisis management coordination and collaboration. Yet, this study is the first to provide a systematic analysis of key features that help boundary spanners to reach this goal.
Developing a pedagogical photoreal virtual environment to teach civil engineering
Authors: Walker James , Towey Dave , Pike Matthew , Kapogiannis Georgios , Elamin Ahmed , Wei Ran
Published: March 2020

Purpose

It is possible for civil engineering (CE) students to graduate from a degree programme without gaining experience on a construction site. The implementation of virtual field trips using virtual reality (VR) in CE education is a development that can address this phenomenon and help facilitate the consolidation of abstract theories into tangible competences. This project aims to solve a fundamental CE education problem: once a structure has been completed, it is often impossible to see how it was built; hence, how can you demonstrate the construction process to a student?

Design/methodology/approach

This research used the opportunity of a new campus library development to record its construction sequence. This was achieved by visiting the site eight times to take panoramic stereoscopic photos of the construction process. By its nature, using VR as a didactic tool facilitates experiential learning, but this project also incorporates discovery learning and situated cognition to develop students’ understanding of the construction process.

Findings

The use of VR in education is becoming increasingly common, but the explicit pedagogy used in these environments is rarely obvious or stated. This project draws upon current VR education discussions and explores the development of a VR environment with a pedagogical context.

Originality/value

The development of the VR resource draws upon the pedagogical frameworks of discovery learning (Bruner, 1961) and situated cognition (Lave and Wenger, 1991). A further unique aspect of this research is the use of stereoscopic cameras to capture the library’s construction over time.