bluuebunny/crossref_metadata_2025 huggingface dataset:
Serum long non‐coding RNA LINC00887 as a potential biomarker for diagnosis of renal cell carcinoma
Authors: Xie Junjie , Zhong Yu , Chen Rong , Li Gang , Luo Yongwen , Yang Jintao , Sun Zhongwei , Liu Yanzhong , Liu Peipei , Wang Na , An Jiaqi , Li Chao , Song Yang
Published: July 2020

The identification of non‐invasive biomarkers for the detection of renal cell carcinoma (RCC) in early‐stage patients may help improve disease outcome. Certain long non‐coding RNAs (lncRNAs) have been reported to be possible biomarkers for the diagnosis and prognosis of cancer. Here, we examined the suitability of the lncRNA LINC00887 as a potential biomarker for RCC because its expression has been shown to be elevated in RCC tissue versus normal tissue in the Gene Expression Profiling Interactive Analysis (GEPIA) database. We found that LINC00887 expression is significantly increased in early‐stage RCC tissues and the serum of early‐stage RCC patients compared to matched normal tissues and the serum of healthy subjects, respectively. We also demonstrated that elevated serum LINC00887 is generated from the tumor tissues of RCC patients. Moreover, a receiver operating characteristic (ROC) curve was generated to analyze the diagnostic value of serum LINC00887. The area under the ROC cure differentiating early‐stage RCC patients from healthy subjects was 0.8001, with a sensitivity of 71.05% and a specificity of 89.87%. Furthermore, we found that LINC00887 promotes RCC cell proliferation in vitro. Taken together, our findings suggest that a serum LINC00887 signature is associated with RCC cell proliferation and may be a potential biomarker for the detection of early‐stage RCC.
“EMERGing” Electronic Health Record Data Metrics: Insights and Implications for Assessing Residents’ Clinical Performance in Emergency Medicine
Authors: Sebok‐Syer Stefanie S. , Shepherd Lisa , McConnell Allison , Dukelow Adam M. , Sedran Robert , Lingard Lorelei
Published: July 2020

Objectives

Competency‐based medical education requires that residents are provided with frequent opportunities to demonstrate competence as well as receive effective feedback about their clinical performance. To meet this goal, we investigated how data collected by the electronic health record (EHR) might be used to assess emergency medicine (EM) residents’ independent and interdependent clinical performance and how such information could be represented in an EM resident report card.

Methods

Following constructivist grounded theory methodology, individual semistructured interviews were conducted in 2017 with 10 EM faculty and 11 EM residents across all 5 postgraduate years. In addition to open‐ended questions, participants were presented with an emerging list of EM practice metrics and asked to comment on how valuable each would be in assessing resident performance. Additionally, we asked participants the extent to which each metric captured independent or interdependent performance. Data collection and analysis were iterative; analysis employed constant comparative inductive methods.

Results

Participants refined and eliminated metrics as well as added new metrics specific to the assessment of EM residents (e.g., time between signup and first orders). These clinical practice metrics based on data from our EHR database were organized along a spectrum of independent/interdependent performance. We conclude with discussions about the relationship among these metrics, issues in interpretation, and implications of using EHR for assessment purposes.

Conclusions

Our findings document a systematic approach for developing EM resident assessments, based on EHR data, which incorporate the perspectives of both clinical faculty and residents. Our work has important implications for capturing residents’ contributions to clinical performances and distinguishing between independent and interdependent metrics in collaborative workplace‐based settings.
Flexible Scheduling Policy for Pregnant and New Parent Residents: A Descriptive Pilot Study
Authors: Chernoby Kimberly A. , Pettit Katie E. , Jansen Jaclyn H. , Welch Julie L.
Published: July 2020

Objectives

Many physicians complete residency training during optimal childbearing years. The literature shows that working nights or on call can lead to pregnancy complications including miscarriage, preterm labor, and preeclampsia. In addition, infant–parent bonding in the postpartum period is crucial for breastfeeding, health, and well‐being. No national standards exist for flexible scheduling options for pregnant or new parent residents. Our project objectives are 1) to describe a policy for scheduling pregnant and new parent residents in an emergency medicine (EM) residency and 2) to report pilot outcomes to assess feasibility of implementation, resident satisfaction, and pregnancy outcomes.

Methods

An EM residency task force developed a proposal of scheduling options for pregnant and new parent residents based on best practice recommendations and resident input. The policy included prenatal scheduling options for pregnant residents and postpartum scheduling options for all new resident parents. Resident support for the policy was evaluated via an anonymous survey. It was piloted for 2 months in an EM residency program.

Results

Policy development resulted in 1) an opt‐out prenatal pregnancy work hour option policy with no nights or call during the first and third trimesters, 2) a 6‐week new parent flexible scheduling policy, and 3) clarified sick call options. A majority of residents approved the new policy. During the 2‐month pilot period, four residents (of 73 total) utilized the policy. The chief residents reported no added burden in scheduling. Of the residents who utilized the policy, all reported high satisfaction. There were no reported pregnancy or postpartum complications.

Conclusions

We successfully adopted a new scheduling policy for pregnant residents and new parents in one of the largest EM residency training programs in the country. This policy can serve as a national model for other graduate medical education programs.
Computational evaluation of effective transport properties of differential microcellular structures
Authors: Otaru Abdulrazak J. , Abdulkadir Mukhtar , Corfield Martin R. , Kenfack Anatole , Tanko Nuradeen
Published: July 2020

This study presents a combined implementation of three‐dimensional (3D) advanced imaging and computational fluid dynamics (CFD) modeling and simulation techniques to interpret the effective transport properties of single and stacked samples of differential microcellular structures. 3D morphological analysis software (ScanIP) was used to create representative elemental volumes via high‐resolution tomography data for samples of tetrakaidekahedron‐shaped Inconel and bottleneck‐type aluminum foams. Pore‐structure‐related information for single and stacked differential samples were obtained with the aid of image analysis software, while their effective transport properties were attained by computationally resolving the pressure drop developed across these materials for superficial fluid velocities in the range from 0 to 6 m s−1. Model validation was demonstrated by tolerable agreement between resulting CFD predicted results and experimentally measured values of flow properties. With these techniques, contributory effects were identified for pore‐structure‐related properties, pore density, and flow entrance on the flow dynamics of microcellular structures. This approach could prove useful in the design of highly efficient porous metallic components for applications specific to fluid transport.
Land for equity? A benefit distribution model for mining‐induced displacement and resettlement
Authors: Wang Han , Owen John R. , Shi Guoqing
Published: July 2020

Land access is central to natural resource development projects. Business strategy for securing continuing tenure to support operational activities is therefore a key factor in determining the overall success of resource projects. A major shortcoming in resettlement planning has been the failure to address basic inequities stemming from the transfer of land assets. Compensation for land in conventional models neglects to account for the potential or intended use of the developer, meaning that affected people (APs) assets are grossly undervalued in the environment in which they acquired. Not only do resource projects under‐compensate APs for their losses, but programming for livelihood restoration and the enjoyment of project benefits more generally has proven to be almost universally poor. Performance outcomes reflect short‐term project milestones but lack a strategic dimension regarding how the company will maintain land access and the continuing support of its nearest stakeholders. Innovations are needed on at least two fronts: (i) the recognition of AP land values in mining project developments and (ii) enterprise financing to avoid the issue of companies driving incurred compensation costs downward. This article outlines the conceptual basis of a land pooling model as the means for securing financial equity for people displaced by mining projects. The authors conclude that the land pooling model of resettlement (LPMR) can improve the short‐ to medium‐term economic conditions of APs and advances suggestions to further promote a balance of interests in mining‐induced displacement and resettlement cases.
Single‐cell RNA sequencing in breast cancer: Understanding tumor heterogeneity and paving roads to individualized therapy
Authors: Ding Shuning , Chen Xiaosong , Shen Kunwei
Published: July 2020

Single‐cell RNA sequencing (scRNA‐seq) is a novel technology that allows transcriptomic analyses of individual cells. During the past decade, scRNA‐seq sensitivity, accuracy, and efficiency have improved due to innovations including more sensitive, automated, and cost‐effective single‐cell isolation methods with higher throughput as well as ongoing technological development of scRNA‐seq protocols. Among the variety of current approaches with distinct features, researchers can choose the most suitable method to carry out their research. By profiling single cells in a complex population mix, scRNA‐seq presents great advantages over traditional sequencing methods in dissecting heterogeneity in cell populations hidden in bulk analysis and exploring rare cell types associated with tumorigenesis and metastasis. scRNA‐seq studies in recent years in the field of breast cancer research have clustered breast cancer cell populations with different molecular subtypes to identify distinct populations that may correlate with poor prognosis and drug resistance. The technology has also been used to explain tumor microenvironment heterogeneity by identifying distinct immune cell subsets that may be associated with immunosurveillance and are potential immunotherapy targets. Moreover, scRNA‐seq has diverse applications in breast cancer research besides exploring heterogeneity, including the analysis of cell‐cell communications, regulatory single‐cell states, immune cell distributions, and more. scRNA‐seq is also a promising tool that can facilitate individualized therapy due to its ability to define cell subsets with potential treatment targets. Although scRNA‐seq studies of therapeutic selection in breast cancer are currently limited, the application of this technology in this field is prospective. Joint efforts and original ideas are needed to better implement scRNA‐seq technologies in breast cancer research to pave the way for individualized treatment management. This review provides a brief introduction on the currently available scRNA‐seq approaches along with their corresponding strengths and weaknesses and may act as a reference for the selection of suitable methods for research. We also discuss the current applications of scRNA‐seq in breast cancer research for tumor heterogeneity analysis, individualized therapy, and the other research directions mentioned above by reviewing corresponding published studies. Finally, we discuss the limitations of current scRNA‐seq technologies and technical problems that remain to be overcome.
Suspension pattern and rising height of sedimentary particles with low concentration in a mechanically stirred vessel
Authors: Tokura Yuichiro , Miyagawa Keita , Uddin Md. Azhar , Kato Yoshiei
Published: July 2020

In this study, the effects of impeller rotation speed, off‐bottom clearance, blade angle, types of solid and liquid, etc., on the suspension pattern of sedimentary particles and particle rise height in liquid were investigated with a hemispherical vessel without baffles under low particle concentration. The transition conditions of suspension pattern between regimes I and II, and regimes II and III, were observed visually, and their non‐dimensional equations were expressed with an acceptable correlation by varying the above operation factors a great deal. Here, regime I is stagnation of particles on a vessel bottom, II is partial suspension, and III is complete suspension in liquid. The non‐dimensional equation of the maximum particle rise height was also successfully obtained. The combination of the non‐dimensional equations of transition and maximum particle rise height permitted us to determine the adequate solid/liquid mixing operation conditions without collision of particles with device parts.
Mechanically mixed ZnO‐Al2O3 catalysts in the synthesis of propylene carbonate via alcoholysis of urea
Authors: Jia Yuchen , Lv Lei , Nie Yingying , Jiao Linyu , Shen Weihua , Zhu Zhiqing , Fang Yunjin
Published: July 2020

Alcoholysis of urea with 1,2‐propylene glycol (PG) is a potential industrial process for the synthesis of propylene carbonate (PC) with many advantages. However, the preparation of industrial catalysts such as Zn‐Al oxide by the co‐precipitation method will inevitably produce a large amount of salty water and building desalting equipment will increase the investment cost. The present work attempts to use a mechanically mixed catalyst consisting of commercial ZnO and Al2O3 to solve these problems. This type of catalyst was capable of catalyzing the reaction more than 5 times. The PC yield was gradually increased with each use. The best PC yield of 96.7% is comparable to the co‐precipitated Zn‐Al oxide catalysts and was achieved during the third use. In the reaction, ZnO and Al2O3 were dissolved into the reactants to form complexes, which homogenously catalyzed the reaction. It was found that the dissolved Zn and Al complex significantly influenced the PC yield and re‐precipitated in the late stage of the reaction. Furthermore, the partial dissolution of Al assisted the dissolution and precipitation of Zn, which improved the PC yield. After several dissolution‐precipitation cycles, ZnO‐Al2O3 was homogeneously mixed at the atomic scale. Interestingly, there was an adequate linear relationship between the amount of dissolved Zn and Al in each reaction, the linear correlation coefficient improved after each reaction, and the slope of the line (the ratio of dissolved Zn/Al) was 7.26 in the third use.
A continuous‐flow surface flotation cell for the separation of scanty mineral samples based on wettability contrast
Authors: Faucher Michaël , Gravel Olivier , Larachi Faïçal
Published: July 2020

Reliable measurements of hydrophobicity of minerals and ores are important to the study of the separation performance of a froth flotation process. However, surface heterogeneity, which is inexorably linked to actual industrial ores, has always been a challenging factor to characterize with currently existing measurement techniques. In this study, a new apparatus of surface flotation that provides surface floatability and wettability evaluation requiring parsimonious needs in sample consumption is presented. It consists of a continuous‐flow macroscopically flat‐interface flotation cell for the selective separation at a moving liquid‐gas interface between hydrophobic mineral and hydrophilic gangue from scanty mineral samples. To prove the concept, comparative experiments were conducted with a mineral matrix composed of graphite and quartz using the new surface flotation apparatus, a micro‐flotation cell, and a Denver cell. The results obtained from the surface flotation cell indicate that its separation efficiency and its reproducibility are better than the two standard laboratory separation techniques. Use of this new technique provides more and better information related to the wettability of mineral/ore surfaces while requiring as low as 3 g of mineral samples.
Catalytic Asymmetric Total Synthesis of Macrocyclic Marine Natural Product (–)‐Haliclonin A†
Authors: Luo Shi‐Peng , Huang Xiong‐Zhi , Guo Lian‐Dong , Huang Pei‐Qiang
Published: July 2020

Summary of main observation and conclusion

We describe the full details of our total synthesis of haliclonin A, a macrocyclic natural product suggested to originate from a common biosynthetic intermediate as sarain A. Central to our synthetic route is the strategic employment of nitromethane for several purposes: (1) as an umpolung surrogate of an aminomethyl group; (2) as an ideal nucleophile for the highly enantioselective catalytic asymmetric conjugate addition to forge the challenging all‐carbon quaternary stereogenic center that was used to induce the formations of all other chiral centers of the molecule; and (3) as a C1N1 building block to form the 3‐azabicyclo[3.3.1]nonane framework. The realization of this strategy relied on the development of a novel organocatalytic asymmetric conjugate addition of nitromethane to 3‐alkenyl cyclohex‐2‐enone, and the first Pd‐promoted intramolecular coupling of a thiocarbamate moiety onto an electron‐deficient alkene (enone) to form the 3‐azabicyclo[3,3,1]nonane core. The synthesis also features a SmI2‐mediated intermolecular reductive coupling of an enone with an aldehyde, ring‐closing alkene and alkyne metathesis reactions to build the two aza‐macrocycles, and an unprecedented direct transformation of enol into enone.
PROTOCOL: Exercise interventions to improve back shape/posture, balance, falls and fear of falling in older adults with hyperkyphosis: A systematic review
Authors: Duangkaew Roongtip , Bettany‐Saltikov Josette , van Schaik Paul , Kandasamy Gokulakannan , Hogg Julie
Published: July 2020

Aim

The aim of this systematic review is to evaluate and synthesize published and unpublished literature on the effectiveness of a diverse range of exercise programs on back shape/posture, balance, falling and fear of falling in older people with hyperkyphosis.

Objectives

The objective of this systematic review is to determine the effects of difference exercise programs on back shape/posture, balance, falling and fear of falling in older adults with hyperkyphosis.
Market Exclusivity Length for Drugs with New Generic or Biosimilar Competition, 2012–2018
Authors: Rome Benjamin N. , Lee ChangWon C. , Kesselheim Aaron S.
Published: July 2020

Brand‐name drugs have periods of market exclusivity before generic competition begins. Due to high brand‐name drug prices charged during this period, market exclusivity is an important determinant of US prescription drug spending. We used claims data to estimate the market exclusivity period for 264 small molecule and 4 biologic drugs that faced new generic or biosimilar competition from 2012–2018. Exclusivity periods were longer for biologics compared with new small molecule drugs (median 21.5 vs. 14.4 years, P = 0.02), longer for drugs with annual revenue < $75 million compared with those with revenue ≥ $500 million (16.6 vs. 14.2 years, P = 0.01), and shorter in cases for which the first generic was granted 180 days of exclusivity, which is an incentive designed to expedite generic competition (14.1 vs. 15.9 years, P < 0.01). Modified versions of existing products had shorter exclusivities than new drugs (9.9 vs. 14.5 years, P < 0.01), with variation by route of administration, therapeutic area, and use of expedited approval pathways. Exclusivity periods for new drugs ranging from 13–17 years are similar to older estimates, but longer exclusivity among the small number of biologics in the cohort raises concern that overall median exclusivity may lengthen in the future because biologics represent a larger fraction of new drug approvals over the last decade than they did the previous decade. Unnecessarily long exclusivity periods delay patient access to lower‐priced medications, and policymakers should consider options to encourage timely competition, particularly among biologic drugs.
Decrease of Non‐Classical and Intermediate Monocyte Subsets in Severe Acute SARS‐CoV‐2 Infection
Authors: Gatti Arianna , Radrizzani Danilo , Viganò Paolo , Mazzone Antonino , Brando Bruno
Published: July 2020

In patients with severe SARS‐CoV‐2 infection, the development of cytokine storm induces extensive lung damage, and monocytes play a role in this pathological process. Non‐classical (NC) and intermediate (INT) monocytes are known to be involved during viral and bacterial infections. In this study, 30 patients with different manifestations of acute SARS‐CoV‐2 infection were investigated with a flow cytometric study of NC, INT, and classical (CL) monocytes. Significantly reduced NC and INT monocytes and a downregulated HLA‐DR were found in acute patients with severe SARS‐CoV‐2 symptoms. Conversely in patients with moderate symptoms NC and INT monocytes and CD11b expression were increased. © 2020 International Society for Advancement of Cytometry
Tracking evoked responses to auditory and visual stimuli in fetuses exposed to maternal high‐risk conditions
Authors: Eswaran Hari , Lau Chrystal , Murphy Pam , Siegel Eric R. , Preissl Hubert , Lowery Curtis
Published: July 2020

Magnetoencephalography (MEG) has been successfully applied to record fetal auditory (auditory evoked response [AER]) and visual evoked responses (VER). In this study, we report the AER and VER development trajectory by tracking the evoked response detectability and latency from recordings starting at 27 weeks of gestation in pregnancies classified as high risk. Fetal MEG and ultrasound recordings were performed on 158 pregnant women, and the total number of fetal auditory and visual tests conducted was 321 and 237, respectively. The overall evoked response analysis showed 237 AER (73.8%) and 164 VER detections (69.2%). The mean AER latency was 290.7 (SD 125.5) ms and the mean VER latency was 293.7 (SD 114.5) ms. The rate of decrease (95% confidence limits) in average AER and VER first‐peak latency between 100–350 ms was 1.97 (−1.86, +5.81) ms/week and 1.35 (−3.83, +6.53) ms/week, respectively. This trend in high‐risk fetuses conforms to the general trajectory of decrease in latency with gestational age progression, even though this decrease was non‐significant, as reported in the case of normal growing fetuses. Although there was a significant difference in detection rates between male and female fetuses, this was not reflected in either latency values or the sensory modality applied. Furthermore, the main factors that had the most significant effect on response detectability included the presence of intervening layers of adipose tissue between the fetal head and stimulus source and an increase in the maternal body mass index.
Species diversity and phylogeography of Cornus kousa (Asian dogwood) captured by genomic and genic microsatellites
Authors: Nowicki Marcin , Houston Logan C. , Boggess Sarah L. , Aiello Anthony S. , Payá‐Milans Miriam , Staton Margaret E. , Hayashida Mitsuhiro , Yamanaka Masahiro , Eda Shigetoshi , Trigiano Robert N.
Published: July 2020

Cornus kousa (Asian dogwood), an East Asia native tree, is the most economically important species of the dogwood genus, owing to its desirable horticultural traits and ability to hybridize with North America‐native dogwoods. To assess the species genetic diversity and to better inform the ongoing and future breeding efforts, we assembled an herbarium and arboretum collection of 131 noncultivated C. kousa specimens. Genotyping and capillary electrophoresis analyses of our C. kousa collection with the newly developed genic and published nuclear genomic microsatellites permitted assessment of genetic diversity and evolutionary history of the species. Regardless of the microsatellite type used, the study yielded generally similar insights into the C. kousa diversity with subtle differences deriving from and underlining the marker used. The accrued evidence pointed to the species distinct genetic pools related to the plant country of origin. This can be helpful in the development of the commercial cultivars for this important ornamental crop with increased pyramided utility traits. Analyses of the C. kousa evolutionary history using the accrued genotyping datasets pointed to an unsampled ancestor population, possibly now extinct, as per the phylogeography of the region. To our knowledge, there are few studies utilizing the same gDNA collection to compare performance of genomic and genic microsatellites. This is the first detailed report on C. kousa species diversity and evolutionary history inference.
Explicit two‐step Runge‐Kutta methods for computational fluid dynamics solvers
Authors: Figueroa Alejandro , Jackiewicz Zdzisław , Löhner Rainald
Published: July 2020

Computational fluid dynamics (CFD) has emerged as a successful tool for industry applications and basic science during the last decades. However, accurate solutions involving vortex propagation, and separated and turbulent flows, are still associated with high computing costs. In particular, large eddy simulations (LES) of complex geometries, such as a complete automobile, require several days on thousands of cores in order to obtain solutions with statistically relevant information. With an increase in the number of available cores, the number of degrees of freedom (DOF) per core can be reduced accordingly. When the number of DOF per core is below a certain threshold the total simulation time is not bounded by floating point operations (FLOPS), but by the time spend on communication between cores. To overcome this impediment we have identified and tested a class of two‐step Runge‐Kutta (TSRK) methods of high order with low number of stages, for time discretization of differential systems resulting from space discretization of weakly compressible Navier‐Stokes equations. These methods have not been used before in CFD simulations. The advantage of using these methods is reduction in communication times between cores. The numerical experiments indicate that the gains in computational performance of this new class of TSRK methods, as compared with classical Runge‐Kutta (RK) methods or low storage Runge‐Kutta (LSRK) schemes, are of the order of 25%, with no loss in accuracy.
Accelerating CFD solver computation time with reduced‐order modeling in a multigrid environment
Authors: Karcher Niklas , Wallraff Marcel
Published: July 2020

Reduced‐order models (ROMs) are more and more considered for use in aerodynamic applications. Benefits of these methods can be expected for optimization problems or predicting aerodynamic loads for the entire flight envelope. For these applications it is often possible to perform computations for various parameter combinations before any ROM evaluations are needed. The order reduction of the CFD solutions in this article is done using proper orthogonal decomposition. Coupled with an interpolation method predictions for unknown parameter combinations can be made. The CFD solutions are computed using a discontinuous Galerkin finite element method combined with a nonlinear multigrid scheme. The nonlinear multigrid solver algorithms depend on a good initial guess of the flow field to be computed. Typically, the initial guess on a fine mesh is obtained by solving the problem on a agglomerated mesh. Alternatively, an initial guess could be obtained from a ROM prediction, if available. The main objective is to identify the benefits of using a ROM in a higher‐order multigrid environment. Integral as well as distributed surface quantities of the ROM predictions originating from several multigrid levels will be compared with fully converged flow solutions on the top level of the multigrid algorithm. Furthermore, initializing the flow solver with predictions from several multigrid levels will be analyzed in comparison to full multigrid computations as well as to a scenario where already converged solutions for similar parameter combinations are used as initial flow solutions on the top multigrid level.
Activation of PLAG1 and HMGA2 by gene fusions involving the transcriptional regulator gene NFIB
Authors: Afshari Maryam Kakay , Fehr André , Nevado Paloma Tejera , Andersson Mattias K. , Stenman Göran
Published: July 2020

The pleomorphic adenoma (PA), which is the most common salivary gland neoplasm, is a benign tumor characterized by recurrent chromosome rearrangements involving 8q12 and 12q14‐15. We have previously shown that the PLAG1 and HMGA2 oncogenes are the targets of these rearrangements. Here, we have identified previously unrecognized subsets of PAs with ins(9;8)/t(8;9) (n = 5) and ins(9;12)/t(9;12) (n = 8) and breakpoints located in the vicinity of the PLAG1 and HMGA2 loci. RNA‐sequencing and reverse transcriptase (RT)‐PCR analyses of a case with an ins(9;8) revealed a novel NFIB‐PLAG1 fusion in which NFIB exon 4 is linked to PLAG1 exon 3. In contrast to the developmentally regulated PLAG1 gene, NFIB was highly expressed in normal salivary gland, indicating that PLAG1 in this case, as in other variant fusions, is activated by promoter swapping. RT‐PCR analysis of three PAs with t(9;12) revealed two tumors with chimeric transcripts consisting of HMGA2 exon 4 linked to NFIB exons 9 or 3 and one case with a fusion linking HMGA2 exon 3 to NFIB exon 9. The NFIB fusion events resulted in potent activation of PLAG1 and HMGA2. Analysis of the chromatin landscape surrounding NFIB revealed several super‐enhancers in the 5′‐ and 3′‐parts of the NFIB locus and its flanking sequences. These findings indicate that PLAG1 and HMGA2, similar to MYB in adenoid cystic carcinoma, may be activated by enhancer‐hijacking events, in which super‐enhancers in NFIB are translocated upstream of PLAG1 or downstream of HMGA2. Our results further emphasize the role of NFIB as a fusion partner to multiple oncogenes in histopathologically different types of salivary gland tumors.
ACSIS Atlantic Ocean medium resolution SST dataset: Reconstructed 5‐day, ½‐degree, Atlantic Ocean SST (1950‐2014)
Authors: Williams Simon David Paul , Berry David I.
Published: July 2020

A new dataset, the ACSIS Atlantic Ocean medium resolution SST dataset, is presented. This new dataset spans the period 1950–2014 at a 5‐day, ½‐degree resolution and covers the Atlantic Ocean. The dataset is based on in situ sea surface temperature (SST) observations from the International Comprehensive Ocean‐Atmosphere Data Set interpolated using Kriging to infill gaps and is available from the Centre for Environmental Data Analysis (CEDA) archive. Compared to existing datasets, the resolution is increased by a factor of 4 spatially and 6 temporally.
Intestinal Virome in Patients With Alcoholic Hepatitis
Authors: Jiang Lu , Lang Sonja , Duan Yi , Zhang Xinlian , Gao Bei , Chopyk Jessica , Schwanemann Leila K. , Ventura‐Cots Meritxell , Bataller Ramon , Bosques‐Padilla Francisco , Verna Elizabeth C. , Abraldes Juan G. , Brown Robert S. , Vargas Victor , Altamirano Jose , Caballería Juan , Shawcross Debbie L. , Ho Samuel B. , Louvet Alexandre , Lucey Michael R. , Mathurin Philippe , Garcia‐Tsao Guadalupe , Kisseleva Tatiana , Brenner David A. , Tu Xin M. , Stärkel Peter , Pride David , Fouts Derrick E. , Schnabl Bernd
Published: July 2020

Background and Aims

Alcoholic hepatitis (AH) is a severe manifestation of alcohol‐associated liver disease (ALD) with high mortality. Although gut bacteria and fungi modulate disease severity, little is known about the effects of the viral microbiome (virome) in patients with ALD.

Approach and Results

We extracted virus‐like particles from 89 patients with AH who were enrolled in a multicenter observational study, 36 with alcohol use disorder (AUD), and 17 persons without AUD (controls). Virus‐like particles from fecal samples were fractionated using differential filtration techniques, and metagenomic sequencing was performed to characterize intestinal viromes. We observed an increased viral diversity in fecal samples from patients with ALD, with the most significant changes in samples from patients with AH. Escherichia‐, Enterobacteria‐, and Enterococcus phages were over‐represented in fecal samples from patients with AH, along with significant increases in mammalian viruses such as Parvoviridae and Herpesviridae. Antibiotic treatment was associated with higher viral diversity. Specific viral taxa, such as Staphylococcus phages and Herpesviridae, were associated with increased disease severity, indicated by a higher median Model for End‐Stage Liver Disease score, and associated with increased 90‐day mortality.

Conclusions

In conclusion, intestinal viral taxa are altered in fecal samples from patients with AH and associated with disease severity and mortality. Our study describes an intestinal virome signature associated with AH.
On the probabilistic modeling of fake news (hoax) persistency in online social networks and the role of debunking and filtering
Authors: Coluccia Angelo
Published: July 2020

Understanding the dynamics of information diffusion, including spreading of fake news, hoaxes, and generally, misinformation/disinformation, has become crucial in post‐truth societies. The paper focuses on the probability that a hoax originated at a given time will continue to spread indefinitely in online social networks; a minimalistic model based on the theory of branching processes is devised, which only considers the basic possible reactions that users can have after reading a post whose content is a hoax, that is, to share it further, to ignore it, or to try to debunk it. The analysis of the resulting dynamics shows that ignoring is indeed not sufficient to stop the spreading, not even if most people do so. More active counter‐measures are needed; in particular, the proposed model formally describes the ways in which retractions and debunking posts, cultural/educational initiatives, and content moderation policies (including filtering) by Internet companies, can impact on the persistency probability of hoaxes and generally fake news.
Role of pharmacists in improving accessibility of antiretrovirals to support the United States President's Emergency Plan for AIDS Relief: Impact on the patient, program, and market
Authors: Malati Christine Y.
Published: July 2020

The United States President's Emergency Plan for AIDS Relief (PEPFAR) is the largest commitment by any nation to combat a single disease through prevention and treatment initiatives; pharmacists play a critical role in improving the accessibility of antiretrovirals (ARVs). When determining the potential use of a medication for a human immunodeficiency virus (HIV) program, it is helpful to consider decisions through the (a) Perspective of a patient, (b) Perspective of the overarching HIV program providing care, and (c) Perspective of the ARV market. Pharmacists are uniquely positioned to contribute to decisions from these three perspectives. At the beginning of PEPFAR, the price of ARVs was cost prohibitive; however, after 17 years since its inception, through the work of pharmacists and other public health professionals, the price to treat one patient for one year is currently 63 USD. This article describes the impact of pharmacists at the U.S. Agency for International Development (USAID) and the Food and Drug Administration (FDA) in facilitating a dramatic reduction in the cost of ARVs, through the use of an expedited approval process and through pooling procurement of ARVs from a limited formulary.
Biophotonics methods for functional monitoring of complications of diabetes mellitus
Authors: Zharkikh Elena , Dremin Viktor , Zherebtsov Evgeny , Dunaev Andrey , Meglinski Igor
Published: July 2020

The prevalence of diabetes complications is a significant public health problem with a considerable economic cost. Thus, the timely diagnosis of complications and prevention of their development will contribute to increasing the length and quality of patient life, and reducing the economic costs of their treatment. This article aims to review the current state‐of‐the‐art biophotonics technologies used to identify the complications of diabetes mellitus and assess the quality of their treatment. Additionally, these technologies assess the structural and functional properties of biological tissues, and they include capillaroscopy, laser Doppler flowmetry and hyperspectral imaging, laser speckle contrast imaging, diffuse reflectance spectroscopy and imaging, fluorescence spectroscopy and imaging, optical coherence tomography, optoacoustic imaging and confocal microscopy. Recent advances in the field of optical noninvasive diagnosis suggest a wider introduction of biophotonics technologies into clinical practice and, in particular, in diabetes care units.
Antibacterial activity of nitric oxide‐releasing carboxymethylcellulose against periodontal pathogens
Authors: Feura Evan S. , Yang Lei , Schoenfisch Mark H.
Published: July 2020

The prevalence of periodontal disease poses a significant global health burden. Treatments for these diseases, primarily focused on removal and eradication of dental plaque biofilms, are challenging due to limited access to periodontal pockets where these oral pathogens reside. Herein, we report on the development and characterization of nitric oxide (NO)‐releasing carboxymethylcellulose (CMC) derivatives and evaluate their in vitro bactericidal efficacy against planktonic Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, two prominent periodontopathogens. Bactericidal exposure assays revealed that three of the synthesized NO‐releasing polymers were capable of reducing bacterial viability of both species by 99.9% in 2 hr at concentrations of 4 mg ml−1 or lower, reflecting NO's potent and rapid bactericidal action. The NO‐releasing CMCs elicited minimal toxicity to human gingival fibroblasts at their bactericidal concentrations following 24‐hr exposure.
Strontium substitution of gelatin modified calcium hydrogen phosphates as porous hard tissue substitutes
Authors: Kruppke Benjamin , Heinemann Christiane , Gebert Annett , Rohnke Marcus , Weiß Manuel , Henß Anja , Wiesmann Hans‐Peter , Hanke Thomas
Published: July 2020

Aiming at the generation of a high strontium‐containing degradable bone substitute, the exchange of calcium with strontium in gelatin‐modified brushite was investigated. The ion substitution showed two mineral groups, the high‐calcium containing minerals with a maximum measured molar Ca/Sr ratio of 80%/20% (mass ratio 63%/37%) and the high‐strontium containing ones with a maximum measured molar Ca/Sr ratio of 21%/79% (mass ratio 10%/90%). In contrast to the high‐strontium mineral phases, a high mass loss was observed for the calcium‐based minerals during incubation in cell culture medium (alpha‐MEM), but also an increase in strength owing to dissolution and re‐precipitation. This resulted for the former in a decrease of cation concentration (Ca + Sr) in the medium, while the pH value decreased and the phosphate ion concentration rose significantly. The latter group of materials, the high‐strontium containing ones, showed only a moderate change in mass and a decrease in strength, but the Ca + Sr concentration remained permanently above the initial calcium concentration in the medium. This might be advantageous for a future planned application by supporting bone regeneration on the cellular level.
A multilayered scaffold for regeneration of smooth muscle and connective tissue layers
Authors: Garrison Carly M. , Singh‐Varma Anya , Pastino Alexandra K. , Steele Joseph A. M. , Kohn Joachim , Murthy N. Sanjeeva , Schwarzbauer Jean E.
Published: July 2020

Tissue regeneration often requires recruitment of different cell types and rebuilding of two or more tissue layers to restore function. Here, we describe the creation of a novel multilayered scaffold with distinct fiber organizations—aligned to unaligned and dense to porous—to template common architectures found in adjacent tissue layers. Electrospun scaffolds were fabricated using a biodegradable, tyrosine‐derived terpolymer, yielding densely‐packed, aligned fibers that transition into randomly‐oriented fibers of increasing diameter and porosity. We demonstrate that differently‐oriented scaffold fibers direct cell and extracellular matrix (ECM) organization, and that scaffold fibers and ECM protein networks are maintained after decellularization. Smooth muscle and connective tissue layers are frequently adjacent in vivo; we show that within a single scaffold, the architecture supports alignment of contractile smooth muscle cells and deposition by fibroblasts of a meshwork of ECM fibrils. We rolled a flat scaffold into a tubular construct and, after culture, showed cell viability, orientation, and tissue‐specific protein expression in the tube were similar to the flat‐sheet scaffold. This scaffold design not only has translational potential for reparation of flat and tubular tissue layers but can also be customized for alternative applications by introducing two or more cell types in different combinations.
Burden of Illness in Adults With Hypophosphatasia: Data From the Global Hypophosphatasia Patient Registry
Authors: Seefried Lothar , Dahir Kathryn , Petryk Anna , Högler Wolfgang , Linglart Agnès , Martos-Moreno Gabriel Ángel , Ozono Keiichi , Fang Shona , Rockman-Greenberg Cheryl , Kishnani Priya S
Published: July 2020

Hypophosphatasia (HPP) is a rare, inherited, metabolic disease caused by deficient tissue non-specific alkaline phosphatase activity. This study aims to assess patient-reported pain, disability and health-related quality of life (HRQoL) in a real-world cohort of adults with HPP who were not receiving asfotase alfa during the analysis. Adults (≥18 years old) with HPP (confirmed by ALPL gene mutation and/or low serum alkaline phosphatase activity for age/sex) were identified from the Global HPP Registry (NCT02306720). Demographics, clinical characteristics, and data on patient-reported pain, disability, and HRQoL (assessed by Brief Pain Inventory Short Form [BPI-SF], Health Assessment Questionnaire Disability Index [HAQ-DI], and 36-Item Short-Form Health Survey version 2 [SF-36v2], respectively) were stratified by pediatric- and adult-onset HPP and summarized descriptively. Of the 304 adults included (median [min, max] age 48.6 [18.8, 79.8] years; 74% women), 45% had adult-onset HPP and 33% had pediatric-onset HPP (unknown age of onset, 22%). Of those with data, 38% had experienced ≥5 HPP manifestations and 62% had a history of ≥1 fracture/pseudofracture. Median (Q1, Q3) BPI-SF scores were 3.5 (1.5, 5.3) for pain severity and 3.3 (0.9, 6.2) for pain interference. Median (Q1, Q3) disability on the HAQ-DI was 0.3 (0.0, 0.7). Median (Q1, Q3) physical and mental component summary scores on the SF-36v2 were 42.4 (32.7, 49.9) and 45.3 (36.3, 54.8), respectively. Greater numbers of HPP manifestations experienced/body systems affected correlated significantly with poorer scores on the BPI-SF, HAQ-DI, and SF-36v2 (all p < 0.05). No significant differences between adults with pediatric- and adult-onset HPP were observed for patient-reported outcomes, except for disability and the BPI-SF question “pain at its worst,” which were significantly higher among adults with pediatric- versus adult-onset HPP (p = 0.03 and 0.04, respectively). These data from the Global HPP Registry show that adults with HPP have a substantial burden of illness that is associated with reduced patient-reported HRQoL, regardless of age of disease onset. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Enolase‐phosphatase 1 acts as an oncogenic driver in glioma
Authors: Wang Bo , Xu Xin , Liu Xi , Wang Dong , Zhuang Hao , He Xin , Han Tong , Hong Jian
Published: July 2020

Enolase‐phosphatase 1 (ENOPH1), a newly identified enzyme involved in l‐methionine biosynthesis, is associated with anxiety and depression. In this study, ENOPH1 was found to play a crucial role in promoting the proliferation and migration of glioma cells. Among high‐grade glioma patients, the overall survival of the group showing high ENOPH1 expression was shorter than that of the group showing low ENOPH1 expression. ENOPH1 knockdown inhibited glioma cell proliferation and migration. In parallel, ENOPH1 knockdown suppressed tumor growth capacity and prolonged survival in an orthotopic glioma model. Mechanistically, we found that ENOPH1 activates the PI3K/AKT/mTOR signaling pathway by regulating THEM4. In conclusion, ENOPH1 is an important mediator that promotes glioma cell proliferation and migration.
Diagnostic potential of presepsin in bacterial infection following hepato‐biliary‐pancreatic surgery: A prospective observational study
Authors: Yao Siyuan , Kaido Toshimi , Uozumi Ryuji , Hirata Masaaki , Iwamura Sena , Miyachi Yosuke , Macshut Mahmoud , Sharshar Mohamed , Yagi Shintaro , Uemoto Shinji
Published: July 2020

Background/Purpose

The aim in the present study was to elucidate the diagnostic ability of presepsin for postoperative infectious complications following major hepato‐biliary‐pancreatic (HBP) surgery.

Methods

Between 2017 and 2019, 50 patients with major hepatectomy and 55 patients with pancreatoduodenectomy were enrolled. Presepsin, the neutrophil‐to‐lymphocyte ratio (NLR), C‐reactive protein (CRP), and procalcitonin (PCT) were prospectively measured for the first 2 weeks after surgery. The diagnostic abilities of these biomarkers were compared multidirectionally.

Results

All biomarkers returned to normal ranges within 2 weeks after surgery. However, presepsin, unlike the other biomarkers, showed less nonspecific elevation in response to the invasiveness of the surgical procedure immediately after surgery. Receiver operating characteristic curve analysis revealed that presepsin (area under the curve (AUC), 0.959) had a greater ability to discriminate bacterial infection than PCT (AUC, 0.723), CRP (AUC, 0.800), and the NLR (AUC, 0.804). A very high sensitivity of 93.3% and a specificity of 89.2% were achieved at the cutoff value of 620 pg/mL. Multivariable analysis revealed that presepsin on day 3 (P = .013) independently predicted bacterial infection after HBP surgery.

Conclusions

Presepsin may have a better predictive ability than existing biomarkers for infection following major HBP surgery, which may help us achieve faster and more accurate detection of bacterial infections.
Prediction of the progression of walled‐off necrosis in patients with acute pancreatitis on whole pancreatic perfusion CT
Authors: Yamamiya Akira , Kitamura Katsuya , Yoshida Hitoshi , Ishii Yu , Mitsui Yuta , Irisawa Atsushi
Published: July 2020

Background/Purpose

This study investigated whether measuring pancreatic blood volume (PBV) on whole pancreatic perfusion computed tomography (P‐CT) can predict the progression of walled‐off necrosis (WON) in patients with acute pancreatitis (AP).

Methods

A single‐center, retrospective cohort study was conducted between December 2015 and December 2016. The participants were divided into two groups: 14 patients with WON and 15 patients without WON. PBV was measured within 72 hours after the diagnosis of AP, and the final diagnosis of WON was made by contrast‐enhanced CT (CE‐CT) or endoscopic ultrasonography (EUS) 4 weeks after the onset of AP.

Results

The minimum CT value did not differ significantly between the two groups. On the other hand, the minimum PBV was significantly lower in the WON group than in the without WON group (1.4 (0.9–9.9) vs 19.8 (8.2–21.7) mL/100 mL, respectively; P = .02). The cutoff value of the minimum PBV for WON was 16.5 mL/100 mL (sensitivity 100%, specificity 67%, AUC 0.85; P = .001).

Conclusions

Whole pancreatic P‐CT can evaluate pancreatic ischemia visually and quantitatively. The minimum PBV measurement on whole pancreatic P‐CT within 72 hours after the diagnosis of AP contributes to the prediction of progression of WON.