bluuebunny/crossref_metadata_2025_split huggingface dataset:
Microstructure and abrasive wear properties of high-vanadium-chromium wear resistant alloy
Authors: Wang Fangfang , Xu Liujie , Zong Le , Luo Chunyang , Wei Shizhong 
Published: January 2021

Abstract
To enhance the wear resistance of high chromium cast iron (HCCI, Cr26), a new wear resistant alloy with high vanadium and chromium contents (HCCI-V, 15Cr5V4MoSiMn) was designed and prepared by sand mold casting. The microstructure and the phase composition were analyzed by SEM, EDS and XRD, and the abrasive wear property was tested compared with HCCI. Results show that the new wear resistant alloy is characterized by multi-scale and multi-type carbides distributed in a metal matrix composed of martensite and retained austensite. The carbides include VC, M7C3, M2C and M23C6 (M stands for (Cr, Fe)), with dimensions ranging from tens of nanometers to tens of micrometers. The hardness and impact toughness of HCCI-V are 65 ± 0.2 HRC and 10 ± 0.12 J cm−2, respectively, far higher than that of HCCI (57 ± 0.2 HRC, 8 ± 0.12 J cm−2). When the abrasive particle size and load are 6.5 μm and 1.41 MPa respectively, the wear weight loss of HCCI and HCCI-V are 5.6 ± 0.1 mg and 0.8 ± 0.1 mg respectively, and the relative wear resistance of HCCI-V is 7. The excellent wear resistance of HCCI-V is attributed to the multi-scale carbides. The micro-scale carbides resist scratch, and the nano-scale carbides strengthens matrix. The multi-scale carbides can work collaboratively to resist abrasive wear efficiently.
Rapid Validation of Whole-Slide Imaging for Primary Histopathology Diagnosis
Authors: Samuelson Megan I , Chen Stephanie J , Boukhar Sarag A , Schnieders Eric M , Walhof Mackenzie L , Bellizzi Andrew M , Robinson Robert A , Rajan K D Anand 
Published: January 2021

Abstract

Objectives
The ongoing global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic necessitates adaptations in the practice of surgical pathology at scale. Primary diagnosis by whole-slide imaging (WSI) is a key component that would aid departments in providing uninterrupted histopathology diagnosis and maintaining revenue streams from disruption. We sought to perform rapid validation of the use of WSI in primary diagnosis meeting recommendations of the College of American Pathologists guidelines.

Methods
Glass slides from clinically reported cases from 5 participating pathologists with a preset washout period were digitally scanned and reviewed in settings identical to typical reporting. Cases were classified as concordant or with minor or major disagreement with the original diagnosis. Randomized subsampling was performed, and mean concordance rates were calculated.

Results
In total, 171 cases were included and distributed equally among participants. For the group as a whole, the mean concordance rate in sampled cases (n = 90) was 83.6% counting all discrepancies and 94.6% counting only major disagreements. The mean pathologist concordance rate in sampled cases (n = 18) ranged from 90.49% to 97%.

Conclusions
We describe a novel double-blinded method for rapid validation of WSI for primary diagnosis. Our findings highlight the occurrence of a range of diagnostic reproducibility when deploying digital methods.
Liver Pathology and SARS-CoV-2 Detection in Formalin-Fixed Tissue of Patients With COVID-19
Authors: Chornenkyy Yevgen , Mejia-Bautista Melissa , Brucal Melanie , Blanke Timothy , Dittmann David , Yeldandi Anjana , Boike Justin R , Lomasney Jon W , Nayar Ritu , Jennings Lawrence J , Pezhouh Maryam Kherad 
Published: January 2021

Abstract

Objectives
The novel coronavirus, severe acute respiratory syndrome coronavirus 2, causing coronavirus disease 2019 (COVID-19) remains a global health threat and a significant source of human morbidity and mortality. While the virus primarily induces lung injury, it also has been reported to cause hepatic sequelae.

Methods
We aimed to detect the virus in formalin-fixed tissue blocks and document the liver injury patterns in patients with COVID-19 compared with a control group.

Results
We were able to detect viral RNA in the bronchioalveolar cell blocks (12/12, 100%) and formalin-fixed, paraffin-embedded tissue of the lung (8/8, 100%) and liver (4/9, 44%) of patients with COVID-19. Although the peak values of the main liver enzymes and bilirubin were higher in the patients with COVID-19 compared with the control group, the differences were not significant. The main histologic findings were minimal to focal mild portal tract chronic inflammation (7/8, 88%, P &lt; .05) and mild focal lobular activity (6/8, 75%, P = .06).

Conclusions
We found that most patients who died of COVID-19 had evidence of mild focal hepatitis clinically and histologically; however, the virus was detected in less than half of the cases.
Differences in phosphatidylcholine profiles and identification of characteristic phosphatidylcholine molecules in meat animal species and meat cut locations
Authors: Yamamoto Shunsuke , Kato Shigeki , Senoo Nanami , Miyoshi Noriyuki , Morita Akihito , Miura Shinji 
Published: January 2021

ABSTRACTPhosphatidylcholine (PC) is an essential component of the plasma membrane. Its profile varies with species and tissues. However, the PC profiles in meat have not been explored in depth. This study aimed to investigate the differences in PC profiles between various meat animal species and meat cut sites, along with the identification of characteristic PC molecules. The results demonstrated that the PC profiles of chicken meat differed from those of other species. Significant differences were also observed between the PC profiles of pork meat and the meat obtained from other species. The amount of PCs containing ether bonds was high in pork meat. PCs containing an odd number of carbon atoms were characteristic of beef and lamb meats. Furthermore, PC profiles differed based on the muscle location in chicken and pork. These results suggest that the PC profiles of skeletal muscles are indicators of animal species and muscle location.
Integrative analyses of transcriptome data reveal the mechanisms of post-transcriptional regulation
Authors: Wang Jinkai 
Published: January 2021

Abstract
Post-transcriptional processing of RNAs plays important roles in a variety of physiological and pathological processes. These processes can be precisely controlled by a series of RNA binding proteins and cotranscriptionally regulated by transcription factors as well as histone modifications. With the rapid development of high-throughput sequencing techniques, multiomics data have been broadly used to study the mechanisms underlying the important biological processes. However, how to use these high-throughput sequencing data to elucidate the fundamental regulatory roles of post-transcriptional processes is still of great challenge. This review summarizes the regulatory mechanisms of post-transcriptional processes and the general principles and approaches to dissect these mechanisms by integrating multiomics data as well as public resources.
ConPlot: web-based application for the visualization of protein contact maps integrated with other data
Authors: Sánchez Rodríguez Filomeno , Mesdaghi Shahram , Simpkin Adam J. , Burgos-Mármol J. Javier , Murphy David L. , Uski Ville , Keegan Ronan M. , Rigden Daniel J. 
Published: January 2021

Abstract

Summary
Covariance-based predictions of residue contacts and inter-residue distances are an increasingly popular data type in protein bioinformatics. Here we present ConPlot, a web-based application for convenient display and analysis of contact maps and distograms. Integration of predicted contact data with other predictions is often required to facilitate inference of structural features. ConPlot can therefore use the empty space near the contact map diagonal to display multiple coloured tracks representing other sequence-based predictions. Popular file formats are natively read and bespoke data can also be flexibly displayed. This novel visualization will enable easier interpretation of predicted contact maps.

Availability and implementation
available online at www.conplot.org, along with documentation and examples. Alternatively, ConPlot can be installed and used locally using the docker image from the project’s Docker Hub repository. ConPlot is licensed under the BSD 3-Clause.

Supplementary information
Supplementary data are available at Bioinformatics online.
Protocol for an open label: phase I trial within a cohort of foetal cell transplants in people with Huntington’s disease
Authors: Drew Cheney J G , Sharouf Feras , Randell Elizabeth , Brookes-Howell Lucy , Smallman Kim , Sewell Bernadette , Burrell Astrid , Kirby Nigel , Mills Laura , Precious Sophie , Pallmann Philip , Gillespie David , Hood Kerry , Busse Monica , Gray William P , Rosser Anne 
Published: January 2021

Abstract
Huntington’s disease is a progressive neurodegenerative disorder characterized by motor, cognitive and psychiatric symptoms. Currently, no disease-modifying therapies are available to slow or halt disease progression. Huntington’s disease is characterized by relatively focal and specific loss of striatal medium spiny neurons, which makes it suitable for cell-replacement therapy, a process involving the transplantation of donor cells to replace those lost due to disease. TRIal DEsigns for delivery of Novel Therapies in neurodegeneration is a phase I Trial Within a Cohort designed to assess safety and feasibility of transplanting human foetal striatal cells into the striatum of people with Huntington’s disease. A minimum of 18 participants will be enrolled in the study cohort, and up to five eligible participants will be randomly selected to undergo transplantation of 12–22 million foetal cells in a dose escalation paradigm. Independent reviewers will assess safety outcomes (lack of significant infection, bleeding or new neurological deficit) 4 weeks after surgery, and ongoing safety will be established before conducting each subsequent surgery. All participants will undergo detailed clinical and functional assessment at baseline (6 and 12 months). Surgery will be performed 1 month after baseline, and transplant participants will undergo regular clinical follow-up for at least 12 months. Evaluation of trial processes will also be undertaken. Transplant participants and their carers will be interviewed ∼1 month before and after surgery. Interviews will also be conducted with non-transplanted participants and healthcare staff delivering the intervention and involved in the clinical care of participants. Evaluation of clinical and functional efficacy outcomes and intervention costs will be carried out to explore plausible trial designs for subsequent randomized controlled trials aimed at evaluating efficacy and cost-effectiveness of cell-replacement therapy. TRIal DEsigns for delivery of Novel Therapies in neurodegeneration will enable the assessment of the safety, feasibility, acceptability and cost of foetal cell transplants in people with Huntington’s disease. The data collected will inform trial designs for complex intra-cranial interventions in a range of neurodegenerative conditions and facilitate the development of stable surgical pipelines for delivery of future stem cell trials. Trial Registration: ISRCTN52651778
The Precaution Presumption
Authors: Sourgens Frédéric Gilles 
Published: January 2021

Abstract
The precautionary principle is a central, if controversial, feature of international legal argument. I explore this controversy through a pluralist lens. What makes the precautionary principle so controversial is that it prevents us from appreciating risk holistically, particularly when appraising responses to policy trilemmas. Instead, claims of precaution focus only on some risks to the exclusion of others. I argue that we can overcome this problem by treating precaution as an evidentiary principle. This approach translates competing precautionary claims into a holistic appreciation of risk in its full factual context. I analyse that existing evidentiary conceptions of precaution (precaution as burden shift and precaution as standard-lowering) do not adequately achieve this goal. I submit that these problems can be overcome when treating precaution as an evidentiary presumption and develop how to formulate it.
Whole-Genome Sequence Data Suggest Environmental Adaptation of Ethiopian Sheep Populations
Authors: Wiener Pamela , Robert Christelle , Ahbara Abulgasim , Salavati Mazdak , Abebe Ayele , Kebede Adebabay , Wragg David , Friedrich Juliane , Vasoya Deepali , Hume David A , Djikeng Appolinaire , Watson Mick , Prendergast James G D , Hanotte Olivier , Mwacharo Joram M , Clark Emily L 
Published: January 2021

AbstractGreat progress has been made over recent years in the identification of selection signatures in the genomes of livestock species. This work has primarily been carried out in commercial breeds for which the dominant selection pressures are associated with artificial selection. As agriculture and food security are likely to be strongly affected by climate change, a better understanding of environment-imposed selection on agricultural species is warranted. Ethiopia is an ideal setting to investigate environmental adaptation in livestock due to its wide variation in geo-climatic characteristics and the extensive genetic and phenotypic variation of its livestock. Here, we identified over three million single nucleotide variants across 12 Ethiopian sheep populations and applied landscape genomics approaches to investigate the association between these variants and environmental variables. Our results suggest that environmental adaptation for precipitation-related variables is stronger than that related to altitude or temperature, consistent with large-scale meta-analyses of selection pressure across species. The set of genes showing association with environmental variables was enriched for genes highly expressed in human blood and nerve tissues. There was also evidence of enrichment for genes associated with high-altitude adaptation although no strong association was identified with hypoxia-inducible-factor (HIF) genes. One of the strongest altitude-related signals was for a collagen gene, consistent with previous studies of high-altitude adaptation. Several altitude-associated genes also showed evidence of adaptation with temperature, suggesting a relationship between responses to these environmental factors. These results provide a foundation to investigate further the effects of climatic variables on small ruminant populations.
A nervous system-specific subnuclear organelle in Caenorhabditis elegans
Authors: Pham Kenneth , Masoudi Neda , Leyva-Díaz Eduardo , Hobert Oliver 
Published: January 2021

Abstract
We describe here phase-separated subnuclear organelles in the nematode Caenorhabditis elegans, which we term NUN (NUclear Nervous system-specific) bodies. Unlike other previously described subnuclear organelles, NUN bodies are highly cell type specific. In fully mature animals, 4–10 NUN bodies are observed exclusively in the nucleus of neuronal, glial and neuron-like cells, but not in other somatic cell types. Based on co-localization and genetic loss of function studies, NUN bodies are not related to other previously described subnuclear organelles, such as nucleoli, splicing speckles, paraspeckles, Polycomb bodies, promyelocytic leukemia bodies, gems, stress-induced nuclear bodies, or clastosomes. NUN bodies form immediately after cell cycle exit, before other signs of overt neuronal differentiation and are unaffected by the genetic elimination of transcription factors that control many other aspects of neuronal identity. In one unusual neuron class, the canal-associated neurons, NUN bodies remodel during larval development, and this remodeling depends on the Prd-type homeobox gene ceh-10. In conclusion, we have characterized here a novel subnuclear organelle whose cell type specificity poses the intriguing question of what biochemical process in the nucleus makes all nervous system-associated cells different from cells outside the nervous system.
The Functional Continuum Scale in Relation to Hospitalization Density in Older Adults: The FRADEA Study
Authors: Alcantud Córcoles Rubén , Andrés-Pretel Fernando , Sánchez-Jurado Pedro Manuel , Avendaño Céspedes Almudena , Gómez Ballesteros Cristina , Sánchez-Flor Alfaro Victoria , López Bru Rita , Tabernero Sahuquillo María Teresa , Romero Rizos Luis , Hoogendijk Emiel O , Abizanda Pedro 
Published: January 2021

Abstract

Background
There is a need to know the relationship between function and hospitalization risk in older adults. We aimed at investigating whether the Functional Continuum Scale (FCS), based on basic (BADL) and instrumental (IADL) activities of daily living and frailty, is associated with hospitalization density in older adults across 12 years of follow-up.

Methods
Cohort study, with a follow-up of 12 years. A total of 915 participants aged 70 years and older from the Frailty and Dependence in Albacete (FRADEA) study, a population-based study in Spain, were included. At baseline, the FCS, sociodemographic characteristics, comorbidity, number of medications, and place of residence were assessed. Associations with first hospitalization, number of hospitalizations, and 12-year density of hospitalizations were assessed using Kaplan–Meier curves, Poisson regression analyses, and density models.

Results
The median time until the first hospitalization was shorter toward the less functionally independent end of the FCS, from 3917 days (95% confidence interval [CI] 3701–3995) to 1056 days (95% CI 785–1645) (p &lt; .001). The incidence rate ratio (IRR) for all hospitalizations increased from the robust category until the frail one (IRR 1.89), and thereafter it decreased until the worse functional category. Those who were BADL dependent presented an increased hospitalization density in the first 4 follow-up years (58%), those who were frail in the third-to-sixth follow-up years (55%), while in those prefrail or robust the hospitalization density was homogeneous during the complete follow-up.

Conclusions
The FCS is useful for stratifying the risk of hospitalization and for predicting the density of hospitalizations in older adults.
KAPOSI SARCOMA IN AN IMMUNOSUPPRESSED PATIENT WITH PRESUMED CROHN’S DISEASE: IATROGENIC OR EPIDEMIC?
Authors: Claytor Jennifer , Viramontes Omar , Conner Stephanie , Wen Kwun Wah , Beck Kendall 
Published: January 2021

Abstract

Introduction
Biologic immunosuppression and HIV infection both carry risks of infection and malignancy. Small series suggest that patients living with well-controlled HIV may safely and efficaciously use biologics, like TNF-alpha inhibitors (TNF-I). However, no current U.S. guidelines exist to screen for HIV infection among high-risk groups prior to starting TNF-I. We describe the case of a patient who received TNF-I for Crohn’s Disease without any HIV testing, who developed potentially avoidable extensive Kaposi Sarcoma.

Case Description
A healthy 32-year-old man presented with 1 month of diarrhea and a 15-lb weight loss. Fecal calprotectin, ESR, and CRP were markedly elevated. Endoscopy demonstrated severe rectal inflammation with perirectal abscess and perianal skin tags, suggestive of inflammatory bowel disease. Biopsies showed active colitis with ulceration, cryptitis, and fibropurulent debris without evidence of granulomata, dysplasia, or CMV. He was treated with IV antibiotics, IV steroids, and 2 infusions of infliximab at 5 mg/kg. He continued to have 4 loose stools an hour, limiting his steroid wean.
One month later, he developed painful, violaceous plaques on his face, buccal mucosa, torso, and lower extremities. Biopsy showed Kaposi Sarcoma, and HIV test was positive, with viral load 3292 and CD4 count 248. Although in a monogamous relationship with his husband, a well-recognized risk factor for HIV acquisition, he had never been tested for HIV. Antiretroviral therapy was initiated promptly.
Repeat rectal biopsies stained positive for HHV-8 and CMV, concerning for rectal KS and CMV proctitis. He started valgancyclovir but self-increased prednisone, with poor symptom relief. Review of the initial endoscopy confirmed no obvious HHV-8 positivity. Three weeks after HIV diagnosis, he developed new red nodules across his chest, suspicious for worsening KS due to immune reconstitution inflammatory syndrome (IRIS). He completed 12 cycles of chemotherapy and had no sign of residual IBD on recent colonoscopy. KS is his presumed original diagnosis.

Discussion
Current U.S. guidelines do not recommend HIV screening prior to TNF-I use, despite the heightened risks of cumulative immune dysregulation. Our patient should have been screened annually for HIV according to CDC guidelines. Further, his uncontrolled HIV infection in combination with TNF-I and high dose steroids led to life-threatening Stage IV malignancy (KS), complicated by immune reconstitution inflammatory syndrome and poor ART absorption. We propose that all patients should be screened for common risk factors for HIV acquisition, such as men who have sex with men or intravenous drug use. For high risk patients, gastroenterologists should consider screening for HIV, in addition to tuberculosis and hepatitis, prior to immunosuppression with TNF-I.
MESENCHYMAL TNFR1 EXPRESSION PRESERVES THE COLONIC EPITHELIAL STEM CELL NICHE
Authors: Gadeock Safina , Liu Cambrian , Polk Brent 
Published: January 2021

Abstract
Tumor necrosis factor (TNF) is a highly expressed cytokine in inflammatory bowel disease (IBD). Although TNF can induce colonic epithelial dysfunction and apoptosis, recent studies suggest that TNF signalling promotes epithelial wound repair and stem cell function. Here we investigated the role of TNF receptor 1 (TNFR1) in mediating TNF’s effects on colonic epithelial stem cells, integral to mucosal healing in colitis. We demonstrate that Tnfr1-/- mice exhibit loss in Lgr5 expression (-52%, p&lt;0.02; N=6) compared to wildtype (WT) controls. However, the opposite result was found in vitro, wherein murine Tnfr1-/- colonoids demonstrated a significant increase in Lgr5 expression (66%, p&lt;0.007; N=6) compared to WT colonoids. Similarly, human colonoids treated with an anti-TNFR1 antibody also demonstrated an increase in Lgr5 expression, relative to IgG controls. To resolve the contradiction in the in vivo versus in vitro environment, we hypothesized that mesenchymal TNFR1 expression regulates the epithelial stem cell niche. To determine the relationships between these cell types, we co-cultured WT or Tnfr1-/- colonoids with WT or Tnfr1-/- colonic myofibroblasts (CMFs). We found that epithelial Lgr5 expression was significantly higher (by 52%, p&lt;0.05; N=3) when co-cultured with WT compared to TNFR1-/- myofibroblasts. The loss of TNFR1 expression in vivo increases the number of αSMA+ mesenchymal cells by nearly 56% (N=6) but considerably reduces the pericryptal PDGFRα+ cells, suggesting modifications in mesenchymal populations that contribute to the epithelial stem cell niche. Functionally, primary Tnfr1-/--CMFs displayed PI3k (p&lt;0.001; N=3) and MAPK (p&lt;0.01; N=3)-dependent increases in migration, proliferation, and differentiation, but RNA profiling demonstrated by diminished levels of stem cell niche factors, Rspo3 (-80%, p&lt;0.0001; N=6) and Wnt2b (-63%, p&lt;0.008; N=6) compared to WT-CMFs. Supplementation with 50ng recombinant Rspo3 for 5 d to Lgr5-GFP organoids co-cultured with TNFR1-/--CMFs restored Lgr5 expression to wildtype levels. Therefore, TNFR1-mediated TNF signalling in mesenchymal cells promotes their ability to support an epithelial stem cell niche. These results should motivate future studies of the stem cell niche in the context of long-term treatment with anti-TNF therapies.