bluuebunny/crossref_metadata_2025 huggingface dataset:
Robotic arm controlled by Android app through Bluetooth connection for organic solarcell manipulation
Authors: Szolga L A , Flueras G
Published: January 2021

In this paper we present the design of a three joint robotic arm printed out in polyethylene terephthalate glycol material which provide durability and has good chemical resistance. To move the arm, we used four servomotors for a complex orientation in horizontal and vertical plane. At the tip of the robotic arm a 5V vacuum pump was mounted to handle organic solar cells printed out on indium tin oxide treated glass sheets with a dimension of 25/24/1mm. For an easy and precise control of the robotic arm an Android application was developed with an intuitive user-friendly interface. The communication between the robotic arm and the Android App is established through Bluetooth protocol. The control of the robotic arm is executed by a custom program on an ATmega328 microcontroller.
High-level model based calibration technique design for SAR ADC
Authors: Skripnichenko M N
Published: January 2021

This article presents a method of developing and debugging algorithms for mixed-signal schemes using mathematical model. SAR ADC is used as an example to present the method. A divided capacitor array with is used in the mathematical model. The Laplase transform is used to replace differential integral equations with algebraic ones. The input dependence of the comparator on the switches in the capacitor array is the basis of the mathematical model. There are two additional models – capacitance mismatch model, which was performed by randomly adding the value of the uniform distribution from -0.01 to 0.01 unit of the smallest capacitance, and noise model, which was performed as randomly changing comparator offset. As a result, there is a mathematical model of SAR ADC with event-driven architecture. Switching of K0 sample switch and bit switches leads to changing of circuit state. Mismatch in the capacitor array during chip manufacturing leads to deterioration of key characteristics of ADC – signal-to-noise ratio and spurious-free dynamic range. There is an algorithm, that can calculate the capacitors mismatch and correct the output code. Such an algorithm shows the efficiency under the conditions of capacitor mismatch and comparator input noise. With this algorithm, the signal-to-noise ratio has been increased by 7.3 dB, which is equivalent to 1.2 bit ENOB. The spurious-free dynamic range has been increased by 16.8 dB. Using the mathematical model when designing and debugging calibration algorithms speeds up these processes.
Information management and monitoring system for a grapes harvesting robot
Authors: Tziridis K , Nikolaou A , Kalampokas T , Vrochidou E , Pachidis T , Papakostas G A , Kaburlasos V G
Published: January 2021

In recent years, there has been an increasing integration of high technology in the execution of agricultural tasks towards improving the quality of the produced products, while reducing production costs. In this context, there is a special interest in the development of automatic agricultural robots (Agrobots) with advanced techniques of collecting, processing data, decision making and applying actions. A key element of the successful integration of such autonomous robots is the information management and monitoring system (IM2S) that accompanies it. This work presents the IM2S developed for an autonomous grapes harvesting robot, as part of a national project. Details regarding the system’s design are presented, covering system requirements, functional specifications, Graphical User Interface (GUI) design, database design and system-robot communication. Along with the presentation of the IM2S design, the special functional and technological requirements that must be met, are also discussed. Thus, the system could be a useful tool for the human operator. Moreover, the designed system can be easily adapted to collaborate with any robot meeting specific communication requirements. This makes the proposed IM2S a universal tool for any grape harvesting Agrobot already deploy or will be developed in the future.
Kinematic model of a cow milking manipulator with simultaneous positioning at four given points
Authors: Ruzin S S , Shilin D V , Dorokhov A S , Pavkin D Yu , Chepurina E L
Published: January 2021

During the study, the authors have solved the problems associated with the kinematics of a manipulator intended for the automatic care of cattle. The working unit of the manipulator is a system positioning all four milking cups in the individual location of the udder teats. A significant advantage of this manipulator kinematics is the ability to simultaneously connect milking cups to the teats of a cow’s udder to provide physiologically more correct milking and reduce the total milking time.
A review on the methods for big data analysis in agriculture
Authors: Evstatiev B I , Gabrovska-Evstatieva K G
Published: January 2021

The integration of information and communication technologies into agriculture lead to the development of precision agriculture. Nowadays it relies on Internet of Things devices, geospatial data, historical and real-time information, which has the potential to transform farming into smart farming. However the use of Big Data requires significantly different skills and knowledge, compared to what many farmers and agronomists possess, which is an obstacle for their effective use. This study aims to summarize and provide insight into the common methods used for data analysis in a wide variety of agricultural applications. Initially, the basic characteristics and sources of agricultural data are explained. Next, a review of the common data analysis methods (classification, clustering and regressions) is provided, containing information about the data sources used as well as the desired goal of the analysis. At the end of the paper, a summary is given on the applicability of data analysis methods depending on the desired goals.
Effect of Si element on the interfacial reaction of Ti3SiC2 reinforced Al matrix aomposites
Authors: Zhang Jianbo , Jin Yiming , Man Xucun , Zeng Hao , Liu Jinping , Zhang Xuehui
Published: January 2021

The interfacial reaction behavior of Ti3SiC2/Al andTi3SiC2/Al-10si matrix composites at high temperature was studied by XRD and SEM. The results showed that the reaction between Ti3SiC2 and Al matrix is

Ti

3

SiC

2

+
Al
→
TiCx
+
Si
+

Al

3

Ti
.

Ti3SiC2 particles in the Ti3SiC2/Al composite were almost completely reacted after 700 °C/1 h treatment, whilea large amount of Ti3SiC2 particles still existed in the Ti3SiC2/Al-10Si composite under the same treatment condition. In addition, the friction coefficient and wear amount of Ti3SiC2/Al composite were 0.54 and 0.167 g, respectively, and that in Ti3SiC2/Al-10Simatrix composites were 0.29 and 0.019 g. According to the critical condition of ΔG = 0, it is calculated that when the activity of Si is greater than 0.57, the interfacial reaction between Ti3SiC2 and Al matrix is inhibited.
ZnO as an anti-reflective layer for GaAs based heterojunction solar cell
Authors: Jin Xin , Tang Naiyun
Published: January 2021

Currently, how to improve the efficiency of solar cells has attracted wide attention. ZnO film is one of the most effective films today, which can act as both emitter and anti-reflective coating of solar cells. In this paper, n-type ZnO/p-type GaAs solar cell is modeled by analyzing the band edge discontinuities, electric field distributions at the ZnO/GaAs interface and cell parameters with varying ZnO layer thickness, affinity values and carrier concentration. Moreover, in order to improve the band offset alignment at the heterojunction, Mg doped ZnO emitter is a possible alternative. Then, the thickness and carrier concentration of MgZnO emitter layer are studied and simulation results show stronger electric field, better fill factor and higher efficiency. After optimization of two solar cells by using Silvaco Atlas, it is observed that the conversion efficiencies of ZnO/GaAs and MgZnO/GaAs solar cells are 22.84% and 23.44% respectively.
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

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.
The TIM22 complex mediates the import of sideroflexins and is required for efficient mitochondrial one-carbon metabolism
Authors: Jackson Thomas D. , Hock Daniella H. , Fujihara Kenji M. , Palmer Catherine S. , Frazier Ann E. , Low Yau C. , Kang Yilin , Ang Ching-Seng , Clemons Nicholas J. , Thorburn David R. , Stroud David A. , Stojanovski Diana
Published: January 2021

Proteomic profiling of Sengers patient fibroblasts and AGK knockout models identifies remodeling of the mitochondrial proteome, including mitochondrial one-carbon metabolism enzymes, inner membrane serine transporters, sideroflexins, and Complex I subunits and assembly factors.
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

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

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 < .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

Phosphatidylcholine (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

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

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

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

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

Great 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

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

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 < .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

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

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<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<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<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<0.001; N=3) and MAPK (p<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<0.0001; N=6) and Wnt2b (-63%, p<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.
CRYPTOGENIC MULTIFOCAL ULCEROUS STENOSING ENTERITIS (CMUSE): A 20-YEAR SINGLE CENTER CLINICAL AND RADIOLOGIC EXPERIENCE
Authors: Ramos Guilherme Piovezani , Bartlett David , Bledsoe Adam , Bruining David , Fidler Jeff , Sheedy Shannon , Murray Joseph
Published: January 2021

Background

Cryptogenic multifocal ulcerous stenosing enteritis (CMUSE) is a rare illness characterized by multiple strictures and shallow ulcers of the small bowel. Even though diagnostic criteria have been described, further ellucidation is needed on therapeutic interventions and potential discriminating factors between CMUSE and other more common causes of intestinal ulcerations, including Crohn’s disease.

Aim

The purpose of this article is to report the clinical, CT, and MR enterography characteristics of confirmed cases of CMUSE.

Materials and Methods

Retrospective review of electronic medical records identified 33 patients considered for a diagnosis CMUSE. Diagnosis was confirmed if all requirements of the previously published diagnostic criteria for CMUSE were met. Patients were excluded if they had less than one year follow-up or incomplete clinical data. Two GI radiologists reviewed all CT and MR enterography (CTE/MRE) exams in consensus of confirmed patients to characterize the cross sectional imaging features.

Results

CMUSE was confirmed in 9 patients (27%) and 24 patients (73%) had a confirmed alternative diagnosis. Crohn’s disease (CD) (30%, n=7) and drug-induced enteropathy (30%, n=7) were the most frequent alternative. Male gender (66.7% vs. 25%, p=0.04) and clinical manifestation of anemia at presentation were more commonly observed on CMUSE-confirmed cases (66.7% vs. 4.2%, p=0.005) when compared to patients with non-CMUSE diagnosis, in which abdominal pain was the most common presenting symptom (44.5% vs 87.5%, p=0.02). Multiple (100%) and circumferential (75%) ulcers with restricted mucosal involvement (55.6%) were major features at endoscopy and pathology. Most common treatments were corticosteroids (78%) or surgical resection (55.6%), with 33% receiving biologics. Disease recurrence after first treatment occurred in the majority (88.9%) after a median time of 6 months (Table 1).

9 CTE and 1 MRE of 8 confirmed cases images were analyzed (Table 2). Major imaging features included multiple (≥ 5; 88%; 7/8), short (< 2 cm; 100%; 8/8) circumferential (100%;8/8) strictures with moderate wall thickening (6–9 cm), and stratified hyper enhancement (100%; 8/8) located in the ileum (100%; 8/8). Median proximal small bowel dilation was 2.95 cm (2.5–4.1 cm). Less common findings included: mesenteric adenopathy (50%; 4/8), increased mesenteric edema/ascites (38%; 3/8), mesenteric vascularity (25%; 2/8), colon inflammation (13%; 1/8), and decreased small bowel fold pattern (13%; 1/8). No patients with confirmed CMUSE cases demonstrated penetrating disease (e.g., abscess, fistula).

Conclusion

CMUSE is rare cause of small bowel strictures with overlapping clinical and imaging features of more common etiologies such as Crohn’s Disease and NSAID enteropathy that need to be excluded through a multidisciplinary approach to confirm the diagnosis.
ULTRASOUND - FIRST-LINE IMAGING MODALITY IN EVALUATION OF THE INFLAMMATORY BOWEL LESIONS IN CHILDREN
Authors: Grzegorczyk Magdalena , Kuczynska Maryla , Siejka Karolina , Zbroja Monika , Cyranka Weronika , Piekarska Monika , Nowakowska Malgorzata , Wozniak Magdalena Maria , Brodzisz Agnieszka
Published: January 2021

Introduction

Crohn’s disease is classified as chronic inflammatory bowel disease. The incidence in Europe ranges from 1 to almost 11.4 per 100,000 population per year. Ultrasound examination plays an important role in imaging diagnostics of inflammatory bowel lesions. It allows for assessing response to therapy as well as recognizing possible penetrating complications of the disease, i.e. fistula or abscess.

Materials and Methods

36 children were included in the study: 16 boys and 20 girls with an active phase of Crohn’s disease. Each patient underwent intestinal ultrasound examination with a high frequency 7–12 Mhz linear probe.

Results

In all patients US examination depicted thickened, hypoechoic ileal wall showing patterns of vascularization. In 8 patients Bauhin’ valve edema was visible. In 16 children, inflammatory infiltration of the periintestinal fat around the affected segment of the intestine was found. In addition, all patients presented mesenteric lymphadenopathy with short-axis diameter of 10–15 mm. 8 patients had penetrating complications of Crohn’s disease: 4 small intestine fistulas and 4 abscesses.

Conclusion

Given its safety profile and diagnostic efficacy, US examination should be considered as the first-line imaging modality for assessing inflammatory bowel disease in children. US proved to be a reliable and easily accessible tool in the diagnosis of enteric inflammatory lesions, evaluating CD activity and assessing potential penetrating complications of the disease.
WEARABLE SWEAT SENSING DEVICE FOR DETECTION OF IBD BIOMARKERS
Authors: Jagannath Badrinath , Muthukumar Sriram , Prasad Shalini
Published: January 2021

Introduction

Inflammatory Bowel Disease affects 1.2 million in the United States. Flare-up of the disease occurs in a random way and current testing methods lack ability for real-time prediction of a flare up. The levels of cytokines elevate during a flareup. Therefore, we hypothesize that real-time monitoring of cytokine biomarkers can be useful for early detection of flare-ups and provide better patient management. In this context, sweat-based diagnostics can be promising for real-time tracking of IBD biomarkers.

Materials and Methods

A wearable SWEATSENSER was developed by functionalization of specific affinity capture probes (IL-1β, CRP antibodies) on metal/semiconducting interface deposited on a porous patch substrate. Electrochemical impedance spectroscopy technique was used to detect the interaction between the specific antibody and target analyte. The developed SWEATSENSER was tested on 20 healthy human subjects in compliance with an approved IRB at UT Dallas. Continuous on-body measurements were recorded to report IL-1β, CRP levels in sweat in real-time.

Results

In this work, a wearable multiplexed sweat sensor for detection of IL-1β, CRP in sweat has been demonstrated. The sensor demonstrates a limit of detection of 1 pg/mL with a dynamic range from 1 pg/mL- 512 pg/mL for both the biomarkers in sweat. The sweat sensor demonstrated excellent correlation with reference ELISA method (Pearson’s r ≥0.95). On-body monitoring using sweat sensor from passively perspired human sweat demonstrated a mean concentration of 28 pg/mL for IL-1β in healthy cohort.

Conclusion

A wearable sweat sensor was developed to monitor potential IBD markers in sweat. The developed device can be useful in better management of IBD patients.
RESULTS FROM A NATIONAL CROSS-SECTIONAL STUDY OF DISEASE BURDEN IN CROHN’S DISEASE
Authors: Seabury Jamison , Zizzi Christine , Weinstein Jennifer , Wagner Ellen , Rosero Spencer , Dilek Nuran , Kaat Aaron , McDermott Michael , Saubermann Lawrence , Temple Larissa , Rogoff Scott , Heatwole Chad
Published: January 2021

Background

Patients with Crohn’s disease experience a wide variety of clinical symptoms that affect how they feel and function. As therapeutic trials are planned for patients with Crohn’s disease, it is important to better understand the symptoms that have the greatest impact on Crohn’s disease patient’s lives.

Objective

To identify the most common and important disease manifestations in Crohn’s disease in a large population of patients. To determine the modifying factors that are associated with these symptoms.

Methods

We conducted a national cross-sectional study of 415 patients from the IBD Partners patient registry sponsored by the Crohn’s & Colitis Foundation to identify the prevalence and relative importance of 148 individual symptoms across 17 unique symptomatic themes. These themes were previously identified through 16 semi-structured qualitative interviews with Crohn’s patients.

Results

Crohn’s disease participants provided over 55,000 symptom rating responses. The symptomatic themes with the highest prevalence in Crohn’s disease were gastrointestinal issues (93.0%), fatigue (86.4%), dietary restrictions (77.9%), impaired sleep or daytime sleepiness (75.6%), and inability to do activities (72.3%). Symptomatic theme prevalence was widely associated with having above the median number of stools per day, having above the median number of bowel movements per day, having perianal disease, having to miss work, and unemployment.

Discussion/Conclusion: Crohn’s disease symptoms, some under-recognized, vary based on disease characteristics and demographic features. These symptoms represent targets for future therapeutic interventions and are potential areas of interest for an upcoming disease-specific patient-reported outcome measure for this population.

Acknowledgements

Funding for this project was provided by UR Ventures. Research activities were conducted in collaboration with the Crohn’s & Colitis Foundation.
IDENTIFYING INADEQUATE RESPONSE AMONG CROHN’S DISEASE PATIENTS ON A BIOLOGIC IN A REAL-WORLD ADMINISTRATIVE CLAIMS DATABASE
Authors: Hunter Theresa , Naegeli April , Grabner Michael , Isenberg Keith , Shan Mingyang , Teng Chia-Chen
Published: January 2021

Objectives

The purpose of this analysis was to assess the frequency of inadequate response (IR) over 1 year from biologic initiation among Crohn’s disease (CD) patients in the United States using a claims-based algorithm. Baseline factors associated with IR to a biologic were also analyzed.

Methods

This was a retrospective cohort study using claims data from the HealthCore Integrated Research Database. Adult patients with CD who initiated a biologic (TNFi: adalimumab, certolizumab, infliximab; non-TNFi: natalizumab, ustekinumab, and vedolizumab) from 7/1/2016 to 8/31/2018 and had continuous enrollment ≥6 months before and ≥12 months after index date (date of first biologic claim) were included. The index biologic was defined as the first biologic prescribed during the study time period. The claims-based algorithm used in this study to identify IR was originally developed and validated in rheumatoid arthritis and was modified for CD patients. Patients were identified as having IR to their index biologic if during the 12 months after index date they had one or more of the following: low adherence (defined as proportion of days covered (PDC)<80%), switched/added new biologic, added a new conventional therapy, increased dose/frequency of biologic, addition or dose increase of oral glucocorticoids, used a new pain medication, or had surgery for CD. Baseline patient characteristics were compared between responders and IRs using Chi-square tests for categorical variables and t-tests for continuous variables. A multivariable logistic regression model was constructed to identify baseline characteristics associated with IR to the index biologic.

Results

A total of 2,437 CD patients were included in this analysis. Mean age was 41 years, 53% were female, 81% initiated a TNFi, and 19% initiated a non-TNFi as their index biologic (Table 1). Over the 1-year follow-up period, 62% of CD patients had an IR to their biologic: 41% of patients had low adherence, 14% switched/added a new biologic, 13% added a new conventional therapy, 12% had a dose/frequency increase of their index biologic, 12% had an addition/dose increase of oral glucocorticoids, 8% used a new pain medication, and 5% had surgery. Inadequate responders were more likely to be female (odds ratio (OR)=1.36; p<0.001), have historical use of TNFi (OR=1.94; p<0.001), and be on a consumer-driven health plan (OR=1.28; p<0.001); while patients with baseline use of conventional therapy were more likely to be responders (OR=0.72; p<0.001) (Table 2).

Conclusion

Over 62% of CD patients had an inadequate response to their index biologic within 1 year after initiation, mostly driven by low adherence. This modified claims-based algorithm for CD appears useful to classify inadequate responders in health plan claims data. Additional research is needed to further validate this algorithm in a clinical setting.
PAIN MEDICATION USE AMONG CROHN’S DISEASE AND ULCERATIVE COLITIS PATIENTS BEFORE AND AFTER INITIATION OF BIOLOGIC THERAPY
Authors: Hunter Theresa , Naegeli April , Nguyen Chi , Shan Mingyang , Smith Joseph , Tan Hiangkiat , Gottlieb Klaus , Isenberg Keith
Published: January 2021

Objective

The purpose of this analysis was to describe pain medication utilization of newly diagnosed patients with Crohn’s disease (CD) and ulcerative colitis (UC) over 12-months before and after initiation of a biologic.

Methods

This is a retrospective study using administrative claims from the HealthCore Integrated Research Database. Patients newly diagnosed with CD or UC who initiated a biologic from 1/1/2014 to 7/31/2017 were included. Medications that could be used for pain control were assessed 12-months prior and 12-months after biologic initiation. Demographics, baseline clinical characteristics, and pain medication use were described using descriptive statistics. Frequencies and percentages were provided for categorical variables and means, standard deviations, and medians were presented for continuous measures. The differences in pain medication use 12 months prior and 12 months after biologic initiation were assessed using McNemar’s Test for categorical variables and Wilcoxon signed-rank test for continuous variables..

Results

540 CD patients and 373 UC patients were included in this analysis. CD patients had a mean age of 36.8 years, 50.0% were female, and the mean time from diagnosis to biologic initiation was 7.1 months. UC patients had a mean age of 39.9 years, 44.0% were female, and the mean time from diagnosis to biologic initiation was 10.9 months. Prior to biologic initiation, 23.1% of CD patients were prescribed NSAIDs, 78.1% glucocorticoids, 49.4% opioids, and 29.3% neuromodulators. Similarly, prior to biologic initiation, 20.9% of UC patients were receiving NSAIDs, 91.4% glucocorticoids, 40.8% opioids, and 29.5% neuromodulators.

Twelve months after biologic initiation, use of NSAIDs (CD: 23.1% vs. 15.0%; UC: 20.9% vs. 15.8%) and glucocorticoids (CD: 78.1% vs. 58.9%; UC: 91.4% vs. 74.3%) significantly decreased among CD and UC patients. Opioid use decreased among UC and CD patients; however this decrease was only statistically significant for CD patients (CD: 49.4% vs. 41.5%; UC: 40.8% vs. 36.5%). Use of neuromodulators significantly increased during 12-months after biologic initiation compared to 12 months prior to initiation among CD (29.3% vs. 33.7%) and UC (29.5% vs. 35.7%) patients.

Conclusion

Use of pain medications such as NSAIDs, glucocorticoids, opioids, and neuromodulators were common among CD and UC patients. Though rates of NSAIDs and glucocorticoids decreased after the initiation of biologics, 59% of CD and 74% of UC patients were still receiving glucocorticoids, and 15% of CD and 16% of UC patients were still receiving NSAIDs 12-months after initiation of a biologic. In addition, 42% of CD and 37% UC patients were still receiving opioids 12-months after initiation of a biologic. The results suggested that CD and UC patients are still receiving pain medication even after initiating biologics.