bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of Plasmacytoid Dendritic Cells, Microbial Sequences, and Identification of a Candidate Public T-Cell Clone in Kikuchi-Fujimoto Disease
Authors: Nelson Nya D , Meng Wenzhao , Rosenfeld Aaron M , Bullman Susan , Sekhar Pedamallu Chandra , Nomburg Jason L , Wertheim Gerald B , Paessler Michele E , Pinkus Geraldine , Hornick Jason L , Meyerson Matthew , Luning Prak Eline T , Pillai Vinodh 
Published: February 2021

Objectives Kikuchi-Fujimoto disease (KFD) is a self-limited lymphadenitis of unclear etiology. We aimed to further characterize this disease in pediatric patients, including evaluation of the CD123 immunohistochemical (IHC) staining and investigation of potential immunologic and infectious causes. Methods Seventeen KFD cases and 12 controls were retrospectively identified, and the histologic and clinical features were evaluated. CD123 IHC staining was quantified by digital image analysis. Next generation sequencing was employed for comparative microbial analysis via RNAseq (5 KFD cases) and to evaluate the immune repertoire (9 KFD cases). Results In cases of lymphadenitis with necrosis, >0.85% CD123+ cells by IHC was found to be six times more likely in cases with a final diagnosis of KFD (sensitivity 75%, specificity 87.5%). RNAseq based comparative microbial analysis did not detect novel or known pathogen sequences in KFD. A shared complementarity determining region 3 (CDR3) sequence and use of the same T-cell receptor beta variable region family was identified in KFD LNs but not controls, and was not identified in available databases. Conclusions: Digital quantification of CD123 IHC can distinguish KFD from other necrotizing lymphadenitides. The presence of a unique shared CDR3 sequence suggests that a shared antigen underlies KFD pathogenesis.
Is Endoscopic Assessment of the Esophagus and Stomach Enough to Determine the Need for Biopsy at These Sites in Pediatric Patients Undergoing Endoscopy for Elevated TTG?
Authors: Pacheco M. Cristina , Green Nicole , Dickerson Jane , Lee Dale 
Published: February 2021

Objectives The goal of our study was to determine whether visual assessment of the esophagus and stomach could predict abnormal histology and determine the frequency of interventions based on biopsies in patients undergoing endoscopy for elevated tissue transglutaminase immunoglobulin A antibody (TTG). Methods Pathology records were searched for patients with biopsy performed for elevated TTG. Pathology report, endoscopy report, and follow-up were obtained and slides from the duodenum reviewed. Pathology was considered gold standard for sensitivity and specificity calculations. Results 240 patients were included. 215 patients had esophageal biopsies performed. Esophageal endoscopic visual assessment had sensitivity of 47% and specificity of 93% for abnormal histology. 16(7%) patients had therapy or referral related to results and, of these, 6(38%) had visually normal endoscopy. 237 biopsies were performed of stomach. Gastric endoscopic visual assessment had a sensitivity and specificity of 20% and 87%. 24(10%) patients had therapy based on findings and, of these, 12 (50%) had visually normal endoscopy. Conclusions Endoscopic assessment of esophagus and stomach has low sensitivity and high specificity for pathologic abnormalities when indication for endoscopy is elevated TTG. When endoscopy is visually normal clinical interventions based on biopsy are rare, and foregoing biopsy may be considered.
Assessment of Adipokines, CXCL16 Chemokine Levels in Patients With Rheumatoid Arthritis Combined With Metabolic Syndrome
Authors: Turgunova Lyudmila Gennadyevna , Shalygina Anna Andreevna , Zalkalns Janis Pavlovich , Klyuyev Dmitriy Anatolyevich , Akhmaltdinova Lyudmila Leonidovna , Dosmagambetova Raushan Sultanovna 
Published: February 2021

Objective: Rheumatoid arthritis (RA), which is a chronic systemic inflammatory disease, is associated with accelerated atherosclerosis and an increased risk of cardiovascular disease (CVD), but the causal factors have yet to be completely elucidated. The studies show that the prevalence of metabolic syndrome (MtS) was significantly higher in RA patients compared to the population. In RA and MetS inflammation and atherosclerosis are closely linked. The level of chemokines and adipokines, which may play a role in the development of atherogenesis in RA with MetS patients is currently unknown. In this study, we investigated the level of chemokine C-X-C motif chemokine ligand 16 (CXCL16) and adipokine in RA with MetS patients and assessed the association of biomarkers with clinical and biochemical activity scores of RA and components of MetS. Methods: Blood serum of 298 people (48—patients with RA and MetS, 82—with RA without MetS, 105—with MetS, 63—control group without both RA and MetS) was tested for (CXCL16), Resistin, Leptin and Fibroblast Growth Factor 21 (FGF21) levels by fluorescent antibody technique. Statistical analysis was performed using SPSS version 18.0. Results: The biomarker study showed the highest level in the RA with MetS patient group; but as compared with the RA group the differences were insignificant. CXCL16 (Me = 426.2 pg/ml (Q25-75 250.5-527.6), resistin (Me = 8685.4 pg/ml (Q25-75 6480.8-13 629.1), and FGF21 (Me = 443.6 pg/ml (Q25-75 772.9-916.3) proved to be significantly augmented in RA with MetS patients group, and in RA without MetS patients group (Me = 312.7 (Q25-75 199.4-517.7) pg/ml; Me = 8265.3 (Q25-75 5779.7-13 340.5) pg/ml; Me = 412.4 (Q25-75 300.4-497.4) pg/ml, respectively) as compared with MetS patients group (Me = 189.4 (Q25-75 130.3-280.6) pg/ml; Me = 5364.8 (Q25-75 2368.9-10 160.9) pg/ml; Me = 133.2 (Q25-75 76.2-268.6) pg/ml, respectively; P = <.001). Leptin level in all groups was higher than in the control group, but there were no differences between groups. The correlation analysis found a positive relationship between the leptin level and the waist circumference (rs = 0.39; P = .007) in the RA with MetS patients, the association of biomarkers with DAS28 score and ESR did not have any statistical significance. Conclusions: The augmented chemokine, resistin and FGF21 in the RA with MetS patients proves the systemic inflammation which is the basis of RA; the augmented leptin is linked to the abdominal obesity. These data are somewhat of an explanation of the increased risk of the CVD development in RA with MetS people. A differentiated specification can be useful to assess the cardiovascular risk of patients and justify prompt personalized treatment.
Evaluation of digital slit-lamp videos for paediatric anterior segment telemedicine consultations
Authors: Mulchandani Divya , Reiser Bibiana J , Ho Tiffany C , Reid Mark W , Stewart Carly , Lee Thomas C , Nallasamy Sudha 
Published: February 2021

Introduction This study aimed to assess the validity of telemedicine consultations using digital slit-lamp videos to detect anterior segment pathology in a paediatric population. Methods A paediatric anterior segment specialist simultaneously performed and recorded anterior segment examinations using the Topcon digital-ready slit lamp. Components of the examination included the eyelids/eyelashes, conjunctiva/sclera, cornea, anterior chamber, iris and lens. Masked to clinical findings, a paediatric ophthalmologist reviewed and graded the live video feed transmitted at 4 Mbps. At least three months later, both ophthalmologists graded the stored videos. We compared the sensitivity, specificity, percent agreement and weighted kappa (κ) of diagnosing anterior segment pathologies via live-streamed and store-and-forward video clips compared to the in-person standard examination. Results Examinations of 89 eyes from 45 children (5–17 years old) with known anterior segment pathology were included. Agreement between live-streamed and in-person standard examinations for conjunctiva/sclera, anterior chamber, iris and lens findings was almost perfect (sensitivity 89–96%, specificity 95–100%, κ = 0.87–0.97). Substantial agreement was found for cornea pathology (sensitivity 88%, specificity 90%, κ = 0.72), and moderate agreement was found for eyelids/eyelashes pathology (sensitivity 54%, specificity 92%, κ = 0.46). Store-and-forward results were similar, though slightly better for eyelids/eyelashes and slightly worse for conjunctiva/sclera. Discussion Digital slit-lamp videos hold promise for synchronous and asynchronous telemedicine in diagnosing paediatric anterior segment pathologies.
The role of the surgical care practitioner during the COVID-19 pandemic: An audit of experiences
Authors: Fletcher Nicholas , Russell Bradley , Broughton Jonathan 
Published: February 2021

Introduction The Surgical Care Practitioner is a medical associate profession role, working to an advanced level, undertaken by registered nurses, operating department practitioners or physiotherapists, on completion of a Royal College of Surgeons accredited course. The COVID-19 pandemic has led to all heath care professionals needing to adapt to help support the health care system as it tackles its effect. Aim Audit of roles undertaken by Surgical Care Practitioners during the COVID-19 pandemic in the context of Royal College of Surgeons (2014) Curriculum to review the utilisation of this medical associate profession role. Method The online questionnaire service, SurveyMonkey®, was used to collect data on the activities being undertaken by the Surgical Care Practitioner during the COVID-19 pandemic. Results Eighty Surgical Care Practitioners from across seven different surgical specialties within the United Kingdom completed the online survey. Nearly half stated that they remained mostly working in their substantive role, just less than a third helped in critical care units, with the remaining redeployed in equal shares to emergency departments or assisting on wards with nurses and as part of medical teams. A brief description of their activities was also recorded. Conclusion This audit has demonstrated the versatility of the Surgical Care Practitioner and ability to adapt during the pandemic.
Targeted inhibition of β-catenin alleviates airway inflammation and remodeling in asthma via modulating the profibrotic and anti-inflammatory actions of transforming growth factor-β1
Authors: Huo Rujie , Tian Xinli , Chang Qin , Liu Dai , Wang Chen , Bai Jingcui , Wang Runjuan , Zheng Guoping , Tian Xinrui 
Published: February 2021

Background: TGF-β1 is a key cytokine involved in both airway inflammation and airway remodeling in asthma because of its anti-inflammatory and profibrotic effect. In our previous study, we found that knockdown of cytosolic β-catenin alleviated the profibrogenic effect of TGF-β1 without influencing its anti-inflammatory effect. However, the exact role of targeting β-catenin in asthma is not yet fully demonstrated. In the present study, we investigated the effect and mechanism of targeting β-catenin in OVA-challenged asthmatic rats with airway inflammation and remodeling features. Methods: We integrated experimental asthma model and asthma related cell model to explore the effect of targeting β-catenin on airway inflammation and remodeling of asthma. Results: Blocking β-catenin with ICG001, a small molecule inhibitor of β-catenin/TCF via binding to cAMP-response elementbinding protein, attenuated airway inflammation by increasing levels of anti-inflammation cytokines IL-10, IL-35 and decreasing levels of T helper (Th)2 cells and Th17 cytokine. Suppressing β-catenin by ICG001 inhibited airway remodeling via reducing the level of TGF-β1 and the expressions of Snail, MMP-7, MMP-9 and, up-regulating expression of E-cadherin, down-regulating expressions of α-SMA and Fn. Inhibition of β-catenin with ICG001 suppressed TGF-β1 induced proliferation and activation of CCC-REPF-1, blocked TGF-β1 induced epithelial–mesenchymal transition (EMT) of RLE-6TN. Conclusion: Blockade of β-catenin/TCF not only prevents TGF-β1 induced EMT and profibrogenic effects involved in pathological remodeling of airway, but also alleviates airway inflammation in asthma by balancing pro-inflammatory and anti-inflammatory cytokine. In conclusion, targeting β-catenin specifically via inhibition of β-catenin/TCF might be a new therapeutic strategy for asthma. The reviews of this paper are available via the supplemental material section.
New Clamp-PID Algorithm for Automated Glucose Clamps Improves Clamp Quality
Authors: Benesch Carsten , Kuhlenkötter Mareike , Nosek Leszek , Heise Tim 
Published: February 2021

Background: In automated glucose clamp experiments, blood glucose (BG) concentrations are kept close to a predefined target level using variable glucose infusion rates (GIRs) determined by implemented algorithms. Clamp quality (ie, the ability to keep BG close to target) highly depends on the quality of these algorithms. We developed a new Clamp algorithm based on the proportional-integral-derivative (PID) approach and compared clamp quality between this and the established Biostator (BS) algorithm. Methods: In numerical simulations, the PID-based algorithm was optimized in silico. The optimized Clamp-PID algorithm was tested in in vitro experiments and finally validated in vivo in a small ( n = 5) clinical study. Results: In silico, in vitro, and in vivo experiments showed better clamp quality for the new Clamp-PID algorithm compared with the BS algorithm: precision and absolute control deviation (ACD) decreased from 3.7% to 1.1% and from 2.9 mg/dL to 0.6 mg/dL, respectively, in the numerical simulation. The in vitro validation demonstrated reductions in precision (from 3.3% ± 0.1% (mean ± SD) to 1.4% ± 0.4%) and in ACD (from 2.3 mg/dL ± 0.4 mg/dL to 0.8 mg/dL ± 0.2 mg/dL), respectively. In the clinical study, precision and ACD improved from 6.5% ± 1.3% to 4.0% ± 1.1% and from 3.6 mg/dL ± 0.9 mg/dL to 2.2 mg/dl ± 0.6 mg/dl, respectively. The quality parameter utility did not change. Conclusions: The new Clamp-PID algorithm improves the clamp quality parameters precision and ACD versus the BS algorithm.
Association of immune-checkpoint inhibitors and the risk of immune-related colitis among elderly patients with advanced melanoma: real-world evidence from the SEER–Medicare database
Authors: Almutairi Abdulaali R. , Slack Marion , Erstad Brian L. , McBride Ali , Abraham Ivo 
Published: February 2021

Background: The use of anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) therapy (ipilimumab) and anti-programmed cell-death 1 (anti-PD1) agents (nivolumab and pembrolizumab) in advanced melanoma have been associated with immune-related adverse events (irAEs) including colitis. We aimed to estimate the incidence and the risk of colitis in elderly patients with advanced melanoma treated with anti-CTLA4 and anti-PD1 in the real-world setting. Methods: Elderly patients (age ⩾ 65 years) diagnosed with advanced melanoma between 2011 and 2015 and treated with anti-CTLA4 or anti-PD1 agents were identified from the Surveillance, Epidemiology, and End Results (SEER)–Medicare data. We estimated the risk of colitis from start of treatment up to 90 days from the last dose of therapy. We used the log-rank test and logistic regression with adjustment for potential confounders using the inverse probability of treatment weighting method. We conducted several sensitivity analyses. Results: A total of 274 elderly patients with advanced melanoma were included in our cohort. The risk of colitis was similar between anti-PD1 users and anti-CTLA4 users based on log-rank test ( p = 0.17) and logistic regression [odds ratio (OR) = 0.35, 95% confidence interval (95%CI) 0.04–2.79]. Sensitivity analyses for patients with all-stage melanoma showed a significantly lower risk of colitis in anti-PD1 compared with anti-CTLA4 treated patients based on log-rank test ( p = 0.017) and logistic regression (OR = 0.21, 95%CI 0.09–0.53). Conclusion: Elderly with advanced melanoma treated with anti-CTLA4 or anti-PD1 had a similar risk of developing colitis. However, there was a statistically significant difference in the risk of colitis between anti-CTLA4 or anti-PD1 users among all-stage-melanoma patients. Plain Language Summary Risk of colitis (inflammation of the large intestine) in elderly patients with melanoma treated with immune-checkpoint inhibitors (a group of medications that uses the patient’s immune system to fight cancer) While the anti-cancer agents known as immune-checkpoint inhibitors have had a great impact on the treatment of melanoma, they may also have side effects. This study estimated the risk of colitis, a chronic inflammation of the colon, in elderly patients with melanoma treated with anti-cytotoxic T-lymphocyte antigen 4 (anti-CTLA4) or anti-programmed cell-death 1 (anti-PD1) agents, using data from the Surveillance, Epidemiology, and End Results (SEER)–Medicare linked database. Overall, we found that the risk of colitis was not different between anti-PD1 users and anti-CTLA4 users with advanced-stage melanoma. However, after including patients across all stages of melanoma, we found a significantly lower risk of colitis with anti-PD1 compared with anti-CTLA4.
Common bile duct obstruction caused by a helminth in a cat in the UK: ultrasonographic findings, histopathology and outcome
Authors: Venier Francesca , Compagnone Krizia , Kerins Annette , Rosa Chantal 
Published: February 2021

Case summary An 11-year-old neutered female domestic shorthair cat presented to our hospital with a 5-day history of vomiting, lethargy, anorexia and hyperbilirubinaemia, despite intravenous fluid therapy, gastroprotectants and antibiotic treatment. An abdominal ultrasound revealed a markedly distended common bile duct (diameter 6.2 mm). The cystic duct and intrahepatic bile ducts were also dilated. A linear structure formed by two parallel hyperechoic lines was identified in the common bile duct and could be traced to the duodenal papilla. The cat underwent laparotomy for surgical decompression of the biliary tree. A tubular, brown-coloured structure was retrieved from the common bile duct. Histological examination was consistent with a degenerate helminth. The cat recovered uneventfully from the surgery and its demeanour and appetite improved rapidly over the following days. Liver and gallbladder wall histopathology was consistent with bacterial cholangitis and cholecystitis. Escherichia coli was cultured from both bile and liver parenchyma. Relevance and novel information To our knowledge, this is the first reported case of extrahepatic biliary duct obstruction caused by a helminth in a cat in the UK. We hypothesised that the obstruction had been caused by the aberrant migration of an intestinal nematode that became lodged in the duodenal papilla. Ultrasound allowed prompt diagnosis and guided the treatment decision.
A Feasibility Evaluation of an Employee-led Brief Health Promotion Program to Promote Lifestyle Change in the Workplace
Authors: Koide Keiko , Okamoto Reiko , Makabe Mika , Tanaka Miho , Nakase Katsumi 
Published: February 2021

Background: In Japan, lifestyle-related diseases are a major issue. It is necessary to support employees in making lifestyle changes. As a result, this study intended to test and evaluate the feasibility of a brief lifestyle change program led by employees in the workplace. Methods: A 2-group before-and-after test design was used, with employees from a plant in Japan as participants. Intervention was carried out by healthcare specialists for the Standard Intervention Group, while employees who previously received the same intervention performed it for the Employee-run Group. Data were collected twice with a questionnaire, provided in the first and last program sessions. The conditions of the participants during the intervention were compared. Results: Of all the participants, 96 were in the Standard Intervention Group and 365 were in the Employee-run Group. The mean age did not differ significantly between the 2 groups. There was a significantly higher ratio of men and night shift workers in the Employee-run Group. Although a significantly smaller proportion of participants set shared behavioral goals for 3 people or self-monitored their lifestyle habits in the Employee-run Group, the lifestyle habits of self-checking, physical measurement, and other items for set goals did not differ. Conclusions: Participants in the Employee-run group completed components of the program to the same extent as those in the Standard Intervention Group, suggesting that this program is feasible. However, as the participation rate was lower in some components, improvements to the program and workbook are needed to make those components easier to complete.
Genomic characterization of relapsed acute myeloid leukemia reveals novel putative therapeutic targets
Authors: Stratmann Svea , Yones Sara A. , Mayrhofer Markus , Norgren Nina , Skaftason Aron , Sun Jitong , Smolinska Karolina , Komorowski Jan , Herlin Morten Krogh , Sundström Christer , Eriksson Anna , Höglund Martin , Palle Josefine , Abrahamsson Jonas , Jahnukainen Kirsi , Munthe-Kaas Monica Cheng , Zeller Bernward , Tamm Katja Pokrovskaja , Cavelier Lucia , Holmfeldt Linda 
Published: February 2021

Abstract
Relapse is the leading cause of death of adult and pediatric patients with acute myeloid leukemia (AML). Numerous studies have helped to elucidate the complex mutational landscape at diagnosis of AML, leading to improved risk stratification and new therapeutic options. However, multi–whole-genome studies of adult and pediatric AML at relapse are necessary for further advances. To this end, we performed whole-genome and whole-exome sequencing analyses of longitudinal diagnosis, relapse, and/or primary resistant specimens from 48 adult and 25 pediatric patients with AML. We identified mutations recurrently gained at relapse in ARID1A and CSF1R, both of which represent potentially actionable therapeutic alternatives. Further, we report specific differences in the mutational spectrum between adult vs pediatric relapsed AML, with MGA and H3F3A p.Lys28Met mutations recurrently found at relapse in adults, whereas internal tandem duplications in UBTF were identified solely in children. Finally, our study revealed recurrent mutations in IKZF1, KANSL1, and NIPBL at relapse. All of the mentioned genes have either never been reported at diagnosis in de novo AML or have been reported at low frequency, suggesting important roles for these alterations predominantly in disease progression and/or resistance to therapy. Our findings shed further light on the complexity of relapsed AML and identified previously unappreciated alterations that may lead to improved outcomes through personalized medicine.