bluuebunny/crossref_metadata_2025 huggingface dataset:
Intelligent Fault Diagnosis of Aeroengine Sensors Using Improved Pattern Gradient Spectrum Entropy
Authors: Li Huihui , Gou Linfeng , Zheng Hua , Li Huacong
Published: January 2021

Timely and effective fault diagnosis of sensors is crucial to enhance the working efficiency and reliability of the aeroengine. A new intelligent fault diagnosis scheme combining improved pattern gradient spectrum entropy (IPGSE) and convolutional neural network (CNN) is proposed in this paper, aiming at the problem of poor fault diagnosis effect and real-time performance when CNN directly processes one-dimensional time series signals of aeroengine. Firstly, raw fault signals are converted into spectral entropy images by introducing pattern gradient spectral entropy (PGSE), which is used as the input of CNN, because of the great advantage of CNN in processing images and the simple and rapid calculation of the modal gradient spectral entropy. The simulation results prove that IPGSE has more stable distinguishing characteristics. Then, we improved PGSE to use particle swarm optimization algorithm to adaptively optimize the influencing parameters (scale factor

λ

), so that the obtained spectral entropy graph can better match the CNN. Finally, CNN mode is proposed to classify the spectral entropy diagram. The method is validated with datasets containing different fault types. The experimental results show that this method can be easily applied to the online automatic fault diagnosis of aeroengine control system sensors.
Mitigation of Imperfect Successive Interference Cancellation and Wavelet‐Based Nonorthogonal Multiple Access in the 5G Multiuser Downlink Network
Authors: Ahmad Muneeb , Baig Sobia , Asif Hafiz Muhammad , Raahemifar Kaamran
Published: January 2021

The fourth Industrial Revolution is expected to lead to an era of technological innovation and digitization that would require connectivity by the users, anywhere and anytime. The fifth generation of wireless communication systems and the technologies therein are being explored to cater to high connectivity needs that encompass high data rates, very low latencies, energy‐efficient systems, etc. A multiuser environment is anticipated that would require multiple access techniques, such as Nonorthogonal Multiple Access (NOMA). The user data in the power domain NOMA is superimposed, at the transmitter base station, which is in turn subjected to Successive Interference Cancellation at the user end. In the multiuser downlink, the desired user’s signal is subjected to imperfect SIC due to incomplete cancellation of the undesired user’s signal. Pulse‐shaping of NOMA symbols using wavelet transform is proposed to mitigate the multiuser interference due to imperfect SIC. Closed‐form symbol error rate (SER) expression is derived for the wavelet NOMA system for a three‐user scenario. Analytical results show that wavelet transform pulse‐shaped NOMA performs better compared to Fourier transform pulse‐shaped NOMA symbols in mitigating SIC and thereby minimize the residual error due to imperfect SIC.
Higher Levels of Triglyceride, Fatty Acid Translocase, and Toll-Like Receptor 4 and Lower Level of HDL-C in Pregnant Women with GDM and Their Close Correlation with Neonatal Weight
Authors: Zhou Jianli , Bai Jie , Guo Yanjuan , Fu Lijun , Xing Jun
Published: January 2021

Objectives: In this study, we aimed to compare the levels of maternal blood lipids, placental and venous blood lipid transporters, and inflammatory factor receptors in pregnant women with and without gestational diabetes mellitus (GDM). We also aimed to figure out the relationship between these values and neonatal weight. Methods: Fifty pregnant women with GDM under blood glucose control belong to the case group, and 50 pregnant women with normal glucose tolerance in concurrent delivery belong to the control group. Fasting venous blood of these pregnant women was taken 2 weeks before delivery, and umbilical cord blood was collected after delivery. The levels of triglyceride (TG), serum total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol (HDL-C) in maternal blood and umbilical cord blood were tested in the laboratory department of our hospital. The level of toll-like receptor 4 (TLR4) in serum of umbilical veins was detected by the double-antibody sandwich ELISA. Western blot and RT-PCR were used to detect the protein and mRNA expressions of TLR4, LPL, and FAT/CD36 in the placenta. Results: The level of TG in maternal blood in the case group was remarkably higher than that in the control group, which was opposite to the level of HDL-C. In the umbilical cord blood of women with GDM, the expression of TLR4 increased and was closely correlated with neonatal weight. In the placenta of women with GDM, the expressions of FAT/CD36 and TLR4 increased, and both of them were closely correlated with neonatal weight. Besides, TLR4 in umbilical cord blood increased and was closely correlated with neonatal weight. Although the expression of LPL in the placenta decreased, it had no obvious correlation with neonatal weight. Conclusions: TG in maternal blood, TLR4 in the placenta and umbilical cord blood, and FAT/CD36 in the placenta were positively correlated with neonatal weight. However, HDL-C in maternal blood was negatively correlated with neonatal weight. Although the expression of LPL in the placenta reduced due to GDM, it had no correlation with neonatal weight.
Colorectal Metastasis from Ovarian Neoplasm Mimicking Primary Colon Cancer
Authors: Aqsa Anum , Droubi Sami , Amarnath Shivantha , Haddad Fady , Deeb Liliane
Published: January 2021

Metastasis to the colon from another primary internal malignancy is an untypical and a seldom reported entity. Direct visualization during colonoscopy is considered the gold standard of diagnosis. Pathologic diagnosis with immunohistochemical staining is essential to differentiate primary colorectal malignancy from secondary metastasis to the colon. We, hereby, present a case of a 53-year-old female status-post resection of left-sided papillary serous ovarian neoplasm who presented 2 years later with a single rectosigmoid intraluminal ulcerative mass imitating a primary colon cancer. Biopsies of the mass were consistent with metastasis from her primary ovarian carcinoma. We believe this case is unique because of the rarity of ovarian cancer metastasizing to the colon intraluminally rather than through direct locoregional invasion. Furthermore, it highlights the importance of considering secondary metastasis in patients with previous history of another primary internal malignancy.
Modification and Validation of the Phosphate Removal Model: A Multicenter Study
Authors: Zhang Weichen , Du Qiuna , Xiao Jing , Bi Zhaori , Yu Chen , Ye Zhibin , Wang Mengjing , Chen Jing
Published: January 2021

Background: Our research group has previously reported a noninvasive model that estimates phosphate removal within a 4-h hemodialysis (HD) treatment. The aim of this study was to modify the original model and validate the accuracy of the new model of phosphate removal for HD and hemodiafiltration (HDF) treatment. Methods: A total of 109 HD patients from 3 HD centers were enrolled. The actual phosphate removal amount was calculated using the area under the dialysate phosphate concentration time curve. Model modification was executed using second-order multivariable polynomial regression analysis to obtain a new parameter for dialyzer phosphate clearance. Bias, precision, and accuracy were measured in the internal and external validation to determine the performance of the modified model. Results: Mean age of the enrolled patients was 63 ± 12 years, and 67 (61.5%) were male. Phosphate removal was 19.06 ± 8.12 mmol and 17.38 ± 6.75 mmol in 4-h HD and HDF treatments, respectively, with no significant difference. The modified phosphate removal model was expressed as Tpo4 = 80.3 × C45 − 0.024 × age + 0.07 × weight + β × clearance − 8.14 (β = 6.231 × 10−3 × clearance − 1.886 × 10−5 × clearance2 – 0.467), where C45 was the phosphate concentration in the spent dialysate measured at the 45th minute of HD and clearance was the phosphate clearance of the dialyzer. Internal validation indicated that the new model was superior to the original model with a significantly smaller bias and higher accuracy. External validation showed that R2, bias, and accuracy were not significantly different than those of internal validation. Conclusions: A new model was generated to quantify phosphate removal by 4-h HD and HDF with a dialyzer surface area of 1.3–1.8 m2. This modified model would contribute to the evaluation of phosphate balance and individualized therapy of hyperphosphatemia.
A Diagnostically Challenging Case of Febrile Ulceronecrotic Mucha-Habermann Disease in an Adult Female Successfully Treated with Methotrexate and Cyclosporine
Authors: Ngo Tracy , Hossain Claudia , Cohen Jason , McLellan Beth , Blasiak Rachel , Balagula Eugene
Published: January 2021

Febrile ulceronecrotic Mucha-Habermann disease (FUMHD) is a rare and severe variant of pityriasis lichenoides et varioliformis acuta (PLEVA) characterized by intermittent pyrexia, acute onset of generalized ulceronecrotic lesions, and histopathology suggestive of PLEVA. Prompt diagnosis and treatment are necessary to halt the progression of this potentially fatal disease; however, the widely variable presentation of FUMHD in addition to its rarity poses a diagnostic challenge. We report the case of a previously healthy 43-year-old woman who presented to the emergency department with 1 month of generalized rash and intermittent fevers. Her only reported new exposure were elective intravenous vitamin infusions received at a medi-spa 1 week prior to onset of lesions. Initial evaluations were inconclusive, and confluent ulceronecrotic, hemorrhagic lesions appeared on approximately 90% of her body despite steroid, antibiotic, and cyclosporine therapy. Repeat histopathology was consistent with PLEVA, and in the context of her clinical presentation she was diagnosed with FUMHD. The patient rapidly attained remission with methotrexate therapy but sustained residual scarring.
Carboplatin-Cyclophosphamide or Paclitaxel without or with Bevacizumab as First-Line Treatment for Metastatic Triple-Negative Breast Cancer (BOOG 2013-01)
Authors: van Rossum Annelot G.J. , Mandjes Ingrid A.M. , van Werkhoven Erik , van Tinteren Harm , van Leeuwen-Stok A. Elise , Nederlof Petra , Portielje Johanna E.A. , van Alphen Robbert J. , Platte Els , van den Broek Daan , Huitema Alwin , Kok Marleen , Linn Sabine C. , Oosterkamp Hendrika M. ,   on behalf of the Triple-B trialists’ group
Published: January 2021

Background: The addition of bevacizumab to chemotherapy conferred a modest progression-free survival (PFS) benefit in metastatic triple-negative breast cancer (mTNBC). However, no overall survival (OS) benefit has been reported. Also, its combination with carboplatin-cyclophosphamide (CC) has never been investigated. Methods: The Triple-B study is a multicenter, randomized phase IIb trial that aims to prospectively validate predictive biomarkers, including baseline plasma vascular endothelial growth factor receptor-2 (pVEGFR-2), for bevacizumab benefit. mTNBC patients were randomized between CC and paclitaxel (P) without or with bevacizumab (CC ± B or P ± B). Here we report on a preplanned safety and preliminary efficacy analysis after the first 12 patients had been treated with CC+B and on the predictive value of pVEGFR-2. Results: In 58 patients, the median follow-up was 22.1 months. Toxicity was manageable and consistent with what was known for each agent separately. There was a trend toward a prolonged PFS with bevacizumab compared to chemotherapy only (7.0 vs. 5.2 months; adjusted HR = 0.60; 95% CI 0.33–1.08; p = 0.09), but there was no effect on OS. In this small study, pVEGFR-2 concentration did not predict a bevacizumab PFS benefit. Both the intention-to-treat analysis and the per-protocol analysis did not yield a significant treatment-by-biomarker test for interaction (pinteraction = 0.69). Conclusions:CC and CC+B are safe first-line regimens for mTNBC and the side effects are consistent with those known for each individual agent. pVEGFR-2 concentration did not predict a bevacizumab PFS benefit.
Higher sRAGE Levels Predict Mortality in Frail Older Adults with Cardiovascular Disease
Authors: Butcher Lee , Carnicero Jose Antonio , Pérès Karine , Colpo Marco , Gomez Cabrero David , Dartigues Jean-François , Bandinelli Stefania , Garcia-Garcia Francisco Jose , Rodríguez-Mañas Leocadio , Erusalimsky Jorge D. ,   FRAILOMIC Consortium
Published: January 2021

Introduction: The evidence that blood levels of the soluble receptor for advanced glycation end products (sRAGE) predict mortality in people with cardiovascular diseases (CVD) is inconsistent. To clarify this matter, we investigated if frailty status influences this association. Methods: We analysed data of 1,016 individuals (median age, 75 years) from 3 population-based European cohorts, enrolled in the FRAILOMIC project. Participants were stratified by history of CVD and frailty status. Mortality was recorded during 8 years of follow-up. Results: In adjusted Cox regression models, baseline serum sRAGE was positively associated with an increased risk of mortality in participants with CVD (HR 1.64, 95% CI 1.09–2.49, p = 0.019) but not in non-CVD. Within the CVD group, the risk of death was markedly enhanced in the frail subgroup (CVD-F, HR 1.97, 95% CI 1.18–3.29, p = 0.009), compared to the non-frail subgroup (CVD-NF, HR 1.50, 95% CI 0.71–3.15, p = 0.287). Kaplan-Meier analysis showed that the median survival time of CVD-F with high sRAGE (>1,554 pg/mL) was 2.9 years shorter than that of CVD-F with low sRAGE, whereas no survival difference was seen for CVD-NF. Area under the ROC curve analysis demonstrated that for CVD-F, addition of sRAGE to the prediction model increased its prognostic value. Conclusions: Frailty status influences the relationship between sRAGE and mortality in older adults with CVD. sRAGE could be used as a prognostic marker of mortality for these individuals, particularly if they are also frail.
S2K Guideline for Diagnosis of Idiopathic Pulmonary Fibrosis
Authors: Behr Jürgen , Günther Andreas , Bonella Francesco , Dinkel Julien , Fink Ludger , Geiser Thomas , Geissler Klaus , Gläser Sven , Handzhiev Sabin , Jonigk Danny , Koschel Dirk , Kreuter Michael , Leuschner Gabriela , Markart Philipp , Prasse Antje , Schönfeld Nicolas , Schupp Jonas Christian , Sitter Helmut , Müller-Quernheim Joachim , Costabel Ulrich
Published: January 2021

Idiopathic pulmonary fibrosis (IPF) is a severe and often fatal disease. Diagnosis of IPF requires considerable expertise and experience. Since the publication of the international IPF guideline in the year 2011 and the update 2018 several studies and technical advances have occurred, which made a new assessment of the diagnostic process mandatory. The goal of this guideline is to foster early, confident, and effective diagnosis of IPF. The guideline focusses on the typical clinical context of an IPF patient and provides tools to exclude known causes of interstitial lung disease including standardized questionnaires, serologic testing, and cellular analysis of bronchoalveolar lavage. High-resolution computed tomography remains crucial in the diagnostic workup. If it is necessary to obtain specimens for histology, transbronchial lung cryobiopsy is the primary approach, while surgical lung biopsy is reserved for patients who are fit for it and in whom a bronchoscopic diagnosis did not provide the information needed. After all, IPF is a diagnosis of exclusion and multidisciplinary discussion remains the golden standard of diagnosis.
Thrombin Generation in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention
Authors: Gurevitz Chen , Eisen Alon , Lev Eli , Itzhaki Ben Zadok Osnat , Perl Leor , Samara Abed , Nissenholtz Adaya , Rozovski Uri , Elis Avishay , Kornowski Ran , Raanani Pia , Ziv Eti , Spectre Galia
Published: January 2021

Background: The optimal antithrombotic treatment for patients with atrial fibrillation (AF) that undergo percutaneous coronary intervention (PCI) is controversial. Dual therapy (clopidogrel and a direct oral anticoagulant [DOAC]) is safer than triple therapy (warfarin, aspirin, and clopidogrel), while efficacy is unclear. We aimed to evaluate thrombin generation (TG) under dual and triple therapy. Methods: A noninterventional prospective trial in patients with AF undergoing PCI. Patients received 4 weeks of triple therapy with aspirin, clopidogrel, and a DOAC followed by aspirin withdrawal. TG was measured in platelet-rich plasma (PRP) and platelet-poor plasma (PPP) at 3 five to 21 points, day 1 after PCI (TIME 0), 4 weeks after PCI (TIME 1), and 2 weeks after aspirin withdrawal (TIME 2). Results: Twenty-three patients (18 men, median age 78 years, 83% with acute coronary syndrome) were included. Endogenous thrombin potential (ETP) in PPP was high at TIME 0 compared with TIME 1 (ETP 3,178 ± 248 nM vs. 2,378 ± 222 nM, p = 0.005). These results remained consistent when measured in PRP. No significant difference in ETP was found before (TIME 1) and after aspirin withdrawal (TIME 2) although few patients had high ETP levels after stopping aspirin. Conclusions: TG potential is high immediately after PCI and decreases 4 weeks after PCI in patients receiving triple therapy. TG remains constant after aspirin withdrawal in most patients, suggesting that after 1 month the antithrombotic effect of dual therapy may be similar to triple therapy.
Safety and Efficacy of Tandem Hemodialysis and Selective Plasma Exchange in Pretransplant Desensitization of ABO-Incompatible Kidney Transplantation
Authors: Hanaoka Ako , Naganuma Toshihide , Kabata Daijiro , Morii Daichi , Takemoto Yoshiaki , Uchida Junji , Shintani Ayumi
Published: January 2021

Introduction: In patients requiring both hemodialysis (HD) and apheresis, the 2 treatments can be performed simultaneously. At our hospital, selective plasma exchange (SePE) is often performed along with HD for removal of isoagglutinins before ABO-incompatible (ABOi) kidney transplantation. The 2 treatments can be completed within the HD schedule, which allows the treatment time to be shortened. This approach is also less stressful for patients because fewer punctures are required. In this study, we investigated the safety and efficacy of tandem HD and SePE. Methods: A total of 58 SePE sessions in 30 ABOi kidney transplant recipients were investigated. The SePE circuit was connected in parallel with the HD circuit, and tandem HD and SePE therapy was performed using filtration methods. The SePE sessions were divided into 2 groups: those with SePE monotherapy (group S, n = 20) and those with tandem therapy (group T, n = 38). Changes in transmembrane pressure (TMP), arterial pressure (AP), venous pressure (VP), and decrease in isoagglutinin titers over time were compared between the groups with adjustment for background data. Results: The internal pressures (AP and VP) were higher in group T, and there were significant differences in changes of TMP and AP over time between groups T and S. Membrane exchange was required in 1 case in group T due to coagulation. There was a more significant decrease of immunoglobulin G isoagglutinin titers in group T compared to group S. No case had antibody-mediated rejection after transplantation. Discussion/Conclusion: In HD/SePE tandem therapy, internal pressures were higher and TMP and AP tended to increase more compared to SePE monotherapy, but we were able to perform the 2 treatments without any functional problems. Tandem therapy was also effective in decreasing isoagglutinin titers, which suggests that this may be a beneficial treatment modality as apheresis before ABOi kidney transplantation.
The Potential of Neurofilament Light as a Biomarker in Alzheimer’s Disease
Authors: Xiong Yong-lan , Meng Tao , Luo Jing , Zhang Hua
Published: January 2021

Background: Alzheimer’s disease (AD) is the most common neurodegenerative disease characterized by progressive memory loss and cognitive impairment. In 2011, the National Institute on Aging and Alzheimer’s Association (NIA-AA) Research Framework has proposed to use biomarkers to diagnose AD in living persons. AD core biomarkers show high diagnostic specificity in distinguishing AD from healthy control subjects, but have little additional value for prognosis or stage of disease. Summary: With the update of detection methods and techniques, other AD biomarkers have been discovered. Neurofilament light (NFL) is currently recognized as a biomarker of nerve axonal injury and one of the candidate markers in AD neurodegeneration, and the relationship between NFL and AD pathophysiology has attracted widespread attention. More and more studies have shown that NFL plays an important role in predicting the clinical progress and prognosis of AD. Recently, the genome-wide association study also found that multiple single-nucleotide polymorphisms are associated with NFL levels and AD risk. Key Messages: In this review, we discuss the relationship between the genetic characteristics of NFL and AD, the NFL levels in AD, and the relationship between NFL and AD core biomarkers, neuroimaging, and cognitive performance.
Mortality and Hospitalizations among Sickle Cell Disease Patients with End-Stage Kidney Disease Initiating Dialysis
Authors: Olaniran Kabir O. , Eneanya Nwamaka D. , Zhao Sophia H. , Ofsthun Norma J. , Maddux Franklin W. , Thadhani Ravi I. , Dalrymple Lorien S. , Nigwekar Sagar U.
Published: January 2021

Background: Sickle cell disease (SCD) is the most common inherited hematological disorder and a well-described risk factor for end-stage kidney disease (ESKD). Mortality and hospitalizations among patients with SCD who develop ESKD remain understudied. Furthermore, prior studies focused only on SCD patients where ESKD was caused by SCD. We aimed to describe mortality and hospitalization risk in all SCD patients initiating dialysis and explore risk factors for mortality and hospitalization. Methods: We performed a national observational cohort study of African American ESKD patients initiating dialysis (2000–2014) in facilities affiliated with a large dialysis provider. SCD was identified by diagnosis codes and matched to a reference population (non-SCD) by age, sex, dialysis initiation year, and geographic region of care. Sensitivity analyses were conducted by restricting to patients where SCD was recorded as the cause of ESKD. Results: We identified 504 SCD patients (mean age: 47 ± 14 years; 48% females) and 1,425 reference patients (mean age: 46 ± 14 years; 49% females). The median follow-up was 2.4 (IQR 1.0–4.5) years. Compared to the reference, SCD was associated with higher mortality risk (hazard ratio 1.66; 95% confidence interval [CI]: 1.36–2.03) and higher hospitalization rates (incidence rate ratio 2.12; 95% CI: 1.88–2.38) in multivariable analyses. Exploratory multivariable mortality risk models showed the largest mortality risk attenuation with the addition of time-varying hemoglobin and high-dose erythropoietin, but the association of SCD with mortality remained significant. Sensitivity analyses (restricted to ESKD caused by SCD) also showed significant associations between SCD and mortality and hospitalizations, but with larger effect estimates. High-dose erythropoietin was associated with the highest risk for mortality and hospitalization in SCD. Conclusions: Among ESKD patients, SCD is associated with a higher risk for mortality and hospitalization, particularly in patients where SCD is identified as the cause of ESKD.
Human Development at the Intersection of Culture and Globalization: Towards a More Inclusive Future
Authors: Maynard Ashley E. , Chaudhary Nandita
Published: January 2021

There is a long history of studies of human development in different cultural groups, but studies of development that explicitly take globalization into account are more recent. Cultural practices change, but cultures have often been considered static. Studying developmental change in changing societies in dynamic global settings presents challenges for researchers. It also presents opportunities to clarify content and processes in research. For such a clarification, it is compulsory to understand how local and global phenomena have been framed in the discourse of human development, and the potential outcomes of this positioning on people’s lives. In this article we lay out five key practices to guide researchers who wish to study culture and development in a globalizing world: engaging diverse groups of people within and across societies, acknowledging multiple pathways of development, attention to the cultural context, using mixed methods, and designing sustainable and relevant interventions.
Irish English PEPS-C (2015 edition) and Learners of ESL
Authors: Lee Alice , Nyland Joseph , Peppé Sue
Published: January 2021

Introduction: Profiling Elements of Prosody in Speech-Communication (PEPS-C) is a computerised test for assessing the abilities to understand and use speech prosody in communication. It has been used to obtain a profile of strengths and weaknesses in different prosodic forms and functions for different clinical populations (e.g., autism spectrum disorders, Down syndrome) and second language learners. The 2015 edition of PEPS-C incorporates four new subtests addressing the understanding and production of lexical stress and phrasal stress, and collapses four form subtests (Intonation/Short-Item Input and Output, Prosody/Long-Item Input and Output) into two (Discrimination, Imitation). However, the suitability of these new tasks has not been reported in any published studies, although they are likely to be relevant for learners of English. Moreover, the present authors update the Irish English (IE) version of PEPS-C to the 2015 edition for another research project on prosodic skills in children with spina bifida. Hence, this paper reports the making of PEPS-C 2015 (IE) and examines the usefulness of this test in assessing a group of non-native speakers of English, as compared to a group of native speakers of IE. Methods: PEPS-C 2015 for Irish English was developed by adapting the test items of the UK English version of the test. The PEPS-C 2015 (IE) was then trialled on 25 native speakers of Irish English and 10 Spanish speakers who speak English as a second language (ESL). Results: All native speakers of Irish English showed competence (scored ≥75% correct) in the comprehension and expression of prosodic form and functions assessed. For the ESL speakers, the test identified two areas of possible difficulty for this group: Phrase Stress Comprehension and Expression, and Contrastive Stress Comprehension. Conclusion: The PEPS-C 2015, with its extra stress tasks, might therefore be useful as a prosody assessment tool for ESL speakers, particularly those with a Romance first language or at an early stage of learning, but further research is needed.
The Ability to Use Epinephrine Autoinjector in Patients Who Receive Prescription Immediately after Anaphylaxis
Authors: Kadivec Saša , Košnik Mitja
Published: January 2021

Background: Epinephrine autoinjector (EAI) is prescribed to prevent a fatal outcome in the case of a repeated anaphylactic reactions. We wanted to determine how adult patients who received their first prescription as part of an urgent treatment of an anaphylactic reaction or at their family physician were instructed on the use of EAI. Methods: Nurses assessing patients’ knowledge asked the patient to demonstrate how to use the EAI training device. Patients who performed the critical steps correctly in 1 min were labelled as competent. Results: Forty-one patients (24% women, 46 ± 5 years) came for the allergy examination 116 ± 145 days after receiving a prescription for EAI. When prescribing, the doctor or nurse explained the instructions for the use of EAI to 63.4% patients, and 31.7 patients practiced the use of EAI using a training device. At the pharmacy, 22% received explanation and 7% also practiced using a training device. Fifty-four percent of patients were able to effectively administer EAI adrenaline within 1 min. Higher education level was associated with sufficient knowledge about the use of EAI (p = 0.026). At the time of the visit to the allergy specialist clinic, 61% of patients had EAI with them. The shelf life of EAI was known to 63% of patients. Conclusions: The activities to increase the prescription rate of EAI immediately after treatment of anaphylactic episode are not sufficient to prevent severe outcome after the repeated episodes of anaphylaxis as nearly a half of patients are not able to use EAI correctly.
Low-Dose Methotrexate Use in Idiopathic Granulomatous Mastitis: An Alternative Treatment Method
Authors: Kafadar Mehmet Tolga , Bahadır Mehmet Veysi , Girgin Sadullah
Published: January 2021

Background: Idiopathic granulomatous mastitis (IGM) is a rare, recurrent and progressive breast disease with an unknown etiology. Patients with IGM will probably face stressful, time-consuming treatment procedures with side effects due to medications. There are different treatment modalities in clinical use including medical and surgical interventions. Objective: The aim of this study was to present the results of using the combination therapy of low-dose methotrexate (MTX) and steroid in IGM. Methods: Seventeen patients diagnosed with IGM and treated with MTX were included into the study. Low-dose MTX at 5 mg/week and 8 mg/day prednisone were given for 2–3 months. Results: After 2–3 months of treatment, 10 patients exhibited (58.5%) complete, 3 patients (17.6%) partial recovery, and no response to the treatment process was observed in 4 patients (23.5%). No side effects of MTX and recurrent events were noted in any of the patients. Conclusion: Low-dose MTX and prednisone treatment for IGM patients, who did not respond to steroids alone, should be considered as an alternative treatment method instead of surgical intervention.
Recursive Partitioning Analysis of Systemic Therapy after Radiotherapy in Patients with Brain Metastases
Authors: Nieder Carsten , Dalhaug Astrid , Haukland Ellinor
Published: January 2021

Purpose: The purpose of this study was to identify factors associated with the initiation or continuation of systemic treatment after brain irradiation. The outcome of interest was a utilization rate of at least 75%, given that active extracranial disease is common in patients with brain metastases. If left untreated, extracranial disease limits survival, regardless of successful local treatment of the brain metastases. In this context, systemic therapy has been shown to improve survival, e.g., after whole-brain radiotherapy. Patients and Methods: The study included 185 patients with active extracranial disease, 60% of whom received systemic therapy. Results: Survival from the start of brain irradiation was longest in patients who received additional immune checkpoint inhibitors, endocrine treatment, or anti-HER-2 drugs. After uni- and multivariate analyses, Eastern Cooperative Oncology Group performance status (PS) was selected as the first prediction criterion in the recursive partitioning analysis (RPA) decision tree analysis. RPA was successful for patients with PS 0–1, but patients with PS 2 had lower treatment utilization rates (maximum 60–70%, with a disease-dependent impact of age and LabBM score [blood test results]). The highest utilization rates were observed in (1) patients with PS 0 and (2) those with breast cancer, small-cell lung cancer, or lung adenocarcinoma with PS 1. Conclusions: These results inform the multidisciplinary discussion and treatment planning for the common scenario of simultaneous intra- and extracranial metastases.
Optimal Range of Fecal Calprotectin for Predicting Mucosal Healing in Patients with Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis
Authors: Xiang Bing-Jie , Jiang Min , Sun Ming-Jun , Dai Cong
Published: January 2021

Objective: Fecal calprotectin (FC) is a promising marker for assessment of inflammatory bowel disease (IBD) activity. However, the utility of FC for predicting mucosal healing (MH) of IBD patients has yet to be clearly demonstrated. The objective of our study was to perform a meta-analysis evaluating the diagnostic accuracy of FC in predicting MH of IBD patients. Methods: We systematically searched the databases for studies from inception to April 2020 that evaluated MH in IBD. The methodological quality of each study was assessed according to the Quality Assessment of Diagnostic Accuracy Studies checklist. The extracted data were pooled using a summary receiver operating characteristic curve model. Random-effects model was used to summarize the diagnostic odds ratio, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio. Results: Sixteen studies comprising 1,682 ulcerative colitis (UC) patients and 4 studies comprising 221 Crohn’s disease (CD) patients were included. The best performance of FC for predicting MH in UC was at cut-off range of 60–75 μg/g with area under the curve (AUC) of 0.88 and pooled sensitivity and specificity of 0.87 and 0.79, respectively. The pooled sensitivity and specificity values of cutoff range 180–250 μg/g for predicting MH in CD were 0.67 and 0.76, respectively. The AUC of 0.79 also revealed improved discrimination for identifying MH in CD with FC concentration. Conclusion: Our meta-analysis has found that FC is a simple, reliable noninvasive marker for predicting MH in IBD patients. FC cutoff range 60–75 μg/g appears to have the best overall accuracy in UC patients.
Prolactin Response to Metformin in Cabergoline-Resistant Prolactinomas: A Pilot Study
Authors: Portari Luiz Henrique Corrêa , Correa-Silva Silvia Regina , Abucham Julio
Published: January 2021

Introduction: Cabergoline is the treatment of choice for prolactinomas. However, 10–20% of prolactinomas are resistant to cabergoline. Metformin, a biguanide widely used in the treatment of diabetes mellitus, has been shown to reduce prolactin secretion in various pituitary tumor-cell lineages both in vitro and in vivo and in human pituitary adenomas in vitro. The aim of this study is to test the effects of metformin addition to cabergoline treatment on prolactin levels in patients with resistant prolactinomas. Subjects and Methods: This is a prospective study performed in an outpatient clinic in a reference center. Ten adult patients (26–61 years) with prolactinomas (7 M), persistent hyperprolactinemia (38–386 ng/mL) under cabergoline treatment (2–7 mg/week) for at least 6 months (6–108 months), features of metabolic syndrome, and not taking metformin were included. Metformin (1.0–2.5 g v.o./day) was given according to patients’ tolerance. Cabergoline doses were kept unchanged. Serum prolactin levels were measured before and after short- (30–60 days) and long-term (120–180 days) metformin treatment. Results: Mean prolactin levels did not show any significant changes (148 ± 39 vs. 138 ± 42 vs. 133 ± 39 ng/mL, before, at 30–60 days, and at 120–180 days, respectively, p = 0.196) after metformin (mean dose: 1.25 g/day; range: 1.0–2.0 g/day). No patient reached a normal prolactin level during metformin treatment. Two patients were considered partial responders for exhibiting prolactin decreases ≥50% at a single time point during metformin. Conclusion: Metformin addition to ongoing high-dose cabergoline treatment in patients with cabergoline-resistant prolactinomas failed to show a consistent inhibitory effect in serum prolactin levels.
Acceptance of a COVID-19 Vaccine and Its Related Determinants among the General Adult Population in Kuwait
Authors: Alqudeimat Yosor , Alenezi Deema , AlHajri Bedour , Alfouzan Heba , Almokhaizeem Zain , Altamimi Saba , Almansouri Waleed , Alzalzalah Sayed , Ziyab Ali H.
Published: January 2021

Objective: The objective of this study was to determine the acceptance of a coronavirus disease 2019 (COVID-19) vaccine among the general adult population in Kuwait and assess its determinants. Subjects and Methods: A web-based cross-sectional study was conducted by enrolling adults living in Kuwait (n = 2,368; aged ≥21 years). Acceptance of a COVID-19 vaccine was inferred if participants indicated that they “definitely or probably will accept vaccination against COVID-19 once a vaccine is available.” Associations were explored by applying a modified Poisson regression to estimate and infer adjusted prevalence ratios (aPR) and their 95% confidence intervals (CI). Results: In total, 53.1% (1,257/2,368) of the participants were willing to accept a COVID-19 vaccine once available. Male subjects were more willing to accept a COVID-19 vaccine than females (58.3 vs. 50.9%, p < 0.001). Subjects who viewed vaccines in general to have health-related risks were less willing to accept vaccination (aPR = 0.39, 95% CI: 0.35–0.44). Moreover, participants who previously received an influenza vaccine were more likely to accept a COVID-19 vaccine (aPR = 1.44, 95% CI: 1.31–1.58). Willingness to get vaccinated against COVID-19 increased as the self-perceived chances of contracting the infection increased (p < 0.001). Conclusion: Overall, 53.1% of the study participants demonstrated willingness to get vaccinated against COVID-19. We found several factors influencing the level of acceptance. Since vaccination appears to be an essential preventive measure that can halt the COVID-19 pandemic, factors relating to low vaccine acceptance need to be urgently addressed by public health strategies.
Unusual Biliary Complication following Christmas Eve Dinner
Authors: Kunovsky Lumir , Tesarikova Pavla , Sethi Amrita , Kroupa Radek , Dastych Milan , Dolina Jiri , Kala Zdenek , Trna Jan
Published: January 2021

We present a case of a fish bone impacted in the papilla of Vater resulting in dyspepsia and mild elevation in liver function tests, which was subsequently treated endoscopically. Fish bones are one of the most commonly encountered swallowed foreign bodies. However, involvement of the biliary tract, such as the one described by us, represents an extremely rare complication of fish bone ingestion. The diagnosis of a foreign body in the biliary tract can be difficult, and early endoscopic or surgical extraction may be required to avoid complications such as biliary stone formation, obstructive jaundice, cholangitis or cholecystitis, and/or biliary sepsis. Prompt endoscopic treatment can avoid severe biliary complications or surgical therapy.
Baleias e Império: os Estados Unidos e a expansão baleeira nos mares do Atlântico Sul (1761-1844)
Authors: Castellucci Junior Wellington
Published: January 2021

Este artigo analisa a expansão baleeira norte-americana, ocorrida entre o final do século XVIII e a primeira metade do XIX, em direção ao litoral brasileiro. Foram escrutinadas fontes em dois arquivos e museus da Nova Inglaterra, o Mystic Sea Port e o Whaling Museum. No primeiro, consultamos as relações de viagens baleeiras ocorridas entre a segunda metade do século XVIII até 1920. Também arrolamos documentos avulsos, cartas de marinheiros e comandantes, relações de embarcações e informações sobre os portos da região. No Whaling Museum analisamos logbooks de viagens ao Brasil, cartas náuticas, mapas e fontes avulsas. Na Gazeta de New Bedford, levantamos informações sobre expedições à costa brasileira realizadas entre 1843 e 1845, os balanços da produção de óleo de baleia, espermacete de cachalotes e ossos de baleias. Foram examinadas e sistematizadas informações sobre os comandantes, as embarcações e suas rotas, além de dados quantitativos a respeito de baleias e cetáceos abatidos no litoral brasileiro. Por fim, destacamos o grande peso da indústria baleeira americana naquela conjuntura de afirmação do capitalismo e globalização da economia.
Single-Cell RNA Sequencing Reveals Heterogeneity of Vascular Cells in Early Stage Murine Abdominal Aortic Aneurysm—Brief Report
Authors: Yang Huan , Zhou Ting , Stranz Amelia , DeRoo Elise , Liu Bo
Published: January 2021

Objective:

Abdominal aortic aneurysm (AAA) is a life-threatening vascular disease characterized by smooth muscle cell depletion, ECM (extracellular matrix) degradation, and infiltration of immune cells. The cellular and molecular profiles that govern the heterogeneity of the AAA aorta are yet to be elucidated.

Approach and Results:

We performed single-cell RNA sequencing on mouse AAA tissues. AAA was induced in C57BL/6J mice by perivascular application of CaCl
2
. Unbiased clustering identified 12 distinct populations of 8 cell types. Percentages of each population and gene expression were compared between sham and AAA tissue. Furthermore, we characterized the transcriptional profiles and potential functional features of populations in smooth muscle cells, fibroblasts, and macrophages and revealed the unique regulons in each cell type.

Conclusions:

Together, these data provide high-resolution insight into the complexity and heterogeneity of mouse AAA and indicate that populations within major cell types such as smooth muscle cells, fibroblasts, and macrophages may contribute differently to AAA pathogenesis.

Graphic Abstract:

A graphic abstract is available for this article.
Developing and Optimizing Innovative Tools to Address Familial Hypercholesterolemia Underdiagnosis
Authors: Campbell-Salome Gemme , Jones Laney K. , Masnick Max F. , Walton Nephi A. , Ahmed Catherine D. , Buchanan Adam H. , Brangan Andrew , Esplin Edward D. , Kann David G. , Ladd Ilene G. , Kelly Melissa A. , Kindt Iris , Kirchner H. Lester , McGowan Mary P. , McMinn Megan N. , Morales Ana , Myers Kelly D. , Oetjens Matthew T. , Rahm Alanna Kulchak , Schmidlen Tara J. , Sheldon Amanda , Simmons Emilie , Snir Moran , Strande Natasha T. , Walters Nicole L. , Wilemon Katherine , Williams Marc S. , Gidding Samuel S. , Sturm Amy C.
Published: January 2021

Background:

Familial hypercholesterolemia (FH) is the most common cardiovascular genetic disorder and, if left untreated, is associated with increased risk of premature atherosclerotic cardiovascular disease, the leading cause of preventable death in the United States. Although FH is common, fatal, and treatable, it is underdiagnosed and undertreated due to a lack of systematic methods to identify individuals with FH and limited uptake of cascade testing.

Methods and Results:

This mixed-method, multi-stage study will optimize, test, and implement innovative approaches for both FH identification and cascade testing in 3 aims. To improve identification of individuals with FH, in Aim 1, we will compare and refine automated phenotype-based and genomic approaches to identify individuals likely to have FH. To improve cascade testing uptake for at-risk individuals, in Aim 2, we will use a patient-centered design thinking process to optimize and develop novel, active family communication methods. Using a prospective, observational pragmatic trial, we will assess uptake and effectiveness of each family communication method on cascade testing. Guided by an implementation science framework, in Aim 3, we will develop a comprehensive guide to identify individuals with FH. Using the Conceptual Model for Implementation Research, we will evaluate implementation outcomes including feasibility, acceptability, and perceived sustainability as well as health outcomes related to the optimized methods and tools developed in Aims 1 and 2.

Conclusions:

Data generated from this study will address barriers and gaps in care related to underdiagnosis of FH by developing and optimizing tools to improve FH identification and cascade testing.
Exercise Ventricular Rates, Cardiopulmonary Exercise Performance, and Mortality in Patients With Heart Failure With Atrial Fibrillation
Authors: Elshazly Mohamed B. , Wilkoff Bruce L. , Tarakji Khaldoun , Wu Yuping , Donnellan Eoin , Abi Khalil Charbel , Asaad Nidal , Jaber Wael , Wazni Oussama , Cho Leslie
Published: January 2021

Background:

In heart failure (HF) with sinus rhythm, resting and exercise heart rates correlate with exercise capacity and mortality. However, in HF with atrial fibrillation (AF), this correlation is unknown. Our aim is to investigate the association of resting and exercise ventricular rates (VRs) with exercise capacity and mortality in HF with AF.

Methods:

We identified 903 patients with HF and AF referred for cardiopulmonary stress testing. AF was defined as history of AF and AF during cardiopulmonary stress testing. We constructed multivariable models to evaluate the association of resting VR, peak exercise VR, VR reserve (peak VR−resting VR), and chronotropic index with (1) peak oxygen consumption (PVO
2
) ≤18 mL/kg per minute, (2) continuous PVO
2
, and (3) 10-year all-cause mortality.

Results:

Median (25th–75th percentile) age was 60 (52–67) years, left ventricular ejection fraction was 25 (15–50)%, and 76.1% were males. Patients with lower (quartile 1) compared with higher (quartile 4) peak VR, VR reserve, and chronotropic index were more likely to have PVO
2
≤18 mL/kg per min (adjusted odds ratio [95% CI]: 14.92 [8.07–27.58], 24.60 [12.36–48.98], and 22.31 [11.24–44.27], respectively), and higher all-cause mortality (adjusted hazard ratio [95% CI]: 2.56 [1.62–4.04], 2.29 [1.47–3.59], and 2.30 [1.51–3.49], respectively). For every 10 beats per minute increase in VR reserve, PVO
2
increased by 1.05 mL/kg per minute (B-coefficient [95% CI]: 1.05 [0.94–1.15]) and mortality decreased by 12% (adjusted hazard ratio [95% CI]: 0.88 [0.83–0.94]). Resting VR was associated with PVO
2
(B-coefficient [95% CI]: −0.46 [−0.70 to −0.23]) but not mortality (adjusted hazard ratio [95% CI]: 0.97 [0.88–1.06]).

Conclusions:

In patients with HF and AF, higher resting VR and lower peak exercise VR, VR reserve, and chronotropic index were all associated with worse peak exercise capacity, but only lower exercise VR parameters were associated with higher mortality. Dedicated studies are needed to gauge whether modulating exercise VR enhances exercise performance and outcomes.