bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of Structural Identification Accuracy Indicators Using Fuzzy Logic
Authors: Woodard Stanley E. , Pappa Richard S. 
Published: February 2021

Abstract
A fuzzy expert system was developed for autonomous in-space identification of spacecraft modal parameters. The in-space identification can be used to validate analytical predictions, detect structural damage, or tune automatic control systems as required. A fuzzy expert system determines accuracy of vibration data analysis performed autonomously using the Eigensystem Realization Algorithm. Evaluation of the data analysis output is imprecise and somewhat subjective. The expert system was developed using the knowledge provided the co-developer of the Eigensystem Realization Algorithm. The accuracy indicator represents the analyst’s degree of confidence in the analysis results. The fuzzy membership functions of the expert system were parameterized and tuned using numerical optimization.
Cardiorespiratory Responses to Constant and Varied-Load Interval Training Sessions
Authors: Beltrami Fernando G. , Roos Elena , von Ow Marco , Spengler Christina M. 
Published: February 2021

Purpose: To compare the cardiorespiratory responses of a traditional session of high-intensity interval training session with that of a session of similar duration and average load, but with decreasing workload within each bout in cyclists and runners. Methods: A total of 15 cyclists (maximal oxygen uptake [] 62 [6] mL·kg−1·min−1) and 15 runners ( 58 [4] mL·kg−1·min−1) performed both sessions at the maximal common tolerable load on different days. The sessions consisted of four 4-minute intervals interspersed with 3 minutes of active recovery. Power output was held constant for each bout within the traditional day, whereas power started 40 W (2 km·h−1) higher and finished 40 W (2 km·h−1) lower than average within each bout of the decremental session. Results: Average oxygen uptake during the high-intensity intervals was higher in the decremental session in cycling (89 [4]% vs 86 [5]% of , P = .002) but not in running (91 [4]% vs 90 [4]% of , P = .38), as was the time spent >90% of and the time spent >90% of peak heart rate. Average heart rate (P < .001), pulmonary ventilation (P < .001), and blood lactate concentration (P < .001) were higher during the decremental sessions in both cycling and running. Conclusions: Higher levels of physiological perturbations were achieved during decremental sessions in both cycling and running. These differences were, however, more prominent in cycling, thus making cycling a more attractive modality for testing the effects of a training intervention.
Opioid prescribing for chronic musculoskeletal pain in UK primary care: results from a cohort analysis of the COPERS trial
Authors: Ashaye Tomi , Hounsome Natalia , Carnes Dawn , Taylor Stephanie J C , Homer Kate , Eldridge Sandra , Spencer Anne , Rahman Anisur , Foell Jens , Underwood Martin R 
Published: February 2021

ObjectiveTo establish the level of opioid prescribing for patients with chronic musculoskeletal pain in a sample of patients from primary care and to estimate prescription costs.DesignSecondary data analyses from a two-arm pragmatic randomised controlled trial (COPERS) testing the effectiveness of group self-management course and usual care against relaxation and usual care for patients with chronic musculoskeletal pain (ISRCTN24426731).Setting25 general practices and two community musculoskeletal services in the UK (London and Midlands).Participants703 chronic pain participants; 81% white, 67% female, enrolled in the COPERS trial.Main outcome measuresAnonymised prescribing data over 12 months extracted from GP electronic records.ResultsOf the 703 trial participants with chronic musculoskeletal pain, 413 (59%) patients were prescribed opioids. Among those prescribed an opioid, the number of opioid prescriptions varied from 1 to 52 per year. A total of 3319 opioid prescriptions were issued over the study period, of which 53% (1768/3319) were for strong opioids (tramadol, buprenorphine, morphine, oxycodone, fentanyl and tapentadol). The mean number of opioid prescriptions per patient prescribed any opioid was 8.0 (SD=7.9). A third of patients on opioids were prescribed more than one type of opioid; the most frequent combinations were: codeine plus tramadol and codeine plus morphine. The cost of opioid prescriptions per patient per year varied from £3 to £4844. The average annual prescription cost was £24 (SD=29) for patients prescribed weak opioids and £174 (SD=421) for patients prescribed strong opioids. Approximately 40% of patients received >3 prescriptions of strong opioids per year, with an annual cost of £236 per person.ConclusionsLong-term prescribing of opioids for chronic musculoskeletal pain is common in primary care. For over a quarter of patients receiving strong opioids, these drugs may have been overprescribed according to national guidelines.Trial registration numberISRCTN24426731; Post-results.
Re-evaluation of potential predictors of calretinin and mesothelin in a population-based cohort study using assays for the routine application in clinical medicine
Authors: Casjens Swaantje , Johnen Georg , Raiko Irina , Pesch Beate , Taeger Dirk , Töpfer Carmen , Schonefeld Sandra , Moebus Susanne , Jöckel Karl-Heinz , Brüning Thomas , Weber Daniel 
Published: February 2021

ObjectivesCalretinin and mesothelin are molecular markers for the detection of malignant mesothelioma at early stages. Our objective was the re-evaluation of factors influencing calretinin and mesothelin concentrations in plasma of cancer-free men in order to minimise false-positive tests when using commercial assays approved for clinical diagnostics.SettingThis re-evaluation used data and archived blood samples of the population-based Heinz Nixdorf Recall Study (HNRS) collected from 2011 to 2014.ParticipantsThe present analysis comprised of 569 cancer-free men at the time of blood sampling (median age 70 years) from HNRS.Primary and secondary outcomesMesothelin plasma concentration was determined using ELISA and CLEIA (chemiluminescent enzyme immunoassay). Calretinin plasma concentration was assessed using ELISA.ResultsCompared with the previous determination of concentrations, we detected less false-positive tests using the commercial assays. In this analysis, we found nine false-positive calretinin tests using the ELISA (specificity 98.4%, 95% CI 97.0% to 99.2%) and 24 false-positive mesothelin tests using both ELISA and CLEIA (specificity 95.8%, 95% CI 93.8% to 97.2%). We confirmed renal dysfunction as major predictor of elevated marker concentrations. Mesothelin was additionally affected by bronchitis. Furthermore, elevated inflammation values and hypertension only affected the mesothelin concentration determined by ELISA.ConclusionsThe newly available assays of calretinin and mesothelin approved for clinical diagnostics showed high specificities in the population-based cohort of elderly men without a malignant disease. The current evaluation provides a basis to consider influencing factors in order to further improve the diagnostic procedure.
Population impact of different hypertension management guidelines based on the prospective population-based Heinz Nixdorf Recall study
Authors: Gronewold Janine , Kropp Rene , Lehmann Nils , Stang Andreas , Mahabadi Amir A , Weimar Christian , Dichgans Martin , Moebus Susanne , Kröger Knut , Hoffmann Barbara , Jöckel Karl-Heinz , Erbel Raimund , Hermann Dirk M 
Published: February 2021

ObjectiveHypertension guidelines strongly differ between societies. The current American College of Cardiology/American Heart Association (ACC/AHA) guideline recommends higher proportions of the general population for antihypertensive medication than the previous American and European guidelines. How cardiovascular risk differs between persons with and without antihypertensive medication recommendation has not been examined. Additionally, the population impact of American, European and international guidelines has not been compared systematically within the same study population.MethodsWe compared the prevalence of antihypertensive medication recommendation according to the American (Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure 7 (JNC7), ACC/AHA 2017), European (European Society of Hypertension (ESH)/European Society of Cardiology (ESC) 2013/2018), and international (WHO/International Society of Hypertension (ISH) 2003, ISH 2020) guidelines in 3092 participants of the population-based Heinz Nixdorf Recall study not taking antihypertensive medication at the baseline examination (58.1±7.5 years, 48.7% males). We furthermore compared incident cardiovascular events during the 5-year follow-up between participants with and without antihypertensive medication recommendation.ResultsThe ACC/AHA 2017 guideline recommended the highest percentage of participants for antihypertensive medication (45.8%) compared with the JNC7 (37.2%), ESH/ESC 2013 (17.8%), ESC/ESH 2018 (26.7%), WHO/ISH 2003 (20.3%) or ISH 2020 (25.0%) guidelines. Participants with antihypertensive medication recommendation according to the ACC/AHA 2017 guideline had a significantly higher incidence of cardiovascular events during the 5-year follow-up compared with participants without this recommendation (2.5% vs 1.1%, p=0.003).ConclusionsOur results call for randomised controlled trials to investigate whether applying the stricter ACC/AHA 2017 recommendation leads to a reduction in cardiovascular disease.
Community-based non-pharmacological interventions for improving pain, disability and quality of life in pregnant women with musculoskeletal conditions: protocol for a systematic review with meta-analyses
Authors: Igwesi-Chidobe Chinonso N , Emmanuel Grace Nneoma , Okezue Obinna Chinedu 
Published: February 2021

IntroductionTwenty five per cent of pregnant women with musculoskeletal pain have disabling symptoms that negatively influence quality of life. Studies have reported varying effects of non-pharmacological interventions including exercise, manipulation and pelvic belts for pregnant women with musculoskeletal problems. The overall effectiveness and acceptability of these interventions is uncertain due to lack of synthesised evidence. This protocol is for the first systematic review of community-based non-pharmacological interventions for improving pain, disability and quality of life in pregnant women with musculoskeletal conditions from studies published until August 2020.Methods and analysisA detailed search of PubMed, CINAHL, CENTRAL, Global Index Medicus, African Index Medicus, African Journal Online, Western Pacific Region Index Medicus, Latin American and Caribbean Centre on Health Science Information, Index Medicus for South-East Asia Region, IRIS (WHO digital publications), British Library for Development Studies and Google Scholar. Additional studies will be located from the reference list of identified studies and relevant systematic reviews. The databases will be searched from inception to August 2020. Appraisal of study quality will be performed with the Mixed Methods Appraisal Tool. Data will be synthesised using a mixed-studies synthesis design—the convergent synthesis. The description of interventions in all study designs will be summarised narratively. Meta-analyses will be used to statistically summarise the effectiveness of interventions in randomised controlled trials and the factors that influence these. Other quantitative studies will be summarised narratively to answer the objectives. Thematic synthesis will be used to summarise results of qualitative studies. The outcomes of interest include pain, disability and quality of life. This paper is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis Protocols 2015 guidelines.Ethics and disseminationEthical clearance is not required. Findings will be presented at conferences and published in peer-reviewed journals.PROSPERO registration numberCRD42020189535.
Population-based otoscopic and audiometric assessment of a birth cohort recruited for a pneumococcal vaccine trial 15–18 years earlier: a protocol
Authors: Chan Kenny H , Carosone-Link Phyllis , Bautista Mary Thatcher G , Sanvictores Diozele , Uhler Kristin , Tallo Veronica , Lucero Marilla G , De Jesus Joanne , Simões Eric A F 
Published: February 2021

IntroductionA cohort of 12 000 children in the Philippines who had enrolled in a 2000–2004 (current ages 16 to 20 years) Phase 3 11-valent pneumococcal conjugate vaccine for the prevention of radiographically confirmed pneumonia are now being asked to participate in a separate study (expected completion date September 2021) to assess the cohort’s current long-term audiometric and otologic status. This new study would allow assessments of the utility of the pneumococcal vaccine in conferring its protective effects on the long-term sequelae of otitis media (OM), if any. Lack of trained local healthcare providers in otolaryngology/audiology and testing equipment in Bohol, Philippines, necessitates the development of a distinct methodology that would lead to meaningful data analysis.Methods and analysisReliable data collection and transfer are achieved by a US otolaryngologist/audiologist team training local nurses on all procedures in a didactic and hands-on process. An assortment of portable otolaryngologic and audiologic equipment suitable for field testing has been acquired, including an operating otoscope (Welch-Allyn), a video-otoscope (JedMed), a tympanometer with distortion product otoacoustic emission measurements (Path Sentiero) and a screening audiometer (HearScreen). Data will then be uploaded to a Research Electronic Data Capture database in the USA.Tympanometric and audiologic data will be codified through separate conventional algorithms. A team of paediatric otolaryngology advanced practice providers (APPs) have been trained and validated in interpreting video otoscopy. The protocol for classification of diagnostic outcome variables based on video otoscopy and tympanometry has been developed and is being used by APPs to evaluate all otoscopy data.Ethics and disseminationThe study was approved by the Research Institute of Tropical Medicine, Alabang, Manila, Philippines, and the institutional review board and the Colorado Multiple Institutional Review Board of the University of Colorado School of Medicine, Aurora, Colorado, USA.Research results will be made available to children and their caregivers with abnormal audiologic outcomes, the funders and other researchers.Trial registration numberISRCTN 62323832; Post-results.
Risk factors for COVID-19 infection, disease severity and related deaths in Africa: a systematic review
Authors: Gesesew Hailay Abrha , Koye Digsu Negese , Fetene Dagnachew Muluye , Woldegiorgis Mulu , Kinfu Yohannes , Geleto Ayele Bali , Melaku Yohannes Adama , Mohammed Hassen , Alene Kefyalew Addis , Awoke Mamaru Ayenew , Birhanu Mulugeta Molla , Gebremedhin Amanuel Tesfay , Gelaw Yalemzewod Assefa , Shifti Desalegn Markos , Muluneh Muluken Dessalegn , Tegegne Teketo Kassaw , Abrha Solomon , Aregay Atsede Fantahun , Ayalew Mohammed Biset , Gebre Abadi Kahsu , Gebremariam Kidane Tadesse , Gebremedhin Tesfaye , Gebremichael Lemlem , Leshargie Cheru Tesema , Kibret Getiye Dejenu , Meazaw Maereg Wagnew , Mekonnen Alemayehu Berhane , Tekle Dejen Yemane , Tesema Azeb Gebresilassie , Tesfay Fisaha Haile , Tesfaye Wubshet , Wubishet Befikadu Legesse , Dachew Berihun Assefa , Adane Akilew Awoke 
Published: February 2021

ObjectiveThe aim of this study was to provide a comprehensive evidence on risk factors for transmission, disease severity and COVID-19 related deaths in Africa.DesignA systematic review has been conducted to synthesise existing evidence on risk factors affecting COVID-19 outcomes across Africa.Data sourcesData were systematically searched from MEDLINE, Scopus, MedRxiv and BioRxiv.Eligibility criteriaStudies for review were included if they were published in English and reported at least one risk factor and/or one health outcome. We included all relevant literature published up until 11 August 2020.Data extraction and synthesisWe performed a systematic narrative synthesis to describe the available studies for each outcome. Data were extracted using a standardised Joanna Briggs Institute data extraction form.ResultsFifteen articles met the inclusion criteria of which four were exclusively on Africa and the remaining 11 papers had a global focus with some data from Africa. Higher rates of infection in Africa are associated with high population density, urbanisation, transport connectivity, high volume of tourism and international trade, and high level of economic and political openness. Limited or poor access to healthcare are also associated with higher COVID-19 infection rates. Older people and individuals with chronic conditions such as HIV, tuberculosis and anaemia experience severe forms COVID-19 leading to hospitalisation and death. Similarly, high burden of chronic obstructive pulmonary disease, high prevalence of tobacco consumption and low levels of expenditure on health and low levels of global health security score contribute to COVID-19 related deaths.ConclusionsDemographic, institutional, ecological, health system and politico-economic factors influenced the spectrum of COVID-19 infection, severity and death. We recommend multidisciplinary and integrated approaches to mitigate the identified factors and strengthen effective prevention strategies.
Phase I study of ABBV-428, a mesothelin-CD40 bispecific, in patients with advanced solid tumors
Authors: Luke Jason J , Barlesi Fabrice , Chung Ki , Tolcher Anthony W , Kelly Karen , Hollebecque Antoine , Le Tourneau Christophe , Subbiah Vivek , Tsai Frank , Kao Steven , Cassier Philippe A , Khasraw Mustafa , Kindler Hedy L , Fang Hua , Fan Frances , Allaire Kathryn , Patel Maulik , Ye Shiming , Chao Debra T , Henner William R , Hayflick Joel S , McDevitt Michael A , Fong Lawrence 
Published: February 2021

BackgroundCD40 agonist immunotherapy can potentially license antigen-presenting cells to promote antitumor T-cell activation and re-educate macrophages to destroy tumor stroma. Systemic administration of CD40 agonists has historically been associated with considerable toxicity, providing the rationale for development of tumor-targeted immunomodulators to improve clinical safety and efficacy. This phase I study assessed the safety, tolerability, preliminary antitumor activity, and preliminary biomarkers of ABBV-428, a first-in-class, mesothelin-targeted, bispecific antibody designed for tumor microenvironment-dependent CD40 activation with limited systemic toxicity.MethodsABBV-428 was administered intravenously every 2 weeks to patients with advanced solid tumors. An accelerated titration (starting at a 0.01 mg/kg dose) and a 3+3 dose escalation scheme were used, followed by recommended phase II dose cohort expansions in ovarian cancer and mesothelioma, tumor types associated with high mesothelin expression.ResultsFifty-nine patients were treated at doses between 0.01 and 3.6 mg/kg. The maximum tolerated dose was not reached, and 3.6 mg/kg was selected as the recommended phase II dose. Seven patients (12%) reported infusion-related reactions. Treatment-related grade ≥3 treatment-emergent adverse events were pericardial effusion, colitis, infusion-related reaction, and pleural effusion (n=1 each, 2%), with no cytokine release syndrome reported. The pharmacokinetic profile demonstrated roughly dose-proportional increases in exposure from 0.4 to 3.6 mg/kg. Best response was stable disease in 9/25 patients (36%) treated at the recommended phase II dose. CD40 receptor occupancy >90% was observed on peripheral B-cells starting from 0.8 mg/kg; however, no consistent changes from baseline in intratumoral CD8+ T-cells, programmed death ligand-1 (PD-L1+) cells, or immune-related gene expression were detected post-ABBV-428 treatment (cycle 2, day 1). Mesothelin membrane staining showed greater correlation with progression-free survival in ovarian cancer and mesothelioma than in the broader dose escalation population.ConclusionsABBV-428 monotherapy exhibited dose-proportional pharmacokinetics and an acceptable safety profile, particularly for toxicities characteristic of CD40 agonism, illustrating that utilization of a tumor-targeted, bispecific antibody can improve the safety of CD40 agonism as a therapeutic approach. ABBV-428 monotherapy had minimal clinical activity in dose escalation and in a small expansion cohort of patients with advanced mesothelioma or ovarian cancer.Trial registration numberNCT02955251.
Use of pembrolizumab with or without pomalidomide in HIV-associated non-Hodgkin’s lymphoma
Authors: Lurain Kathryn , Ramaswami Ramya , Mangusan Ralph , Widell Anaida , Ekwede Irene , George Jomy , Ambinder Richard , Cheever Martin , Gulley James L , Goncalves Priscila H , Wang Hao-Wei , Uldrick Thomas S , Yarchoan Robert 
Published: February 2021

BackgroundNon-Hodgkin’s lymphoma (NHL) is currently the most common malignancy among people living with HIV (PLWH) in the USA. NHL in PLWH is more frequently associated with oncogenic viruses than NHL in immunocompetent individuals and is generally associated with increased PD-1 expression and T cell exhaustion. An effective immune-based second-line approach that is less immunosuppressive than chemotherapy may decrease infection risk, improve immune control of oncogenic viruses, and ultimately allow for better lymphoma control.MethodsWe conducted a retrospective study of patients with HIV-associated lymphomas treated with pembrolizumab±pomalidomide in the HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute.ResultsWe identified 10 patients with stage IV relapsed and/or primary refractory HIV-associated NHL who were treated with pembrolizumab, an immune checkpoint inihibitor, with or without pomalidomide. Five patients had primary effusion lymphoma (PEL): one had germinal center B cell-like (GCB) diffuse large B cell lymphoma (DLBCL); two had non-GCB DLBCL; one had aggressive B cell lymphoma, not otherwise specified; and one had plasmablastic lymphoma. Six patients received pembrolizumab alone at 200 mg intravenously every 3 weeks, three received pembrolizumab 200 mg intravenously every 4 weeks plus pomalidomide 4 mg orally every day for days 1–21 of a 28-day cycle; and one sequentially received pembrolizumab alone and then pomalidomide alone. The response rate was 50% with particular benefit in gammaherpesvirus-associated tumors. The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95% CI: 2.96 to not reached). Three patients with PEL had leptomeningeal disease: one had a complete response and the other two had long-term disease control. There were four immune-related adverse events (irAEs), all CTCAEv5 grade 2–3; three of the four patients were able to continue receiving pembrolizumab. No irAEs occurred in patients receiving the combination of pembrolizumab and pomalidomide.ConclusionsTreatment of HIV-associated NHL with pembrolizumab with or without pomalidomide elicited responses in several subtypes of HIV-associated NHL. This approach is worth further study in PLWH and NHL.