bluuebunny/crossref_metadata_2025_split huggingface dataset:
The exhaustion of lymphocytes is the main factors that affect the sensitivity of QFT-GIT assays decrease in silicosis
Authors: Xu Jun-Chi , Yu Xin , Huang Li-Na , Song Yi-Yan , Chen Hui , Shi Cui-Lin , Tang Pei-Jun , Zhu Ye-Han 
Published: March 2022

Abstract
Background: Tuberculosis infection is a major complication of silicosis but there is no study on whether the silicosis can affect the sensitivity of QuantiFERON-TB Gold In-Tube (QFT-GIT) assays. This study will analysis the relationship between silicosis and QFT-GIT, figure out the main factor of the QFT-GIT sensitivity decrease in silicosis and exploring the methods to increase the sensitivity.Methods: Silicosis patients with positive tubercle bacillus cultures were collected. The QFT-GIT, flow cytometry and blocking antibodies were used. Results: The sensitivity of QFT-GIT in silicosis patients(58.46%) was significantly decreased and the expression of PD-1 on T cells and CD56+NK cells in pulmonary tuberculosis combined with silicosis were higher than normal tuberculosis patients. Further analysis found that the ratio of PD-1+CD4+T and IFN-γwere negatively correlated and blockaded the PD-1 pathway with antibodies can restore the sensitivity of QFT-GIT in silicosis.Conclusions: This is the first study which analysis the relationship between the immune exhaustion and QFT-GIT in silicosis and found the sensitivity of QFT-GIT was decreased by the expression of PD-1 on lymphocytes. Antibody blocking experiments increased the expression of IFN-γ and provide a new method to improve the sensitivity of QFT in silicosis. The study also found silicosis can increased the PD-1 expression, as the PD-1 function in infectious diseases, it will promote the immune exhaustion in silicosis and lead the tuberculosis from latent infection to active. The study provided theoretical evidence for the diagnosis and immunotherapy of silicosis complications, and it has great value in clinical diagnostics and treatment.
A Quantitative Systems Pharmacology Model for Simulating Off-time in Augmentation Trials for Parkinson’s Disease. Application to Preladenant
Authors: ROSE RACHEL , MITCHELL EMMA , GRAAF PIET DER , GEERTS HUGO 
Published: March 2022

Abstract
The clinical impact of therapeutic interventions in Parkinson’s disease is often measured as a reduction in OFF-time when the beneficial effects of the standard-of-care L-DOPA formulations wanes off. We investigated the pharmacodynamic interactions of augmentation therapy to standard-of-care using a quantitative systems pharmacology (QSP) of the basal ganglia motor circuit, essentially a computer model of the different basal ganglia subregions with the appropriate connectivity and cell-specific expression of G-protein coupled receptors. The calculated beta/gamma power spectrum of the local field potentials in the subthalamic nucleus was previously calibrated on a UPDRS scale. We combine this QSP model with PK modeling of different formulations of L-DOPA and the adenosine 2A antagonist preladenant to predict the liability of OFF-time, non-troublesome and troublesome dyskinesia. Model calibration with clinical observations showed favorable correlations. Simulations show that augmentation with the adenosine A2A antagonist preladenant reduces in OFF-time ranges between 6 minutes for Rytary 950 mg 5-times daily and 37 minutes for 100 mg L-DOPA – 3 or 5 times daily. Exploring delays between preladenant and L-DOPA intake did not improve the outcome. A2A antagonists with an ideal PK and pharmacology profile can achieve range from 9.5 minutes with DuoDopa to 55 minutes with low dose L-DOPA formulations. There is a strong non-linear relationship between drug exposure and clinical efficacy. With the development of digital wearables for real-time estimation of clinical outcome, this predictive approach can support both the design of clinical trials with new therapeutic agents and the optimization of combination therapy in clinical practice.
Impact of Sea Ice Transport on Beaufort Gyre Iiquid Freshwater Content
Authors: Cornish Sam Benjamin , Muilwijk Morven , Scott Jeffery , Marson Juliana , Myers Paul , Zhang Wenhao , Wang Qiang , Kostov Yavor , Johnson Helen , Marshall John 
Published: March 2022

Abstract
The Arctic Ocean's Beaufort Gyre (BG) is a wind-driven reservoir of relatively fresh seawater, situated beneath time-mean anticyclonic atmospheric circulation, and is covered by mobile pack ice for most of the year. Liquid freshwater accumulation in and expulsion from this gyre is of critical interest to the climate modelling community, due to its potential to affect the Atlantic meridional overturning circulation (AMOC) and due to the importance of freshwater in modulating vertical fluxes of heat, nutrients and carbon in the ocean, and exchanges of heat and moisture with the atmosphere. Here, we investigate the hypothesis that wind-driven sea ice transport into/from the BG region influences the freshwater content of the gyre and its variability. To test this hypothesis, we use the results of a coordinated climate response function (CRF) experiment with four ice-ocean models, in combination with targeted experiments using a regional setup of the MITgcm, in which we rotate the surface wind forcing vectors (thereby changing the ageostrophic component of these winds). Our results show that, via an effect on the net thermodynamic growth rate, anomalies in sea ice transport into the BG affect liquid freshwater adjustment. Specifically, increased ice import increases freshwater retention in the gyre, whereas ice export decreases freshwater in the gyre. Our results demonstrate that uncertainty in the ageostrophic component of surface winds, and in the dynamic sea ice response to these winds, has important implications for ice thermodynamics and freshwater. This sensitivity may explain some of the observed inter-model spread in simulations of Beaufort Gyre freshwater and its adjustment in response to wind forcing.
Co-Designing High-Risk Drug Alerts for Health and Community Service Practitioners
Authors: Brien Rita , Volpe Isabelle , Grigg Jasmin , Lyons Tom , Hughes Caitlin , McKinnon Ginny , Tzanetis Stephanie , Crawford Sione , Eade Alan , Lee Nicole , Barratt Monica J. 
Published: March 2022

Abstract
Background
Alerts about drug market changes (e.g., drug strength, purity, adulterations, or other trends) may be useful to assist health and community workers to anticipate, prevent and respond to unexpected adverse drug events. This study aimed to establish factors influencing the successful design and implementation of drug alerts for use in clinical and community settings in Victoria, Australia.
Methods
We used an iterative, parallel mixed methods participatory design to co-produce drug alert prototypes with practitioners and managers working across alcohol and other drugs and emergency medicine settings. A quantitative needs-analysis survey (n = 184) informed five qualitative co-design workshops (n = 31). Alert prototypes were drafted based on findings and presented for testing of utility and acceptability. Applicable constructs from the Consolidated Framework for Implementation Research helped to identify key barriers and facilitators to successful alert design.
Results
Timely and reliable alerts about high-risk single substances were important to nearly all practitioners (98%) yet many reported insufficient access to timely information about drug markets and emerging threat (64%). Alerts were useful for increasing exposure to drug market intelligence; facilitating risk communication; and improving capacity for effective responses. Alerts must be ‘shareable’ across a range of settings to meet the needs of diverse professional and public audiences. Practitioners and managers considered themselves ‘conduits’ for information sharing. To maximize engagement and impact, alerts must be attention-grabbing and easily recognisable; available on multiple platforms; published in printable and electronic formats in varying levels of detail; and disseminated using appropriate notification mechanisms. Three clinical drug alert prototypes (SMS prompt, summary flier, and detailed PDF) were developed and considered acceptable and useful for a range of audiences and settings.
Discussion
Adequate planning and resourcing for effective drug alert design and evaluation arising from jurisdictional and national early warning systems is imperative to their utility. Such systems need to have access to reliable multidisciplinary drug market intelligence for rapid assessment and verification of risk to report timely and effective risk communications. Systems that offer close to real-time detection of adulterants/contaminants (e.g., drug checking services) are best-placed to provide rapid, evidence-based drug market intelligence to inform preventive and responsive action.
Does Types of Atrial Fibrillation Matter in The Impairment of Global and Regional Left Ventricular Mechanics and Intra-ventricular Dyssynchrony?
Authors: Song Nianpeng , Zhen Xiaowen , Li Wencai , Wang Hua , Zhong Lin 
Published: March 2022

Abstract
Background: Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which is associated with cardiac dysfunction. This study aimed to compare the impairment severity of left ventricular strain and intra-ventricular dyssynchrony using echocardiography-derived velocity vector imaging in patients with different types of AF without heart failure.Methods: 84 nonvalvular AF patients with normal left ventricular ejection fraction (49 paroxysmal AF patients and 35 persistent AF patients) and 43 healthy control subjects were included in this study. Standard grayscale 2-dimension echocardiographic images were acquired for offline velocity vector imaging analysis to measure regional and global left ventricular longitudinal and circumferential strain. Time to regional peak longitudinal strain was measured and the standard deviation of all 12 segments (SDT-S) was used as a measure of intra-ventricular dyssynchrony. Global longitudinal left ventricular strain (GLS), global left ventricular circumferential strain (GCS), and intra-ventricular dyssynchrony were compared among healthy control patients, paroxysmal AF patients, and persistent AF patients. Results： Significantly lower GLS and GCS were observed in either persistent AF subjects or paroxysmal AF subjects compared with healthy control subjects (P <0.05). The impairment was much worse in persistent AF subjects compared with paroxysmal AF subjects (P <0.001). Intraventricular dyssynchrony was found in both persistent AF patients and paroxysmal AF patients, and it’s worse in persistent AF patients (P <0.05). Multivariate regression analysis revealed heart rate was an independent risk factor of GLS and GCS, while age was an independent risk factor of intraventricular dyssynchrony.Conclusions: AF is not only associated with impaired longitudinal and circumferential left ventricle mechanics but also impaired intra-ventricular mechanical synchrony. Worse systolic mechanics and intra-ventricular dyssynchrony were found in patients with persistent AF compared with these in patients with paroxysmal AF.
Detection of angiolipoma nuclei in H&amp;E staining image by tissue segmentation using tissue filters
Authors: Radak Mahyar 
Published: March 2022

Abstract
Angiolipoma is an unusually benign neoplasm composed of mature lipocytes mixed with abnormal blood vessels. In this paper, we used cellular tissue segmentation using an intelligent tissue filtering algorithm to identify tissue-based image regions containing thick-walled capillaries with fibrin clots, between mature lipocytes and fibrin septum, and HE angiolipoma stains. Our algorithm was able to detect and extract angiolipoma tissue nuclei. The image in question is 591 X 800 pixels, which is stained with HE, which we use to detect. There are many algorithms, techniques and applications for dividing the nucleus of a tissue tumor, but in the proposed algorithm method, it can be extracted with high accuracy and sensitivity. This method can also be used to detect other angiolipoma tissue nuclei stained with HE variable stains.
Retinoic acid-induced 1 gene haploinsufficiency alters lipid metabolism and causes autophagy defects in Smith-Magenis syndrome
Authors: Turco Elisa Maria , Giovenale Angela Maria Giada , Sireno Laura , Cammareri Alessandra , Goracci Laura , Veroli Alessandra Di , Marchesan Elena , D’Andrea Daniel , Torres Barbara , Bernardini Laura , Marchioretti Caterina , Paone Alessio , Rinaldo Serena , Magnifico Maria Chiara , Monica Matteo Della , Postorivo Diana , Nardone Anna Maria , Zampino Giuseppe , Onesimo Roberta , Leoni Chiara , Caicci Federico , Raimondo Domenico , Trobiani Laura , De Jaco Antonella , Tata Ada Maria , Ferrari Daniela , Cutruzzolà Francesca , Mazzoccoli Gianluigi , Ziviani Elena , Pennuto Maria , Vescovi Angelo Luigi , Rosati Jessica 
Published: March 2022

Abstract
Smith-Magenis syndrome (SMS) is a neurodevelopmental disorder characterized by cognitive and behavioral symptoms, obesity, and sleep disorder. There is no therapy to alleviate symptoms or delay disease onset. SMS is due to the haploinsufficiency of the retinoic-acid-induced-1 gene (RAI1) caused by either chromosomal deletions (SMS-del) or RAI1 missense/nonsense mutations. The molecular mechanisms underlying SMS are not known. Here we generated and characterized primary cells derived from four SMS patients, two carrying the SMS-del, two with RAI1 point mutations, and four control subjects to investigate pathogenetic processes underlying SMS. By combining transcriptomic and lipidomic analyses, we show altered expression of lipid and lysosomal genes, deregulation of lipid metabolism, accumulation of lipid droplets, and a block of autophagy flux. SMS cells show increased cell death associated with mitochondrial pathology and reactive oxygen species production. Treatment with N-acetyl-cysteine reduces cell death and lipid accumulation, suggesting a causative link between metabolic dyshomeostasis and cell viability. Our results highlight pathological processes in human SMS cells involving lipid metabolism, autophagy defects and mitochondrial dysfunction and suggest new potential therapeutic targets for patient treatment.
A Survey of Residency Directors in Academic Trauma Centers for Policies on Airway Management in the Trauma Ward
Authors: Tewfik George , Gajewski Michal , Salem Jena , Borad Neil , Zales Michael , Govindaraj Gopal 
Published: March 2022

Abstract
BackgroundDespite its presence as a critical procedure in the trauma setting, airway management is not performed uniformly, varying between institutions, particularly with personnel involved in decision-making. Past literature has noted a trend in which emergency medicine physicians assumed greater responsibility for primary management of airways in the trauma ward. Many institutions have adopted tiered activation systems for traumas in order to improve patient care, deploying resources more effectively.MethodsIn this study, a survey of residency directors was deployed to assess trends in airway management. A validated survey was distributed to residency directors in anesthesiology, general surgery and emergency medicine in 190 Level I trauma centers in the United States. Questions assessed personnel management, complication tracking and difficult airway prediction factors, amongst other considerations for airway management in the trauma bay.ResultsRespondents completed the survey at a rate of 23.8% of those solicited. A majority of respondents indicated that emergency medicine physicians are primary airway managers in the trauma bay and that their institutions utilize tiered trauma activation systems at 77.4% and 95.6% respectively. Anesthesia providers were immediately available in 81% of respondent institutions with inconclusive data regarding protocols for delineating anesthesia involvement in difficult airways. More than a third of respondents indicated their institution either does not track airway complications or they did not know if complications were tracked. Finally, nine different criteria were used in varying degrees by respondents’ institutions to predict the presence of a difficult airway, including such factors as head/face trauma, airway fluid and obesity. ConclusionsEmergency medicine physicians are the primary airway managers in many trauma centers, although they are often supported by the presence of anesthesiology for advanced airway interventions. Delineation of anesthesia involvement is unclear, and criteria to determine a difficult airway varies amongst institutions.
Preoperative and postoperative nomograms in predicting early recurrence of hepatocellular carcinoma without macrovascular invasion after curative resection
Authors: Zhang Yanfang , Lei Xuezhong , Xu Liangliang , Lv Xiaoju , Xu Mingqing , Tang Hong 
Published: March 2022

Abstract
Background: Postoperative early recurrence (ER) is a major obstacle for long-term survival in patients with hepatocellular carcinoma (HCC) after curative liver resection (LR). This study aimed to establish pre- and postoperative nomograms in predicting ER for HCC without macrovascular invasion.Methods: The patients who underwent curative LR for HCC from January 2012 to December 2016 were divided into training and internal prospective validation cohorts. Nomograms were constructed based on the independent risk factors derived from multivariate logistic regression analyses in training cohort. The predictive performance of nomograms was validated by internal prospective validation cohort.Results: A total of 698 patients fulfilled with eligible criteria. Among them, 265 out of 482 patients (55.0%) in training cohort and 120 out 216 (55.6%) patients in validation cohort developed ER. The preoperative risk factors associated with ER were age, alpha fetoprotein (AFP), tumor diameter, tumor number; the postoperative risk factors associated with ER were age, tumor diameter, tumor number, microvasular invasion (MVI) and differentiation. The pre- and postoperative nomograms based on these factors showed good accuracy with C-indices of 0.712 and 0.850 in training cohort, and 0.754 and 0.857 in validation cohort, respectively. The calibration curves showed optimal agreement between the prediction by the nomograms and actual observation. The area under the receiver operating characteristic curves of pre- and postoperative nomograms were 0.721 and 0.848 in training cohort, and 0.754 and 0.844 in validation cohort, respectively. Conclusions: Present nomograms showed good performance in predicting ER for HCC without macrovascular invasion before and after surgery, which were helpful for doctors in designation of treatments and selection of patients for regularly surveillance or administration of neoadjuvant therapies.
Type 2 diabetes and its effects on microRNA-155 and microRNA-133a expression in lung tissue of male rats
Authors: Khezri Maria , Rahbarghazi Reza , Ahmadi Mahdi , Sandoghchian Siamak , Nourazarian Alireza , shademan behrouz , Abdi Meysam , Khaki-Khatibi Fatemeh 
Published: March 2022

Abstract
Backgrounds:
The presence of extensive vascular and large amounts of collagen and elastin in lung tissue makes the lung parenchyma vulnerable to damage in diabetes. However, there are few studies on the pathophysiological effects of diabetes on lung tissue. In this study, we investigated the effects of type 2 diabetes on lung tissue pathology and the expression of miRNA-155 and miRNA-133a in lung tissue of male rats.
Methods and results:
In this study, 20 male rats were divided into a control group and a group with diabetes. The diabetic group received a high-fat diet for 4 weeks. Rats were injected with a single dose of streptozotocin (STZ) after the fourth week. 4 days after STZ injection, blood glucose and glucose tolerance (GTT) tests were measured. Immediately after the tests, the mice were sacrificed and lung tissue was collected to measure microRNAs and to examine tissue changes. When lung tissue sections from diabetic rats were examined, the normal structure of the alveoli and alveolar sacs and bronchioles was disturbed. The extensive alveolar collapse was the main cause of lung tissue structure disruption, and the accumulation of inflammatory cells and exudate secretions resulted in an interstitial pneumonia-like appearance. The expression of miRNA-155 was increased, and the expression of miRNA-133a was decreased in the lungs of diabetic rats compared with control rats.
Conclusion
We found significant changes in the lung tissue of diabetic rats. By studying the changes in the expression of microRNAs in the lungs of diabetic patients, microRNA can be used as a diagnostic biomarker. These changes can provide appropriate treatment strategies.
Analyzability of Photoplethysmographic Smartwatch Data by the Preventicus Heartbeats Algorithm During Everyday Life: Feasibility Study
Authors: Merschel Steve , Reinhardt Lars 
Published: March 2022

Background
Continuous heart rate monitoring via mobile health technologies based on photoplethysmography (PPG) has great potential for the early detection of sustained cardiac arrhythmias such as atrial fibrillation. However, PPG measurements are impaired by motion artifacts.

Objective
The aim of this investigation was to evaluate the analyzability of smartwatch-derived PPG data during everyday life and to determine the relationship between the analyzability of the data and the activity level of the participant.

Methods
A total of 41 (19 female and 22 male) adults in good cardiovascular health (aged 19-79 years) continuously wore a smartwatch equipped with a PPG sensor and a 3D accelerometer (Cardio Watch 287, Corsano Health BV) for a period of 24 hours that represented their individual daily routine. For each participant, smartwatch data were analyzed on a 1-minute basis by an algorithm designed for heart rhythm analysis (Preventicus Heartbeats, Preventicus GmbH). As outcomes, the percentage of analyzable data (PAD) and the mean acceleration (ACC) were calculated. To map changes of the ACC and PAD over the course of one day, the 24-hour period was divided into 8 subintervals comprising 3 hours each.

Results
Univariate analysis of variance showed a large effect (ηp2> 0.6; P<.001) of time interval (phase) on the ACC and PAD. The PAD ranged between 34% and 100%, with an average of 71.5% for the whole day, which is equivalent to a period of 17.2 hours. Between midnight and 6 AM, the mean values were the highest for the PAD (>94%) and the lowest for the ACC (<6×10-3 m/s2). Regardless of the time of the day, the correlation between the PAD and ACC was strong (r=–0.64). A linear regression analysis for the averaged data resulted in an almost perfect coefficient of determination (r2=0.99).

Conclusions
This study showed a large relationship between the activity level and the analyzability of smartwatch-derived PPG data. Given the high yield of analyzable data during the nighttime, continuous arrhythmia screening seems particularly effective during sleep phases.