bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic–pharmacodynamic modeling for hepatic delivery and efficacy of antisense oligonucleotides with lipophilic ligands in mice
Authors: Watanabe Ayahisa , Katsube Takayuki 
Published: March 2021

AbstractConjugation with lipophilic ligands such as cholesterol and α‐tocopherol dramatically improves the delivery and efficacy of antisense oligonucleotides (ASOs) in the liver. To estimate the hepatic ASO concentration and the efficacy of ASOs conjugated with lipophilic ligands in mice, we constructed a pharmacokinetic‐pharmacodynamic (PK‐PD) model that consisted of a two‐linear compartment model for the plasma and the hepatic ASO concentration, and two indirect response models for the hepatic apolipoprotein B (Apo‐B) mRNA and plasma total cholesterol. The model provided a good fit of the hepatic ASO concentration although it showed an overprediction of Apo‐B mRNA and an underprediction of the plasma total cholesterol within 2‐fold at a later time after single intravenous administration of ASOs conjugated with lipophilic ligands. In addition, the model simulations indicated that the efficacy at a dose regimen of ASOs conjugated with lipophilic ligands (0.2 mg/kg, once a week) in mice was comparable to that at an effective dose of unchanged ASO (2.5 mg/kg, once a week). Although further studies are required to refine the parameters of the PK–PD model, this approach could be used to guide dose‐ranging pharmacological studies for ASOs conjugated with lipophilic ligands in mice.
Epigenetic editing: Dissecting chromatin function in context
Authors: Policarpi Cristina , Dabin Juliette , Hackett Jamie A. 
Published: March 2021

AbstractHow epigenetic mechanisms regulate genome output and response to stimuli is a fundamental question in development and disease. Past decades have made tremendous progress in deciphering the regulatory relationships involved by correlating aggregated (epi)genomics profiles with global perturbations. However, the recent development of epigenetic editing technologies now enables researchers to move beyond inferred conclusions, towards explicit causal reasoning, through 'programing’ precise chromatin perturbations in single cells. Here, we first discuss the major unresolved questions in the epigenetics field that can be addressed by programable epigenome editing, including the context‐dependent function and memory of chromatin states. We then describe the epigenetic editing toolkit focusing on CRISPR‐based technologies, and highlight its achievements, drawbacks and promise. Finally, we consider the potential future application of epigenetic editing to the study and treatment of specific disease conditions.
Interphase fluorescence in situ hybridization analysis of CD19‐selected cells: Utility in detecting disease in post‐therapy samples of B‐cell neoplasms
Authors: Parrott Andrew M. , Murty Vundavalli V. , Walsh Caitlin , Christiano Alecia , Bhagat Govind , Alobeid Bachir 
Published: March 2021

AbstractContextThe detection of low‐level persistent or relapsed B‐cell neoplasms, particularly post‐therapy, can be challenging, often requiring multiple testing modalities.ObjectiveHere we investigate the utility of CD19‐based selection of neoplastic B‐cells (CD19S) as an enrichment strategy to improve the detection rate of cytogenetic abnormalities in post‐therapy samples of B‐cell neoplasms, especially those with low‐level disease.DesignIn a cohort largely comprised of post‐therapy B‐ALL and CLL samples, we performed fluorescence in situ hybridization (FISH) analysis on CD19‐selected cells (CD19S FISH) in 128 specimens from 88 patients, and on non‐selected cells (NS FISH) in a subset of cases. The FISH findings were compared with the concurrent flow cytometry (FC) results in all samples and molecular analysis in a subset.ResultsCD19S FISH was able to detect cytogenetic aberrations in 86.0% of post‐therapy samples with evidence of disease as determined by routine or MRD FC, compared to 59.1% of samples by NS FISH. CD19S FISH detected significantly higher percentages of positive cells compared to NS FISH (p < 0.001). Importantly, CD19S FISH enabled the detection of emergent subclones (clonal evolution) associated with poor prognosis.ConclusionsCD19S FISH can be useful in daily diagnostic practice. Compared to NS FISH, CD19S FISH is quantitatively and qualitatively superior for the detection of cytogenetic aberrations in B‐cell neoplasms, which are important for risk stratification and optimal management of patients with B‐cell neoplasms, especially in the relapsed setting. Although CD19S FISH has a diagnostic sensitivity inferior to that of MRD FC, the sensitivity of this modality is comparable to routine FC for the evaluation of low‐level disease in the post‐therapy setting. Moreover, CD19S samples are invaluable for additional molecular and genetic analyses.
Characteristics and risk differences of different tumor size on localized prostate cancer: A retrospective cohort study in the SEER database
Authors: Zhou Zhen , Yue Feng , Jin Liang , Liu Xiang , Zhai Ting‐Shuai , Zhang Jia‐Xin , Gu Wen‐Yu , Liu Sheng‐Hua , Luo Ming , Peng Bo , Yao Xu‐Dong , Ye Lin 
Published: March 2021

AbstractObjectiveWe aimed to evaluate the role of tumor size in predicting tumor risk for localized prostate cancer (PCa) patients undergoing radical prostatectomy (RP).MethodsTwenty‐five thousand, one hundred twenty‐seven men with PCa receiving RP from 2010 to 2015 were extracted from the Surveillance, Epidemiology, and End Results database. Kaplan–Meier plots and multivariable Cox regression analyses were used to illustrate overall survival (OS) according to the tumor size. The tumor size was confirmed by postoperative pathology after RP.ResultsAmong overall localized PCa, 84.6% were high‐risk PCa, 9.2% were intermediate‐risk PCa, and 6.2% were low‐risk PCa. Multivariate analyses demonstrated that tumor size ≥21 mm was an independent risk predict factor of low‐risk PCa (odds ratio [OR]: 11.940; 95% CI, 9.404–15.161; p < 0.001) and intermediate‐risk PCa (OR: 1.887; 95% CI, 1.586–2.245; p < 0.001). Tumor sizes ≤5 mm significantly correlated with high‐risk PCa (p < 0.001). Tumor size ≤5 mm had the worst OS in overall localized PCa and high‐risk PCa (p < 0.001).ConclusionsIn localized PCa, tumor sizes ≥21 mm may help predict low or intermediate‐risk PCa, while tumor sizes ≤5 mm might help predict high‐risk PCa. In clinical practice, we should be on high alert for patients with tumors size ≤5 mm due to its poor prognosis after RP.
Fatal invasive pulmonary aspergillosis in an immunocompetent patient with COVID‐19 due to Aspergillusterreus: A case study
Authors: Abolghasemi Sara , Hakamifard Atousa , Sharifynia Somayeh , Pourabdollah Toutkaboni Mihan , Azhdari Tehrani Hamed 
Published: March 2021

AbstractCase reports of CAPA emerged. In most of the reports, the predominant species is Aspergillus fumigatus. Uncommon species are less reported. Due to poor clinical outcome with Aspergillus terreus, the increasing reports with this agent require attention.
Simulation and Analysis of a Factory Building's Energy Consumption Using eQuest Software
Authors: Mathews Roy Abel , Prasanna Venkatesan R. , Shanmugapriya T. 
Published: March 2021

AbstractConsidering the global energy consumption, it is imperative to focus on energy‐efficient buildings. For a multi‐storey factory building case study, the base case and design case energy consumption were compared with the actual one. The simulation proved that the design case values were less than that of the base case, and 18.9 % of energy saving could be achieved. The design case value was compared with the actual value and the simulation accuracy was assessed in terms of mean base error and cumulative root mean square error. A comparison was done for two conventional heating, ventilation, and air conditioning systems with evaporative cooling pad system, which was found to be both energy‐ and cost‐efficient. A model for integrating the key factors during the construction of an energy‐efficient building is suggested.
Peptization Control of Aluminum Chloride‐Containing Composites for Catalysts with Active Matrix
Authors: Carrasco Saavedra Andres , Seifert Markus , Hauck Mathias , Brünner Andrea , Doert Thomas , Busse Oliver , Weigand Jan J. 
Published: March 2021

AbstractAluminum‐based composite particles are widely applied complex catalyst materials in oil refining. Due to their tunable shape, porosity, and acidity, they are commonly used for the production of cracking catalysts. Shaping of well‐defined particles remains a challenge for industrial catalyst preparation by spray drying, because catalyst properties must satisfy local demands of a refinery. The selectivity can be modified and the cracking activity enhanced with acid binders, e.g., AlCl3. Therefore, peptization of AlCl3‐containing suspensions with zeolite Y and kaolin was characterized by pH value, 27Al NMR spectroscopy, and zeta potential. A new control strategy for binding of kaolin and zeolite Y in spray drying was developed by adjusting the pH and binder Al/Cl ratio.
Clinical predictors for bradycardia and supraventricular tachycardia necessitating therapy in patients with unexplained syncope monitored by insertable cardiac monitor
Authors: Onuki Tatsuya , Shoji Makoto , Sugiyama Hiroto , Arai Shuhei , Yoshikawa Kosuke , Mase Hiroshi , Kurata Masaaki , Kikuchi Miwa , Wakatsuki Daisuke , Asano Taku , Suzuki Hiroshi , Tanno Kaoru , Kobayashi Youichi , Shinke Toshiro 
Published: March 2021

AbstractBackgroundInsertable cardiac monitors (ICMs) improve diagnostic yield in patients with unexplained syncope. The most of cardiac syncope is arrhythmic causes include paroxysmal bradycardia and supraventricular tachycardia (SVT) in patients with unexplained syncope receiving ICM. Predictors for bradycardia and SVT that necessitate therapy in patients with unexplained syncope are not well known.HypothesisThis study aimed to investigate predictors of bradycardia and SVT necessitating therapy in patients with unexplained syncope receiving ICMs.MethodsWe retrospectively reviewed medical records of consecutive patients who received ICMs to monitor unexplained syncope. We performed Cox's stepwise logistic regression analysis to identify significant independent predictors for bradycardia and SVT.ResultsOne hundred thirty‐two patients received ICMs to monitor unexplained syncope. During the 17‐month follow‐up period, 19 patients (14%) needed pacemaker therapy for bradycardia; 8 patients (6%) received catheter ablation for SVT. The total estimated diagnostic rates were 34% and 48% at 1 and 2 years, respectively. Stepwise logistic regression analysis indicated that syncope during effort (odds ratio [OR] = 3.41; 95% confidence interval [CI], 1.21 to 9.6; p = .02) was an independent predictor for bradycardia. Palpitation before syncope (OR = 9.46; 95% CI, 1.78 to 50.10; p = .008) and history of atrial fibrillation (OR = 10.1; 95% CI, 1.96 to 52.45; p = .006) were identified as significant independent predictors for SVT.ConclusionSyncope during effort, and palpitations or history of atrial fibrillation were independent predictors for bradycardia and for SVT. ICMs are useful devices for diagnosing unexplained syncope.
Performance of pulse palpation compared to one‐lead ECG in atrial fibrillation screening
Authors: Gudmundsdottir Katrin Kemp , Fredriksson Tove , Svennberg Emma , Al‐Khalili Faris , Friberg Leif , Häbel Henrike , Frykman Viveka , Engdahl Johan 
Published: March 2021

AbstractBackgroundThe 2020 European Society of Cardiology atrial fibrillation guidelines recommend opportunistic screening for atrial fibrillation by pulse taking or ECG rhythm strip in those aged over 65 years.HypothesisWe aimed to compare the diagnostic accuracy of pulse palpation to ECG rhythm strip when screening for atrial fibrillation. A secondary aim was to investigate whether participants with palpitations were more likely to be diagnosed with new atrial fibrillation.MethodsThe study population were 75/76 year old individuals that participated in the STROKESTOP II study, a Swedish screening study for atrial fibrillation. Pulse palpation of the radial pulse for 30 sec was performed by healthcare professionals and recorded as regular or irregular. Thereafter a 30‐sec single‐lead ECG was registered. Patients were asked also if they had a history of palpitations.ResultsOf the 6159 participants included in the study, 461 (7.5%) had irregular pulse. Twenty‐two (4.8%) of those with irregular pulse were diagnosed with atrial fibrillation on single‐lead ECG rhythm strip. Among those with regular pulse, 6 (0.1%) cases of new atrial fibrillation were found. The sensitivity of the pulse palpation test was 78.6% and positive predictive value 4.8%. The proportion of newly diagnosed atrial fibrillation was not different between those with and without history of palpitations.ConclusionPulse palpation was inferior to single‐lead ECG when screening for atrial fibrillation. We therefore advocate the use of single‐lead ECG rather than pulse palpation when screening for atrial fibrillation. Palpitations did not predict atrial fibrillation.
Unsolicited patient complaints among radiation, medical, and surgical oncologists
Authors: Raldow Ann , Adefres Bethel , Warso Michael , Shinohara Eric , Anand Sidharth , Domenico Henry J. , Galloway Mitchell B. , Pichert James W. , Cooper William O. 
Published: March 2021

BACKGROUNDUnsolicited patient complaints (UPCs) about physician practices are nonrandomly associated with malpractice claims and clinical quality. The authors evaluated the distributions and types of UPCs associated with oncologists by specialty and assessed oncologist characteristics associated with UPCs.METHODSThis retrospective study reviewed UPCs associated with US radiation oncologists (ROs), medical oncologists (MOs), and surgical oncologists (SOs) from 35 health care systems from 2015 to 2018. Average total UPCs were compared by specialty in addition to sex, medical school graduation year, degree, medical school location, residency location, practice setting, and practice region. For continuous variables, linear regression was used to test for an association with total complaints.RESULTSThe study included 1576 physicians: 318 ROs, 1020 MOs, and 238 SOs. The average number of UPCs per physician was different and depended on the oncologic specialty: ROs had significantly fewer complaints (1.28; 95% confidence interval [CI], 1.02‐1.54) than MOs (3.81; 95% CI, 3.52‐4.10) and SOs (6.89; 95% CI, 5.99‐7.79; P < .0001). In a multivariable analysis, oncologic specialty, recency of graduation, and academic practice were predictive of higher total UPCs (P < .05). UPCs described concerns with care and treatment (42.8%), communication (26.4%), accessibility (17.5%), concern for patient (10.3%), and billing (2.9%).CONCLUSIONSROs had significantly fewer complaints than MOs and SOs and may have a lower risk of malpractice claims as a group. In addition to oncologic specialty, a more recent year of medical school graduation and working at an academic center were independent risk factors for UPCs. Further research is needed to clarify the reasons underlying these associations and to identify interventions that decrease UPCs and associated risks.LAY SUMMARY

This study of 1576 oncologists found that radiation oncologists had significantly fewer complaints than medical oncologists, who in turn had significantly fewer complaints than surgical oncologists.

Other characteristics associated with more patient complaints included recency of medical school graduation and practice in an academic setting.

Oncologists' patient complaints provide information that may have practical applications for patient safety and risk management. Understanding and addressing the characteristics that increase the risk for complaints could improve patients' experiences and outcomes.
Chemical Modification and Transformation Strategies of Guide RNAs in CRISPR‐Cas9 Gene Editing Systems
Authors: Zhang Yu , Wang Qian , Wang Jing , Tang Xinjing 
Published: March 2021

AbstractThe CRISPR (clustered regularly interspaced short palindromic repeat)‐Cas9 (CRISPR‐associated protein 9) is a most powerful tool and has been widely used in gene editing and gene regulation since its discovery. However, wild‐type CRISPR‐Cas9 suffers from off‐target effects and low editing efficiency. To overcome these limitations, engineered Cas9 proteins have been extensively investigated. In addition to Cas9 protein engineering, chemically synthesized guide RNAs have been developed to improve the efficiency and specificity of genome editing as well as spatiotemporal controllability, which broadens the biological applications of CRISPR‐Cas9 gene editing system and increases their potentials as therapeutics. In this review, we summarize the latest research advances in remodeling guide RNAs through length optimization, chemical modifications, and conditional control, as well as their powerful applications in gene editing tools and promising therapeutic agents.
Grid‐connected buck–boost inverter without shoot‐through issue and with reduced voltage stress
Authors: Yao Zhilei 
Published: March 2021

SummaryGrid‐connected buck–boost inverters are used in wide input‐voltage range application. However, there is a shoot‐through problem in traditional grid‐connected inverters. Moreover, voltage stress of semiconductors is high in conventional buck–boost inverters. Therefore, a grid‐connected buck–boost inverter without shoot‐through issue and with reduced voltage stress is presented. The proposed inverter is a single‐stage system. When input voltage is higher than the grid voltage, the proposed inverter works in buck mode; when input voltage is lower than the grid voltage, it operates in boost mode. Thus, voltage stress of semiconductors is reduced. Only one switch is operated in high frequency in each period, so efficiency of the inverter can be improved. Operating principle of the proposed inverter is illustrated. Voltage stress analysis, loss calculation, and filter design guidelines and example are given. Finally, simulation and experimental results of a 300‐W proposed inverter confirm the theoretical analysis.
Markov Modulated Bernoulli Prediction Process‐based Cluster Head Selection Mechanism for improving resilience in wireless sensor networks
Authors: Arulmurugan A. , Amuthan A. 
Published: March 2021

SummaryThe clustering process in wireless sensor networks is considered to be predominant for facilitating minimized energy consumptions through the selection of potential cluster heads that are efficient in energy and trust. The significant cluster head selection is deterministic in topology control with the view to manage the sensor member nodes of the cluster with the view to enhance energy efficiency in the network. In this paper, a Markov Modulated Bernoulli Prediction Process‐based Cluster Head Selection Mechanism (MMBPP‐CHSM) is proposed by modeling the success probability of sensor nodes' state into a Bernoulli process that dynamically evolves over time based on Markov chain for extending the lifetime of the network. This proposed MMBPP‐CHSM scheme is vital in quantifying the reliability and availability of the sensor nodes in a dynamically evolving wireless sensor network through the estimation of trust and energy in order to facilitate effective cluster head selection. The simulation results of the proposed MMBPP‐CHSM scheme confirmed a superior enhancement in percentage of alive nodes and death nodes in the network to a maximum level of 28% and 23% on par with the baseline cluster head selection approaches used for investigation.
Pharmacokinetics and effects on arachidonic acid metabolism of low doses of cannabidiol following oral administration to horses
Authors: Ryan Declan , McKemie Dan S. , Kass Philip H. , Puschner Birgit , Knych Heather K. 
Published: March 2021

AbstractThe increasing availability of cannabidiol (CBD) and anecdotal reports of its anti‐inflammatory effects has garnered it much interest in the equine industry. The objectives of the current study were to (1) describe the pharmacokinetics of oral CBD in exercising thoroughbreds, (2) characterize select behavioral and physiologic effects, and (3) evaluate effects on biomarkers of inflammation using an ex vivo model. This study was conducted in a randomized balanced 3‐way crossover design with a two‐week washout period between doses. Horses received a single oral dose (0.5, 1, and 2 mg/kg) of CBD suspended in sesame oil. Blood and urine samples were collected prior to and for 72 hr post drug administration. Additional blood samples collected at select time points were challenged ex vivo with calcium ionophore or lipopolysaccharide to induce eicosanoid production. Drug, metabolite, and eicosanoid concentrations were determined using LC–MS/MS. Cannabidiol was well tolerated with no significant behavioral, gastrointestinal, or cardiac abnormalities observed. CBD was readily absorbed, with parent drug detected in blood at all time points. The carboxylated and hydroxylated metabolites predominated in serum and urine, respectively. The terminal half‐life for CBD was 10.7 ± 3.61, 10.6 ± 3.84 and 9.88 ± 3.53 for 0.5, 1, and 2 mg/kg. Although the effects were mixed, results of eicosanoid analysis suggest CBD affects COX‐1, COX‐2 and LOX at the doses studied here. Results of this study coupled with previous reports in other species, suggest further study of CBD in horses is warranted before its use as an anti‐inflammatory can be recommended.
Determination of drugs in exhumed liver and brain tissue after over 9 years of burial by liquid chromatography–tandem mass spectrometry—Part 2: Benzodiazepines, opioids, and further drugs
Authors: Bolte Katarina , Dziadosz Marek , Kono Naomi , Vennemann Benedikt , Klintschar Michael , Teske Jörg 
Published: March 2021

AbstractIn this publication, benzodiazepines, opioids, and further drugs were analyzed in exhumed brain and liver tissue samples in 116 cases (total) after 9.5–16.5 years of burial. Solid phase extraction followed by liquid chromatography–tandem mass spectrometry was applied. Data from literature is listed summarizing the detectability of the presented analytes after a certain time of burial. In our study, 60% of the analyzed benzodiazepines, 100% of the opioids, and 82% of further drugs were detectable. Only the benzodiazepines lorazepam, nitrazepam, flunitrazepam, and its metabolite norflunitrazepam, and the drugs butylscopolamine, metronidazole, and omeprazole were not detectable at all. Percentage of positive findings (total, and separately for brain and liver tissue) and postmortem period are listed for each analyte. Correlation of detectability depending on postmortem period and condition of tissue are presented exemplarily for midazolam. No substantial correlation was observed. Despite a long time of burial, most benzodiazepines, opioids, and further drugs were detectable in the examined tissue samples. Our results may be a good support for future exhumations in which toxicological analyses are relevant.