bluuebunny/crossref_metadata_2025_split huggingface dataset:
Development of a sensitive and rapid UHPLC–MS/MS method for simultaneous quantification of nine compounds in rat plasma and application in a comparative pharmacokinetic study after oral administration of Xuefu Zhuyu Decoction and nimodipine
Authors: Fu Chunyan , Wu Qian , Zhang Zhimin , Xia Zian , Liu Zhaoying , Lu Hongmei , Wang Yang , Huang Gang 
Published: May 2020

AbstractXuefu Zhuyu Decoction (XFZYD) is a traditional Chinese medicine prescription used for the clinical treatment of traumatic brain injury (TBI). The purpose of this work was to develop a sensitive and rapid UHPLC–MS/MS method to simultaneously study the pharmacokinetics of nimodipine and eight components of XFZYD, namely, amygdalin, hydroxysafflor yellow A, rutin, liquiritin, narirutin, naringin, neohesperidin and saikosaponin A, in rats with and without TBI. Multiple reaction monitoring was highly selective in the detection of nine analytes and the internal standard without obvious interference. The calibration curves displayed good linearity (r > 0.99) over a wide concentration range. The mean absolute recoveries of the nine analytes were 85–106%, and all matrix effects were in the range 80–120%. The intra‐ and inter‐day precision and accuracy were acceptable (RSD, <15%; RE%, ±20%). The validated method was successfully applied to compare the pharmacokinetics in four experimental groups, including control rats orally administered XFZYD and TBI model rats orally administered XFZYD, XFZYD and nimodipine, or nimodipine alone. The results showed that herb–drug interactions occurred between XFZYD and nimodipine in the treatment of TBI, nimodipine affected the pharmacokinetics of XFZYD, and XFZYD affected the absorption, distribution and excretion of nimodipine in vivo.
Nitrosoarenes as Nitrogen Source for Generation of Sulfonamides with the Insertion of Sulfur Dioxide under Metal‐Free Conditions†
Authors: Wang Xuefeng , Lin Yanmei , Liu Jin‐Biao , He Fu‐Sheng , Kuang Yunyan , Wu Jie 
Published: May 2020

Summary of main observation and conclusionA metal‐free reaction of nitrosoarenes, aryldiazonium tetrafluoroborates, and sulfur dioxide under mild conditions is developed, giving rise to sulfonamides in moderate to good yields. This transformation proceeds efficiently at room temperature in the presence of cyclohexa‐1,4‐diene with a broad reaction scope. Good functional group compatibility is observed, including cyano, halo, and ester. A plausible mechanism involving a radical process with the insertion of sulfur dioxide is proposed, and cyclohexa‐1,4‐diene serves as the reductant during the transformation.
Selenophene‐Flanked Diketopyrrolopyrrole Based Conjugated Polymers for Ambipolar Field‐Effect Transistors
Authors: Shi Dandan , Yu Xiaobo , Chen Liangliang , Chen Daoliang , Liu Zitong , Zhang Xisha , Zhang Guanxin , Zhang Deqing 
Published: May 2020

Summary of main observation and conclusionThe development of selenophene‐flanked DPP (SeDPP) based copolymers, especially for the ambipolar ones, lags behind other aromatic group flanked DPP‐based polymers. Herein, we report two new ambipolar SeDPP‐based conjugated polymers. One is the alternating polymer PSeDPPFT with normal SeDPP and 3,4‐difluorothiophene units. The other is PSeFDFT, in which the electron acceptor unit is replaced by a new SeDPP derivative, referred as to half‐fused SeDPP. The more planar structure of half‐fused SeDPP endows the backbone of PSeFDFT with good rigidity and planarity. Both polymers exhibit ambipolar transporting properties in air. The PSeFDFT based field‐effect transistors (FETs) display higher and more balanced ambipolar properties with μhave of 0.27 cm2·V–1·s–1, μeave of 0.18 cm2·V–1·s–1, and μhave/μeave of 1.5 than those of PSeDPPFT (μhave = 0.11 cm2·V–1·s–1, μeave = 0.042 cm2·V–1·s–1, and μh/μe = 2.6). This is attributed to the more planar structure, lower LUMO level, higher HOMO level, and better interchain packing orientations of PSeFDFT by comparing with PSeDPPFT. Therefore, a new molecular design strategy to modulate the hole and electron transporting properties is proposed for conjugated D‐A polymers.
Hemodynamics and tissue biomechanics of the thoracic aorta with a trileaflet aortic valve at different phases of valve opening
Authors: Sundström Elias , Jonnagiri Raghuvir , Gutmark‐Little Iris , Gutmark Ephraim , Critser Paul , Taylor Michael D. , Tretter Justin T. 
Published: May 2020

AbstractIn a normal cardiac cycle, the trileaflet aortic valve opening is progressive, which correlates with the phasic blood flow. Therefore, we aimed to determine the impact of including an anatomically accurate reconstructed trileaflet aortic valve within a fluid‐structure interaction (FSI) simulation model and determine the cyclical hemodynamic forces imposed on the thoracic aortic walls from aortic valve opening to closure. A pediatric patient with a normal trileaflet valve was recruited. Using the Cardiac Magnetic Resonance Data (CMR), a 3D model of the aortic valve and thoracic aorta was reconstructed. FSI simulations were employed to assess the tissue stress during a cardiac cycle as the result of changes in the valve opening. The blood flow was simulated as a mixture of blood plasma and red blood cells to account for non‐Newtonian effects. The computation was validated with phase‐contrast CMR. Windkessel boundary conditions were employed to ensure physiological pressures during the cardiac cycle. The leaflets' dynamic motion during the cardiac cycle was defined with an analytic grid velocity function. At the beginning of the valve opening a thin jet is developing. From mid‐open towards full opening the stress level increases where the jet impinges the convex wall. At peak systole two counter‐rotating Dean‐like vortex cores manifest in the ascending aorta, which correlates with increased integrated mean stress levels. An accurate trileaflet aortic valve is needed for capturing of both primary and secondary flow features that impact the forces on the thoracic aorta wall. Omitting the aortic valve underestimates the biomechanical response.
Evolution of guidelines for respiratory cytology by the Papanicolaou Society of Cytopathology
Authors: Moreira Andre L. 
Published: May 2020

AbstractCytology serves a fundamental role in the evaluation of the lower respiratory tract. Cytological specimens are often the first diagnostic attempt for the evaluation of radiographic alterations. The categorization of the pathological process as infectious, inflammatory or neoplastic is critical in guiding further clinical management of the affected patient. Therefore it is imperative that cytopathologists use a standardized approach to sample handling and reporting in order to establish clear communication with the treating physician. The Papanicolaou Society of cytopathology has been an active leader in this field and has proposed several guidelines for sampling, handling, and reporting of lower respiratory tract cytology. These guidelines have been updated to incorporate new emerging concepts and technologies in the field. Respiratory medicine is a fast growing area with constant new challenges, thus requiring an ever demanding adaptation from cytopathologists and cytology specific guidelines.
Bat community response to intensification of biomass production for bioenergy across the southeastern United States
Authors: Ober Holly K. , Jones Gavin M. , Gottlieb Isabel G. W. , Johnson Shelly A. , Smith Lora , Brosi Berry J. , Fletcher Robert J. 
Published: May 2020

AbstractHuman demand for food, fiber, and space is accelerating the rate of change of land cover and land use. Much of the world now consists of a matrix of natural forests, managed forests, agricultural cropland, and urbanized plots. Expansion of domestic energy production efforts in the United States is one driver predicted to influence future land‐use and land management practices across large spatial scales. Favorable growing conditions make the southeastern United States an ideal location for producing a large portion of the country’s renewable bioenergy. We investigated patterns of bat occurrence in two bioenergy feedstocks commonly grown in this region (corn,Zea mays, and pine,Pinus taedaandP. elliottii). We also evaluated potential impacts of the three major pathways of woody biomass extraction (residue removal following clearcut harvest, short‐rotation energy plantations, and mid‐rotation forest thinning) to bat occurrence through a priori land‐use contrasts. We acoustically sampled bat vocalizations at 84 sites in the Southeastern Plains and Southern Coastal Plains of the southeastern United States across three years. We found that mid‐rotation thinning resulted in positive effects on bat occurrence, and potential conversion of unmanaged (reference) forest to managed forest for timber and/or bioenergy harvest resulted in negative effects on bat occurrence when effects were averaged across all species. The effects of short‐rotation energy plantations, removal of logging residues from plantation clearcuts, and corn were equivocal for all bat species examined. Our results suggest that accelerated production of biomass for energy production through either corn or intensively managed pine forests is not likely to have an adverse effect on bat communities, so long as existing older unmanaged forests are not converted to managed bioenergy or timber plantations. Beyond bioenergy crop production, mid‐rotation thinning of even‐aged pine stands intended for timber production, increases to the duration of plantation rotations to promote older forest stands, arranging forest stands and crop fields to maximize edge habitat, and maintaining unmanaged forests could benefit bat communities by augmenting roosting and foraging opportunities.
A device for investigation of natural cell mobility and deformability
Authors: Ledvina Vojtěch , Klepárník Karel , Legartová Soňa , Bártová Eva 
Published: May 2020

AbstractA microfluidic device made of polydimethylsiloxane was developed for continuous evaluation of natural migration mobility of many eukaryotic cells in relaxed and deformed state. The device was fabricated by standard photolithography and soft lithography techniques using the SU‐8 3010 negative photoresist on a glass wafer as the master mold. The simple flow‐free device exploits the chemotactic movement of cells through a set of mechanical barriers in the direction of concentration gradients of attractants. The barriers are formed by arrays of circular cross‐section pillars with decreasing spacing 7, 5, and 3 μm. To pass through the obstacles, the cells are deformed and change their cytoskeletal architecture. The instantaneous migration velocities of cells are monitored in a time‐lapse setup of the scanning confocal microscope. Thus, the cellular deformability and migratory activity can easily be evaluated. The functionality of the device was tested with model HeLa cells stably transfected with fluorescent Premo FUCCI Cell Cycle Sensor. The designed device has the potential to be implemented for testing the tendency of patients’ tumors to metastasis.
Longitudinal Association Between Markers of Liver Injury and Mortality in COVID‐19 in China
Authors: Lei Fang , Liu Ye‐Mao , Zhou Feng , Qin Juan‐Juan , Zhang Peng , Zhu Lihua , Zhang Xiao‐Jing , Cai Jingjing , Lin Lijin , Ouyang Shan , Wang Xiaoming , Yang Chengzhang , Cheng Xu , Liu Weifang , Li Haomiao , Xie Jing , Wu Bin , Luo Huiming , Xiao Fei , Chen Jing , Tao Liang , Cheng Gang , She Zhi‐Gang , Zhou Jianghua , Wang Haitao , Lin Jun , Luo Pengcheng , Fu Shouzhi , Zhou Jihui , Ye Ping , Xiao Bing , Mao Weiming , Liu Liming , Yan Youqin , Liu Ling , Chen Guohua , Li Hongliang , Huang Xiaodong , Zhang Bing‐Hong , Yuan Yufeng 
Published: May 2020

Background and Aims
Coronavirus disease 2019 (COVID‐19) is a new infectious disease. To reveal the hepatic injury related to this disease and its clinical significance, we conducted a multicenter retrospective cohort study that included 5,771 adult patients with COVID‐19 pneumonia in Hubei Province.

Approach and Results
We reported the distributional and temporal patterns of liver injury indicators in these patients and determined their associated factors and death risk. Longitudinal liver function tests were retrospectively analyzed and correlated with the risk factors and death. Liver injury dynamic patterns differed in alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), and total bilirubin (TBIL). AST elevated first, followed by ALT, in severe patients. ALP modestly increased during hospitalization and largely remained in the normal range. The fluctuation in TBIL levels was mild in the non‐severe and the severe groups. AST abnormality was associated with the highest mortality risk compared with the other indicators of liver injury during hospitalization. Common factors associated with elevated liver injury indicators were lymphocyte count decrease, neutrophil count increase, and male gender.

Conclusion
The dynamic patterns of liver injury indicators and their potential risk factors may provide an important explanation for the COVID‐19‐associated liver injury. Because elevated liver injury indicators, particularly AST, are strongly associated with the mortality risk, our study indicates that these parameters should be monitored during hospitalization.
Using hysteretic behaviour and hydrograph classification to identify hydrological function across the “hillslope–depression–stream” continuum in a karst catchment
Authors: Zhang Runrun , Chen Xi , Zhang Zhicai , Soulsby Chris 
Published: May 2020

AbstractIn cockpit karst landscapes, fluxes from upland areas contribute large volumes of water to low‐lying depressions and stream flow. Hydrograph hysteresis and similarity between monitoring sites is important for understanding the space–time variability of hydrologic responses across the “hillslope–depression–stream” continuum. In this study, the hysteretic feature of hydrographs was assessed by characterizing the loop‐like relationships between responses at upstream sites relative to subsurface discharge at the outlet of a small karst catchment. A classification of hydrograph responses based on the multi‐scale smoothing Kernel ‐derived distance classifies the hydrograph responses on the basis of similarities between hillslope and depression sites, and those at the catchment outlet. Results demonstrate that the temporal and spatial variability of hydrograph hysteresis and similarity between hillslope flow and outlet stream flow can be explained by the local heterogeneity of depression aquifer. Large depression storage deficits emerging in the highly heterogeneous aquifer produce strong hysteresis and multiple relationships of upstream hydrographs relative to the outlet subsurface discharge. In contrast, when depression storage deficits are filled during consecutive rainfall events, depression hydrographs at the high permeability sites are almost synchronous or exhibit a monotonous function with the hydrographs at the outlet. This reduced hydrograph hysteresis enhances preferential flow paths in fractured rocks and conduits that can accelerate the hillslope flow to the outlet. Therefore, classification of hydrograph similarities between any upstream sites and the catchment outlet can help to identify the dominant hydrological functions in the heterogeneous karst catchment.
Efficacy and safety of pembrolizumab for the treatment of advanced biliary cancer: Results from the KEYNOTE‐158 and KEYNOTE‐028 studies
Authors: Piha‐Paul Sarina A. , Oh Do‐Youn , Ueno Makoto , Malka David , Chung Hyun Cheol , Nagrial Adnan , Kelley Robin K. , Ros Willeke , Italiano Antoine , Nakagawa Kazuhiko , Rugo Hope S. , de Braud Filippo , Varga Andrea Iolanda , Hansen Aaron , Wang Hui , Krishnan Suba , Norwood Kevin G. , Doi Toshihiko 
Published: May 2020

AbstractWe present data from patients with advanced biliary tract cancer (BTC) receiving pembrolizumab in the KEYNOTE‐158 (NCT02628067; phase 2) and KEYNOTE‐028 (NCT02054806; phase 1b) studies. Eligible patients aged ≥18 years from both studies had histologically/cytologically confirmed incurable BTC that progressed after standard treatment regimen(s), measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, Eastern Cooperative Oncology Group performance status 0/1, and no prior immunotherapy. Programmed death ligand 1 (PD‐L1)‐positive tumors were required for eligibility in KEYNOTE‐028 only. Patients received pembrolizumab 200 mg every three weeks (KEYNOTE‐158) or 10 mg/kg every two weeks (KEYNOTE‐028) for ≤2 years. Primary efficacy endpoint was objective response rate (ORR) by RECIST v1.1. Response assessed by independent central review is reported. KEYNOTE‐158 enrolled 104 patients and KEYNOTE‐028 enrolled 24 patients. Median (range) follow‐up was 7.5 months (0.6‐34.3) in KEYNOTE‐158 and 5.7 months (0.6‐55.4) in KEYNOTE‐028. In KEYNOTE‐158, ORR was 5.8% (6/104; 95% CI, 2.1%‐12.1%); median duration of response (DOR) was not reached (NR) (range, 6.2‐26.6+ months). Median (95% CI) OS and PFS were 7.4 (5.5‐9.6) and 2.0 (1.9‐2.1) months. Among PD‐L1‐expressers (n = 61) and PD‐L1‐nonexpressers (n = 34), respectively, ORR was 6.6% (4/61) and 2.9% (1/34). In KEYNOTE‐028, ORR was 13.0% (3/23; 95% CI, 2.8%‐33.6%); median DOR was NR (range, 21.5‐53.2+ months). Median (95% CI) OS and PFS were 5.7 (3.1‐9.8) and 1.8 (1.4‐3.1) months. Grade 3 to 5 treatment‐related adverse events occurred in 13.5% of patients in KEYNOTE‐158 (no grade 4; grade 5 renal failure, n = 1) and 16.7% in KEYNOTE‐028 (no grade 4/5). In summary, pembrolizumab provides durable antitumor activity in 6% to 13% of patients with advanced BTC, regardless of PD‐L1 expression, and has manageable toxicity.
Assessment of the clinical utility of pharmacogenetic guidance in a comprehensive medication management service
Authors: Rodríguez‐Escudero Idaliz , Cedeño Julio A. , Rodríguez‐Nazario Ileana , Reynaldo‐Fernández Gledys , Rodríguez‐Vera Leyanis , Morales Niretzy , Jiménez‐Vélez Braulio , Ruaño Gualberto , Duconge Jorge 
Published: May 2020

AbstractIntroductionPharmacists are poised to be the health care professionals best suited to provide medication‐related consults and services based on a patient's genetics. Despite its potential benefits, the implementation of pharmacogenetic (PGx) testing into primary clinical settings has been slow among medically underserved populations. To our knowledge, this is the first time that PGx‐driven recommendations have been incorporated into a Comprehensive Medication Management (CMM) service in a Hispanic population.ObjectivesThe aim of this study is to evaluate the clinical utility of adding PGx guidance into pharmacist‐driven CMM.MethodsThis is a pre‐ and post‐interventional design study. Patients were recruited from a psychologist's clinic. A total of 24 patients had a face‐to‐face interview with a pharmacist to complete a CMM, Personal Medication Record, and Medication‐Related Action Plan (MAP) blind to PGx findings. Collected buccal DNA samples were genotyped using drug‐metabolizing enzymes and transporters (DMET) Plus Array.ResultsThe pharmacist generated new MAPs for each patient based on PGx results. Genetic variants that could potentially affect the safety and effectiveness of at least one drug in the pharmacotherapy were identified in 96% of patients, for whom the pharmacist changed the initial recommendations. Polymorphisms in genes encoding for isoenzymes CYP2D6, CYP2C19, and CYP2C9 were identified in 83%, 52%, and 41% of patients, respectively. Pharmacists performing CMM identified 22 additional medication problems after PGx determinations. Moreover, they agreed with the clinical utility of PGx in the studied sample based on perceived value of adding PGx to traditional CMM and its utility in the decision‐making process of pharmacists.ConclusionsThe study confirmed the critical role to be played by pharmacists in facilitating the clinical usage of relevant genetic information to optimize drug therapy decisions as well as their involvement on many levels of these multidisciplinary implementation efforts, including championing and leading PGx‐guided CMM services.
Interplane bulk motion analysis and removal based on normalized cross‐correlation in optical coherence tomography angiography
Authors: Fan Jinyu , He Yi , Wang Pinghe , Liu Guangxing , Shi Guohua 
Published: May 2020

AbstractBulk motion seriously degrades the image quality of optical coherence tomography angiography (OCTA). Conventional correction methods focus on in‐plane displacement, while the bulk motion component perpendicular to B‐scans also introduces noise. This work first presents an evaluation of this component using a specific scan protocol and an approximate expression derived from peak‐normalized cross‐correlation values, and then quantitatively assesses how interplane bulk motion noise reduce the sensitivity of cross‐sectional angiograms. Finally, we developed a repetitive bulk motion correction method based on the estimated displacements and redundant volume scans. The correction does not require registration and angiogram reconstruction of low flow sensitivity frames, and the results of in vivo mice skin OCTA imaging experiments show that the proposed method can effectively reduce bulk motion noise caused by cardiac and respiratory motion and occasional shaking, and improve OCTA image quality, which has practical significance for clinical OCTA diagnosis and analysis.
How to unmask septal local abnormal ventricular activities with the new LUMIPOINTTM software
Authors: Solimene Francesco , Maddaluno Francesco , Malacrida Maurizio , Stabile Giuseppe 
Published: May 2020

AbstractWe report the use of the new automated tool LumipointTM for the detection of LAVA (local abnormal ventricular activities) when they are buried within the far‐field ventricular signal, especially in regions of preserved myocardial thickness, such as the left ventricular (LV) septum. The LV substrate and the tachycardia circuit during ventricular tachycardias of a 60‐year‐old man with dilated cardiomyopathy were mapped using an ultra‐high‐density mapping system and then the LumipointTM, analyzing the EGMs of interest, identified the LAVA in the inferoseptal region. This algorithm may be helpful to quickly target the septal substrate avoiding misleading interpretation.