bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative histogram parameters of dynamic contrast‐enhanced MRI as a potential imaging biomarker for assessing the expression of Ki‐67 in prostate cancer
Authors: Zhang Yongsheng , Li Zhiping , Gao Chen , Shen Jianliang , Chen Mingtao , Liu Yufeng , Cao Zhijian , Pang Peipei , Cui Feng , Xu Maosheng 
Published: June 2021

AbstractPurposeTo investigate whether preoperative histogram parameters of dynamic contrast‐enhanced MRI (DCE‐MRI) can assess the expression of Ki‐67 in prostate cancer (PCa).Materials and methodsA consecutive series of 76 patients with pathology‐proven PCa who underwent routine DCE‐MRI scans were retrospectively recruited. Quantitative parameters including the volume transfer constant (Ktrans), rate contrast (Kep), extracellular‐extravascular volume fraction (Ve), and plasma volume (Vp) by outlining the three‐dimensional volume of interest (VOI) of all lesions were processed. Then, the histogram analyses of these quantitative parameters were performed. The Spearman rank correlation analysis was used to evaluate the correlation of these parameters and Ki‐67 expression of PCa. Receiver operating characteristic (ROC) curve analysis was adopted to evaluate the efficacy of these quantitative histogram parameters in identifying high Ki‐67 expression from low Ki‐67 expression of PCa.ResultsEighty‐eight PCa lesions were enrolled in this study, including 31 lesions with high Ki‐67 expression and 57 lesions with low Ki‐67 expression. The median, mean, 75th percentile, and 90th percentile derived from Ktrans and Kep had a moderately positive correlation with Ki‐67 expression (r = 0.361–0.450, p < 0.05), in which both the median and mean of Ktrans had the highest positive correlation (r = 0.450, p < 0.05). The diagnostic efficacy of the Ktrans median, mean, 75th percentile, and 90th percentile, along with the Kep‐based median and mean was assessed by the ROC curve. The area under the curve (AUC) of the mean for Ktrans was the highest (0.826). When the cut‐off of the mean for Ktrans was ≥0.47/min, its Youden index, sensitivity, and specificity were 0.625, 0.871, and 0.754, respectively. The AUC of the median of Kep was the lowest (0.772).ConclusionThe histogram of DCE‐MRI quantitative parameters is correlated with Ki‐67 expression, which has the potential to noninvasively assess the expression of Ki‐67 with patients of PCa.
Indocyanine green is a sensitive adjunct in the identification and surgical management of local and metastatic hepatoblastoma
Authors: Lake Charissa M. , Bondoc Alexander J. , Dasgupta Roshni , Jenkins Todd M. , Towbin Alexander J. , Smith Ethan A. , Alonso Maria H. , Geller James I. , Tiao Gregory M. 
Published: June 2021

AbstractBackgroundHepatoblastoma is the most common primary pediatric liver malignancy. Indocyanine green (ICG) has been described as an adjunct to resection in small series. Its utility remains undefined in larger cohorts.MethodsRecords for 29 patients diagnosed with hepatoblastoma who received ICG prior to surgical resection from 2017 to 2020 at a single institution were retrospectively reviewed. The primary outcome was correlation between intraoperative ICG‐avidity and histologic presence of hepatoblastoma. A secondary outcome included the histologic margin designation for resected liver specimens.ResultsICG sensitivity was 91% for 120 resected thoracic specimens from 21 patients. Specificity was 57%. In 10% of operations, HB‐positive specimens were resected solely on ICG‐avidity. In an additional 40% of cases, ICG assisted in localizing a preoperatively diagnosed lesion. ICG sensitivity during thoracotomy and thoracoscopic surgery was 95 and 74%, respectively; primary and relapsed disease demonstrated sensitivity of 94 and 73%, respectively. Sensitivity was 92% for 25 resected liver specimens from nine patients with all parenchymal margins grossly negative for disease. Four multifocal lesions were identified with two resected solely by ICG‐avidity.ConclusionsICG is a sensitive adjunct for identifying local and metastatic hepatoblastoma, including lesions not visualized on preoperative imaging, and delineating margins during liver resection. False positives limit specificity; however, there were no adverse outcomes from additional resections. We noted that thoracoscopic surgery can be completed safely in patients with less significant disease burden, and conversion to thoracotomy, if necessary, is straightforward.
Effects of Apigenin on the Expression of LOX‐1, Bcl‐2, and Bax in Hyperlipidemia Rats
Authors: Xu Qian , Li Yan‐Chao , Du Chao , Wang Li‐Na , Xiao Yan‐Hong 
Published: June 2021

AbstractWe aimed to investigate the impact of apigenin on LOX‐1, Bcl‐2, and Bax expression in hyperlipidemia rats and explore the possible molecular pathological mechanism of apigenin in improving hyperlipidemia and preventing atherosclerosis. In hyperlipidemia models, the levels of total cholesterol (TC), triglyceride (TG), low‐density lipoprotein cholesterol (LDL‐c) and the LOX‐1 protein expression were apparently increased (P<0.01), while the high‐density lipoprotein cholesterol (HDL‐c) levels and the ratio of Bcl‐2/Bax were reduced significantly (P<0.01) in comparison with the standard control group. After the treatment of apigenin, the levels of TC, TG, LDL‐c, and the LOX‐1 protein expression were noticeably decreased (P<0.01), while the levels of HDL‐c and the Bcl‐2/Bax ratio were increased (P<0.01). The intima was thickened and had protrusions in the hyperlipidemia model group compared to the normal control group. In comparison with the atherosclerosis model group, the degree of aortic lesions in the low‐dose, middle‐dose, high‐dose groups was alleviated. Apigenin can reduce the level of blood lipid, improve hyperlipidemia, and prevent atherosclerosis in hyperlipidemia rats. The molecular mechanism may be related to inhibiting LOX‐1 gene expression and increasing the Bcl‐2/Bax ratio.
Future competencies for three demanding careers of industry 4.0: Robotics engineers, data scientists, and food designers
Authors: Rawboon Khwanruethai , Yamazaki Atsuko K. , Klomklieng Wannaphop , Thanomsub Wisa 
Published: June 2021

AbstractIntroductionThe Asian region is now a pivotal driver of global economic growth. Urgent discussions are thus mandated on the forthcoming demands for qualifications generating broad‐based knowledge and skillsets related to emergent challenges posed by the new industrial revolution. A survey of competencies that will be required is crucial for Asian universities and higher education institutions in other regions because a large percentage of university graduates are shortly likely to work in Asian countries.ObjectiveThis paper identified the future competencies for three careers that are representative of the demand for highly skilled personnel needed in potential industries during Industry 4.0: robotics engineers, data scientists, and food designers.MethodsThis study describes the insights attained through a literature review, followed by an intensive investigation of the required competencies via focus group discussions and individual interviews. A questionnaire survey was administered and in‐depth interviews were conducted to confirm the future competencies essential for the three stated careers. Finally, the robustness of the conducted analyses was verified.ResultsThe findings revealed the demand for a diverse mix of competencies in the current and prospective Industry 4.0 environment. Future employers are likely to highlight multidisciplinary skills that may be categorized into three crucial groups: social, personal, and methodological.ConclusionUniversities and higher education institutions across the world should inculcate the required competencies in students to foster necessary knowledge and skills to meet the demands of changing workplaces and promising opportunities over the next decade.
Genetic Incorporation of ϵ‐N‐Benzoyllysine by Engineering Methanomethylophilus alvus Pyrrolysyl‐tRNA Synthetase
Authors: Cao Li , Liu Jun , Ghelichkhani Farid , Rozovsky Sharon , Wang Lei 
Published: June 2021

AbstractPost‐translational modifications regulate protein structure and function. Lysine benzoylation is a newly discovered histone modification with unique physiological relevance. To construct proteins with this modification site‐specifically, we generated orthogonal tRNAPyl‐MaBzKRS pairs by engineering Methanomethylophilus alvus pyrrolysyl‐tRNA synthetase, allowing the genetic incorporation of ϵ‐N‐benzoyllysine (BzK) into proteins with high efficiency in E. coli and mammalian cells. Two types of MaBzKRS were identified to incorporate BzK using mutations located at different positions of the amino acid binding pocket. These MaBzKRS are small in size and highly expressed, which will afford broad utilities in studying the biological effects of lysine benzoylation.
Incidence, predictors and clinical impact of permanent pacemaker insertion in women following transcatheter aortic valve implantation: Insights from a prospective multinational registry
Authors: Nicolas Johny , Guedeney Paul , Claessen Bimmer E. , Mehilli Julinda , Petronio Anna Sonia , Sartori Samantha , Lefèvre Thierry , Presbitero Patrizia , Capranzano Piera , Iadanza Alessandro , Cao Davide , Chiarito Mauro , Goel Ridhima , Roumeliotis Anastasios , Chandiramani Rishi , Chen Siyan , Sardella Gennaro , Van Mieghem Nicolas M. , Sorrentino Sabato , Meliga Emanuele , Tchétché Didier , Dumonteil Nicolas , Fraccaro Chiara , Trabattoni Daniela , Mikhail Ghada W. , Ferrer‐Gracia Maria‐Cruz , Naber Christoph , Kievit Peter C. , Baber Usman , Sharma Samin K. , Morice Marie‐Claude , Dangas George D. , Chandrasekhar Jaya , Chieffo Alaide , Mehran Roxana 
Published: June 2021

AbstractObjectivesTo describe the incidence, predictors, and clinical impact of permanent pacemaker insertion (PPI) following transcatheter aortic valve replacement (TAVR) in women.BackgroundData on pacemaker insertion complicating TAVR in women are scarce.MethodsThe Women's International Transcatheter Aortic Valve implantation (WIN‐TAVI) is a prospective registry evaluating the safety and efficacy of TAVR in women. We included patients without preprocedural pacemakers and divided them into two groups: (1) PPI and (2) no‐PPI. We identified PPI predictors using logistic regression and studied its clinical impact on the Valve Academic Research Consortium (VARC)‐2 efficacy and safety endpoints.ResultsOut of 1019 patients, 922 were included in the analysis. Post‐TAVR PPI occurred in 132 (14.3%) patients. Clinical and procedural characteristics were similar in both groups. Pre‐existing right bundle branch block (RBBB) was associated with a high risk of post‐TAVR PPI (OR 3.62, 95% CI 1.85–7.06, p < 0.001), while implantation of balloon‐expandable prosthesis was associated with a lower risk (OR 0.47, 95% CI 0.30–0.74, p < 0.001). Post‐TAVR PPI prolonged in‐hospital stay by a median of 2 days (11 [9–16] days in PPI vs. 9 [7–14] days in no‐PPI, p = 0.005), yet risks of VARC‐2 efficacy and safety endpoints at 1 year were similar in both groups (adjHR 0.95, 95% CI 0.60–1.52, p = 0.84 and adjHR 1.22, 95% CI 0.83–1.79, p = 0.31, respectively).ConclusionPacemaker implantation following TAVR is frequent among women and is associated with pre‐existing RBBB and valve type. PPI prolongs hospital stay, albeit without any significant impact on 1‐year outcomes.
Versatile Reaction Pathways of 1,1,3,3,3‐Pentafluoropropene at Rh(I) Complexes [Rh(E)(PEt3)3] (E=H, GePh3, Si(OEt)3, F, Cl): C‐F versus C‐H Bond Activation Steps
Authors: Talavera Maria , Braun Thomas 
Published: June 2021

AbstractThe reaction of the rhodium(I) complexes [Rh(E)(PEt3)3] (E=GePh3 (1), H (6), F (7)) with 1,1,3,3,3‐pentafluoropropene afforded the defluorinative germylation products Z/E‐2‐(triphenylgermyl)‐1,3,3,3‐tetrafluoropropene and the fluorido complex [Rh(F)(CF3CHCF2)(PEt3)2] (2) together with the fluorophosphorane E‐(CF3)CH=CF(PFEt3). For [Rh(Si(OEt)3)(PEt3)3] (4) the coordination of the fluoroolefin was found to give [Rh{Si(OEt)3}(CF3CHCF2)(PEt3)2] (5). Two equivalents of complex 2 reacted further by C−F bond oxidative addition to yield [Rh(CF=CHCF3)(PEt3)2(μ‐F)3Rh(CF3CHCF2)(PEt3)] (9). The role of the fluorido ligand on the reactivity of complex 2 was assessed by comparison with the analogous chlorido complex. The use of complexes 1, 4 and 6 as catalysts for the derivatization of 1,1,3,3,3‐pentafluoropropene provided products, which were generated by hydrodefluorination, hydrometallation and germylation reactions.
Effect of Alkyl Structures on the Anti‐stacking and Anchoring of Pd/Diamine‐Functionalized Graphene Nanoparticles in Application in Suzuki Reaction
Authors: Tian Yinbing , Tang Zijie , Ru Yu , Wang Yuanyuan , Dai Liyi 
Published: June 2021

Main observation and conclusionThree diamines (1,8‐diaminooctane/p‐phenylenediamine/biphenylenediamine) with different alkyl groups were used to synthesize the functionalized graphene networks. Pd as the common metal catalyst was used to explore the effects of alkyl types of diamines on anti‐stacking, metal anchoring ability of functional graphene and hence the catalytic performance. The results were discussed by characterization of the material and its catalytic properties. All catalysts showed excellent catalytic performance on the Suzuki cross‐coupling reaction with a high yield of up to 100%. The p‐phenylenediamine and biphenylenediamine functionalized graphene with larger specific surface area was beneficial to improve the stability of the graphene catalyst and maintain good catalytic activity after 5 cycles. The Pd nanoparticles in 1,8‐octanediamine materials have smaller size and a smaller loading with the same or even better catalytic performance than p‐phenylenediamine, biphenylenediamine materials, due to the stronger electron donating ability of N of octanediamine than that of p‐phenylenediamine.
Exploratory echocardiographic strain parameters for the estimation of myocardial infarct size in ST‐elevation myocardial infarction
Authors: Dannenberg Varius , Christiansen Finn , Schneider Matthias , Kastl Stefan , Hofbauer Thomas Martin , Scherz Thomas , Mascherbauer Julia , Beitzke Dietrich , Testori Christoph , Lang Irene Marthe , Mangold Andreas 
Published: June 2021

AbstractBackgroundOutcome after ST‐elevation myocardial infarction (STEMI) can be most reliably estimated by cardiac magnetic resonance (CMR) imaging. However, CMR is expensive, laborious, and has only limited availability. In comparison, transthoracic echocardiography (TTE) is widely available and cost‐efficient.HypothesisTTE strain parameters can be used as surrogate markers for CMR‐measured parameters after STEMI.MethodsTTE strain analysis was performed of patients included in a controlled, prospective STEMI trial (NCT01777750) 4 ± 2 days after the event. Longitudinal peak strain (LPS), post‐systolic shortening, early systolic lengthening, early systolic lengthening time, and time to peak shortening were measured, and index parameters were computed. Global longitudinal strain (GLS) and ejection fraction (EF) were compiled. Parameters were correlated with CMR‐measured variables 4 ± 2 days after STEMI.ResultsIn 70 STEMI patients, high quality CMR and TTE data were available. Highest correlation with CMR‐measured infarct size was observed with GLS (r = 0.577, p < 0.0001), LPS (r = 0.571, p < 0.0001), and EF (r = −0.533, p < 0.0001). Highest correlation with CMR‐measured area at risk was observed with GLS (r = 0.666, p < 0.0001), LPS (0.661, p < 0.0001) and early systolic lengthening index (r = 0.540, p < 0.0001). Receiver operating characteristics for the detection of large infarcts (quartile with highest infarct size) showed the highest area under the curve for LPS, GLS, EF, and myocardial dysfunction index. Multiple linear regression displayed the best association between GLS and infarct size.ConclusionExploratory strain parameters significantly correlate with CMR‐measured area at risk and infarct size and are of potential interest as endpoint variables in clinical trials.
Identification of the FDA‐Approved Drug Pyrvinium as a Small‐Molecule Inhibitor of the PD‐1/PD‐L1 Interaction
Authors: Fattakhova Elena , Hofer Jeremy , DiFlumeri Juliette , Cobb Madison , Dando Timothy , Romisher Zachary , Wellington Justin , Oravic Michael , Radnoff Madison , Patil Sachin P. 
Published: June 2021

AbstractImmune checkpoint blockade involving inhibition of the PD‐1/PD‐L1 interaction has provided unprecedented clinical benefits in treating a variety of tumors. To date, a total of six antibodies that bind to either PD‐1 or PD‐L1 protein and in turn inhibit the PD‐1/PD‐L1 interaction have received clinical approvals. Despite being highly effective, these expensive large biotherapeutics possess several inherent pharmacokinetic limitations that can be successfully overcome through the use of low‐molecular‐weight inhibitors. One such promising approach involves small‐molecule induced dimerization and sequestration of PD‐L1, leading to effective PD‐1/PD‐L1 inhibition. Herein, we present the discovery of such potential bioactive PD‐L1 dimerizers through a structure‐ and ligand‐based screening of a focused library of approved and investigational drugs worldwide. Pyrvinium, an FDA‐approved anthelmintic drug, showed the highest activity in our study with IC50 value of ∼29.66 μM. It is noteworthy that Pyrvinium, being an approved drug, may prove especially suitable as a good starting point for further medicinal chemistry efforts, leading to design and development of even more potent structural analogs as selective PD‐1/PD‐L1 inhibitors. Furthermore, the adopted integrated virtual screening protocol may prove useful in screening other larger databases of lead‐ and drug‐like molecules for hit identification in the domain of small‐molecule PD‐1/PD‐L1 inhibitors.
Single‐Dose Pharmacokinetics and Tolerability of the Oral Epidermal Growth Factor Receptor Inhibitor Mobocertinib (TAK‐788) in Healthy Volunteers: Low‐Fat Meal Effect and Relative Bioavailability of 2 Capsule Products
Authors: Zhang Steven , Jin Shu , Griffin Celina , Feng Zhongling , Lin Jianchang , Baratta Mike , Brake Rachael , Venkatakrishnan Karthik , Gupta Neeraj 
Published: June 2021

AbstractMobocertinib (TAK‐788) is a tyrosine kinase inhibitor under investigation for treatment of non–small cell lung cancer with activating EGFR exon 20 insertions. This study examined the safety; tolerability; pharmacokinetics (PK), including food effects; and bioavailability of mobocertinib in healthy volunteers. In part 1, fasted volunteers were randomized to placebo or mobocertinib in single‐ascending‐dose cohorts (20‐160 mg). In part 2, mobocertinib (120/160 mg) was administered on day 1 of periods 1 and 2 under fasted or low‐fat meal conditions (2‐period, 2‐sequence crossover design). In part 3, fasted volunteers received mobocertinib 160 mg in 1 of 2 capsule products on day 1 of periods 1 and 2 with 7‐day washout. Safety and PK parameters were assessed. Sixty‐nine volunteers were enrolled (mean age, 29 years; 75% male). The most common adverse events (AEs; ≥10% of volunteers) were gastrointestinal AEs (25%‐50%) and headache (8%‐31%). No serious AEs were reported. A low‐fat meal did not affect the PK of mobocertinib or its active metabolites. The geometric mean terminal disposition phase half‐life (20 hours) supported once‐daily dosing. The 2 capsule products were bioequivalent. These data guided dosing and supported administration of mobocertinib without regard to low‐fat meal intake in ongoing and planned clinical studies.
3D Electron Diffraction Structure Determination of Terrylene, a Promising Candidate for Intermolecular Singlet Fission
Authors: Hall Charlie L. , Andrusenko Iryna , Potticary Jason , Gao Siyu , Liu Xingyu , Schmidt Werner , Marom Noa , Mugnaioli Enrico , Gemmi Mauro , Hall Simon R. 
Published: June 2021

AbstractHerein we demonstrate the prowess of the 3D electron diffraction approach by unveiling the structure of terrylene, the third member in the series of peri‐condensed naphthalene analogues, which has eluded structure determination for 65 years. The structure was determined by direct methods using electron diffraction data and corroborated by dispersion‐inclusive density functional theory optimizations. Terrylene crystalizes in the monoclinic space group P21/a, arranging in a sandwich‐herringbone packing motif, similar to analogous compounds. Having solved the crystal structure, we use many‐body perturbation theory to evaluate the excited‐state properties of terrylene in the solid‐state. We find that terrylene is a promising candidate for intermolecular singlet fission, comparable to tetracene and rubrene.
Rsg1.a3: A new allele conferring unique resistance to greenbug Biotype H at the Rsg1 locus in Hordeum vulgare ssp. spontaneum
Authors: Xu Xiangyang , Mornhinweg Dolores W. , Bai Guihua , Steffenson Brian , Bian Ruolin , Li Genqiao , Bernardo Amy 
Published: June 2021

AbstractGreenbug (Schizaphisgraminum Rondani) is one of the aphids causing significant cereal yield losses worldwide, and greenbug Biotype H is virulent to all known greenbug resistance genes in barley (Hordeum L.). Wild barley (Hordeum vulgare ssp. spontaneum) accession WBDC336 (PI 682028) exhibits resistance to greenbug Biotypes C, E, H, I, WY81, WY12 MC, and WY86. To investigate the genetics of greenbug resistance in WBDC336, a recombinant inbred line (RIL) population was developed from the cross Weskan × WBDC336. The RIL population was evaluated for responses to greenbug Biotype E and genotyped using genotyping‐by‐sequencing. Among 67,238 single nucleotide polymorphisms (SNPs) identified, 3,907 high quality SNPs were selected for gene mapping after several filtering steps. Linkage analysis positioned the greenbug resistance gene to a 1.14‐Mb interval in the terminal region of the long arm of chromosome 3H in WBDC336, where the greenbug resistance gene Rsg1 resides. Greenbug assays and an allelism test indicated that the greenbug resistance gene in WBDC336 is likely an allele at the Rsg1 locus and was given the allele designation Rsg1.a3. Two Kompetitive allele‐specific polymerase chain reaction (KASP) markers were developed from SNPs closely linked to Rsg1.a3, and these markers can be used to tag both alleles at the Rsg1 locus in breeding program utilizing marker‐assisted selection.